Intervenciones para mejorar la calidad del sueño en pacientes con enfermedad renal crónica
Resumen
Antecedentes
Los trastornos del sueño son frecuentes en los pacientes con enfermedad renal crónica (ERC). Se utilizan varios enfoques para mejorar la calidad del sueño en la práctica clínica, como las técnicas de relajación, el ejercicio, la acupresión y la medicación.
Objetivos
Evaluar la efectividad y los eventos adversos asociados de las intervenciones para mejorar la calidad del sueño en adultos y niños con ERC, incluidos los pacientes con insuficiencia renal terminal (IRT) tratados con diálisis o trasplante renal.
Métodos de búsqueda
Se realizaron búsquedas en el registro de estudios del Grupo Cochrane de Riñón y Trasplante hasta el 8 de octubre 2018, mediante contacto con el especialista en información y el uso de términos de búsqueda relevantes para esta revisión. Los estudios en el registro especializado se identifican mediante búsquedas en CENTRAL, MEDLINE y EMBASE, en el portal de búsqueda del International Clinical Trials Register (ICTRP) y en ClinicalTrials.gov.
Criterios de selección
Se incluyeron ensayos controlados aleatorios (ECA) o ECA cuasialeatorios de cualquier intervención en que los investigadores informaron de los efectos sobre la calidad del sueño. Dos autores, de forma independiente, examinaron los títulos y los resúmenes de los artículos identificados.
Obtención y análisis de los datos
Dos revisores extrajeron los datos de forma independiente y evaluaron el riesgo de sesgo de los estudios incluidos. Los resultados primarios fueron: la calidad, la latencia de inicio, la duración, la interrupción y la eficiencia del sueño. Se evaluaron los riesgos de sesgo con la herramienta Cochrane. La certeza de la evidencia se evaluó con los criterios GRADE. Se calcularon las variables de tratamiento como cocientes de riesgos (CR) para los resultados dicotómicos o la diferencia de medias (DM) o DM estandarizada (DME) para los resultados continuos con objeto de dar cuenta de la heterogeneidad en las medidas de calidad del sueño.
Resultados principales
Sesenta y siete estudios con 3427 participantes cumplieron con los criterios de elegibilidad. En los metanálisis se incluyeron 36 estudios con 2239 participantes. El seguimiento de los resultados clínicos osciló entre 0,3 y 52,8 semanas (mediana cinco semanas). Las intervenciones incluyeron: técnicas de relajación, ejercicio, acupresión, terapia cognitivo‐conductual (TCC), intervenciones educativas, tratamiento con benzodiazepinas, agonistas dopaminérgicos, apoyo telefónico, melatonina, reflexología, luminoterapia, diferentes formas de diálisis peritoneal, música, aromaterapia y masajes. El informe incompleto de los detalles metodológicos clave dio lugar a un riesgo de sesgo incierto en muchos estudios.
Según la evidencia de certeza muy baja, las técnicas de relajación tuvieron efectos inciertos sobre la calidad y la duración del sueño, la calidad de vida relacionada con la salud (CdVRS), la depresión, la ansiedad y la fatiga. Los estudios no fueron diseñados para evaluar los efectos de la relajación sobre la latencia del sueño ni la hospitalización. El ejercicio presentó efectos inciertos sobre la calidad del sueño (DME ‐1,10; IC del 95%: ‐2,26 a 0,05; I2 = 90%; cinco estudios, 165 participantes; evidencia de certeza muy baja). El ejercicio probablemente redujo la depresión (DM ‐9,05; IC del 95%: ‐13,72 a ‐4,39; I2 = 0%; dos estudios, 46 participantes; evidencia de certeza moderada) y la fatiga (DME ‐0,68; IC del 95%: ‐1,07 a ‐0,29; I2 = 0%; dos estudios, 107 participantes; evidencia de certeza moderada). En comparación con la intervención sin acupresión, la acupresión tuvo efectos inciertos sobre la calidad del sueño (Pittsburgh Sleep Quality Index [PSQI] escala 0‐21) (DM ‐1,27; IC del 95%: ‐2,13 a ‐0,40; I2 = 89%; seis estudios, 367 participantes: evidencia de certeza muy baja). La acupresión probablemente mejoró levemente la latencia del sueño (escala 0 ‐ 3) (DM ‐0,59; IC del 95%: ‐0,92 a ‐0,27; I2 = 0%; tres estudios, 173 participantes; pruebas de certeza moderada) y el tiempo de sueño (escala 0 ‐ 3) (DM ‐0,60; IC del 95%: ‐1,12 a ‐0).09; I2 = 68%; tres estudios, 173 participantes; evidencia de certeza moderada), aunque los efectos sobre las alteraciones del sueño fueron inciertos ya que la certeza de la evidencia fue muy baja (escala 0 ‐ 3) (DM ‐0,49; IC del 95%: ‐1,16 a 0,19; I2 = 97%). Según la evidencia de certeza moderada, la acupresión probablemente reduzca la fatiga (DM ‐1,07; IC del 95%: ‐1,67 a ‐0,48;2 = 0%; dos estudios, 137 participantes). La acupresión presentó efectos inciertos sobre la depresión (DM ‐3,65; IC del 95%: ‐7,63 a 0,33; I2 = 27%; dos estudios, 137 participantes;evidencia de certeza muy baja) y los estudios no fueron diseñados para evaluar el efecto de la acupresión en la CdVRS, la ansiedad ni la hospitalización. No estaba claro si la acupresión comparada con la acupresión simulada mejoró la calidad del sueño (escala de ICPQ 0 a 21) porque la certeza de la evidencias fue muy baja (DM ‐2,25; IC del 95%: ‐6,33 a 1,82; I2 = 96%; dos estudios; 129 participantes), pero el tiempo total de sueño puede haber mejorado (DME ‐0,34; IC del 95%: ‐0,73 a 0,04; I2 = 0%; dos estudios; 107 participantes; evidencia de certeza baja). 2 =2 = No hubo estudios diseñados para examinar o correlacionar de modo directo la eficacia de cualquier intervención orientada a mejorar el sueño en cuanto a los trastornos de la respiración durante el mismo. Ningún estudio informó de efectos del tratamiento en niños. Los efectos adversos de los tratamientos fueron muy inciertos.
Conclusiones de los autores
Es escasa la base de la evidencia para mejorar la calidad del sueño y los resultados relacionados en adultos y niños con ERC. Las técnicas de relajación y el ejercicio tuvieron efectos inciertos sobre los resultados del sueño. La acupresión puede mejorar la latencia y la duración del sueño, aunque estos resultados se basan en pocos estudios. Los efectos de la acupresión no se confirmaron en los estudios en que se utilizó la acupresión simulada como control. Según la evidencia de certeza muy baja, es muy probable que la investigación futura cambie la base de la evidencia. Dada la importancia del tratamiento de los síntomas en los pacientes, los cuidadores y los médicos, deben ser prioritarios los estudios futuros de las intervenciones para el sueño en los pacientes con ERC.
PICO
Resumen en términos sencillos
Intervenciones para mejorar el sueño en adultos y niños con enfermedades renales
¿Cuál es el problema?
Los pacientes con una nefropatía pueden presentar graves trastornos del sueño relacionados con la administración de fármacos, la depresión, la ansiedad, el dolor y el prurito, que afectan la calidad del sueño, incluido el tiempo requerido para conciliarlo, el insomnio y el tiempo total de sueño. Las enfermedades del riñón se asocian a trastornos de la respiración que pueden disminuir la calidad del sueño. Se analizó si el tratamiento podía ayudar a mejorar la calidad del sueño para los pacientes con una nefropatía. Se buscaron estudios que incluyeran niños y adultos con enfermedades del riñón, incluidos los sometidos a diálisis o con un trasplante renal.
¿Qué se hizo?
Se buscaron en las bases de datos electrónicas estudios de investigación de cualquier tratamiento para aliviar los trastornos del sueño. Los estudios debían ser aleatorios (los pacientes debían tener la misma oportunidad de recibir uno de los tratamientos del estudio). Se recopiló la información de los estudios y se combinaron los datos para identificar si el tratamiento fue útil o si hubo efectos secundarios importantes. Se evaluó si los tratamientos tenían efectos a partir del modo en que se realizaron los estudios (calidad). La información de esta revisión se actualizó hasta octubre 2018.
¿Qué se encontró?
Se hallaron 67 estudios con 3427 adultos. No se encontró ningún estudio en niños. Los tratamientos para el reposo incluyeron: relajación, ejercicio, fármacos, educación, apoyo psicológico, acupresión, música, aromaterapia y masajes. En general, los estudios fueron pequeños y la mayoría no permitió constatar beneficios ni la seguridad de los tratamientos. No se encontró información adecuada acerca de la relajación, el ejercicio ni los fármacos. Se halló que la acupresión puede reducir la cantidad de tiempo necesario para conciliar el sueño y puede aumentar el tiempo total de sueño. Sin embargo, no se observaron estos efectos sobre el sueño cuando se comparó la acupresión con la acupresión "simulada". No hubo suficiente información para saber acerca de los efectos secundarios de los tratamientos, o acerca de los tratamientos diseñados para ayudar a mejorar la respiración durante el sueño.
Conclusiones
La información sobre las maneras de ayudar a mejorar el sueño en pacientes con enfermedades del riñón no está preparada para ayudar a los pacientes de modo directo. Es muy probable que nuevos estudios de investigación modifiquen el conocimiento acerca de los tratamientos para el sueño en los pacientes con una nefropatía.
Authors' conclusions
Summary of findings
| Relaxation versus control for sleep outcomes in people with CKD | ||||||
| Patient or population: people with CKD Intervention: relaxation1 Comparison: without relaxation technique/training | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No. of participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Without relaxation training/technique | Relaxation training/technique | |||||
| Sleep quality PSQI (median follow‐up: 8 weeks) | The mean sleep quality index score ranged across control groups from 1.53 to 11.09 | The mean sleep quality index score in the intervention groups was 1.62 lower (95% CI ‐5.03 to 1.79) A lower score is indicative of higher sleep quality | MD ‐1.62 (95% CI ‐5.03 to 1.79) | 259 (4) | ⊕⊝⊝⊝ | It is very uncertain whether relaxation makes any difference to sleep quality |
| Sleep latency PSQI (median follow‐up: 8 weeks) | Only one study reported sleep latency | Not estimable as only a single study reported this measure | Not estimable. | Insufficient data observations | Not estimable | Studies were not designed to measure effects of relaxation on sleep latency |
| Quality of life Quality of Life Index ‐ dialysis version and Medical Outcome Studies 36‐Item Short Form Health Survey (median follow‐up: 6 weeks) | The mean quality of life index score ranged across control groups from 17.73 to 43.08 | The mean quality of life index score in the intervention groups was 0.47 higher (95% CI ‐0.09 to 1.04) A higher score is indicative of higher perceived of quality of life | SMD 0.47 (95% CI ‐0.09 to 1.04) | 138 (2) | ⊕⊕⊝⊝ | It is uncertain whether relaxation makes any difference to quality of life |
| Depression Center for Epidemiologic Studies Depression Scale and The Beck Depression Inventory II (median follow‐up: 6 weeks) | The mean depression index score ranged across control groups from 9.1 to 9.56 | The mean depression index score in the intervention groups was 0.04 higher (95% ‐1.27 to 1.35) A higher score is indicative of more depressive symptoms | SMD 0.04 (95% CI ‐1.27 to 1.35) | 108 (2) | ⊕⊝⊝⊝ | It is very uncertain whether relaxation makes any difference to depressive symptoms |
| Anxiety Beck Anxiety Inventory and Spielberger State‐Trait Anxiety Inventory (median follow‐up: 8 weeks) | The mean anxiety index score ranged across control groups from 31.61 to 34.9 | The mean anxiety index score in the intervention groups was 0.11 higher (95% CI ‐0.55 to 0.77) A higher score is indicative of more anxiety symptoms | SMD 0.11 (95% CI ‐0.55 to 0.77) | 119 (2) | ⊕⊝⊝⊝ | It is very uncertain whether relaxation makes any difference to anxiety |
| Fatigue PROMIS‐Fatigue Short Form 1.0 and Rhoten and Piper fatigue (median follow‐up: 8 weeks) | The mean fatigue score ranged across control groups from 55.5 to 81.17 | The mean fatigue score in the intervention groups was 0.61 lower (95% CI ‐2.09 to 0.87) A higher score is indicative of worse fatigue | SMD ‐0.61 (95% CI ‐2.09 to 0.87) | 119 (2) | ⊕⊝⊝⊝ | It is very uncertain whether relaxation makes any difference to fatigue |
| Hospitalisation (median follow‐up: 4 weeks) | Not estimable8 | Not estimable | Not estimable. | Insufficient data observations | Not estimable | Studies were not designed to measure effects of relaxation on hospitalisation |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 Relaxation techniques included progressive muscle relaxation, nurse‐led breathing training, mindfulness, and the Benson relaxation technique. 2 Three out of four studies had high or unclear risks of bias for allocation concealment, blinding of participants or investigators, and blinding of outcome assessment. 3 There was substantial heterogeneity in the findings of available studies that appeared related to a single study (Amini 2016). 4 The certainty in the evidence was downgraded due to imprecision in the treatment estimates, consistent with benefit or harm. 5 There was moderate heterogeneity in the findings of available studies. 6 There was substantial heterogeneity in the findings of available studies (two downgrades). 7 Risks of bias for the included studies were high for allocation concealment. 8 The estimated risk of hospitalisation was not estimable as a single study reported this outcome. | ||||||
| Exercise compared to control for sleep outcomes in people with chronic kidney disease (CKD) | ||||||
| Patient or population: people with CKD Settings: CKD Intervention: exercise1 Comparison: without exercise | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No. of participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Without exercise | Exercise | |||||
| Sleep quality PSQI, ESS and tri‐axial accelerometer (median follow‐up: 26.4 weeks) | The mean sleep quality score ranged across control groups from 8.85 to 43.6 | The mean sleep quality index score in the intervention groups was 1.10 lower (95% CI ‐2.26 to 0.05). A lower score is indicative of higher sleep quality | SMD ‐1.10 (95% CI ‐2.26 to 0.05) | 165 (5) | ⊕⊝⊝⊝ | It is very uncertain whether exercise makes any difference to sleep quality |
| Sleep latency | No data observations | Not estimable | No observations | Insufficient data observations | Not estimable | Studies were not designed to measure effects of exercise on sleep latency |
| Quality of life | No data observations | Not estimable | No observations | Insufficient data observations | Not estimable | Studies were not designed to measure effects of exercise on quality of life |
| Depression Zung Self‐Rating Depression Scale (ZUNG) (median follow‐up: 26.4 weeks) | The mean depression index score ranged across control groups from 43.7 to 43.71 | The mean depression index score in the intervention groups was 9.05 lower (95% CI ‐13.72 to ‐4.39) A higher score is indicative of worse depressive symptoms | MD ‐9.05 (95% CI ‐13.72 to ‐4.39) | 46 (2) | ⊕⊕⊕⊝ | Exercise probably decreases depressive symptoms |
| Anxiety Beck Anxiety Inventory (BECK) (median follow‐up: 8 weeks) | Only one study reported anxiety. | Not estimable as only a single study reported this measure | Not estimable. | Insufficient data observation | Not estimable | Studies were not designed to measure effects of exercise on anxiety |
| Fatigue PIPER Fatigue Scale (PFS) and Visual Analogue Scale (VAS) (median follow‐up: 13.2 weeks) | The mean fatigue index score ranged across control groups from 6.9 to 81.17 | The mean fatigue index score in the intervention groups was 0.68 lower (95% CI ‐1.07 to ‐0.29). A higher score is indicative of worse fatigue | SMD ‐0.68 (95% CI ‐1.07 to ‐0.29) | 107 (2) | ⊕⊕⊕⊝ | Exercise probably improves fatigue |
| Hospitalisation | No data observations | Not estimable | No observations. | Insufficient data observations | Not estimable | Studies were not designed to measure effects of exercise on hospitalisation |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; SMD: standardised mean difference; MD: mean difference | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 Exercise interventions were aerobic exercise daily, exercise during HD, and yoga‐based exercise 2 All studies in this analysis had unclear methods for allocation concealment, and outcomes were not clearly blinded in two of three studies 3 The certainty in the evidence was downgraded due to imprecision in the treatment estimates, leading to a treatment estimate consistent with benefit or harm 4 There was substantial heterogeneity in the findings of available studies (two downgrades) 5 None of the available studies reported low risk methods for allocation concealment 6 None of the available studies reported low risk methods for allocation concealment or blinding of outcome measures | ||||||
| Acupressure versus control for sleep outcomes in people with chronic kidney disease (CKD) | ||||||
| Patient or population: people with CKD Settings: CKD Intervention: acupressure Comparison: without acupressure (no treatment) | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No. of participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Without acupressure | Acupressure | |||||
| Sleep quality PSQI (median follow‐up: 4 weeks) | The mean sleep quality index score ranged across control groups from 1.29 to 11 | The mean sleep quality index score in the intervention groups was 1.27 lower (95% CI ‐2.13 to ‐0.40) A lower score is indicative of higher sleep quality | MD ‐1.27 (95% CI ‐2.13 to ‐0.40) | 367 (6) | ⊕⊝⊝⊝ | It is very uncertain whether acupressure makes any difference to sleep quality |
| Sleep latency PSQI (median follow‐up: 4 weeks) | The mean sleep latency index score ranged across control groups from 1.74 to 2.4 | The mean sleep latency index score in the intervention groups was 0.59 lower (95% CI ‐0.92 to ‐0.27) A lower score is indicative of shorter sleep latency | MD ‐0.59 (95% CI ‐0.92 to ‐0.27) | 173 (3) | ⊕⊕⊕⊝ | Accupressure may shorten sleep latency |
| Quality of life | No data observations. | Not estimable | No observations | Insufficient data observations | Not estimable. | Studies were not designed to measure effects of acupressure on quality of life |
| Depression Beck Depression Inventory (BECK) (median follow‐up: 4 weeks) | The mean depression index score ranged across control groups from 18.88 to 21.61 | The mean depression index score in the intervention groups was 3.65 lower (95% CI ‐7.63 to 0.33) A higher score is indicative of worse depressive symptoms. | MD ‐3.65 (95% CI ‐7.63 to 0.33) | 137 (2) | ⊕⊝⊝⊝ | It is very uncertain whether acupressure makes any difference to depressive symptoms |
| Anxiety | No data observations | Not estimable | No observations | Insufficient data observations | Not estimable. | Studies were not designed to measure effects of acupressure on anxiety |
| Fatigue PIPER Fatigue Scale (PSF) (median follow‐up: 4 weeks) | The mean fatigue index score ranged across control groups from 5.7 to 5.71 | The mean fatigue index score in the intervention groups was 1.07 lower (95% CI ‐1.67 to ‐0.48) A higher score is indicative of worse fatigue | MD ‐1.07 (95% CI ‐1.67 to ‐0.48) | 137 (2) | ⊕⊕⊕⊝ | Accupressure may reduce fatigue |
| Hospitalisation | No data observations | Not estimable | No observations | Insufficient data observations | Not estimable | Studies were not designed to measure effects of acupressure on hospitalisation |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; SMD: standardised mean difference; MD: mean difference | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 None of the studies reported low risk methods for allocation concealment but one was unblinded for participants and investigators 2 There was substantial heterogeneity in the findings of available studies (2 downgrades) 3 None of the studies reported low risk methods for allocation concealment or was blinded for participants and investigators 4 The certainty in the evidence was downgraded due to imprecision in the treatment estimates, leading to a treatment estimate consistent with benefit or harm 5 There was moderate heterogeneity in the findings of available studies | ||||||
Background
Description of the condition
Sleep duration and quality is commonly decreased in people with chronic kidney disease (CKD) and sleep disorders are often present even in the early stages of CKD. The prevalence rate of any sleep disorder in CKD ranges from 45% to 80% in adults with end‐stage kidney disease (ESKD) and affects approximately half of patients with earlier stages of CKD (Iliescu 2004). The true prevalence is uncertain due to heterogeneous definitions of sleep quality including problems initiating or maintaining sleep, early or difficulty waking, restlessness, tiredness on waking, and daytime sleepiness (Murtagh 2010). Risk factors of sleep disturbance in the general population such as older age, male gender, obesity, smoking, increased neck circumference and diabetes are also prevalent in the CKD population (Roumelioti 2011). Dialysis treatment modality may impact sleep dysfunction. People treated with automated peritoneal dialysis (PD) appear to have less severe sleep‐related breathing disorders (SBD) compared to continuous ambulatory PD patients (Roumelioti 2016). Kidney transplantation is associated with a low rate of sleep disorders (Mavanur 2010).
