Quinine for muscle cramps

Sherif El‐Tawil; Tarique Al Musa; Haseeb Valli; Michael PT Lunn; Tariq El‐Tawil; Markus Weber

doi:10.1002/14651858.CD005044.pub2

Scolaris Content Display Scolaris Content Display

Contenido relacionado

Ir a:

Revisiones y protocolos relacionados
Podcasts
Guías
Temas

Revisiones y protocolos relacionados

Topics

Temas

Figure 1

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 2

Forest plot of comparison: 1 Quinine versus placebo, outcome: 1.2 Difference in number of cramps over 2 weeks ‐ random‐effects (minus Connolly 1992).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 3

Forest plot of comparison: 2 Quinine versus vitamin E, outcome: 2.1 Difference in number of cramps in 2 weeks ‐ random‐effects (minus Connolly 1992).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 4

Forest plot of comparison: 3 Quinine versus a quinine‐vitamin E combination (Q‐Vel), outcome: 3.1 Difference in number of cramps in 2 weeks ‐ random‐effects.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 5

Forest plot of comparison: 1 Quinine versus placebo, outcome: 1.7 Participants suffering minor adverse events ‐ fixed‐effect.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 6

Forest plot of comparison: 1 Quinine versus placebo, outcome: 1.8 Participants suffering specific minor adverse events.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 7

Forest plot of comparison: 1 Quinine versus placebo, outcome: 1.9 Participants suffering major adverse events.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 8

Forest plot of comparison: 1 Quinine versus placebo, outcome: 1.10 Participants suffering specific major adverse events (gastrointestinal).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.1

Comparison 1 Quinine versus placebo, Outcome 1 Difference in number of cramps over 2 weeks (GIV) ‐ fixed‐effect.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.2

Comparison 1 Quinine versus placebo, Outcome 2 Difference in number of cramps over 2 weeks ‐ random‐effects (minus Connolly 1992).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.3

Comparison 1 Quinine versus placebo, Outcome 3 Difference in number of cramps according to quinine dose (GIV) ‐ fixed‐effect.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.4

Comparison 1 Quinine versus placebo, Outcome 4 Difference in cramp intensity (GIV) ‐ fixed‐effect.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.5

Comparison 1 Quinine versus placebo, Outcome 5 Change in cramp duration (mins) ‐ random‐effects.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.6

Comparison 1 Quinine versus placebo, Outcome 6 Difference in number of cramp days over 2 weeks (GIV) ‐ random‐effects (minus Connolly 1992.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.7

Comparison 1 Quinine versus placebo, Outcome 7 Participants suffering minor adverse events ‐ fixed‐effect.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.8

Comparison 1 Quinine versus placebo, Outcome 8 Participants suffering specific minor adverse events.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.9

Comparison 1 Quinine versus placebo, Outcome 9 Participants suffering major adverse events.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.10

Comparison 1 Quinine versus placebo, Outcome 10 Participants suffering specific major adverse events (gastrointestinal).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.1

Comparison 2 Quinine versus vitamin E, Outcome 1 Difference in number of cramps in 2 weeks ‐ random‐effects (minus Connolly 1992).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.2

Comparison 2 Quinine versus vitamin E, Outcome 2 Difference in cramp intensity ‐ fixed‐effect.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.3

Comparison 2 Quinine versus vitamin E, Outcome 3 Difference in number of cramp days over 2 weeks ‐ random‐effects (minus Connolly 1992).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.4

Comparison 2 Quinine versus vitamin E, Outcome 4 Participants suffering minor adverse events ‐ random‐effects.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.5

Comparison 2 Quinine versus vitamin E, Outcome 5 Participants suffering major adverse events ‐ random‐effects.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.1

Comparison 3 Quinine versus a quinine‐vitamin E combination (Q‐Vel), Outcome 1 Difference in number of cramps in 2 weeks ‐ random‐effects.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.2

Comparison 3 Quinine versus a quinine‐vitamin E combination (Q‐Vel), Outcome 2 Difference in cramp intensity ‐ random‐effects.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.3

Comparison 3 Quinine versus a quinine‐vitamin E combination (Q‐Vel), Outcome 3 Difference in number of cramp days over 2 weeks ‐ random‐effects.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.4

