The effectiveness and cost-effectiveness of pimecrolimus and tacrolimus for atopic eczema: a systematic review and economic evaluation.

OBJECTIVES: To consider the effectiveness and cost-effectiveness of pimecrolimus for mild to moderate atopic eczema and tacrolimus for moderate to severe atopic eczema compared with current standard treatment in adults and children. DATA SOURCES: Electronic databases. Experts and the manufacturers of these agents were also approached for information. REVIEW METHODS: The systematic review was carried out using standard methodological guidelines and a stringent quality assessment strategy. A state transition (Markov) model was developed to estimate cost--utility of tacrolimus and pimecrolimus separately, compared with current standard practice with topical corticosteroids, (a) as first-line treatment and (b) as second-line treatment. Pimecrolimus was also compared to emollients only. RESULTS: The pimecrolimus trial reports were of varying quality; however when compared with a placebo (emollient), pimecrolimus was found to be more effective and to provide quality of life improvements. There is very little evidence available about pimecrolimus compared with topical corticosteroids. Compared with a placebo (emollient), both 0.03% and 0.1% tacrolimus were found to be more effective. Compared with a mild corticosteroid, 0.03% tacrolimus is more effective in children as measured by a 90% or better improvement in the Physician's Global Evaluation (PGE). Compared with potent topical corticosteroids, no significant difference in effectiveness is seen with 0.1% tacrolimus as measured by a 75% or greater improvement in the PGE. Minor application site adverse effects are common with tacrolimus. However, this did not lead to increased rates of withdrawal from treatment in trial populations. The PenTag economic model demonstrates a large degree of uncertainty, which was explored in both deterministic and stochastic analyses. This is the case for the cost-effectiveness of pimecrolimus and tacrolimus in first- or second-line use compared with topical steroids. In all cases immunosuppressant regimes were estimated to be more costly than alternatives and differences in benefits to be small and subject to considerable uncertainty. CONCLUSIONS: There is limited evidence from a small number of randomised controlled trials (RCTs) that pimecrolimus is more effective than placebo treatment in controlling mild to moderate atopic eczema. Although greater than for pimecrolimus, the evidence base for tacrolimus in moderate to severe atopic eczema is also limited. At both 0.1% and 0.03% potencies, tacrolimus appears to be more effective than the placebo treatment and mild topical corticosteroids. However, these are not the most clinically relevant comparators. Compared with potent topical corticosteroids, no significant difference was shown. Short-term adverse effects with both immunosuppressants are relatively common, but appear to be mild. Experience of long-term use of the agents is lacking so the risk of rare but serious adverse effects remains unknown. No conclusions can be confidently drawn about the cost-effectiveness of pimecrolimus or tacrolimus compared with active topical corticosteroid comparators. Areas for further research should focus on the effectiveness and safety of the treatments through good-quality RCTs and further economic analysis.

Selective serotonin reuptake inhibitors for premenstrual syndrome.

BACKGROUND: Severe premenstrual syndrome affects between 3-5% of women of reproductive age. Such severe PMS is classified under the Diagnostic and Statistical Manual of Mental Disorders as premenstrual dysphoric disorder, PMDD. Selective serotonin reuptake inhibitors (SSRIs) are increasingly being used as a front-line therapy for premenstrual syndrome (PMS). A systematic review was undertaken on the efficacy of SSRIs in the management of severe PMS/PMDD, to assess the evidence for this treatment option. OBJECTIVES: The objective of this review was to evaluate the effectiveness of SSRIs in reducing premenstrual syndrome symptoms in women diagnosed with severe premenstrual syndrome. SEARCH STRATEGY: Electronic searches for relevant randomised controlled trials of the Cochrane Menstrual Disorders and Subfertility Group specialised register of controlled trials, Cochrane Controlled Trials Register, MEDLINE, EMBASE and PsychLit were undertaken. References were searched interactively to identify missed trials. Where insufficient data were presented original authors were contacted for further details. SELECTION CRITERIA: All trials were considered in which women with a prospective diagnosis of PMS/ PMDD were randomised to receive SSRIs or placebo in a double blind trial for the treatment of premenstrual syndrome. DATA COLLECTION AND ANALYSIS: 31 randomised controlled trials were identified which reported the use of SSRIs in the management of PMS. 16 trials were excluded, 15 trials were included in the systematic review, and ten trials were included in the main analyses. The reviewers extracted the data independently and standardised mean differences for continuous outcomes were estimated from the data. MAIN RESULTS: The primary analysis of reduction in overall symptomatology included data on 844 women with premenstrual syndrome. SSRIs were found to be highly effective in treating premenstrual symptoms. Secondary analysis showed that they were as effective in treating physical as well as behavioural symptoms. There was no significant difference between trials funded by pharmaceutical companies and those independently funded. Withdrawals due to side effects were 2.5 times more likely to occur in the treatment group, particularly at higher doses. REVIEWER'S CONCLUSIONS: There is now very good evidence to support the use of selective serotonin reuptake inhibitors in the management of severe premenstrual syndrome.