Among people with CKD, sleep disorders have been associated with impaired neurocognition, including inattention, lower performance at school or productivity at work, and driving related accidents (Ezzat 2015; Stabouli 2016). CKD is associated with sleep apnoea (central and obstructive), in part due to altered ventilatory control and upper airway obstruction (Markou 2006; Sim 2009). Poor sleep quality is a source of patient stress and is linked to lower health‐related quality of life (HRQoL) (Iliescu 2003), depression and greater use of antidepressants, narcotics and hypnotic medications, and worse life expectancy in people with a range of kidney function (Elder 2008; Kumar 2010; Unruh 2006). Overall, impaired sleep is experienced by patients as changes in their sleep‐wake cycle (insomnia, excessive sleepiness or both) and sleep‐disordered breathing (Young 2004). Contributing factors include restless legs syndrome (RLS) or periodic leg movement, night‐time dialysis care, depressed mood and anxiety, increased prescribing of neuroactive medications and analgesia, pain and itch, and altered sleep hygiene including napping during the day (Ogna 2016). Sleep disorders have been associated with increased cardiovascular risk and may contribute to the morbidity and mortality of people with advanced (stages 4 to 5) CKD and those treated with dialysis (Roumelioti 2011). Some studies have shown that sleep disturbances are associated with increased cardiovascular risk and arterial hypertension (Gonçalves 2007), subclinical atherosclerosis (Drager 2009), coronary heart disease (Hung 1990), heart failure (Hedner 1990), arrhythmias (Hoffstein 1994), cerebrovascular disease (Munoz 2006), type 2 diabetes mellitus and dysglycaemia (Botros 2009; Shpirer 2011), metabolic syndrome and its components (Assoumou 2012; Kono 2007) and dyslipidaemia (Assoumou 2012;Drager 2010). The major causes for a disordered sleep in CKD derive from biological, psychological, and environmental factors (Ahmad 2013; Ezzat 2015). Putative determinants of sleep disorders in people with ESKD include serum concentrations of creatinine, urea, phosphorus, parathyroid hormone (PTH), anaemia, nocturnal hypoxaemia, blood pressure, disease intrusiveness, time on dialysis, and comorbidity. Psychological factors and treatment‐related factors (such as nocturnal dialysis) may cause alterations in sleep and insomnia in CKD patients (De Santo 2008).
Description of the intervention
Due to the variable causes of altered sleep quality in people with CKD, a range of interventions are used including behavioural therapy with or without medication. A suggested approach to management of sleep has been to identify and treat any specific cause including disordered breathing, restless leg syndrome, pruritus, depression and anxiety, or pain (Murtagh 2010). General approaches to sleep management include a range of behavioural therapies such as sleep hygiene, stimulus control, and avoidance of caffeine, alcohol, and daytime sleeping, short‐term hypnotics to re‐establish sleep patterns, exercise, and complementary therapies (Jespersen 2015). CKD may constrain the use of neuroactive medications, which can lead to dependence if used in the longer‐term.
How the intervention might work
Numerous interventions including behavioural therapy, exercise, pharmacological agents and complementary therapy in addition to specific treatments for conditions associated with sleep impairment have individual mechanisms of action. In general, the effectiveness and safety of treatments may differ in people with CKD due to the frequency of additional severe symptoms including fatigue, pain, and depression, inactivity and frailty, and the altered metabolism of commonly‐used medications that may cause over‐sedation or lead to interactions with other treatments.
Why it is important to do this review
People with CKD have identified the importance of research focused on developing better treatments to reduce symptoms of CKD (Manns 2014; Tong 2008). In this review, we aimed to summarise the current evidence for treatments to improve sleep quality in CKD. This review is required given the range of causes of impaired sleep, the heterogeneity in available treatments and their potential for adverse effects, the impact of sleep changes on quality of life and prognosis, and the relative priority placed on research to manage symptoms by patients and caregivers.
Objectives
To assess the effectiveness and associated adverse events of interventions designed to improve sleep quality among adults and children with CKD.
Métodos
Obtención y análisis de los datos
Evaluación de la heterogeneidad
Results
Description of studies
Characteristics of included studies; Characteristics of excluded studies; Characteristics of studies awaiting classification; Characteristics of ongoing studies
Results of the search
The electronic search strategy of the Cochrane Kidney and Transplant Specialised Register (8 October 2018) identified 127 records (Figure 1). After duplicates were removed we screened the titles and abstracts and 10 records were excluded (not RCTs). The full text of the remaining 114 records was evaluated. We included 67 studies (92 records) and excluded 3 studies (10 records). We also identified 11 ongoing studies and one study is completed but with no published results ‐ these studies will be assessed in a future update of this review.
Study flow diagram.
Included studies
Sixty‐seven studies (3427 participants) reported in 92 publications were included in the systematic review (Afshar 2011; Amini 2016; Aoike 2018; Arab 2016; Bro 1999; Burkhalter 2015; Champagne 2008; Chen 2008a; Chen 2011a; Cho 2018; Chow 2010; Dai 2007a; Dashti‐Khavidaki 2011; Dauvilliers 2016; Duarte 2009; Edalat‐Nejad 2013; EMSCAP 2009; Farrokian 2016; Ghavami 2016; Giannaki 2013; Giannaki 2013a; Hanna 2013; Hou 2014; IRCT2013021212448N1; IRCT2014061717237N3; IRCT2015051122218N1; Jean 1995; Kolner 1989; Li 2014b; MELODY 2013; Micozkadioglu 2004; Momennasab 2018; Muz 2017; Nasiri 2011; Natarajan 2003; NCT02825589; Parker 2007; Pellecchia 2004; Pellizzaro 2013; Pieta 1998; Pooranfar 2014; Rambod 2013; Razazian 2015; Reilly‐Spong 2015; Ren 2017a; Sabbatini 2003; Saeedi 2014; Shariati 2012; SIESTA 2017; Silva 2017; Sklar 1998; Solak 2012; Soleimani 2016; Soreide 1991; Sun 2017; Tol 2010; Trenkwalder 1995; Tsai 2015; Tsay 2003a; Tsay 2004; Turk 2010; Unal 2016; Walker 1996; Williams 2017; Yurtkuran 2007; Zhao 2011; Zou 2015). Thirty‐six studies involving 2239 participants were included in meta‐analysis. Thirty‐one studies were not included in meta‐analyses as outcome data were not reported in a format that could be extracted for analysis (Aoike 2018; Champagne 2008; Chen 2008a; Edalat‐Nejad 2013; EMSCAP 2009; Ghavami 2016; Hanna 2013; IRCT2013021212448N1; IRCT2014061717237N3; IRCT2015051122218N1; Jean 1995; Kolner 1989; Micozkadioglu 2004; Nasiri 2011; NCT02825589; Parker 2007; Pellecchia 2004; Pellizzaro 2013; Pieta 1998; Pooranfar 2014; Ren 2017a; Sabbatini 2003; Silva 2017; Sklar 1998; Solak 2012; Soreide 1991; Tol 2010; Trenkwalder 1995; Turk 2010; Walker 1996; Williams 2017).
Studies were published between 1989 and 2018. Thirty‐seven studies received funding from governmental or healthcare organisations, and thirty studies did not report a funding source. Sixty‐one studies enrolled 3201 people treated with long‐term dialysis. Of these, 57 studies involved participants on haemodialysis and four studies involved participants treated with peritoneal dialysis (Bro 1999; Chen 2008a; Chow 2010; Li 2014b). One study reported 14 patients treated with either haemodialysis and peritoneal dialysis (Pieta 1998), one study involved 63 kidney transplant candidates who were treated with haemodialysis, or peritoneal dialysis or who were pre‐dialysis (Reilly‐Spong 2015). Three studies enrolled 104 kidney transplant recipients (Burkhalter 2015; Hanna 2013; Pooranfar 2014) and one study enrolled 45 people with CKD stages 3 and 4 (Aoike 2018).
Studies were conducted in Australia (SIESTA 2017), Brazil (Aoike 2018; Duarte 2009; Pellizzaro 2013; Silva 2017), Canada (Champagne 2008; Pieta 1998; Walker 1996), China (Chow 2010; Dai 2007a; Hou 2014; Li 2014b; Ren 2017a; Sun 2017; Zhao 2011; Zou 2015), Denmark (Bro 1999), France (Jean 1995), Germany (Trenkwalder 1995), Greece (Giannaki 2013; Giannaki 2013a), Iran (Afshar 2011; Amini 2016; Arab 2016; Dashti‐Khavidaki 2011; Edalat‐Nejad 2013; Farrokian 2016; Ghavami 2016; IRCT2013021212448N1; IRCT2014061717237N3; IRCT2015051122218N1; Momennasab 2018; Nasiri 2011; Pooranfar 2014; Rambod 2013; Razazian 2015; Saeedi 2014; Shariati 2012; Soleimani 2016), Italy (Pellecchia 2004; Sabbatini 2003), Korea (Cho 2018), Slovakia (Tol 2010), Switzerland (Burkhalter 2015; Hanna 2013), Taiwan (Chen 2008a; Chen 2011a; Tsai 2015; Tsay 2003a; Tsay 2004), Thailand (NCT02825589), The Netherlands (EMSCAP 2009; MELODY 2013; Parker 2007), Turkey (Micozkadioglu 2004; Muz 2017; Solak 2012; Turk 2010; Unal 2016; Yurtkuran 2007), and the USA (Kolner 1989; Natarajan 2003; Reilly‐Spong 2015; Sklar 1998; Soreide 1991; Williams 2017). One study was conducted both in the USA and Europe (Dauvilliers 2016).
The mean age of participants in the 36 studies contributing outcome data was 54.3 years. Follow‐up for clinical outcomes ranged between 0.3 and 52.8 weeks (median 5 weeks).
Sleep interventions
The methods for implementation, tailoring, and measurement of adherence of interventions are provided in Table 1 using a TIDIeR (Template for Intervention Description and Replication) checklist (Hoffmann 2014).
| Study ID | Intervention | Control | Materials | Sleep intervention | Adherence | ||||
| Why | What | How | Who provided, where and when | Tailoring/modification | How well: Planned | How well: Actual | |||
| Exercise | Control | To determine the effects of aerobic training on sleep quality, serum leptin, and inflammatory status | People in the intervention group cycled during the 1st two hours of each dialysis | Regular aerobic training which consisted | 3 sessions per week, for 3 weeks in the clinic | Patients were asked to cycle at an intensity of 12 to 15 of 20 at the rate of perceived exertion of Borg scale, of an individual’s maximal capacity | Blood pressure and heart rate of the participants | The number of patients who completed the study interventions was not reported | |
| Relaxation | Control 1: Exercise Control 2: Control | Investigate aerobic exercise and progressive muscle relaxation on anxiety, fatigue, and sleep disorders | Explained to patients while undergoing HD. Recording about muscle relaxation shown | Recording shown to patients. Patients were corrected on technique. Patients then did exercises at home using recording | There was the supervision of a researcher. The intervention was performed daily in the clinic or at home, for 60 days for 8 weeks | ‐ | Researcher followed up every two weeks to encourage exercise program or exclude patients who did not adhere | The number of patients who completed the study interventions was not reported | |
| Exercise | Control 1: Exercise Control 2: Control | To test if home‐based | The patients included in the exercise | The home‐based performed exercise at home, the others at an exercise centre | A physiologist provided the intervention. Exercises were performed in the centre or at home for 30 min for 8 weeks | The exercise training intensity was prescribed according to | ‐ | 40 patients completed the study | |
| Acupressure | Control 1: Sham Control 2: Control | To investigate the effect of acupressure on the sleep and quality of life | The intervention group received acupressure in the bilateral Shenmen points. The others received either sham acupressure or no treatment | Acupressure was applied using a circular movement. The sham was performed on points at 0.5 cm from the true points | A trained researcher provided the intervention in the clinic for 8 minutes, 3 times a week for 8 weeks | ‐ | To establish consistency of performance, the amount of pressure applied was measured using a scale; 30 measurements were recorded | 93 patients completed the study | |
| CAPD | APD | To test if there should be a difference between the effects of APD compared to CAPD on quality of life and clinical outcomes | 17 patients were | CAPD and APD devices | Skilled PD nurses provided the intervention in the clinic. APD and CAPD were delivered for 26.4 weeks | One patient on CAPD needed an additional exchange to achieve the target dialysis dose | During the study, patients were seen at monthly controls in the CAPD unit. Adequacy tests were performed every 3 months | 25 patients completed | |
| Light | Control | To evaluate the feasibility of the intervention and to assess its efficacy for improving sleep | To receive the appropriate dosage, at a time determined by individual chronotype | The patient sited 30–50 cm from the light box lamp, which produced light at eye level | The principal investigator instructed participants on the light box’s use to perform at home, 30 min daily for 3 weeks | We allowed for a 1.5 h deviation from the optimum starting time | ‐ | 28 patients completed | |
| HDF | HD | To compare sleep apnoea severity in HD and HDF | Polysomnography was used to assess the efficacy of the intervention | After the prescribed period, these treatments were inverted | Thrice‐weekly schedules for 13.2 weeks (first phase) in the clinic | ‐ | ‐ | At the end of phases II, 6 patients completed | |
| CBT | Education | To investigate the effectiveness | To assist participants in identifying, challenging, and changing misconceptions about sleep | Participants were instructed to relieve muscular tension and perform rhythmic breathing | Research staff (psychiatrist, nephrologist, nurse) provided the intervention at home, 1 hour weekly for 4 weeks | ‐ | ‐ | 24 patients completed | |
| CBT | Education | To validate the efficacy of | To assist participants in identifying, challenging, | The intervention included a psychiatrist‐oriented, video assisted | 2 psychiatrists | ‐ | ‐ | All patients who received the treatment completed the study | |
| Exercise (aerobic exercise) | Control 1: Exercise (resistance exercise) Control 2: Exercise (combination exercise) Control 3: Control | To investigate the effect of intra dialytic exercise on daily physical activity and sleep quality, measured by an accelerometer | To perform recumbent stationary | A stationary bike or Coloured elastic resistive bands and soft weights were used. All the exercises were performed in a supine or a sitting position | A researcher provided the intervention in the clinic: 5‐min warm‐up and maximum of 30 min for 12 weeks | According to patients’ performance, training loads were adjusted | Participants were encouraged to perform each exercise to optimise movement speed and muscle power | 46 patients completed | |
| Education | Control | To examine the effectiveness of a | Patients received a comprehensive discharge planning protocol and a standardized | All calls focused on health‐related behaviours and were | A nurse provided the training program of 24 hours in the clinic. A nurse contacted patients by telephone weekly for 6 weeks | Patients could referral to the community nurse, the renal team or to | Realistic action plan and participation of family members in | 85 patients completed | |
| Acupressure | Estazolam | To study the effect of lower extremity point massage for improving quality of sleep | 1 mg of estazolam tablets orally half an hour before sleep or acupressure | ‐ | Intervention was performed in the clinic or at home once a day, 20 to 30 seconds each time for 4 weeks | ‐ | ‐ | The number of patients who completed the study was not reported | |
| Benzodiazepine (zolpidem) | Benzodiazepine (clonazepam) | To compare zolpidem with clonazepam in terms of on sleep quality | 5 to 10 mg of zolpidem or 1 mg of clonazepam, orally | After the prescribed period these treatments were inverted | Daily for 2 weeks (first phase) at home | ‐ | ‐ | All patients completed the | |
| Dopaminergic agonist (rotigotine) | Control | To investigate the efficacy on periodic legs movement, sleep, RLS and quality of life | Polysomnography was performed on the 2 consecutive nights | ‐ | Trained personnel provided the intervention that was performed at home (1 to 3 mg of rotigotine) for 6 weeks | ‐ | ‐ | 25 patients completed the study | |
| CBT | Control | To assess the effectiveness | The patients attended sessions when they were | Educating on kidney disease, dialysis, depression and the therapeutic cognitive model. All sessions involved homework | 2 psychologists provided the intervention in the clinic: 12 weekly sessions for 13.2 weeks | Individualized psychotherapy session for providing guidelines | ‐ | 74 patients completed the study | |
| Melatonin | Control | Melatonin 3 mg | To assess the effect of the intervention on sleep quality | After the prescribed period these treatments were inverted | Melatonin 3 mg orally per day for 6 weeks (first phase) at home | ‐ | Compliance was confirmed by pill count | At the end of phases II, 68 patients completed the study | |
| Melatonin | Control | To investigate the effects of exogenous melatonin on | Actigraphy was used to assess the efficacy of the intervention | After the prescribed period these treatments were inverted | 3 mg of melatonin orally per day for 6 weeks (first phase) | ‐ | ‐ | At the end of phases II, 20 patients completed the study | |
| Reflexology | Control | To determine the effect of reflexology massage on sleep quality | Massage will be done by nurse of the same sex of the patient | Slow and regular rhythm massage | Trained nurses provided the intervention in the clinic: 12 sessions of 30 minutes, 3 day a week for 4 weeks | The depth of the massage depended on the patient's tolerance | ‐ | All patients completed the study | |
| Massage | Control | To determine the effectiveness of hot stone massage therapy on sleep quality level | Massage compared with routine health care | ‐ | 12 sessions | ‐ | ‐ | The number of patients who completed the study was not reported | |
| Exercise | Control 1: Dopaminergic agonist (ropinirole) Control 2: Control | To compare the changes across groups on RLS symptoms to evaluate quality of life | Cycling compared with ropinirole 0.25 mg orally | Exercise consisted of cycling in a recumbent cycle | A specialized neurologist provided exercises in the clinic 3 times per week, ropinirole was delivered 0.25 mg daily for 26.4 weeks | The exercise intensity was readjusted on a monthly base | ‐ | 29 patients completed the study | |
| Exercise | Control | To investigate the intervention that reduce RLS | The exercise session in both groups included intra‐dialytic cycling for 45 min at 50 rpm | The exercise included aerobic exercise performed in a recumbent cycle | A neurologist provided the intervention in the clinic for 45 min, 3 times per week for 26.4 weeks | The exercise intensity was readjusted every 4 weeks to account for the patients’ | ‐ | All patients completed the study | |
| Light | Control | To evaluate the efficacy of the intervention in people with sleep‐wake disturbance and depressive symptomatology | Morning light was scheduled according to chronotype daily. The rest‐activity cycle was monitored with a wrist actimeter | ‐ | 30 minutes daily for 3 weeks | ‐ | ‐ | The number of patients who completed the study was not reported | |
| CBT | Control | To verify the effects of sleep‐related behaviour modification in combination with progressive muscle relaxation on insomnia | During the interval of training, they did progressive | The physician did the progressive muscle relaxation for the patients and guided the patients | A physician provided the intervention in the clinic for 20 minutes every 2 days, 3 times week. Relaxation was performed daily at home for 30 min for 13.2 weeks | ‐ | ‐ | 98 patients completed the study | |