Comparison 3 Quinine versus a quinine‐vitamin E combination (Q‐Vel), Outcome 4 Participants suffering minor adverse events ‐ random‐effects.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.5

Comparison 3 Quinine versus a quinine‐vitamin E combination (Q‐Vel), Outcome 5 Participants suffering major adverse events ‐ fixed‐effect.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Summary of findings for the main comparison. Quinine for muscle cramps

Quinine for muscle cramps
Patient or population: patients with muscle cramps Settings: Mainly outpatients Intervention: Quinine versus placebo
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	Quinine versus placebo
Number of cramps over 2 weeks	The mean number of cramps over 2 weeks in the control groups was 8.8 cramps	The mean Number of cramps over 2 weeks in the intervention groups was 2.45 lower (1.36 to 3.54 lower)		952 (13 studies)	⊕⊕⊕⊝ moderate¹	The difference was statistically significant.
Cramp intensity (on 3‐point scale; 1=mild; 2=moderate; 3=severe)	The mean cramp intensity in the control groups was 1.2 units	The mean Cramp intensity in the intervention groups was 0.12 lower (0.2 to 0.05 lower)		666 (7 studies)	⊕⊕⊕⊝ moderate¹	The difference was statistically significant.
Participants suffering major adverse events	14 per 1000	15 per 1000 (4 to 35)	See comment	1103 (18 studies)	⊕⊕⊕⊝ moderate²	Risks were calculated from pooled risk differences. The difference was not statistically significant.
Participants suffering minor adverse events	94 per 1000	127 per 1000 (94 to 154)	See comment	969 (16 studies)	⊕⊕⊕⊝ moderate³	Risks were calculated from pooled risk differences. The difference was statistically significant.
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; RR: Risk ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ There were significant shortcomings in study design in some trials, but the majority of those included in this meta‐analysis were of moderate to high quality ² Major adverse events were defined as those being severe enough to warrant participant withdrawal from the trial. As specific hypersensitivity reactions are so rare, larger studies are needed to clarify the incidence of such adverse events in particular. Some trials did not pre‐specify adverse events as an outcome but simply reported them retrospectively, thus compromising slightly on the quality of evidence. ³ Minor adverse events were defined as being those that did not warrant participant withdrawal from the trial. Some trials did not pre‐specify adverse events as an outcome but simply reported them retrospectively, thus compromising slightly on the quality of evidence. Otherwise, a well reported outcome.

Summary of findings for the main comparison. Quinine for muscle cramps

Ir a la tabla de la revisión

Summary of findings 2. Quinine versus vitamin E for muscle cramps

Quinine versus vitamin E for muscle cramps
Patient or population: patients with muscle cramps Settings: Outpatients Intervention: Quinine versus vitamin E
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	Quinine versus vitamin E
Number of cramps over 2 weeks	The mean number of cramps over 2 weeks in the control groups was 7.22	The mean Number of cramps over 2 weeks in the intervention groups was 0.24 lower (1.29 lower to 0.81 higher)		513 (3 studies)	⊕⊕⊝⊝ low^1,2	The difference was not statistically significant.
Cramp intensity (on 3‐point scale; 1=mild; 2=moderate; 3=severe)	The mean cramp intensity in the control groups was 1.04 units	The mean Cramp intensity in the intervention groups was 0.06 lower (0.17 lower to 0.04 higher)		513 (3 studies)	⊕⊕⊕⊝ moderate¹	The difference was not statistically significant.
Participants suffering major adverse events	3 per 1000	9 per 1000 (‐8 to 25)	See comment	513 (3 studies)	⊕⊕⊕⊝ moderate¹	Risks were calculated from pooled risk differences. The difference between the two groups was not statistically significant.
Participants suffering minor adverse events	167 per 1000	189 per 1000 (127 to 257)	See comment	483 (2 studies)	⊕⊕⊕⊝ moderate³	Risks were calculated from pooled risk differences. The difference between the two groups was not statistically significant.
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; RR: Risk ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Only three trials were available for this comparison, two of which were conducted by pharmaceutical investigators on behalf of manufacturers of quinine. A deficiency in the design of one of these trials meant that there was only a two‐day washout between crossover treatments. ² The effect on cramp number was inconsistent among the three included trials. ³ Only two studies were available for this comparison; one of them having a very short washout period (two days) between treatments.