| Collaborative care model | Control | To determine the effect of collaborative care model on the fatigue | Care model included motivation, preparation, and evaluation | Sessions about the illness and the proper behaviour to deal with | Researchers, doctors and nurses provide the intervention in the clinic, 2 hours per day for 12 weeks | Half‐hour meetings were held to deal with specific needed | ‐ | The number of patients who completed the study was not reported | |
| Chamomile | Control | To determine the effect of camomile | The intervention group will take syrup of chamomile | ‐ | Chamomile 400 mg/day orally for 4 weeks at home | ‐ | ‐ | The number of patients who completed the study was not reported | |
| Acupressure | Control 1: Sham Control 2: Control | To determine the relationship between anxiety and sleep quality | In intervention group will receive acupressure in true acupoint | Acupressure will be done using pressure with the thumb | 2 trained practitioners provided the intervention in the clinic, 3 times a week for 4 weeks | ‐ | ‐ | The number of patients who completed the study was not reported | |
| Acetate dialysis | Bicarbonate dialysis | To assess the influence of buffer, acetate or bicarbonate, on sleep and ventilation | Polysomnography was used to assess the efficacy of the intervention | After the prescribed period these treatments were inverted. | The medical team provided the intervention in the clinic | ‐ | ‐ | At the end of phases II, all patients completed the study | |
| Benzodiapine (triazolam) | Control | To test the efficacy of Triazolam in HD patients with sleep disorder | ‐ | ‐ | Daily for 1 week at home | ‐ | ‐ | The number of patients who completed the study was not reported | |
| Telephone support | Control | To develop an original telephone support model for | Patients received a standardized nurse‐led | Sessions to optimise health outcomes. After discharge started telephone call | A nurse provided the intervention in the clinic. Telephone‐ | The patient’s needs were assessed with an individualized program | Each telephone call was guided by the protocol and were audio taped to ensure consistency | 135 patients had completed the follow‐up questionnaires | |
| Melatonin | Control | To investigate the effects of drug on sleep and quality of life in patients with | Actigraphy was used to assess the efficacy of the intervention | The actiwatch was placed on the wrist of the arm without fistula | Physicians provided the intervention in the clinic or at home: 3 mg of melatonin daily for 52.4 weeks | ‐ | ‐ | 42 patients completed the study | |
| Levodopa | Gabapentin | To find the efficacy of gabapentin compared with levodopa in the treatment of RLS | 125 mg/day of levodopa 2 hours before sleep. 200 mg of gabapentin after HD | After the prescribed period these treatments were inverted | 4‐week management for each drug (first phase) in the clinic or at home | ‐ | ‐ | 14 patients completed the study | |
| Music | Control 1: Music Control 2: Control | To compare the effectiveness | The music used was a 6‐pieces piano improvisation in | Participants were exposed to music via | Researchers provided the intervention that was performed in the clinic or at home for 4 weeks | The patient could stop or play the music whenever he/she liked or listen to it again | Patients were assessed about fulfilling the intervention | 102 patients completed the study | |
| Aromatherapy | Control | To determine the effect of aromatherapy on the sleep quality and fatigue | Aromatherapy group (sweet orange oil and lavender oil) | Lavender and sweet orange oils were dropped to a gauze bandage. Patients had to smell the aromatic mixture for 2 min | Researchers provided the intervention that was performed at home for one month for 2 min before sleeping | ‐ | Patients were called to report any problems. Answers were recorded, and support was provided | 62 patients completed the study | |
| Acupressure | Control | To evaluate the effectiveness of acupressure on quality of sleep | 4 points were pressured: this pressure was continuous with finger circularly for 1‐2 second | ‐ | Researcher and his cooperator provided the intervention in the clinic, 12 times for 5 min, 3 days per week for 4 weeks | ‐ | The force of pressure (consistency /reliability) were confirmed by using a scale | The number of patients who completed the study was not reported | |
| Melatonin | Control | To assess the effect of melatonin administration on sleep quality | Actigraphy was used to assess the efficacy of the intervention | Melatonin 3 mg orally per day, for 4 weeks (first phase) at home | ‐ | ‐ | At the end the first phase, all patients completed the study | ||
| Bioelectrical impedance | Control | To assess the effect of bioelectrical impedance analysis on sleep | ‐ | ‐ | 13.2 weeks | ‐ | ‐ | The number of patients who completed the study was not reported | |
| Dialysate 37° | Dialysate 35° | To test if cool dialysate would improve blood flow, heat dissipation and sleep | Subjects received HD in warm condition (37°C) or cool condition (35°C) | After the prescribed period these treatments were inverted | Trained nurses and nephrology co‐investigator provided the intervention in the clinic | ‐ | The personnel ensured the integrity and proper functioning of the equipment | The number of patients who completed the study was not reported | |
| Levodopa | Ropinirole | To determine the efficacy and adverse event profile of ropinirole as compared with levodopa | Levodopa dosage was 100 to 200 mg/d and ropinirole dosage was 0.25 to 2 mg/d | After the prescribed period these treatments were inverted | Medications were performed orally for 6 weeks (first phase) in the clinic or at home | Doses could be doubled according to the investigators’ and patients’ opinions | ‐ | 10 patients completed the study | |
| Respiratory muscle training | Control 1: Peripheral muscle training Control 2: Control | To assess the effects of interventions on functional parameters, inflammatory state, and quality of life | Spirometry was used to assess the efficacy of the intervention | Patients performed three sets of 15 inspirations and rested for 60 seconds | 30 training sessions for 10 weeks in the clinic | The exercise load was changed throughout | ‐ | 39 patients completed the study | |
| Dopaminergic agonist (pergolide) | Control | To test the effect of pergolide on leg movements and sleep disturbance | Polysomnography was used to assess the efficacy of the intervention | After the prescribed period these treatments were inverted | Pergolide from 0.05 to 0.25 for 1.5 weeks (first phase) at home | ‐ | ‐ | At the end of phases II, 8 patients completed the study | |
| Exercise | Control | To assess the effect of a period of exercise on sleep quality and quantity | Participants were acquainted with cycling method on bicycle ergometer, | The sessions | A researcher provided the intervention: 3 days a week for 10 weeks in 60–90 minute exercise sessions | The exercise | ‐ | The number of patients who completed the study was not reported | |
| Relaxation | Control | To evaluate the effect of the intervention on the sleep quality | The intervention group listened to the audiotape of Benson’s | The patients were instructed and were comfortably at rest in bed in a separate room | An expert provided the intervention that was performed twice a day for twenty minutes for 8 weeks, in the clinic or at home | ‐ | A CD on relaxation technique and research's number was given to the patients. Weekly Were provided | 83 patients completed the study | |
| Gabapentin | Dopaminergic agonist (levodopa/carbidopa) | To compare drugs in reducing symptoms and sleep problems | Gabapentin 200 mg orally compared to levodopa‐c 110 mg orally | ‐ | Gabapentin 200 mg (3 times weekly), levodopa‐c 110 mg in a single dose for 4 weeks at home | ‐ | ‐ | 83 patients completed the study | |
| Relaxation | Control | To reduce symptoms and improve quality of life using a multi‐modal telephone‐adapted program | Intervention was a bookend program. Actigraphy was used to assess the efficacy of the intervention | Workshops and teleconferences that included discussions, homework and practice | Certified teachers and a psychologist provided the intervention at the University. Teleconferences were held from patients' home for 8 weeks | Teacher ensured that yoga poses could be modified for people with disabilities. Emails were also used to document any deviations from checklists | Teleconferences used standard guidelines and each group had a unique password. | 52 patients completed the study | |
| Foot‐bath | Control | To explore the intervention effect of herb foot‐bath therapy to improve sleep quality and symptom | Herbs packed by gauze bag were put into a footbath with | Feet were put above the footbath in water | A course of treatment was four weeks; the | Once uncomfortableness and problems occurred, patient should stop the intervention and reported symptoms | ‐ | The number of patients who completed the study was not reported | |
| Benzodiazepine (zaleplon) | Control | To test the effects of | 5 to 10 mg of zaleplon | After the prescribed period these treatments were inverted | A nephrologist provided the intervention that was performed at home (5 to 10 mg of zaleplon) for 2 weeks (first phase) | ‐ | ‐ | At the end of phases II, 10 patients completed the study | |
| Education | Control | To investigate the effect of the intervention on the sleep quality for | Patients in the intervention | Direct teaching methods, combination of face‐to‐face | A researcher provided the intervention: 6 weekly sessions of half‐hour for 4 weeks | ‐ | ‐ | 76 patients completed the study | |
| Acupressure | Control | To investigate the effects of acupressure on sleep quality | Acupressure applied consistent pressure on the correct acupoints with small rotational | The intervention group | The investigators provided the intervention in the clinic: 15 min, 3 times per week for 4 weeks | Three acupoints that could be used to enhance sleep were chosen for the subjects | The precision was confirmed if subjects | 40 patients completed the study | |
| Acupressure | Sham | To investigate the effect and safety of acupressure on the sleep quality | ‐ | All selected acupoints were stimulated bilaterally | An accredited practitioner provided the intervention in the clinic (3 min, 3 times a week) for 4 weeks | The intensity was adjusted according to the | ‐ | 41 patients completed the study | |
| Continuous Positive Airway Pressure | Compression stockings | To evaluate the short‐term impact of treatments on the severity of sleep apnoea | Polysomnography was used to assess the efficacy of the intervention | After the prescribed period these treatments were inverted | A technician provided the intervention in the clinic for 1 week (first phase) | The lowest pressure was initially applied to all patients and increased progressively as needed | ‐ | At the end of phases II, 14 patients completed the study | |
| Dialyzer with cuprophan membrane | Dialyzer with poly‐methylmethacrylate membrane | To evaluate | Using two different types of membranes | After the prescribed period these treatments were inverted | The Medical team provided the intervention in the clinic thrice weekly, for 1 week (first phase) | ‐ | ‐ | At the end of phases II, 16 patients completed the study | |
| Gabapentin | Pregabalin | To compare the effects of drugs on sleep quality and depression | Electromyography was used to assess the efficacy of the intervention | After the prescribed period these treatments were inverted | A neurologist provided the intervention that was performed in the clinic or at home (gabapentin 300 mg thrice weekly, pregabalin 75 mg daily), for 6 weeks (first phase) | ‐ | ‐ | At the end of phases II, 48 patients completed the study | |
| Education | Control | To improve sleep quality through face‐to‐face sleep health education | Sleep hygiene education was performed. in two sections | The materials and a face‐to‐face session were provided | Researcher provided the intervention. This protocol was taught within an hour | ‐ | The participants asked questions and the materials were assessed | 57 patients completed the study | |
| Branch‐chain amino acid | Control | To assess the effect of the branch‐chain amino acid on sleep apnoea | Polysomnography was used to assess the efficacy of the intervention | After the prescribed period these treatments were inverted | For 2 study nights (first phase) | ‐ | ‐ | At the end of phases II, all patients completed the study | |
| Massage | Control | To assess if stimulating gastric activity improves relax and sleep | Abdominal massage, patient's education and training exercise | Massage to improve below contractility | Nurses provided the intervention in the clinic or at home for 4 weeks | ‐ | ‐ | Data were reported for all patients | |
| Gabapentin | Control | To determine changes on pruritus, quality of life, depression and sleep quality | Gabapentin 300 mg compared with placebo | After the prescribed period these treatments were inverted | Gabapentin 300 mg orally for 8 weeks (first phase) in the clinic or at home | ‐ | ‐ | At the end of phases II, all patients completed the study | |
| L‐dopa + benserazide | Control | To assess the effects of L‐dopa on sleep quality in restless leg syndrome | Polysomnography was used to assess the efficacy of the intervention | After the prescribed period these treatments were inverted | L‐dopa + benserazide (200mg + 50mg) orally for 4 weeks (first phase) at home | ‐ | Patients were monitored by phone calls | At the end of phases II, 28 patients completed the study | |
| Relaxation | Control | To examine the efficacy of a nurse‐led, | The dialysis nurse administered the audio device–guided breathing training in a quiet room | Patients listened to prerecorded | A trained nurse provided the intervention in the clinic: 8 sessions, twice weekly for 4 weeks | Each patient received an individual coaching session | The nurse supervised each practice session and evaluated | 57 patients completed the study | |
| Acupressure | Control 1: Sham Control 2: Control | To test the effectiveness of acupressure on sleep quality and fatigue | The intervention group received acupressure. The | Four acupoints were used to decrease fatigue | Researchers trained provided the intervention: 15 min, 3 times a week for 4 weeks | ‐ | The precision of acupressure was confirmed if | 98 patients completed the study | |
| Acupressure | Control 1: Acupressure (Transcutaneous Electrical Acupoint Stimulation) Control 2: Control | To test the effectiveness of the interventions on fatigue, sleep quality and depression | Acupressure compare with | Four acupoints were used to decrease fatigue | Investigators provided the intervention: 15 minutes of treatment | ‐ | The reliability of the pressure was assesses using a | 106 patients completed the study | |
| Phosphodiesterase type 5 (sildenafil) | Phosphodiesterase type 5 (vardenafil) | To compare the | Sildenafil 50 mg orally compared with Vardenafil 10 mg orally | After the prescribed period these treatments were inverted | The drugs were administered | ‐ | ‐ | The number of patients who completed the study was not reported | |
| Reflexology | Control 1: Massage Control 2: Control | To examine the effectiveness the interventions on | Foot reflexology compared with back massage and control group | 3 drops of baby oil were applied at room temperature to facilitate the massage | A researcher provided the intervention in the clinic: 30 minutes, 2 days a week for 4 weeks | ‐ | ‐ | 105 patients completed the study | |
| L‐dopa/carbidopa | Control | To determine if levodopa/carbidopa decreased leg movements and improved sleep | L‐dopa/carbidopa 100 mg + 25 mg compared with placebo | After the prescribed period these treatments were inverted | L‐dopa/carbidopa 100 mg + 25 mg daily for 1 week (first phase) at home | ‐ | ‐ | At the end of phases II, 5 patients completed the study | |
| Feedback group | Control | To determine if providing feedback | All participants were equipped with the tracking bracelet. Intervention group received feedback | Patients in the feedback group received their activity and sleep data at each dialysis treatment | Research coordinators provided the intervention in the clinic or at home. All participants wore the tracking bracelet at all times for 5 weeks | ‐ | ‐ | 29 patients completed the study | |
| Exercise | Control | To assess if yoga exercise can improve pain, fatigue, sleep disorder and biochemical markers | Yoga‐based exercises were done in groups | Using some yogic postures and breathing exercises in the rehabilitation of dialysis patients | A yoga teacher provided the intervention. Exercises were performed in the clinic or at home, 30 min/day twice a week for 13.2 weeks | Some modifications to the program were done to increase patient compliance. The exercise has to be stopped if there is severe fatigue or pain | The exercises was explained to each patient until the physiotherapist was satisfied that all of them could do the exercises | 37 patients completed the study | |
| Acupressure | Control | To assess the efficacy of acupressure | 4 auricular magnetic bead plaster points in fixed points | Take the side of each ear, 2 days later using another ear | Patient provided a self‐pressure twice daily for 56 days, for 8 weeks (at home) | ‐ | ‐ | The number of patients who completed the study was not reported | |
| Acupressure | Control | To assess the feasibility and | Participants received acupressure on five active acupoints | Participants were instructed to press the beads until a slight soreness were felt | Trained nurse practitioner provided the intervention in the clinic for 8 weeks | If the plasters or beads detached, the patients came to hospital | Feasibility was assessed by the percentage of recruitment, retention, | 58 patients completed the 8 weeks of treatment, 55 completed the 12 weeks of follow‐up | |
APD ‐ automated peritoneal dialysis; CAPD continuous ambulatory peritoneal dialysis; CBT ‐ cognitive‐behavioural therapy; HD ‐ haemodialysis; HDF ‐ haemodiafiltration; RLS ‐ restless legs syndrome
Among studies included in the meta‐analyses, interventions included relaxation techniques (progressive muscle relaxation, nurse‐led breathing training, mindfulness, and the Benson relaxation technique) in four studies (Amini 2016; Rambod 2013; Reilly‐Spong 2015; Tsai 2015) (291 participants), exercise in four studies (Afshar 2011; Cho 2018; Giannaki 2013a; Yurtkuran 2007) (138 participants), acupressure in eight studies (493 participants) (Arab 2016; Dai 2007a; Shariati 2012; SIESTA 2017; Tsay 2003a; Tsay 2004; Zhao 2011; Zou 2015), cognitive‐behavioural therapy (CBT) in three studies (255 participants) (Chen 2011a; Duarte 2009; Hou 2014), sleep hygiene education in three studies (Chow 2010; Saeedi 2014; Soleimani 2016) (220 participants), benzodiazepine medication in Dashti‐Khavidaki 2011 (23 participants), dopaminergic agonists in three studies (Giannaki 2013; Razazian 2015; Dauvilliers 2016) (136 participants), telephone support in Li 2014b (135 participants), melatonin in two studies (MELODY 2013; Natarajan 2003) (75 participants), reflexology in two studies (Farrokian 2016; Unal 2016) (167 participants), light therapy in Burkhalter 2015 (28 participants), different forms of peritoneal dialysis in Bro 1999 (34 participants), music in Momennasab 2018 (102 participants), aromatherapy in Muz 2017 (62 participants), and massage in Sun 2017 (80 participants).
Seven studies reported three treatment groups. In Amini 2016, relaxation techniques were compared with exercise or no treatment control. In Arab 2016 and Tsay 2003a, acupressure was compared with sham acupressure or no treatment control. In Tsay 2004 acupressure was compared with Transcutaneous Electrical Acupoint Stimulation (TEAS) or no treatment control. In Giannaki 2013, exercise was compared with a dopamine agonist (ropinirole) or placebo. In Momennasab 2018 music during haemodialysis was compared with music at bedtime or no treatment control. In Unal 2016, reflexology was compared with massage or no treatment control. Cho 2018 reported four treatment groups in which aerobic exercise was compared with resistance exercise, combination exercise or no treatment control.
Excluded studies
After full‐text review we excluded three studies. Cooper 2004 enrolled patients with uncontrolled hypertension while ACTIVE Dialysis 2015 and Deng 2017 did not report sleep outcomes (see Characteristics of excluded studies).
Risk of bias in included studies
See Figure 2; Figure 3 for summary of 'Risk of bias' assessments. Reporting of study methodology was incomplete for most studies. The summary risks of bias are shown in Figure 2 and risk of bias in each individual study is shown in Figure 3.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Allocation
Random sequence generation
Fifteen studies reported low risk methods for random sequence generation (Chen 2008a; Chen 2011a; Chow 2010; Farrokian 2016; Li 2014b; Pellecchia 2004; Rambod 2013; Reilly‐Spong 2015; Dauvilliers 2016; SIESTA 2017; Solak 2012; Tsai 2015; Turk 2010; Yurtkuran 2007; Zou 2015). One study reported inadequate (high risk) random sequence generation (Duarte 2009).The risk of bias from random sequence generation methods was unclear in the remaining 51 studies.
Allocation concealment
Five studies reported low risk methods for allocation concealment (Burkhalter 2015; Dauvilliers 2016; SIESTA 2017; Tsai 2015; Turk 2010). In one study (Chen 2008a) allocation concealment methods were at high risk of bias. Risk of bias from allocation concealment was unclear in the remaining 61 studies.
Blinding
Performance bias
Sixteen studies reported low risk methods for performance bias (Amini 2016; Edalat‐Nejad 2013; Giannaki 2013; EMSCAP 2009; Kolner 1989; IRCT2014061717237N3; MELODY 2013; IRCT2015051122218N1; Natarajan 2003; Pieta 1998; Razazian 2015; Dauvilliers 2016; Soreide 1991; Trenkwalder 1995; Walker 1996; Zou 2015). Performance bias was judged as high risk in 48 studies (Afshar 2011; Aoike 2018; Arab 2016; Bro 1999; Burkhalter 2015; Champagne 2008; Chen 2008a; Chen 2011a; Cho 2018; Chow 2010; Dai 2007a; Duarte 2009; Farrokian 2016; Ghavami 2016; Giannaki 2013a; Hanna 2013; Hou 2014; IRCT2013021212448N1; Li 2014b; Micozkadioglu 2004; Momennasab 2018; Muz 2017; Nasiri 2011; Parker 2007; Pellecchia 2004; Pellizzaro 2013; Pooranfar 2014; Rambod 2013; Reilly‐Spong 2015; Ren 2017a; Sabbatini 2003; Saeedi 2014; NCT02825589; Shariati 2012; SIESTA 2017; Silva 2017; Sklar 1998; Solak 2012; Soleimani 2016; Sun 2017; Tsai 2015; Tsay 2003a; Tsay 2004; Turk 2010; Unal 2016; Williams 2017; Yurtkuran 2007; Zhao 2011). Risks from performance bias was unclear in the remaining three studies.
Detection bias
Detection bias was judged to be low risk in 17 studies (Arab 2016; Cho 2018; Edalat‐Nejad 2013; Giannaki 2013; Hanna 2013; Jean 1995; EMSCAP 2009; MELODY 2013; Natarajan 2003; Parker 2007; Reilly‐Spong 2015; Dauvilliers 2016; SIESTA 2017; Soreide 1991; Tsay 2003a; Tsay 2004; Zou 2015) and high risk in 37 (Afshar 2011; Aoike 2018; Bro 1999; Chen 2008a; Chen 2011a; Chow 2010; Dai 2007a; Duarte 2009; Farrokian 2016; Ghavami 2016; Giannaki 2013a; Hou 2014; IRCT2013021212448N1; Micozkadioglu 2004; Momennasab 2018; Muz 2017; Nasiri 2011; Pellecchia 2004; Pieta 1998; Pooranfar 2014; Rambod 2013; Ren 2017a; Saeedi 2014; NCT02825589; Silva 2017; Sklar 1998; Solak 2012; Soleimani 2016; Sun 2017; Tol 2010; Trenkwalder 1995; Tsai 2015; Turk 2010; Unal 2016; Walker 1996; Williams 2017; Yurtkuran 2007). Risk of detection bias was unclear in the remaining 13 studies.
Incomplete outcome data
Attrition bias was low risk in 21 studies (Burkhalter 2015; Chen 2008a; Chen 2011a; Chow 2010; Dashti‐Khavidaki 2011; Farrokian 2016; Giannaki 2013a; Li 2014b; Momennasab 2018; Natarajan 2003; Rambod 2013; Saeedi 2014; SIESTA 2017; Solak 2012; Soleimani 2016; Soreide 1991; Tol 2010; Trenkwalder 1995; Tsay 2004; Unal 2016; Yurtkuran 2007) and high risk in 24 studies (Aoike 2018; Arab 2016; Bro 1999; Champagne 2008; Cho 2018; Duarte 2009; Giannaki 2013; Hou 2014; MELODY 2013; Micozkadioglu 2004; Muz 2017; Pellecchia 2004; Pellizzaro 2013; Pieta 1998; Razazian 2015; Reilly‐Spong 2015; Dauvilliers 2016; Sabbatini 2003; Silva 2017; Sklar 1998; Tsay 2003a; Tsai 2015; Walker 1996; Zou 2015). Risks from attrition bias were unclear in the remaining 22 studies.
Selective reporting
Thirty‐five studies were at low risk of reporting bias (Afshar 2011; Amini 2016; Aoike 2018; Arab 2016; Bro 1999; Burkhalter 2015; Chen 2008a; Chen 2011a; Cho 2018; Chow 2010; Dai 2007a; Dashti‐Khavidaki 2011; Dauvilliers 2016; Duarte 2009; Farrokian 2016; Giannaki 2013; Giannaki 2013a; Hou 2014; Li 2014b; MELODY 2013; Momennasab 2018; Muz 2017; Rambod 2013; Razazian 2015; Reilly‐Spong 2015; Saeedi 2014; Shariati 2012; Soleimani 2016; Sun 2017; Tsai 2015; Tsay 2003a; Tsay 2004; Unal 2016; Yurtkuran 2007; Zou 2015), and high risk in 23 studies (Edalat‐Nejad 2013; Ghavami 2016; Jean 1995; EMSCAP 2009; Micozkadioglu 2004; Nasiri 2011; Parker 2007; Pellecchia 2004; Pellizzaro 2013; Pieta 1998; Pooranfar 2014; Ren 2017a; Sabbatini 2003; SIESTA 2017; Silva 2017; Sklar 1998; Solak 2012; Soreide 1991; Tol 2010; Trenkwalder 1995; Turk 2010; Walker 1996; Williams 2017). The remaining nine studies were at unclear risk of reporting bias.
Other potential sources of bias
Thirty‐four studies were judged to be at low risk of other potential biases (Aoike 2018; Arab 2016; Bro 1999; Burkhalter 2015; Chen 2008a; Chen 2011a; Cho 2018; Chow 2010; Dai 2007a; Duarte 2009; Farrokian 2016; Giannaki 2013; Giannaki 2013a; Hou 2014; IRCT2013021212448N1; Li 2014b; MELODY 2013; Momennasab 2018; Muz 2017; Nasiri 2011; Pellizzaro 2013; Rambod 2013; Razazian 2015; Reilly‐Spong 2015; Saeedi 2014; Shariati 2012; Tsai 2015; Tsay 2003a; Tsay 2004; Unal 2016; Williams 2017; Yurtkuran 2007; Zhao 2011; Zou 2015), four studies were judged to be high risk of bias (Champagne 2008; Dauvilliers 2016; SIESTA 2017; Walker 1996), and risks of bias were unclear in the remaining 29 studies.
Effects of interventions
See: Summary of findings for the main comparison Summary of findings: relaxation versus control for sleep outcomes in people with chronic kidney disease (CKD); Summary of findings 2 Summary of findings: exercise versus control; Summary of findings 3 Summary of findings: acupressure versus control
There were no studies designed to directly examine and/or correlate efficacy of any interventions aimed at improving sleep that may have been attempted for the spectrum of sleep disordered breathing.
Relaxation versus control
Four studies (Amini 2016; Rambod 2013; Reilly‐Spong 2015; Tsai 2015) (259 participants) compared relaxation techniques with no treatment intervention. Interventions included progressive muscle relaxation, nurse‐led breathing, mindfulness, and the Benson relaxation technique. The median follow‐up in these studies was eight weeks. The certainty of the evidence was graded as low or very low for all outcomes (summary of findings Table for the main comparison) and several analyses showed evidence of moderate to substantial statistical heterogeneity.
Relaxation techniques had uncertain effects on the global Pittsburgh Sleep Quality Index (PSQI) score (scale 0 ‐ 21) (Analysis 1.1 (4 studies, 259 participants): MD ‐1.62, 95% CI ‐5.03 to 1.79; I2 = 97%; very low certainty evidence). Single studies reported no difference between relaxation and control for sleep latency (Analysis 1.2), total sleep time (Analysis 1.3), and hospitalisation (Analysis 1.5), and improved sleep disturbance with relaxation (Analysis 1.4); however meta‐analyses were not possible leading to very low certainty about the effects of relaxation on these outcomes. Relaxation techniques had very uncertain effects on anxiety (Analysis 1.6 (2 studies; 119 participants): SMD 0.11, 95% CI ‐0.55 to 0.77; I2 = 69%; very low certainty evidence). Relaxation techniques had uncertain effects on pain (Analysis 1.7 (3 studies, 189 participants): SMD ‐0.26, 95% CI ‐0.67 to 0.15; I2 = 49%; low certainty evidence), fatigue (Analysis 1.8 (2 studies, 119 participants): SMD ‐0.61, 95% CI ‐2.09 to 0.87; I2 = 93%; very low certainty evidence), quality of life (Analysis 1.9 (2 studies, 138 participants): SMD 0.47, 95% CI ‐0.09 to 1.04; I2 = 62%; low certainty evidence), and depressive symptoms (Analysis 1.10 (2 studies, 108 participants): SMD 0.04, 95% CI ‐1.27 to 1.35; I2 = 91%; very low certainty evidence). Studies were not designed to measure the effects of relaxation on death. Adverse events of relaxation techniques were rarely reported (Table 2).
| Study ID | Treatment | Control | Adverse events in treatment arm | Adverse events in control arm | Comment |
| CAPD | APD | Peritonitis (2); exit‐site infection (1) | Peritonitis (1); exit‐site infection (1); tunnel infection (1); leakage (1); hernia (1); over‐hydration (2) | Quote: "No proper statistics could be applied due to the low numbers of patients and events." | |
| Light | Control | No participants experienced an adverse event | No participants experienced an adverse event | Quote: "No adverse reactions or symptom complaints were registered." | |
| CBT | Education | No participants experienced an adverse event | No participants experienced an adverse event | Quote: "No adverse events were reported during the intervention." | |
| Exercise (aerobic exercise) | Control 1: Exercise (resistance exercise) Control 2: Exercise (combination exercise) Control 3: Control | No participants experienced an adverse event | No participants experienced an adverse event | Quote: "There were no reported adverse events, such as musculoskeletal injuries, hypoglycaemic episodes, cardiovascular events, or hospitalizations, as result of the intervention." | |
| Acupressure | Estazolam | No participants experienced an adverse event | No participants experienced an adverse event | This study was not in English Quote from the "Acupuncture and related interventions for symptoms of chronic kidney disease (Review)": "Whether adverse events related to administration of estazolam such as somnolence, dizziness, hypokinesia and abnormal coordination occurred was not reported in the control group. Potential adverse events of estazolam might have been regarded as one of outcomes (complaints of adverse reaction), not as adverse events." | |
| Benzodiazepine (zolpidem) | Benzodiazepine (clonazepam) | No participants experienced an adverse event | No participants experienced an adverse event | Quote: "In this study, zolpidem was not associated with undesirable sleep side effects such as daytime drowsiness, headache, or amnesia, at least during the short‐term course of our study. [...] Meanwhile, the patients who received zolpidem did not complain of any particular side effects." | |
| Dopaminergic agonist (rotigotine) | Control | Application site reaction of mild pruritus(1); anxiety (1); foot fracture (1); abdominal pain (1); chest pain (1); dyspnoea (2); nausea (4); vomiting (3); diarrhoea (1); hypertension (2); headache (2) | Gastrointestinal infection (1); diarrhoea (2) | Quote: "AEs were reported by 12 (60%) patients receiving rotigotine and 5 (50%) patients receiving placebo (Table 4). Two patients had hypertension of moderate intensity while receiving rotigotine. Both patients were receiving medications for this condition prior to study start. One patient reported an application site reaction (MedDRA [Medical Dictionary for Regulatory Activities] high‐level term “application and instillation site reactions”) of mild pruritus while receiving 2 mg/24 h of rotigotine; no application site reactions were reported for placebo. Serious AEs were reported for 3 patients receiving rotigotine (foot fracture [n = 1]; anxiety, chest pain, and dyspnoea [n = 1]; and abdominal pain [n = 1]) and 1 patient receiving placebo (gastrointestinal infection)." | |
| CBT | Control | Death (4) | Death (4) | Quote; "None of the patients in the intervention group were discontinued because of a CBT adverse effect. [...] Most of these losses were due to death, which is somewhat expected for ESRD patients after almost 1 year of follow‐up." Comment: Figure 1 showed the number of deaths for each group | |
| Exercise | Control 1: Dopaminergic agonist (ropinirole) Control 2: Control | No participants experienced an adverse event | No participants experienced an adverse event in both control groups | Quote: "Finally, none of the patients reported any drug adverse reactions or augmentation phenomena from the three interventions." | |
| Exercise | Control | No participants experienced an adverse event | No participants experienced an adverse event | Quote: "All patients completed the exercise programme with no adverse effects." | |
| Melatonin | Control | Death (3) | Death (3) | No adverse events were reported. However, Figure 2 showed the number of deaths for each group | |
| Relaxation | Control | No participants experienced an adverse event | No participants experienced an adverse event | Quote: "In this study, no one reported any undesirable side effects or unintended harm sign, symptom, or disease related to participation in the study or the relaxation technique." | |
| Gabapentin | Dopaminergic agonist (levodopa/carbidopa) | Somnolence and lethargy (2) | Allergy (1); death for myocardial infarction (1) | Quote: "During the course of the study period, two patients dropped out during the study secondary to somnolence and lethargy. These patients were administered gabapentin when the symptoms developed. One patient died because of myocardial infarction." | |
| Relaxation | Control | No participants experienced an adverse event | No participants experienced an adverse event | Quote from Gross 2017: "No intervention‐related adverse events occurred." | |
| Acupressure | Sham | Fluid overload (1); ocular haemorrhage (1) | Necrotizing fasciitis (1); physical trauma (1); chest muscle pain (1); arteriovenous graft failure (1) | Quote: "There were six adverse events (6 participants) recorded during the study (Table 4), all of which were rated as serious adverse events (SAEs) as they led to hospitalisation. Two SAEs occurred in the intervention group (fluid overload and ocular haemorrhage) and the remaining four SAEs occurred in the control group (necrotizing fasciitis, physical trauma, chest muscle pain, and arteriovenous graft failure). No adverse event was considered by investigators to be causally related to the study intervention. No local skin reaction (e.g., bruise) from repeated acupressure was reported during the study." | |
| Acupressure | Control | Death (3) | No participants experienced an adverse event | Quote: "Three participants died during the follow‐up period. No evidence supported their deaths were related to the AA intervention. No other adverse event was observed." |
APD ‐ automated peritoneal dialysis; CAPD ‐ continuous ambulatory peritoneal dialysis; CBT ‐ cognitive‐behavioural therapy
Exercise versus control
Six studies (Afshar 2011; Amini 2016; Cho 2018; Giannaki 2013; Giannaki 2013a; Yurtkuran 2007) (205 participants) compared exercise with a no treatment control. Exercise interventions included daily aerobic exercise, exercise during haemodialysis, and yoga‐based exercise. The median follow‐up was 26.4 weeks. The certainty of the evidence was moderate or very low for all outcomes (summary of findings Table 2). One meta‐analysis (sleep quality) showed evidence of substantial statistical heterogeneity.
Exercise interventions had very uncertain effects on sleep quality (Analysis 2.1 (5 studies, 165 participants): SMD ‐1.10 , 95% CI ‐2.26 to 0.05; I2 = 90%; very low certainty evidence). Single studies reported no differences in total sleep time (Analysis 2.2), sleep efficiency (Analysis 2.3), sleep disturbance (Analysis 2.4), anxiety (Analysis 2.5), or pain (Analysis 2.6) between exercise and control; however meta‐analyses were not possible. Exercise probably decreased fatigue (Analysis 2.7 (2 studies, 107 participants): SMD ‐0.68, 95% CI ‐1.07 to ‐0.29; I2 = 0%; moderate certainty evidence). Exercise probably decreased depressive symptoms (Analysis 2.8 (2 studies, 46 participants): MD ‐9.05, 95% CI ‐13.72 to ‐4.39; I2 = 0%; moderate certainty evidence). Studies were not designed to measure the effects of exercise on sleep latency, quality of life, death, or hospitalisation. Adverse events related to exercise interventions were rarely reported (Table 2).