Summary of findings 2. Quinine versus vitamin E for muscle cramps

Ir a la tabla de la revisión

Summary of findings 3. Quinine versus a quinine‐vitamin E combination (Q‐Vel) for muscle cramps

Quinine versus a quinine‐vitamin E combination (Q‐Vel) for muscle cramps
Patient or population: patients with muscle cramps Settings: Outpatients Intervention: Quinine versus a quinine‐vitamin E combination (Q‐Vel)
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	Quinine versus a quinine‐vitamin E combination (Q‐Vel)
Number of cramps over 2 weeks	The mean number of cramps over 2 weeks in the control groups was 8.37	The mean Number of cramps over 2 weeks in the intervention groups was 1.07 higher (1.08 lower to 3.23 higher)		486 (2 studies)	⊕⊕⊝⊝ low^1,2	The difference was not statistically significant.
Cramp intensity (on 3‐point scale; 1=mild; 2=moderate; 3=severe)	The mean cramp intensity in the control groups was 0.87 units	The mean Cramp intensity in the intervention groups was 0.1 higher (0.06 lower to 0.26 higher)		510 (3 studies)	⊕⊕⊝⊝ low^3,4	The difference was not statistically significant.
Participants suffering major adverse events	8 per 1000	8 per 1000 (‐2 to 18)	See comment	510 (3 studies)	⊕⊕⊕⊝ moderate³	Risks were calculated from pooled risk differences.
Participants suffering minor adverse events	173 per 1000	202 per 1000 (133 to 273)	See comment	510 (3 studies)	⊕⊕⊕⊝ moderate³	Risks were calculated from pooled risk differences. The difference was not statistically significant.
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; RR: Risk ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ The results for cramp number in these two trials were not consistent, each suggesting opposite effects. ² Only two studies were available for this comparison. Both were conducted by pharmaceutical investigators on behalf of manufacturers of quinine and the quinine‐vitamin E combination. ³ All three trials were conducted by pharmaceutical companies who manufacture quinine and the quinine‐vitamin E combination. ⁴ There was no consistency between the results for intensity in these 3 trials.

Summary of findings 3. Quinine versus a quinine‐vitamin E combination (Q‐Vel) for muscle cramps