Exercise versus dopaminergic agonist (ropinirole)
Giannaki 2013 (22 participants) reported no differences between exercise intervention and dopaminergic agonist (ropinirole) on sleep quality (Analysis 3.1) or depression (Analysis 3.2); meta‐analysis was not conducted.
Aerobic versus resistance exercise
Cho 2018 (21 participants) reported no differences between aerobic and resistance exercise on sleep quality (Analysis 4.1), total sleep time (Analysis 4.2), or sleep efficiency (Analysis 4.3). As only a single study was available, meta‐analysis was not conducted.
Acupressure versus no intervention
Six studies (Arab 2016; Shariati 2012; Tsay 2003a; Tsay 2004; Zhao 2011; Zou 2015) involving 304 participants compared acupressure with no intervention. The median follow‐up was four weeks. The certainty of the evidence is shown in the summary of findings Table 3 and one analysis (on sleep quality) showed evidence of substantial statistical heterogeneity.
It is uncertain whether acupressure improved the PSQI score (scale 0 to 21) because the certainty of the evidence was very low (Analysis 5.1 (6 studies, 367 participants): MD ‐1.27, 95% CI ‐2.13 to ‐0.40; I2 = 89%). Acupressure probably slightly improved sleep latency (scale 0 to 3) (Analysis 5.2 (3 studies, 173 participants): MD ‐0.59, 95% CI ‐0.92 to ‐0.27; I2 = 0%; moderate certainty evidence) and may have slightly increased total sleep time (scale 0 to 3) (Analysis 5.3 (3 studies, 173 participants): MD ‐0.60, 95% CI ‐1.12 to ‐0.09; I2 = 68%; low certainty evidence). It was uncertain whether acupressure decreased sleep disturbance because the certainty of the evidence was very low (scale 0 to 3) (Analysis 5.4 (3 studies, 173 participants): MD ‐0.49, 95% CI ‐1.16 to 0.19; I2 = 97%; very low certainty evidence). Acupressure probably leads to slightly better sleep efficiency (scale 0 to 3) (Analysis 5.6 (2 studies, 107 participants): MD ‐0.18, 95% CI ‐0.39 to 0.03; I2 = 0%; moderate certainty evidence). Acupressure probably improved fatigue (Analysis 5.8 (2 studies, 137 participants): MD ‐1.07, 95% CI ‐1.67 to ‐0.48; I2 = 0%; moderate certainty evidence). It was uncertain whether acupressure decreased depressive symptoms (Analysis 5.9 (2 studies, 137 participants): MD ‐3.65, 95% CI ‐7.63 to 0.33; I2 = 27%; very low certainty evidence). Studies were not designed to measure the effects of acupressure on quality of life, anxiety, or hospitalisation. Adverse events related to acupressure interventions were rarely reported (Table 2).
Single studies reported no differences in sleep interruption (Analysis 5.5) or death (all causes) (Analysis 5.7); meta‐analyses were not possible.
Acupressure versus sham acupressure control
Three studies (Arab 2016; SIESTA 2017; Tsay 2003a) involving 107 participants compared acupressure with sham acupressure. The median follow‐up was 4 weeks. Compared with sham acupressure, it is uncertain whether acupressure improves sleep quality because the certainty of the evidence is very low (Analysis 6.1 (2 studies, 129 participants): MD ‐2.25, 95% CI ‐6.33 to 1.82; I2 = 96%). One study reported the effects of acupressure or sham acupressure on sleep latency (Analysis 6.2) and sleep interruption (Analysis 6.3). Acupressure probably improve total sleep time (Analysis 6.4 (2 studies, 107 participants): SMD ‐0.34, 95% CI ‐0.73 to 0.04; I2 = 0%; moderate certainty evidence) compared with sham acupressure.
Single studies reported no differences in sleep disturbance (Analysis 6.5), hospitalisation (Analysis 6.6), fatigue (Analysis 6.7), or depressive symptoms (Analysis 6.8); meta‐analyses were not possible.
Acupressure versus transcutaneous electrical acupoint stimulation
Tsay 2004 (70 participants) compared acupressure with another form of acupressure, Transcutaneous Electrical Acupoint Stimulation (TEAS). This study reported no differences in sleep quality (Analysis 7.1), fatigue (Analysis 7.2), or depression (Analysis 7.3); meta‐analyses were not performed.
Acupressure versus benzodiazepine
Dai 2007a (82 participants) reported sleep quality was improved with acupressure compared to benzodiazepine therapy (Analysis 8.1); meta‐analysis was not conducted.
Cognitive‐behavioural therapy versus control
Two studies (Duarte 2009; Hou 2014) involving 183 participants compared CBT with no intervention. The median follow‐up was 13.2 weeks. Duarte 2009 used KDOL‐SR (higher score is better); we have multiplied the mean values by –1 to account for the different direction of the scale. Compared with no intervention, CBT may improve sleep quality however the certainty of the evidence was very low (Analysis 9.1 (2 studies, 183 participants): SMD ‐0.65, 95% CI ‐1.03 to ‐0.26; I2 = 39%). Single studies reported improvement in sleep latency (Analysis 9.2), total sleep time (Analysis 9.3), sleep efficiency (Analysis 9.4), anxiety (Analysis 9.6), and quality of life (Analysis 9.7), and no differences in death (all causes) (Analysis 9.5); meta‐analyses were not performed. CBT probably improved depressive symptoms (Analysis 9.8 (2 studies, 183 participants): SMD ‐0.76, 95% CI ‐1.06 to ‐0.46; I2 = 0%; moderate certainty evidence) compared with no intervention.
Cognitive‐behavioural therapy versus education
Chen 2011a (72 participants) compared CBT with education. This study reported possible improvement in sleep quality with CBT (Analysis 10.1), no differences in sleep latency (Analysis 10.2), or total sleep time (Analysis 10.3); possible improvement in sleep efficiency with education (Analysis 10.4), and no differences in depression (Analysis 10.5), anxiety (Analysis 10.6), or fatigue (Analysis 10.7). Meta‐analyses were not performed.
Education versus control
Three studies (Chow 2010; Saeedi 2014; Soleimani 2016) involving 220 participants compared sleep hygiene or health behaviour education with no treatment intervention. Chow 2010 used KDOL‐SR (higher score is better); we have multiplied the mean values by –1 to account for the different direction of the scale.
The median follow‐up was 4 weeks. Compared with no intervention, education may improve sleep quality however the certainty of the evidence was very low (Analysis 11.1 (3 studies, 220 participants): SMD ‐0.50, 95% CI ‐0.77 to ‐0.23; I2 = 0%). Education probably improved sleep latency (Analysis 11.2 (2 studies, 135 participants): MD ‐0.50, 95% CI ‐0.76 to ‐0.23; I2 = 0%; moderate certainty evidence), total sleep time (Analysis 11.3 (2 studies, 135 participants): MD ‐0.27, 95% CI ‐0.59 to 0.05; I2 = 0%; moderate certainty evidence), sleep efficiency (Analysis 11.4 (2 studies, 135 participants): MD ‐0.30, 95% CI ‐0.66 to 0.06; I2 = 0%; moderate certainty evidence), and sleep disturbance (Analysis 11.5 (2 studies, 135 participants): MD ‐0.38, 95% CI ‐0.52 to ‐0.24; I2 = 0%; moderate certainty evidence) compared with no intervention. Chow 2010 reported no differences between education or no intervention on pain (Analysis 11.6), fatigue (Analysis 11.7), and quality of life (Analysis 11.8); meta‐analyses were not performed.
Benzodiazepine 1 versus benzodiazepine 2
Dashti‐Khavidaki 2011 (23 participants) compared benzodiazepine (zolpidem) with treatment using another benzodiazepine (clonazepam). This study reported no difference in sleep quality (Analysis 12.1); meta‐analysis was not performed.
Dopaminergic agonist versus control
Two studies (Dauvilliers 2016; Giannaki 2013) involving 39 participants compared dopaminergic agonist (rotigotine or ropinirole) with no intervention. The median follow‐up was 16.2 weeks. Giannaki 2013 reported no difference in sleep quality (Analysis 13.1). Dauvilliers 2016 reported no differences in sleep latency (Analysis 13.2), or quality of life (Analysis 13.5), and possible improvement in total sleep time (Analysis 13.3), sleep efficiency (Analysis 13.4) with rotigotine; meta‐analyses were not performed.
Telephone support versus control
Li 2014b (135 participants) reported telephone support may improve sleep quality compared to no intervention (Analysis 14.1), but no differences in pain (Analysis 14.2), fatigue (Analysis 14.3), or quality of life (Analysis 14.4); meta‐analyses were not performed.
Melatonin versus control
Two studies (Natarajan 2003; MELODY 2013) involving 75 participants compared melatonin with no intervention. The median follow‐up was 30.9 weeks. Natarajan 2003 reported sleep quality improved from baseline with melatonin (Analysis 15.1) and MELODY 2013 reported no difference in the number of deaths (Analysis 15.2); meta‐analyses were not performed.
Reflexology versus control
Two studies (Farrokian 2016; Unal 2016) involving 132 participants compared reflexology with no intervention. The median follow‐up was 4 weeks. Compared with no intervention, reflexology probably slightly improves sleep quality (Analysis 16.1 (2 studies, 132 participants): MD ‐5.90, 95% CI ‐6.56 to ‐5.23; I2 = 0%; moderate certainty evidence). Unal 2016 reported reflexology probably improved fatigue (Analysis 16.2); meta‐analysis was not performed.
Reflexology versus massage
Unal 2016 (70 participants) compared reflexology with back massage. This study reported reflexology improved sleep quality (Analysis 17.1) and fatigue (Analysis 17.2); meta‐analyses were not performed.
Light therapy versus control
Burkhalter 2015 (28 participants) compared light therapy with no intervention. This study reported sleep latency improved from baseline with light therapy (Analysis 18.1), and no differences in sleep efficiency (Analysis 18.2) or depressive symptoms (Analysis 18.3); meta‐analyses were not performed.
Gabapentin versus dopaminergic agonist
Razazian 2015 (82 participants) compared gabapentin with treatment using a dopaminergic agonist (levodopa/carbidopa). This study reported sleep latency (Analysis 19.1) and sleep disturbance (Analysis 19.3) improved with gabapentin, and there were no differences in total sleep time (Analysis 19.2) or cardiovascular death (Analysis 19.4); meta‐analyses were not performed.
Continuous ambulatory peritoneal dialysis (CAPD) versus automated peritoneal dialysis (APD)
Bro 1999 (34 participants) compared CAPD with APD. This study reported no differences in sleep quality (Analysis 20.1); meta‐analysis was not preformed.
Music during haemodialysis versus control
Momennasab 2018 (69 participants) compared music during haemodialysis with no intervention. This study reported music improved sleep quality (Analysis 21.1), sleep latency (Analysis 21.2), total sleep time (Analysis 21.3) and sleep disturbance (Analysis 21.4); meta‐analyses were not performed.
Music during haemodialysis versus music at bedtime
Momennasab 2018 (67 participants) compared music during haemodialysis with music at bedtime. This study reported music at bedtime improved sleep quality (Analysis 22.1), sleep latency (Analysis 22.2), total sleep time (Analysis 22.3) and sleep disturbance (Analysis 22.4); meta‐analyses were not performed.
Aromatherapy versus control
Muz 2017 compared aromatherapy with no intervention. This study reported aromatherapy improved sleep quality (Analysis 23.1), sleep latency (Analysis 23.2), total sleep time (Analysis 23.3), sleep efficiency (Analysis 23.4), and sleep disturbance (Analysis 23.5); meta‐analyses were not performed.
Massage versus control
Sun 2017 (80 participants) compared abdominal massage with no intervention. This study reported massage improved sleep quality (Analysis 24.1), pain (Analysis 24.2), and quality of life (Analysis 24.3); meta‐analyses were not performed.
Subgroup and sensitivity analysis
Overall, the planned subgroup and sensitivity analyses to explore for sources of heterogeneity were not possible due to the lack of data observations. However, we were not able to determine if Afshar 2011 was eligible for our review because the study design was not clearly defined. We provided a sensitivity analysis for the comparator education versus control and explored data removing this study from our analysis. In this additional analysis, exercise interventions had very uncertain effects on sleep quality (4 studies, 137 participants: SMD ‐0.97, 95% CI ‐2.42 to 0.48; I2 = 92%; very low certainty evidence).
Discussion
Summary of main results
This review summarises 67 studies involving 3427 participants with CKD that reported the effects of a variety of therapies on sleep quality and related outcomes. All studies were in adults; no studies were identified that evaluated therapy for children with CKD. Nearly all studies involved patients with ESKD treated with dialysis, while a small number included people with milder stages of kidney disease, and recipients of a kidney transplant. Sleep interventions were evaluated during very short‐term follow‐up. Studies continued for a median of 5 weeks. The most common interventions were relaxation techniques, exercise, acupressure, CBT, and sleep hygiene or health behaviour education. Other therapies included benzodiazepines, dopaminergic agonist therapy, telephone support, melatonin, reflexology, light therapy, different forms of peritoneal dialysis, music, aromatherapy and massage. Risks of bias in the included studies were often high or unclear, and these risks combined with imprecision in effect estimates led frequently to very low certainty evidence. The effect of sleep management on sleep quality, sleep latency, total sleep time, depression and fatigue were documented often using different outcome measures which limited our ability to combine studies.
In general, relaxation techniques and exercise had uncertain effects on sleep quality. In moderate quality evidence, acupressure may increase total sleep duration, but had uncertain effects on other aspects of sleep quality when compared with no treatment control. Sleep hygiene education may decrease the time taken to sleep, increases sleep duration, and may reduce sleep disturbance. There were no studies designed to directly examine and/or correlate efficacy of any interventions aimed at improving sleep that may have been attempted for the spectrum of sleep disordered breathing. Adverse event reporting was sparse. Insufficient evidence was available to determine the long‐term effectiveness and safety of all approaches.
Overall, this review suggests that current evidence for sleep interventions in people with CKD is insufficient to guide clinical practice. Due to limitations in the evidence because of inconsistent treatment effects measured by different studies, and limitations in studies based on the reporting of methods, the confidence in the evidence for most outcomes was downgraded from high confidence, meaning that future studies might have different results and lead to changing in our knowledge about the impact of sleep intervention in people with CKD. Possible beneficial effects of sleep interventions such as sleep hygiene education and acupressure suggest that research in this field may have an important impact on clinical outcomes.
Overall completeness and applicability of evidence
This review found that studies specifically designed to evaluate interventions for sleep disorders in CKD were generally sparse and infrequent. Notably, most studies focused on care for people with ESKD, reflecting the burden of symptoms for this group of patients. There were no studies among children, who may be considerably impacted by sleep disorders, including impaired social and educational attainment and neurocognitive development and reduced quality of life (Mitchell 2006). Studies generally did not routinely report or were not designed to evaluate unintended adverse effects of therapy. The limited number of relevant studies identified for inclusion also prevented examination of the impact of interventions within specific clinical settings such as gender, stage of kidney disease, or duration or intensity of treatment. Some interventions (such as CBT) included different techniques and approaches to manage sleep disorders. The lack of sufficient studies and differences in outcome measures precluded analyses that combined these treatments. The external validity of the review may be limited as most of the studies were not specifically designed to examine interventions in patients with a prespecified diagnosis of sleep impairment, were conducted in higher income countries, and were short‐term. Although sleep related outcomes and HRQoL were reported using validated tools for CKD, there was a lack of consistency in estimating outcomes among the current studies. In the future research studies, standardised outcome measures of sleep quality would enhance our ability to compare different treatments.
Quality of the evidence
We assessed the quality of study evidence using standard risks of bias domains within the Cochrane tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach (GRADE 2011), which considers study limitations, imprecision, indirectness, inconsistency and publication bias. Overall, most studies had unclear risks of bias for sequence generation and allocation concealment, which may have led to over‐estimated treatment effects (Page 2016). We rated the certainty of the evidence for relaxation techniques as low or very low, downgraded for unexplained heterogeneity, methodological limitations, and imprecision in summary effects. We assessed the certainty of the evidence for exercise on sleep quality as very low due to an imprecise treatment effect, study risk of bias, and unexplained statistical heterogeneity. The limited number of studies prevented exploration of potential sources of heterogeneity in the analyses. We rated the certainty of the evidence for acupressure interventions on sleep quality as very low, similarly due to methodological limitations in available studies, and marked unexplained heterogeneity. Such assessments suggest that the true effects of relaxation techniques, exercise, and acupressure may be substantially different from the intervention effects reported in the review, with future research very likely to change the treatment estimates observed in this review.
Potential biases in the review process
This review was conducted according to a pre‐specified protocol, used a highly sensitive search strategy, was conducted by two independent review authors, and considered evidence certainty in interpretation of the results. However, the study has limitations which need to be noted when interpreting the results. First, we excluded studies in which sleep disorders were not reported as a clinical outcome. This restriction may have led to low power in analyses for adverse effects of the included interventions. Second, we only included studies targeting interventions for sleep outcomes. Other interventions that may be less amenable to a randomised study design, such as home based dialysis therapies, could not be included. Third, we used only end of treatment values for sleep outcomes to maximise data for inclusion in meta‐analysis. We did not include change in sleep scores from baseline to end of treatment, that may have provided further insights into treatment effects. Fourth, we pooled data from a range of clinical settings including stage of kidney disease; due to insufficient studies, we were not able to evaluate whether treatments had different benefits or harms for different clinical settings. We included other outcomes not directly related to sleep endpoints in the review and summary of findings tables. Fifth, as our search strategy and eligibility criteria did not aim to include all studies reporting these outcomes, we could not include all available studies in the literature for these endpoints; the results of these meta‐analyses may not reflect the overall evidence. Finally, we did not grade the certainty of all evidence for all outcomes. However, it is likely, due to the very small number of studies in the meta‐analyses, that evidence certainty was low or very low for many of these ungraded outcomes.
Agreements and disagreements with other studies or reviews
The findings in this review are more cautious compared with those from a review of non‐pharmacological interventions for improving sleep quality in patients treated with dialysis published in 2015 (Yang 2015). In that review of 12 RCTs and one cohort study, the authors concluded that CBT, physical training, and acupressure could improve sleep quality, measured using the PSQI. Differences between the Yang 2015 review and the present Cochrane review included use of change in sleep quality scores, meta‐analysis of single studies, inclusion of non‐randomised data, and limited consideration of evidence certainty when drawing conclusions about treatment effects. In a recently published Cochrane review (Kim 2016), Kim and colleagues evaluated acupressure and related interventions among patients with CKD and included sleep outcomes. As reported in the present review, the review authors documented very low certainty evidence that manual acupressure improved sleep quality (PSQI decrease of 2.46 on average) at four weeks. Similarly, there was no evidence that manual acupressure made any difference to sleep quality compared with sham acupressure. In a recent Cochrane review of interventions for restless legs syndrome amongst patients on dialysis (Gopaluni 2016), meta‐analyses of studies evaluating gabapentin, levodopa, vitamin C and E, iron dextran, or ropinirole were not possible.