Ir a la tabla de la revisión

Table 1. Study design of the 23 included trials

Study	Number of participants Study design Patient focus	Mean age (yrs)	Female	Male	F: M ratio	Quinine dose (mg)	Treatment period (d)	Washout period (d)	Treatment comparisons
CIBA 1988^a	n = 556 Study design = P^b Patient focus = I^b	45	393	163	2.4	260	14	n/a^c	Placebo ✓ Vitamin E ✓ Quinine‐vitamin E combination (Q‐Vel^®d) ✓
Leo Winter 1986^a	n = 205 Study design = C^b Patient focus = I^b	44	173	32	5.4	260	5	2	Placebo ✓ Vitamin E ✓ Quinine‐vitamin E combination (Q‐Vel^®) ✓
Gorlich 1991	n = 164 Study design = P Patient focus = I	56	119	45	2.6	260	14	n/a	Placebo ✓ Quinine‐theophylline combination (Limptar^®d)✓
Jansen 1997	n = 106 Study design = P Patient focus = I	51	68	44	1.5	300	14	n/a	Placebo ✓
Diener 2002	n = 94 Study design = P Patient focus = I	49	66	32	2.1	400	14	n/a	Placebo ✓
Bottner 1984^a	n = 69 Study design = C Patient focus = I	51	66	3	22.0	260	14	14	Placebo ✓
Hays 1986^a	n = 62 Study design = C Patient focus = I	47	49	13	3.8	325	14	14	Placebo ✓
Lee 1991	n = 31 Study design = P Patient focus = L^b	62	5	26	0.2	400	28	n/a	Placebo ✓
Connolly 1992	n = 30 Study design = C Patient focus = I	59	0	30	0.0	500	28	28	Placebo ✓ Vitamin E ✓^e
Roca 1992	n = 30 Study design = P Patient focus = H^b	48	10	19	0.5	325	60^f	n/a	Vitamin E ✓
Dunn 1993	n = 28 Study design = C Patient focus = I	67	17	11	1.5	300	30	3	Placebo ✓
Lim 1986	n = 25 Study design = P Patient focus = I	_	_	_	_	300	≤ 14	n/a	Placebo ✓
BioDesign 1984^a	n = 24 Study design = C Patient focus = I	57	11	13	0.8	260	7	7	Quinine‐vitamin E combination (Q‐Vel^®) ✓
Prateepavanich 1999	n = 24 Study design = P Patient focus = I^g	64	21	3	7.0	300	28	n/a	Xylocaine injection ✓
Warburton 1987	n = 22 Study design = C Patient focus = I	74	16	6	2.7	300	21	0	Placebo ✓
Jansen 1994	n = 20 Study design = P Patient focus = I	55	14	6	2.3	300	14	n/a	Placebo ✓
Sidorov 1993	n = 19 Study design = C Patient focus = I	58	14	2	7.0	200	14	14	Placebo ✓
Smith 1985	n = 21 Study design = C Patient focus = I	73	_	_	_	300	21	0	Placebo ✓
Maule 1990	n = 16 Study design = C Patient focus = I	76	10	6	1.7	300	21	0	Placebo ✓
Woodfield 2005	n = 13 Study design = N‐of‐1 Patient focus = I	75	7	6	1.2	200 ‐300	42	0	Placebo ✓
Kaji 1976	n = 9 Study design = C Patient focus = H	_	_	_	_	320^h	42^h	0	Placebo ✓
Jones 1983	n = 9 Study design = C Patient focus = I	_	_	_	_	300	14	14	Placebo ✓
Fung 1989	n = 9 Study design = C Patient focus = I	63	7	1	7.0	200	28	7	Placebo ✓
^aUnpublished. ^bC: crossover, P: parallel, H: haemodialysis‐induced cramps, I: idiopathic, L: patients with liver cirrhosis. ^cNA: not available. ^dQ‐Vel^®: trade name for quinine‐vitamin E combination; Limptar^®:trade name for quinine‐theophylline combination. ^eConnolly 1992 did not directly compare quinine versus vitamin E ‐ using the data provided we were able to draw comparison. ^fA 60‐day trial but results only reported from first month of treatment. ^gInclusion criteria included presence of myofascial trigger point in gastrocnemius.^hQuinine dose given at beginning of each dialysis session (three times per wk) and not daily.

Table 1. Study design of the 23 included trials

Ir a la tabla de la revisión

Comparison 1. Quinine versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Difference in number of cramps over 2 weeks (GIV) ‐ fixed‐effect Show forest plot	14		Cramp number (Fixed, 95% CI)	‐1.81 [‐2.20, ‐1.42]

2 Difference in number of cramps over 2 weeks ‐ random‐effects (minus Connolly 1992) Show forest plot	13		Cramp Number (Random, 95% CI)	‐2.45 [‐3.54, ‐1.36]

3 Difference in number of cramps according to quinine dose (GIV) ‐ fixed‐effect Show forest plot	14		Cramp Number (Fixed, 95% CI)	‐1.81 [‐2.20, ‐1.42]

3.1 500 mg quinine	1		Cramp Number (Fixed, 95% CI)	‐8.7 [‐10.30, ‐7.10]
3.2 400 mg quinine	2		Cramp Number (Fixed, 95% CI)	‐3.36 [‐4.83, ‐1.89]
3.3 300 to 325 mg quinine	5		Cramp Number (Fixed, 95% CI)	‐0.79 [‐1.31, ‐0.26]
3.4 260 mg quinine	3		Cramp Number (Fixed, 95% CI)	‐1.29 [‐2.15, ‐0.42]
3.5 200 mg quinine	3		Cramp Number (Fixed, 95% CI)	‐3.22 [‐4.40, ‐2.04]
4 Difference in cramp intensity (GIV) ‐ fixed‐effect Show forest plot	7		Cramp intensity (Fixed, 95% CI)	‐0.12 [‐0.20, ‐0.05]

5 Change in cramp duration (mins) ‐ random‐effects Show forest plot	2		Change in duration (Random, 95% CI)	‐1.35 [‐4.00, 1.30]

6 Difference in number of cramp days over 2 weeks (GIV) ‐ random‐effects (minus Connolly 1992 Show forest plot	7		Cramp days (Random, 95% CI)	‐1.15 [‐1.93, ‐0.38]

7 Participants suffering minor adverse events ‐ fixed‐effect Show forest plot	16	1447	Risk Difference (M‐H, Fixed, 95% CI)	0.03 [0.00, 0.06]

8 Participants suffering specific minor adverse events Show forest plot	18		Risk Difference (M‐H, Fixed, 95% CI)	Subtotals only

8.1 Gastrointestinal	18	1581	Risk Difference (M‐H, Fixed, 95% CI)	0.03 [0.01, 0.05]
8.2 Headache	18	1581	Risk Difference (M‐H, Fixed, 95% CI)	0.00 [‐0.02, 0.02]
8.3 Tinnitus	18	1581	Risk Difference (M‐H, Fixed, 95% CI)	0.01 [‐0.00, 0.02]
9 Participants suffering major adverse events Show forest plot	18	1613	Risk Difference (M‐H, Fixed, 95% CI)	0.00 [‐0.01, 0.02]

10 Participants suffering specific major adverse events (gastrointestinal) Show forest plot	18	1613	Risk Difference (M‐H, Fixed, 95% CI)	0.01 [‐0.00, 0.02]

Comparison 1. Quinine versus placebo

Ir a la tabla de la revisión

Comparison 2. Quinine versus vitamin E

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Difference in number of cramps in 2 weeks ‐ random‐effects (minus Connolly 1992) Show forest plot	3		No. cramps (Random, 95% CI)	‐0.24 [‐1.29, 0.81]

2 Difference in cramp intensity ‐ fixed‐effect Show forest plot	3		Cramp intensity (Fixed, 95% CI)	‐0.06 [‐0.17, 0.04]

3 Difference in number of cramp days over 2 weeks ‐ random‐effects (minus Connolly 1992) Show forest plot	2		Cramp days (Random, 95% CI)	‐0.28 [‐0.98, 0.43]

4 Participants suffering minor adverse events ‐ random‐effects Show forest plot	2	688	Risk Difference (M‐H, Random, 95% CI)	0.02 [‐0.04, 0.09]

5 Participants suffering major adverse events ‐ random‐effects Show forest plot	3	748	Risk Difference (M‐H, Random, 95% CI)	0.01 [‐0.01, 0.02]

Comparison 2. Quinine versus vitamin E

Ir a la tabla de la revisión

Comparison 3. Quinine versus a quinine‐vitamin E combination (Q‐Vel)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Difference in number of cramps in 2 weeks ‐ random‐effects Show forest plot	2		No. cramps (Random, 95% CI)	1.07 [‐1.08, 3.23]

2 Difference in cramp intensity ‐ random‐effects Show forest plot	3		Cramp intensity (Random, 95% CI)	0.10 [‐0.06, 0.26]

3 Difference in number of cramp days over 2 weeks ‐ random‐effects Show forest plot	2		Cramp days (Random, 95% CI)	0.18 [‐1.13, 1.49]

4 Participants suffering minor adverse events ‐ random‐effects Show forest plot	3	739	Risk Difference (M‐H, Random, 95% CI)	0.03 [‐0.04, 0.10]

5 Participants suffering major adverse events ‐ fixed‐effect Show forest plot	3	739	Risk Difference (M‐H, Fixed, 95% CI)	‐0.00 [‐0.01, 0.01]

Comparison 3. Quinine versus a quinine‐vitamin E combination (Q‐Vel)

Ir a la tabla de la revisión

The Cochrane Library

Scolaris Language Selector Scolaris Language Selector

Idioma de la Revisión Cochrane

Idioma de la web

Scolaris Content Language Banner Portlet Scolaris Content Language Banner Portlet