Study flow diagram.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Comparison 1 Relaxation versus control, Outcome 1 Sleep quality.
Comparison 1 Relaxation versus control, Outcome 2 Sleep latency.
Comparison 1 Relaxation versus control, Outcome 3 Total sleep time.
Comparison 1 Relaxation versus control, Outcome 4 Sleep disturbance.
Comparison 1 Relaxation versus control, Outcome 5 Hospitalisation.
Comparison 1 Relaxation versus control, Outcome 6 Anxiety.
Comparison 1 Relaxation versus control, Outcome 7 Pain.
Comparison 1 Relaxation versus control, Outcome 8 Fatigue.
Comparison 1 Relaxation versus control, Outcome 9 Quality of life.
Comparison 1 Relaxation versus control, Outcome 10 Depression.
Comparison 2 Exercise versus control, Outcome 1 Sleep quality.
Comparison 2 Exercise versus control, Outcome 2 Total sleep time.
Comparison 2 Exercise versus control, Outcome 3 Sleep efficiency.
Comparison 2 Exercise versus control, Outcome 4 Sleep disturbance.
Comparison 2 Exercise versus control, Outcome 5 Anxiety.
Comparison 2 Exercise versus control, Outcome 6 Pain.
Comparison 2 Exercise versus control, Outcome 7 Fatigue.
Comparison 2 Exercise versus control, Outcome 8 Depression.
Comparison 3 Exercise versus dopaminergic agonist, Outcome 1 Sleep quality.
Comparison 3 Exercise versus dopaminergic agonist, Outcome 2 Depression.
Comparison 4 Aerobic versus resistance exercise, Outcome 1 Sleep quality.
Comparison 4 Aerobic versus resistance exercise, Outcome 2 Total sleep time.
Comparison 4 Aerobic versus resistance exercise, Outcome 3 Sleep efficiency.
Comparison 5 Acupressure versus control, Outcome 1 Sleep quality.
Comparison 5 Acupressure versus control, Outcome 2 Sleep latency.
Comparison 5 Acupressure versus control, Outcome 3 Total sleep time.
Comparison 5 Acupressure versus control, Outcome 4 Sleep disturbance.
Comparison 5 Acupressure versus control, Outcome 5 Sleep interruption.
Comparison 5 Acupressure versus control, Outcome 6 Sleep efficiency.
Comparison 5 Acupressure versus control, Outcome 7 Death (all causes).
Comparison 5 Acupressure versus control, Outcome 8 Fatigue.
Comparison 5 Acupressure versus control, Outcome 9 Depression.
Comparison 6 Acupressure versus sham acupressure, Outcome 1 Sleep quality.
Comparison 6 Acupressure versus sham acupressure, Outcome 2 Sleep latency.
Comparison 6 Acupressure versus sham acupressure, Outcome 3 Sleep interruption.
Comparison 6 Acupressure versus sham acupressure, Outcome 4 Total sleep time.
Comparison 6 Acupressure versus sham acupressure, Outcome 5 Sleep disturbance.
Comparison 6 Acupressure versus sham acupressure, Outcome 6 Hospitalisation.
Comparison 6 Acupressure versus sham acupressure, Outcome 7 Fatigue.
Comparison 6 Acupressure versus sham acupressure, Outcome 8 Depression.
Comparison 7 Acupressure versus transcutaneous electrical acupoint stimulation, Outcome 1 Sleep quality.
Comparison 7 Acupressure versus transcutaneous electrical acupoint stimulation, Outcome 2 Fatigue.
Comparison 7 Acupressure versus transcutaneous electrical acupoint stimulation, Outcome 3 Depression.
Comparison 8 Acupressure versus benzodiazepine, Outcome 1 Sleep quality.
Comparison 9 Cognitive‐behavioural therapy versus control, Outcome 1 Sleep quality.
Comparison 9 Cognitive‐behavioural therapy versus control, Outcome 2 Sleep latency.
Comparison 9 Cognitive‐behavioural therapy versus control, Outcome 3 Total sleep time.
Comparison 9 Cognitive‐behavioural therapy versus control, Outcome 4 Sleep efficiency.
Comparison 9 Cognitive‐behavioural therapy versus control, Outcome 5 Death (all causes).
Comparison 9 Cognitive‐behavioural therapy versus control, Outcome 6 Anxiety.
Comparison 9 Cognitive‐behavioural therapy versus control, Outcome 7 Quality of life.
Comparison 9 Cognitive‐behavioural therapy versus control, Outcome 8 Depression.
Comparison 10 Cognitive‐behavioural therapy versus education, Outcome 1 Sleep quality.
Comparison 10 Cognitive‐behavioural therapy versus education, Outcome 2 Sleep latency.
Comparison 10 Cognitive‐behavioural therapy versus education, Outcome 3 Total sleep time.
Comparison 10 Cognitive‐behavioural therapy versus education, Outcome 4 Sleep efficiency.
Comparison 10 Cognitive‐behavioural therapy versus education, Outcome 5 Depression.
Comparison 10 Cognitive‐behavioural therapy versus education, Outcome 6 Anxiety.
Comparison 10 Cognitive‐behavioural therapy versus education, Outcome 7 Fatigue.
Comparison 11 Education versus control, Outcome 1 Sleep quality.
Comparison 11 Education versus control, Outcome 2 Sleep latency.
Comparison 11 Education versus control, Outcome 3 Total sleep time.
Comparison 11 Education versus control, Outcome 4 Sleep efficiency.
Comparison 11 Education versus control, Outcome 5 Sleep disturbance.
Comparison 11 Education versus control, Outcome 6 Pain.
Comparison 11 Education versus control, Outcome 7 Fatigue.
Comparison 11 Education versus control, Outcome 8 Quality of life.
Comparison 12 Benzodiazepine versus benzodiazepine, Outcome 1 Sleep quality.
Comparison 13 Dopaminergic agonist versus control, Outcome 1 Sleep quality.
Comparison 13 Dopaminergic agonist versus control, Outcome 2 Sleep latency.
Comparison 13 Dopaminergic agonist versus control, Outcome 3 Total sleep time.
Comparison 13 Dopaminergic agonist versus control, Outcome 4 Sleep efficiency.
Comparison 13 Dopaminergic agonist versus control, Outcome 5 Quality of life.
Comparison 14 Telephone support versus control, Outcome 1 Sleep quality.
Comparison 14 Telephone support versus control, Outcome 2 Pain.
Comparison 14 Telephone support versus control, Outcome 3 Fatigue.
Comparison 14 Telephone support versus control, Outcome 4 Quality of life.
Comparison 15 Melatonin versus control, Outcome 1 Sleep quality.
Comparison 15 Melatonin versus control, Outcome 2 Death (all causes).
Comparison 16 Reflexology versus control, Outcome 1 Sleep quality.
Comparison 16 Reflexology versus control, Outcome 2 Fatigue.
Comparison 17 Reflexology versus massage, Outcome 1 Sleep quality.
Comparison 17 Reflexology versus massage, Outcome 2 Fatigue.
Comparison 18 Light therapy versus control, Outcome 1 Sleep latency.
Comparison 18 Light therapy versus control, Outcome 2 Sleep efficiency.
Comparison 18 Light therapy versus control, Outcome 3 Depression.
Comparison 19 Gabapentin versus dopaminergic agonist, Outcome 1 Sleep latency.
Comparison 19 Gabapentin versus dopaminergic agonist, Outcome 2 Total sleep time.
Comparison 19 Gabapentin versus dopaminergic agonist, Outcome 3 Sleep disturbance.
Comparison 19 Gabapentin versus dopaminergic agonist, Outcome 4 Cardiovascular death.
Comparison 20 CAPD versus APD, Outcome 1 Sleep quality.
Comparison 21 Music versus control, Outcome 1 Sleep quality.
Comparison 21 Music versus control, Outcome 2 Sleep latency.
Comparison 21 Music versus control, Outcome 3 Total sleep time.
Comparison 21 Music versus control, Outcome 4 Sleep disturbance.
Comparison 22 Music versus music, Outcome 1 Sleep quality.
Comparison 22 Music versus music, Outcome 2 Sleep latency.
Comparison 22 Music versus music, Outcome 3 Total sleep time.
Comparison 22 Music versus music, Outcome 4 Sleep disturbance.
Comparison 23 Aromatherapy versus control, Outcome 1 Sleep quality.
Comparison 23 Aromatherapy versus control, Outcome 2 Sleep latency.
Comparison 23 Aromatherapy versus control, Outcome 3 Total sleep time.
Comparison 23 Aromatherapy versus control, Outcome 4 Sleep efficiency.
Comparison 23 Aromatherapy versus control, Outcome 5 Sleep disturbance.
Comparison 24 Massage versus control, Outcome 1 Sleep quality.
Comparison 24 Massage versus control, Outcome 2 Pain.
Comparison 24 Massage versus control, Outcome 3 Quality of life.
| Relaxation versus control for sleep outcomes in people with CKD | ||||||
| Patient or population: people with CKD Intervention: relaxation1 Comparison: without relaxation technique/training | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No. of participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Without relaxation training/technique | Relaxation training/technique | |||||
| Sleep quality PSQI (median follow‐up: 8 weeks) | The mean sleep quality index score ranged across control groups from 1.53 to 11.09 | The mean sleep quality index score in the intervention groups was 1.62 lower (95% CI ‐5.03 to 1.79) A lower score is indicative of higher sleep quality | MD ‐1.62 (95% CI ‐5.03 to 1.79) | 259 (4) | ⊕⊝⊝⊝ | It is very uncertain whether relaxation makes any difference to sleep quality |
| Sleep latency PSQI (median follow‐up: 8 weeks) | Only one study reported sleep latency | Not estimable as only a single study reported this measure | Not estimable. | Insufficient data observations | Not estimable | Studies were not designed to measure effects of relaxation on sleep latency |
| Quality of life Quality of Life Index ‐ dialysis version and Medical Outcome Studies 36‐Item Short Form Health Survey (median follow‐up: 6 weeks) | The mean quality of life index score ranged across control groups from 17.73 to 43.08 | The mean quality of life index score in the intervention groups was 0.47 higher (95% CI ‐0.09 to 1.04) A higher score is indicative of higher perceived of quality of life | SMD 0.47 (95% CI ‐0.09 to 1.04) | 138 (2) | ⊕⊕⊝⊝ | It is uncertain whether relaxation makes any difference to quality of life |
| Depression Center for Epidemiologic Studies Depression Scale and The Beck Depression Inventory II (median follow‐up: 6 weeks) | The mean depression index score ranged across control groups from 9.1 to 9.56 | The mean depression index score in the intervention groups was 0.04 higher (95% ‐1.27 to 1.35) A higher score is indicative of more depressive symptoms | SMD 0.04 (95% CI ‐1.27 to 1.35) | 108 (2) | ⊕⊝⊝⊝ | It is very uncertain whether relaxation makes any difference to depressive symptoms |
| Anxiety Beck Anxiety Inventory and Spielberger State‐Trait Anxiety Inventory (median follow‐up: 8 weeks) | The mean anxiety index score ranged across control groups from 31.61 to 34.9 | The mean anxiety index score in the intervention groups was 0.11 higher (95% CI ‐0.55 to 0.77) A higher score is indicative of more anxiety symptoms | SMD 0.11 (95% CI ‐0.55 to 0.77) | 119 (2) | ⊕⊝⊝⊝ | It is very uncertain whether relaxation makes any difference to anxiety |
| Fatigue PROMIS‐Fatigue Short Form 1.0 and Rhoten and Piper fatigue (median follow‐up: 8 weeks) | The mean fatigue score ranged across control groups from 55.5 to 81.17 | The mean fatigue score in the intervention groups was 0.61 lower (95% CI ‐2.09 to 0.87) A higher score is indicative of worse fatigue | SMD ‐0.61 (95% CI ‐2.09 to 0.87) | 119 (2) | ⊕⊝⊝⊝ | It is very uncertain whether relaxation makes any difference to fatigue |
| Hospitalisation (median follow‐up: 4 weeks) | Not estimable8 | Not estimable | Not estimable. | Insufficient data observations | Not estimable | Studies were not designed to measure effects of relaxation on hospitalisation |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 Relaxation techniques included progressive muscle relaxation, nurse‐led breathing training, mindfulness, and the Benson relaxation technique. 2 Three out of four studies had high or unclear risks of bias for allocation concealment, blinding of participants or investigators, and blinding of outcome assessment. 3 There was substantial heterogeneity in the findings of available studies that appeared related to a single study (Amini 2016). 4 The certainty in the evidence was downgraded due to imprecision in the treatment estimates, consistent with benefit or harm. 5 There was moderate heterogeneity in the findings of available studies. 6 There was substantial heterogeneity in the findings of available studies (two downgrades). 7 Risks of bias for the included studies were high for allocation concealment. 8 The estimated risk of hospitalisation was not estimable as a single study reported this outcome. | ||||||
| Exercise compared to control for sleep outcomes in people with chronic kidney disease (CKD) | ||||||
| Patient or population: people with CKD Settings: CKD Intervention: exercise1 Comparison: without exercise | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No. of participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Without exercise | Exercise | |||||
| Sleep quality PSQI, ESS and tri‐axial accelerometer (median follow‐up: 26.4 weeks) | The mean sleep quality score ranged across control groups from 8.85 to 43.6 | The mean sleep quality index score in the intervention groups was 1.10 lower (95% CI ‐2.26 to 0.05). A lower score is indicative of higher sleep quality | SMD ‐1.10 (95% CI ‐2.26 to 0.05) | 165 (5) | ⊕⊝⊝⊝ | It is very uncertain whether exercise makes any difference to sleep quality |
| Sleep latency | No data observations | Not estimable | No observations | Insufficient data observations | Not estimable | Studies were not designed to measure effects of exercise on sleep latency |
| Quality of life | No data observations | Not estimable | No observations | Insufficient data observations | Not estimable | Studies were not designed to measure effects of exercise on quality of life |
| Depression Zung Self‐Rating Depression Scale (ZUNG) (median follow‐up: 26.4 weeks) | The mean depression index score ranged across control groups from 43.7 to 43.71 | The mean depression index score in the intervention groups was 9.05 lower (95% CI ‐13.72 to ‐4.39) A higher score is indicative of worse depressive symptoms | MD ‐9.05 (95% CI ‐13.72 to ‐4.39) | 46 (2) | ⊕⊕⊕⊝ | Exercise probably decreases depressive symptoms |
| Anxiety Beck Anxiety Inventory (BECK) (median follow‐up: 8 weeks) | Only one study reported anxiety. | Not estimable as only a single study reported this measure | Not estimable. | Insufficient data observation | Not estimable | Studies were not designed to measure effects of exercise on anxiety |
| Fatigue PIPER Fatigue Scale (PFS) and Visual Analogue Scale (VAS) (median follow‐up: 13.2 weeks) | The mean fatigue index score ranged across control groups from 6.9 to 81.17 | The mean fatigue index score in the intervention groups was 0.68 lower (95% CI ‐1.07 to ‐0.29). A higher score is indicative of worse fatigue | SMD ‐0.68 (95% CI ‐1.07 to ‐0.29) | 107 (2) | ⊕⊕⊕⊝ | Exercise probably improves fatigue |
| Hospitalisation | No data observations | Not estimable | No observations. | Insufficient data observations | Not estimable | Studies were not designed to measure effects of exercise on hospitalisation |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; SMD: standardised mean difference; MD: mean difference | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 Exercise interventions were aerobic exercise daily, exercise during HD, and yoga‐based exercise 2 All studies in this analysis had unclear methods for allocation concealment, and outcomes were not clearly blinded in two of three studies 3 The certainty in the evidence was downgraded due to imprecision in the treatment estimates, leading to a treatment estimate consistent with benefit or harm 4 There was substantial heterogeneity in the findings of available studies (two downgrades) 5 None of the available studies reported low risk methods for allocation concealment 6 None of the available studies reported low risk methods for allocation concealment or blinding of outcome measures | ||||||
| Acupressure versus control for sleep outcomes in people with chronic kidney disease (CKD) | ||||||
| Patient or population: people with CKD Settings: CKD Intervention: acupressure Comparison: without acupressure (no treatment) | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No. of participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Without acupressure | Acupressure | |||||
| Sleep quality PSQI (median follow‐up: 4 weeks) | The mean sleep quality index score ranged across control groups from 1.29 to 11 | The mean sleep quality index score in the intervention groups was 1.27 lower (95% CI ‐2.13 to ‐0.40) A lower score is indicative of higher sleep quality | MD ‐1.27 (95% CI ‐2.13 to ‐0.40) | 367 (6) | ⊕⊝⊝⊝ | It is very uncertain whether acupressure makes any difference to sleep quality |
| Sleep latency PSQI (median follow‐up: 4 weeks) | The mean sleep latency index score ranged across control groups from 1.74 to 2.4 | The mean sleep latency index score in the intervention groups was 0.59 lower (95% CI ‐0.92 to ‐0.27) A lower score is indicative of shorter sleep latency | MD ‐0.59 (95% CI ‐0.92 to ‐0.27) | 173 (3) | ⊕⊕⊕⊝ | Accupressure may shorten sleep latency |
| Quality of life | No data observations. | Not estimable | No observations | Insufficient data observations | Not estimable. | Studies were not designed to measure effects of acupressure on quality of life |
| Depression Beck Depression Inventory (BECK) (median follow‐up: 4 weeks) | The mean depression index score ranged across control groups from 18.88 to 21.61 | The mean depression index score in the intervention groups was 3.65 lower (95% CI ‐7.63 to 0.33) A higher score is indicative of worse depressive symptoms. | MD ‐3.65 (95% CI ‐7.63 to 0.33) | 137 (2) | ⊕⊝⊝⊝ | It is very uncertain whether acupressure makes any difference to depressive symptoms |
| Anxiety | No data observations | Not estimable | No observations | Insufficient data observations | Not estimable. | Studies were not designed to measure effects of acupressure on anxiety |
| Fatigue PIPER Fatigue Scale (PSF) (median follow‐up: 4 weeks) | The mean fatigue index score ranged across control groups from 5.7 to 5.71 | The mean fatigue index score in the intervention groups was 1.07 lower (95% CI ‐1.67 to ‐0.48) A higher score is indicative of worse fatigue | MD ‐1.07 (95% CI ‐1.67 to ‐0.48) | 137 (2) | ⊕⊕⊕⊝ | Accupressure may reduce fatigue |
| Hospitalisation | No data observations | Not estimable | No observations | Insufficient data observations | Not estimable | Studies were not designed to measure effects of acupressure on hospitalisation |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; SMD: standardised mean difference; MD: mean difference | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 None of the studies reported low risk methods for allocation concealment but one was unblinded for participants and investigators 2 There was substantial heterogeneity in the findings of available studies (2 downgrades) 3 None of the studies reported low risk methods for allocation concealment or was blinded for participants and investigators 4 The certainty in the evidence was downgraded due to imprecision in the treatment estimates, leading to a treatment estimate consistent with benefit or harm 5 There was moderate heterogeneity in the findings of available studies | ||||||
| Study ID | Intervention | Control | Materials | Sleep intervention | Adherence | ||||
| Why | What | How | Who provided, where and when | Tailoring/modification | How well: Planned | How well: Actual | |||
| Exercise | Control | To determine the effects of aerobic training on sleep quality, serum leptin, and inflammatory status | People in the intervention group cycled during the 1st two hours of each dialysis | Regular aerobic training which consisted | 3 sessions per week, for 3 weeks in the clinic | Patients were asked to cycle at an intensity of 12 to 15 of 20 at the rate of perceived exertion of Borg scale, of an individual’s maximal capacity | Blood pressure and heart rate of the participants | The number of patients who completed the study interventions was not reported | |
| Relaxation | Control 1: Exercise Control 2: Control | Investigate aerobic exercise and progressive muscle relaxation on anxiety, fatigue, and sleep disorders | Explained to patients while undergoing HD. Recording about muscle relaxation shown | Recording shown to patients. Patients were corrected on technique. Patients then did exercises at home using recording | There was the supervision of a researcher. The intervention was performed daily in the clinic or at home, for 60 days for 8 weeks | ‐ | Researcher followed up every two weeks to encourage exercise program or exclude patients who did not adhere | The number of patients who completed the study interventions was not reported | |
| Exercise | Control 1: Exercise Control 2: Control | To test if home‐based | The patients included in the exercise | The home‐based performed exercise at home, the others at an exercise centre | A physiologist provided the intervention. Exercises were performed in the centre or at home for 30 min for 8 weeks | The exercise training intensity was prescribed according to | ‐ | 40 patients completed the study | |
| Acupressure | Control 1: Sham Control 2: Control | To investigate the effect of acupressure on the sleep and quality of life | The intervention group received acupressure in the bilateral Shenmen points. The others received either sham acupressure or no treatment | Acupressure was applied using a circular movement. The sham was performed on points at 0.5 cm from the true points | A trained researcher provided the intervention in the clinic for 8 minutes, 3 times a week for 8 weeks | ‐ | To establish consistency of performance, the amount of pressure applied was measured using a scale; 30 measurements were recorded | 93 patients completed the study | |
| CAPD | APD | To test if there should be a difference between the effects of APD compared to CAPD on quality of life and clinical outcomes | 17 patients were | CAPD and APD devices | Skilled PD nurses provided the intervention in the clinic. APD and CAPD were delivered for 26.4 weeks | One patient on CAPD needed an additional exchange to achieve the target dialysis dose | During the study, patients were seen at monthly controls in the CAPD unit. Adequacy tests were performed every 3 months | 25 patients completed | |
| Light | Control | To evaluate the feasibility of the intervention and to assess its efficacy for improving sleep | To receive the appropriate dosage, at a time determined by individual chronotype | The patient sited 30–50 cm from the light box lamp, which produced light at eye level | The principal investigator instructed participants on the light box’s use to perform at home, 30 min daily for 3 weeks | We allowed for a 1.5 h deviation from the optimum starting time | ‐ | 28 patients completed | |
| HDF | HD | To compare sleep apnoea severity in HD and HDF | Polysomnography was used to assess the efficacy of the intervention | After the prescribed period, these treatments were inverted | Thrice‐weekly schedules for 13.2 weeks (first phase) in the clinic | ‐ | ‐ | At the end of phases II, 6 patients completed | |
| CBT | Education | To investigate the effectiveness | To assist participants in identifying, challenging, and changing misconceptions about sleep | Participants were instructed to relieve muscular tension and perform rhythmic breathing | Research staff (psychiatrist, nephrologist, nurse) provided the intervention at home, 1 hour weekly for 4 weeks | ‐ | ‐ | 24 patients completed | |
| CBT | Education | To validate the efficacy of | To assist participants in identifying, challenging, | The intervention included a psychiatrist‐oriented, video assisted | 2 psychiatrists | ‐ | ‐ | All patients who received the treatment completed the study | |
| Exercise (aerobic exercise) | Control 1: Exercise (resistance exercise) Control 2: Exercise (combination exercise) Control 3: Control | To investigate the effect of intra dialytic exercise on daily physical activity and sleep quality, measured by an accelerometer | To perform recumbent stationary | A stationary bike or Coloured elastic resistive bands and soft weights were used. All the exercises were performed in a supine or a sitting position | A researcher provided the intervention in the clinic: 5‐min warm‐up and maximum of 30 min for 12 weeks | According to patients’ performance, training loads were adjusted | Participants were encouraged to perform each exercise to optimise movement speed and muscle power | 46 patients completed | |
| Education | Control | To examine the effectiveness of a | Patients received a comprehensive discharge planning protocol and a standardized | All calls focused on health‐related behaviours and were | A nurse provided the training program of 24 hours in the clinic. A nurse contacted patients by telephone weekly for 6 weeks | Patients could referral to the community nurse, the renal team or to | Realistic action plan and participation of family members in | 85 patients completed | |
| Acupressure | Estazolam | To study the effect of lower extremity point massage for improving quality of sleep | 1 mg of estazolam tablets orally half an hour before sleep or acupressure | ‐ | Intervention was performed in the clinic or at home once a day, 20 to 30 seconds each time for 4 weeks | ‐ | ‐ | The number of patients who completed the study was not reported | |
| Benzodiazepine (zolpidem) | Benzodiazepine (clonazepam) | To compare zolpidem with clonazepam in terms of on sleep quality | 5 to 10 mg of zolpidem or 1 mg of clonazepam, orally | After the prescribed period these treatments were inverted | Daily for 2 weeks (first phase) at home | ‐ | ‐ | All patients completed the | |
| Dopaminergic agonist (rotigotine) | Control | To investigate the efficacy on periodic legs movement, sleep, RLS and quality of life | Polysomnography was performed on the 2 consecutive nights | ‐ | Trained personnel provided the intervention that was performed at home (1 to 3 mg of rotigotine) for 6 weeks | ‐ | ‐ | 25 patients completed the study | |
| CBT | Control | To assess the effectiveness | The patients attended sessions when they were | Educating on kidney disease, dialysis, depression and the therapeutic cognitive model. All sessions involved homework | 2 psychologists provided the intervention in the clinic: 12 weekly sessions for 13.2 weeks | Individualized psychotherapy session for providing guidelines | ‐ | 74 patients completed the study | |
| Melatonin | Control | Melatonin 3 mg | To assess the effect of the intervention on sleep quality | After the prescribed period these treatments were inverted | Melatonin 3 mg orally per day for 6 weeks (first phase) at home | ‐ | Compliance was confirmed by pill count | At the end of phases II, 68 patients completed the study | |
| Melatonin | Control | To investigate the effects of exogenous melatonin on | Actigraphy was used to assess the efficacy of the intervention | After the prescribed period these treatments were inverted | 3 mg of melatonin orally per day for 6 weeks (first phase) | ‐ | ‐ | At the end of phases II, 20 patients completed the study | |
| Reflexology | Control | To determine the effect of reflexology massage on sleep quality | Massage will be done by nurse of the same sex of the patient | Slow and regular rhythm massage | Trained nurses provided the intervention in the clinic: 12 sessions of 30 minutes, 3 day a week for 4 weeks | The depth of the massage depended on the patient's tolerance | ‐ | All patients completed the study | |
| Massage | Control | To determine the effectiveness of hot stone massage therapy on sleep quality level | Massage compared with routine health care | ‐ | 12 sessions | ‐ | ‐ | The number of patients who completed the study was not reported | |
| Exercise | Control 1: Dopaminergic agonist (ropinirole) Control 2: Control | To compare the changes across groups on RLS symptoms to evaluate quality of life | Cycling compared with ropinirole 0.25 mg orally | Exercise consisted of cycling in a recumbent cycle | A specialized neurologist provided exercises in the clinic 3 times per week, ropinirole was delivered 0.25 mg daily for 26.4 weeks | The exercise intensity was readjusted on a monthly base | ‐ | 29 patients completed the study | |
| Exercise | Control | To investigate the intervention that reduce RLS | The exercise session in both groups included intra‐dialytic cycling for 45 min at 50 rpm | The exercise included aerobic exercise performed in a recumbent cycle | A neurologist provided the intervention in the clinic for 45 min, 3 times per week for 26.4 weeks | The exercise intensity was readjusted every 4 weeks to account for the patients’ | ‐ | All patients completed the study | |
| Light | Control | To evaluate the efficacy of the intervention in people with sleep‐wake disturbance and depressive symptomatology | Morning light was scheduled according to chronotype daily. The rest‐activity cycle was monitored with a wrist actimeter | ‐ | 30 minutes daily for 3 weeks | ‐ | ‐ | The number of patients who completed the study was not reported | |
| CBT | Control | To verify the effects of sleep‐related behaviour modification in combination with progressive muscle relaxation on insomnia | During the interval of training, they did progressive | The physician did the progressive muscle relaxation for the patients and guided the patients | A physician provided the intervention in the clinic for 20 minutes every 2 days, 3 times week. Relaxation was performed daily at home for 30 min for 13.2 weeks | ‐ | ‐ | 98 patients completed the study | |
| Collaborative care model | Control | To determine the effect of collaborative care model on the fatigue | Care model included motivation, preparation, and evaluation | Sessions about the illness and the proper behaviour to deal with | Researchers, doctors and nurses provide the intervention in the clinic, 2 hours per day for 12 weeks | Half‐hour meetings were held to deal with specific needed | ‐ | The number of patients who completed the study was not reported | |
| Chamomile | Control | To determine the effect of camomile | The intervention group will take syrup of chamomile | ‐ | Chamomile 400 mg/day orally for 4 weeks at home | ‐ | ‐ | The number of patients who completed the study was not reported | |
| Acupressure | Control 1: Sham Control 2: Control | To determine the relationship between anxiety and sleep quality | In intervention group will receive acupressure in true acupoint | Acupressure will be done using pressure with the thumb | 2 trained practitioners provided the intervention in the clinic, 3 times a week for 4 weeks | ‐ | ‐ | The number of patients who completed the study was not reported | |
| Acetate dialysis | Bicarbonate dialysis | To assess the influence of buffer, acetate or bicarbonate, on sleep and ventilation | Polysomnography was used to assess the efficacy of the intervention | After the prescribed period these treatments were inverted. | The medical team provided the intervention in the clinic | ‐ | ‐ | At the end of phases II, all patients completed the study | |
| Benzodiapine (triazolam) | Control | To test the efficacy of Triazolam in HD patients with sleep disorder | ‐ | ‐ | Daily for 1 week at home | ‐ | ‐ | The number of patients who completed the study was not reported | |
| Telephone support | Control | To develop an original telephone support model for | Patients received a standardized nurse‐led | Sessions to optimise health outcomes. After discharge started telephone call | A nurse provided the intervention in the clinic. Telephone‐ | The patient’s needs were assessed with an individualized program | Each telephone call was guided by the protocol and were audio taped to ensure consistency | 135 patients had completed the follow‐up questionnaires | |
| Melatonin | Control | To investigate the effects of drug on sleep and quality of life in patients with | Actigraphy was used to assess the efficacy of the intervention | The actiwatch was placed on the wrist of the arm without fistula | Physicians provided the intervention in the clinic or at home: 3 mg of melatonin daily for 52.4 weeks | ‐ | ‐ | 42 patients completed the study | |
| Levodopa | Gabapentin | To find the efficacy of gabapentin compared with levodopa in the treatment of RLS | 125 mg/day of levodopa 2 hours before sleep. 200 mg of gabapentin after HD | After the prescribed period these treatments were inverted | 4‐week management for each drug (first phase) in the clinic or at home | ‐ | ‐ | 14 patients completed the study | |
| Music | Control 1: Music Control 2: Control | To compare the effectiveness | The music used was a 6‐pieces piano improvisation in | Participants were exposed to music via | Researchers provided the intervention that was performed in the clinic or at home for 4 weeks | The patient could stop or play the music whenever he/she liked or listen to it again | Patients were assessed about fulfilling the intervention | 102 patients completed the study | |
| Aromatherapy | Control | To determine the effect of aromatherapy on the sleep quality and fatigue | Aromatherapy group (sweet orange oil and lavender oil) | Lavender and sweet orange oils were dropped to a gauze bandage. Patients had to smell the aromatic mixture for 2 min | Researchers provided the intervention that was performed at home for one month for 2 min before sleeping | ‐ | Patients were called to report any problems. Answers were recorded, and support was provided | 62 patients completed the study | |
| Acupressure | Control | To evaluate the effectiveness of acupressure on quality of sleep | 4 points were pressured: this pressure was continuous with finger circularly for 1‐2 second | ‐ | Researcher and his cooperator provided the intervention in the clinic, 12 times for 5 min, 3 days per week for 4 weeks | ‐ | The force of pressure (consistency /reliability) were confirmed by using a scale | The number of patients who completed the study was not reported | |
| Melatonin | Control | To assess the effect of melatonin administration on sleep quality | Actigraphy was used to assess the efficacy of the intervention | Melatonin 3 mg orally per day, for 4 weeks (first phase) at home | ‐ | ‐ | At the end the first phase, all patients completed the study | ||
| Bioelectrical impedance | Control | To assess the effect of bioelectrical impedance analysis on sleep | ‐ | ‐ | 13.2 weeks | ‐ | ‐ | The number of patients who completed the study was not reported | |
| Dialysate 37° | Dialysate 35° | To test if cool dialysate would improve blood flow, heat dissipation and sleep | Subjects received HD in warm condition (37°C) or cool condition (35°C) | After the prescribed period these treatments were inverted | Trained nurses and nephrology co‐investigator provided the intervention in the clinic | ‐ | The personnel ensured the integrity and proper functioning of the equipment | The number of patients who completed the study was not reported | |
| Levodopa | Ropinirole | To determine the efficacy and adverse event profile of ropinirole as compared with levodopa | Levodopa dosage was 100 to 200 mg/d and ropinirole dosage was 0.25 to 2 mg/d | After the prescribed period these treatments were inverted | Medications were performed orally for 6 weeks (first phase) in the clinic or at home | Doses could be doubled according to the investigators’ and patients’ opinions | ‐ | 10 patients completed the study | |
| Respiratory muscle training | Control 1: Peripheral muscle training Control 2: Control | To assess the effects of interventions on functional parameters, inflammatory state, and quality of life | Spirometry was used to assess the efficacy of the intervention | Patients performed three sets of 15 inspirations and rested for 60 seconds | 30 training sessions for 10 weeks in the clinic | The exercise load was changed throughout | ‐ | 39 patients completed the study | |
| Dopaminergic agonist (pergolide) | Control | To test the effect of pergolide on leg movements and sleep disturbance | Polysomnography was used to assess the efficacy of the intervention | After the prescribed period these treatments were inverted | Pergolide from 0.05 to 0.25 for 1.5 weeks (first phase) at home | ‐ | ‐ | At the end of phases II, 8 patients completed the study | |
| Exercise | Control | To assess the effect of a period of exercise on sleep quality and quantity | Participants were acquainted with cycling method on bicycle ergometer, | The sessions | A researcher provided the intervention: 3 days a week for 10 weeks in 60–90 minute exercise sessions | The exercise | ‐ | The number of patients who completed the study was not reported | |
| Relaxation | Control | To evaluate the effect of the intervention on the sleep quality | The intervention group listened to the audiotape of Benson’s | The patients were instructed and were comfortably at rest in bed in a separate room | An expert provided the intervention that was performed twice a day for twenty minutes for 8 weeks, in the clinic or at home | ‐ | A CD on relaxation technique and research's number was given to the patients. Weekly Were provided | 83 patients completed the study | |
| Gabapentin | Dopaminergic agonist (levodopa/carbidopa) | To compare drugs in reducing symptoms and sleep problems | Gabapentin 200 mg orally compared to levodopa‐c 110 mg orally | ‐ | Gabapentin 200 mg (3 times weekly), levodopa‐c 110 mg in a single dose for 4 weeks at home | ‐ | ‐ | 83 patients completed the study | |
| Relaxation | Control | To reduce symptoms and improve quality of life using a multi‐modal telephone‐adapted program | Intervention was a bookend program. Actigraphy was used to assess the efficacy of the intervention | Workshops and teleconferences that included discussions, homework and practice | Certified teachers and a psychologist provided the intervention at the University. Teleconferences were held from patients' home for 8 weeks | Teacher ensured that yoga poses could be modified for people with disabilities. Emails were also used to document any deviations from checklists | Teleconferences used standard guidelines and each group had a unique password. | 52 patients completed the study | |
| Foot‐bath | Control | To explore the intervention effect of herb foot‐bath therapy to improve sleep quality and symptom | Herbs packed by gauze bag were put into a footbath with | Feet were put above the footbath in water | A course of treatment was four weeks; the | Once uncomfortableness and problems occurred, patient should stop the intervention and reported symptoms | ‐ | The number of patients who completed the study was not reported | |
| Benzodiazepine (zaleplon) | Control | To test the effects of | 5 to 10 mg of zaleplon | After the prescribed period these treatments were inverted | A nephrologist provided the intervention that was performed at home (5 to 10 mg of zaleplon) for 2 weeks (first phase) | ‐ | ‐ | At the end of phases II, 10 patients completed the study | |
| Education | Control | To investigate the effect of the intervention on the sleep quality for | Patients in the intervention | Direct teaching methods, combination of face‐to‐face | A researcher provided the intervention: 6 weekly sessions of half‐hour for 4 weeks | ‐ | ‐ | 76 patients completed the study | |
| Acupressure | Control | To investigate the effects of acupressure on sleep quality | Acupressure applied consistent pressure on the correct acupoints with small rotational | The intervention group | The investigators provided the intervention in the clinic: 15 min, 3 times per week for 4 weeks | Three acupoints that could be used to enhance sleep were chosen for the subjects | The precision was confirmed if subjects | 40 patients completed the study | |
| Acupressure | Sham | To investigate the effect and safety of acupressure on the sleep quality | ‐ | All selected acupoints were stimulated bilaterally | An accredited practitioner provided the intervention in the clinic (3 min, 3 times a week) for 4 weeks | The intensity was adjusted according to the | ‐ | 41 patients completed the study | |
| Continuous Positive Airway Pressure | Compression stockings | To evaluate the short‐term impact of treatments on the severity of sleep apnoea | Polysomnography was used to assess the efficacy of the intervention | After the prescribed period these treatments were inverted | A technician provided the intervention in the clinic for 1 week (first phase) | The lowest pressure was initially applied to all patients and increased progressively as needed | ‐ | At the end of phases II, 14 patients completed the study | |
| Dialyzer with cuprophan membrane | Dialyzer with poly‐methylmethacrylate membrane | To evaluate | Using two different types of membranes | After the prescribed period these treatments were inverted | The Medical team provided the intervention in the clinic thrice weekly, for 1 week (first phase) | ‐ | ‐ | At the end of phases II, 16 patients completed the study | |
| Gabapentin | Pregabalin | To compare the effects of drugs on sleep quality and depression | Electromyography was used to assess the efficacy of the intervention | After the prescribed period these treatments were inverted | A neurologist provided the intervention that was performed in the clinic or at home (gabapentin 300 mg thrice weekly, pregabalin 75 mg daily), for 6 weeks (first phase) | ‐ | ‐ | At the end of phases II, 48 patients completed the study | |
| Education | Control | To improve sleep quality through face‐to‐face sleep health education | Sleep hygiene education was performed. in two sections | The materials and a face‐to‐face session were provided | Researcher provided the intervention. This protocol was taught within an hour | ‐ | The participants asked questions and the materials were assessed | 57 patients completed the study | |
| Branch‐chain amino acid | Control | To assess the effect of the branch‐chain amino acid on sleep apnoea | Polysomnography was used to assess the efficacy of the intervention | After the prescribed period these treatments were inverted | For 2 study nights (first phase) | ‐ | ‐ | At the end of phases II, all patients completed the study | |
| Massage | Control | To assess if stimulating gastric activity improves relax and sleep | Abdominal massage, patient's education and training exercise | Massage to improve below contractility | Nurses provided the intervention in the clinic or at home for 4 weeks | ‐ | ‐ | Data were reported for all patients | |
| Gabapentin | Control | To determine changes on pruritus, quality of life, depression and sleep quality | Gabapentin 300 mg compared with placebo | After the prescribed period these treatments were inverted | Gabapentin 300 mg orally for 8 weeks (first phase) in the clinic or at home | ‐ | ‐ | At the end of phases II, all patients completed the study | |
| L‐dopa + benserazide | Control | To assess the effects of L‐dopa on sleep quality in restless leg syndrome | Polysomnography was used to assess the efficacy of the intervention | After the prescribed period these treatments were inverted | L‐dopa + benserazide (200mg + 50mg) orally for 4 weeks (first phase) at home | ‐ | Patients were monitored by phone calls | At the end of phases II, 28 patients completed the study | |
| Relaxation | Control | To examine the efficacy of a nurse‐led, | The dialysis nurse administered the audio device–guided breathing training in a quiet room | Patients listened to prerecorded | A trained nurse provided the intervention in the clinic: 8 sessions, twice weekly for 4 weeks | Each patient received an individual coaching session | The nurse supervised each practice session and evaluated | 57 patients completed the study | |
| Acupressure | Control 1: Sham Control 2: Control | To test the effectiveness of acupressure on sleep quality and fatigue | The intervention group received acupressure. The | Four acupoints were used to decrease fatigue | Researchers trained provided the intervention: 15 min, 3 times a week for 4 weeks | ‐ | The precision of acupressure was confirmed if | 98 patients completed the study | |
| Acupressure | Control 1: Acupressure (Transcutaneous Electrical Acupoint Stimulation) Control 2: Control | To test the effectiveness of the interventions on fatigue, sleep quality and depression | Acupressure compare with | Four acupoints were used to decrease fatigue | Investigators provided the intervention: 15 minutes of treatment | ‐ | The reliability of the pressure was assesses using a | 106 patients completed the study | |
| Phosphodiesterase type 5 (sildenafil) | Phosphodiesterase type 5 (vardenafil) | To compare the | Sildenafil 50 mg orally compared with Vardenafil 10 mg orally | After the prescribed period these treatments were inverted | The drugs were administered | ‐ | ‐ | The number of patients who completed the study was not reported | |
| Reflexology | Control 1: Massage Control 2: Control | To examine the effectiveness the interventions on | Foot reflexology compared with back massage and control group | 3 drops of baby oil were applied at room temperature to facilitate the massage | A researcher provided the intervention in the clinic: 30 minutes, 2 days a week for 4 weeks | ‐ | ‐ | 105 patients completed the study | |
| L‐dopa/carbidopa | Control | To determine if levodopa/carbidopa decreased leg movements and improved sleep | L‐dopa/carbidopa 100 mg + 25 mg compared with placebo | After the prescribed period these treatments were inverted | L‐dopa/carbidopa 100 mg + 25 mg daily for 1 week (first phase) at home | ‐ | ‐ | At the end of phases II, 5 patients completed the study | |
| Feedback group | Control | To determine if providing feedback | All participants were equipped with the tracking bracelet. Intervention group received feedback | Patients in the feedback group received their activity and sleep data at each dialysis treatment | Research coordinators provided the intervention in the clinic or at home. All participants wore the tracking bracelet at all times for 5 weeks | ‐ | ‐ | 29 patients completed the study | |
| Exercise | Control | To assess if yoga exercise can improve pain, fatigue, sleep disorder and biochemical markers | Yoga‐based exercises were done in groups | Using some yogic postures and breathing exercises in the rehabilitation of dialysis patients | A yoga teacher provided the intervention. Exercises were performed in the clinic or at home, 30 min/day twice a week for 13.2 weeks | Some modifications to the program were done to increase patient compliance. The exercise has to be stopped if there is severe fatigue or pain | The exercises was explained to each patient until the physiotherapist was satisfied that all of them could do the exercises | 37 patients completed the study | |
| Acupressure | Control | To assess the efficacy of acupressure | 4 auricular magnetic bead plaster points in fixed points | Take the side of each ear, 2 days later using another ear | Patient provided a self‐pressure twice daily for 56 days, for 8 weeks (at home) | ‐ | ‐ | The number of patients who completed the study was not reported | |
| Acupressure | Control | To assess the feasibility and | Participants received acupressure on five active acupoints | Participants were instructed to press the beads until a slight soreness were felt | Trained nurse practitioner provided the intervention in the clinic for 8 weeks | If the plasters or beads detached, the patients came to hospital | Feasibility was assessed by the percentage of recruitment, retention, | 58 patients completed the 8 weeks of treatment, 55 completed the 12 weeks of follow‐up | |
| APD ‐ automated peritoneal dialysis; CAPD continuous ambulatory peritoneal dialysis; CBT ‐ cognitive‐behavioural therapy; HD ‐ haemodialysis; HDF ‐ haemodiafiltration; RLS ‐ restless legs syndrome | |||||||||
| Study ID | Treatment | Control | Adverse events in treatment arm | Adverse events in control arm | Comment |
| CAPD | APD | Peritonitis (2); exit‐site infection (1) | Peritonitis (1); exit‐site infection (1); tunnel infection (1); leakage (1); hernia (1); over‐hydration (2) | Quote: "No proper statistics could be applied due to the low numbers of patients and events." | |
| Light | Control | No participants experienced an adverse event | No participants experienced an adverse event | Quote: "No adverse reactions or symptom complaints were registered." | |
| CBT | Education | No participants experienced an adverse event | No participants experienced an adverse event | Quote: "No adverse events were reported during the intervention." | |
| Exercise (aerobic exercise) | Control 1: Exercise (resistance exercise) Control 2: Exercise (combination exercise) Control 3: Control | No participants experienced an adverse event | No participants experienced an adverse event | Quote: "There were no reported adverse events, such as musculoskeletal injuries, hypoglycaemic episodes, cardiovascular events, or hospitalizations, as result of the intervention." | |
| Acupressure | Estazolam | No participants experienced an adverse event | No participants experienced an adverse event | This study was not in English Quote from the "Acupuncture and related interventions for symptoms of chronic kidney disease (Review)": "Whether adverse events related to administration of estazolam such as somnolence, dizziness, hypokinesia and abnormal coordination occurred was not reported in the control group. Potential adverse events of estazolam might have been regarded as one of outcomes (complaints of adverse reaction), not as adverse events." | |
| Benzodiazepine (zolpidem) | Benzodiazepine (clonazepam) | No participants experienced an adverse event | No participants experienced an adverse event | Quote: "In this study, zolpidem was not associated with undesirable sleep side effects such as daytime drowsiness, headache, or amnesia, at least during the short‐term course of our study. [...] Meanwhile, the patients who received zolpidem did not complain of any particular side effects." | |
| Dopaminergic agonist (rotigotine) | Control | Application site reaction of mild pruritus(1); anxiety (1); foot fracture (1); abdominal pain (1); chest pain (1); dyspnoea (2); nausea (4); vomiting (3); diarrhoea (1); hypertension (2); headache (2) | Gastrointestinal infection (1); diarrhoea (2) | Quote: "AEs were reported by 12 (60%) patients receiving rotigotine and 5 (50%) patients receiving placebo (Table 4). Two patients had hypertension of moderate intensity while receiving rotigotine. Both patients were receiving medications for this condition prior to study start. One patient reported an application site reaction (MedDRA [Medical Dictionary for Regulatory Activities] high‐level term “application and instillation site reactions”) of mild pruritus while receiving 2 mg/24 h of rotigotine; no application site reactions were reported for placebo. Serious AEs were reported for 3 patients receiving rotigotine (foot fracture [n = 1]; anxiety, chest pain, and dyspnoea [n = 1]; and abdominal pain [n = 1]) and 1 patient receiving placebo (gastrointestinal infection)." | |
| CBT | Control | Death (4) | Death (4) | Quote; "None of the patients in the intervention group were discontinued because of a CBT adverse effect. [...] Most of these losses were due to death, which is somewhat expected for ESRD patients after almost 1 year of follow‐up." Comment: Figure 1 showed the number of deaths for each group | |
| Exercise | Control 1: Dopaminergic agonist (ropinirole) Control 2: Control | No participants experienced an adverse event | No participants experienced an adverse event in both control groups | Quote: "Finally, none of the patients reported any drug adverse reactions or augmentation phenomena from the three interventions." | |
| Exercise | Control | No participants experienced an adverse event | No participants experienced an adverse event | Quote: "All patients completed the exercise programme with no adverse effects." | |
| Melatonin | Control | Death (3) | Death (3) | No adverse events were reported. However, Figure 2 showed the number of deaths for each group | |
| Relaxation | Control | No participants experienced an adverse event | No participants experienced an adverse event | Quote: "In this study, no one reported any undesirable side effects or unintended harm sign, symptom, or disease related to participation in the study or the relaxation technique." | |
| Gabapentin | Dopaminergic agonist (levodopa/carbidopa) | Somnolence and lethargy (2) | Allergy (1); death for myocardial infarction (1) | Quote: "During the course of the study period, two patients dropped out during the study secondary to somnolence and lethargy. These patients were administered gabapentin when the symptoms developed. One patient died because of myocardial infarction." | |
| Relaxation | Control | No participants experienced an adverse event | No participants experienced an adverse event | Quote from Gross 2017: "No intervention‐related adverse events occurred." | |
| Acupressure | Sham | Fluid overload (1); ocular haemorrhage (1) | Necrotizing fasciitis (1); physical trauma (1); chest muscle pain (1); arteriovenous graft failure (1) | Quote: "There were six adverse events (6 participants) recorded during the study (Table 4), all of which were rated as serious adverse events (SAEs) as they led to hospitalisation. Two SAEs occurred in the intervention group (fluid overload and ocular haemorrhage) and the remaining four SAEs occurred in the control group (necrotizing fasciitis, physical trauma, chest muscle pain, and arteriovenous graft failure). No adverse event was considered by investigators to be causally related to the study intervention. No local skin reaction (e.g., bruise) from repeated acupressure was reported during the study." | |
| Acupressure | Control | Death (3) | No participants experienced an adverse event | Quote: "Three participants died during the follow‐up period. No evidence supported their deaths were related to the AA intervention. No other adverse event was observed." | |
| APD ‐ automated peritoneal dialysis; CAPD ‐ continuous ambulatory peritoneal dialysis; CBT ‐ cognitive‐behavioural therapy | |||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Sleep quality Show forest plot | 4 | 259 | Mean Difference (IV, Random, 95% CI) | ‐1.62 [‐5.03, 1.79] |
| 2 Sleep latency Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 3 Total sleep time Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 4 Sleep disturbance Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 5 Hospitalisation Show forest plot | 1 | Risk Ratio (IV, Random, 95% CI) | Totals not selected | |
| 6 Anxiety Show forest plot | 2 | 119 | Std. Mean Difference (IV, Random, 95% CI) | 0.11 [‐0.55, 0.77] |
| 7 Pain Show forest plot | 3 | 189 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.26 [‐0.67, 0.15] |
| 8 Fatigue Show forest plot | 2 | 119 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.61 [‐2.09, 0.87] |
| 9 Quality of life Show forest plot | 2 | 138 | Std. Mean Difference (IV, Random, 95% CI) | 0.47 [‐0.09, 1.04] |
| 10 Depression Show forest plot | 2 | 108 | Std. Mean Difference (IV, Random, 95% CI) | 0.04 [‐1.27, 1.35] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Sleep quality Show forest plot | 5 | 165 | Std. Mean Difference (IV, Random, 95% CI) | ‐1.10 [‐2.26, 0.05] |
| 2 Total sleep time Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 3 Sleep efficiency Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 4 Sleep disturbance Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 5 Anxiety Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 6 Pain Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 7 Fatigue Show forest plot | 2 | 107 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.68 [‐1.07, ‐0.29] |
| 8 Depression Show forest plot | 2 | 46 | Mean Difference (IV, Random, 95% CI) | ‐9.05 [‐13.72, ‐4.39] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Sleep quality Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 2 Depression Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Sleep quality Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 2 Total sleep time Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 3 Sleep efficiency Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Sleep quality Show forest plot | 6 | 367 | Mean Difference (IV, Random, 95% CI) | ‐1.27 [‐2.13, ‐0.40] |
| 2 Sleep latency Show forest plot | 3 | 173 | Mean Difference (IV, Random, 95% CI) | ‐0.59 [‐0.92, ‐0.27] |
| 3 Total sleep time Show forest plot | 3 | 173 | Mean Difference (IV, Random, 95% CI) | ‐0.60 [‐1.12, ‐0.09] |
| 4 Sleep disturbance Show forest plot | 3 | 173 | Mean Difference (IV, Random, 95% CI) | ‐0.49 [‐1.16, 0.19] |
| 5 Sleep interruption Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 6 Sleep efficiency Show forest plot | 2 | 107 | Mean Difference (IV, Random, 95% CI) | ‐0.18 [‐0.39, 0.03] |
| 7 Death (all causes) Show forest plot | 1 | Risk Ratio (IV, Random, 95% CI) | Totals not selected | |
| 8 Fatigue Show forest plot | 2 | 137 | Mean Difference (IV, Random, 95% CI) | ‐1.07 [‐1.67, ‐0.48] |
| 9 Depression Show forest plot | 2 | 137 | Mean Difference (IV, Random, 95% CI) | ‐3.65 [‐7.63, 0.33] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Sleep quality Show forest plot | 2 | 129 | Mean Difference (IV, Random, 95% CI) | ‐2.25 [‐6.33, 1.82] |
| 2 Sleep latency Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 3 Sleep interruption Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 4 Total sleep time Show forest plot | 2 | 107 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.34 [‐0.73, 0.04] |
| 5 Sleep disturbance Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 6 Hospitalisation Show forest plot | 1 | Risk Ratio (IV, Random, 95% CI) | Totals not selected | |
| 7 Fatigue Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 8 Depression Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Sleep quality Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 2 Fatigue Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 3 Depression Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Sleep quality Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Sleep quality Show forest plot | 2 | 183 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.65 [‐1.03, ‐0.26] |
| 2 Sleep latency Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 3 Total sleep time Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 4 Sleep efficiency Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 5 Death (all causes) Show forest plot | 1 | Risk Ratio (IV, Random, 95% CI) | Totals not selected | |
| 6 Anxiety Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 7 Quality of life Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 8 Depression Show forest plot | 2 | 183 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.76 [‐1.06, ‐0.46] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Sleep quality Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 2 Sleep latency Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 3 Total sleep time Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 4 Sleep efficiency Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 5 Depression Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 6 Anxiety Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 7 Fatigue Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Sleep quality Show forest plot | 3 | 220 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.50 [‐0.77, ‐0.23] |
| 2 Sleep latency Show forest plot | 2 | 135 | Mean Difference (IV, Random, 95% CI) | ‐0.50 [‐0.76, ‐0.23] |
| 3 Total sleep time Show forest plot | 2 | 135 | Mean Difference (IV, Random, 95% CI) | ‐0.27 [‐0.59, 0.05] |
| 4 Sleep efficiency Show forest plot | 2 | 135 | Mean Difference (IV, Random, 95% CI) | ‐0.30 [‐0.66, 0.06] |
| 5 Sleep disturbance Show forest plot | 2 | 135 | Mean Difference (IV, Random, 95% CI) | ‐0.38 [‐0.52, ‐0.24] |
| 6 Pain Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 7 Fatigue Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 8 Quality of life Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Sleep quality Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Sleep quality Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 2 Sleep latency Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 3 Total sleep time Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 4 Sleep efficiency Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 5 Quality of life Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Sleep quality Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 2 Pain Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 3 Fatigue Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 4 Quality of life Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Sleep quality Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 2 Death (all causes) Show forest plot | 1 | Risk Ratio (IV, Random, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Sleep quality Show forest plot | 2 | 132 | Mean Difference (IV, Random, 95% CI) | ‐5.90 [‐6.56, ‐5.23] |
| 2 Fatigue Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Sleep quality Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 2 Fatigue Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Sleep latency Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 2 Sleep efficiency Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 3 Depression Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Sleep latency Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 2 Total sleep time Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 3 Sleep disturbance Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 4 Cardiovascular death Show forest plot | 1 | Risk Ratio (IV, Random, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Sleep quality Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Sleep quality Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 2 Sleep latency Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 3 Total sleep time Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 4 Sleep disturbance Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Sleep quality Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 2 Sleep latency Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 3 Total sleep time Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 4 Sleep disturbance Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Sleep quality Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 2 Sleep latency Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 3 Total sleep time Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 4 Sleep efficiency Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 5 Sleep disturbance Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Sleep quality Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 2 Pain Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
| 3 Quality of life Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Totals not selected | |