Using village theatre to increase knowledge about eclampsia in Bangladesh.

OBJECTIVE: To assess the impact of a theatre based educational initiative on the knowledge and attitudes to eclampsia and its treatment in a rural Bangladeshi village. METHODS: An established theatre company, Theatre Centre for Social Development, performed scenarios regarding eclamptic pregnant women to a diverse audience of village observers. Before the performance 15 men and 15 women were randomly selected from the audience and asked a series of questions regarding eclampsia. After the performance the series of questions were repeated to the same people. RESULTS: The plays were enthusiastically received by the villagers. The level of knowledge of the villagers interviewed increased significantly after seeing the two plays. CONCLUSION: The intervention successfully raised both the awareness of eclampsia and the level of knowledge of effective treatments for eclampsia. Village theatre has shown the potential to be a very effective tool in Bangladeshi rural society.

Efficacy of progesterone and progestogens in management of premenstrual syndrome: systematic review.

OBJECTIVE: To evaluate the efficacy of progesterone and progestogens in the management of premenstrual syndrome. DESIGN: Systematic review of published randomised, placebo controlled trials. STUDIES REVIEWED: 10 trials of progesterone therapy (531 women) and four trials of progestogen therapy (378 women). MAIN OUTCOME MEASURES: Proportion of women whose symptoms showed improvement with progesterone preparations (suppositories and oral micronised). Proportion of women whose symptoms showed improvement with progestogens. Secondary analysis of efficacy of progesterone and progestogens in managing physical and behavioural symptoms. RESULTS: Overall standardised mean difference for all trials that assessed efficacy of progesterone (by both routes of administration) was -0.028 (95% confidence interval -0.017 to -0.040). The odds ratio was 1.05 (1.03 to 1.08) in favour of progesterone, indicating no clinically important difference between progesterone and placebo. For progestogens the overall standardised mean was -0.036 (-0.014 to -0.060), which corresponds to an odds ratio of 1.07 (1.03 to 1.11) showing a statistically, but not clinically, significant improvement for women taking progestogens. CONCLUSION: The evidence from these meta-analyses does not support the use of progesterone or progestogens in the management of premenstrual syndrome.

A randomised controlled trial to compare methods of milk expression after preterm delivery.

OBJECTIVES: Primary: to compare sequential and simultaneous breast pumping on volume of milk expressed and its fat content. Secondary: to measure the effect of breast massage on milk volume and fat content. DESIGN: Sequential randomised controlled trial. SETTING: Neonatal intensive care unit, North Staffordshire Hospital NHS Trust. SUBJECTS: Data on 36 women were analysed; 19 women used simultaneous pumping and 17 used sequential pumping. INTERVENTIONS: Women were randomly allocated to use either simultaneous (both breasts simultaneously) or sequential (one breast then the other) milk expression. Stratification was used to ensure that the groups were balanced for parity and gestation. A crossover design was used for massage, with patients acting as their own controls. Women were randomly allocated to receive either massage or non-massage first. MAIN OUTCOME MEASURES: Volume of milk expressed per expression and its fat content (estimated by the creamatocrit method). RESULTS: Milk yield per expression was: sequential pumping with no massage, 51.32 g (95% confidence interval (CI) 56.57 to 46.07); sequential pumping with massage, 78.71 g (95% CI 85.19 to 72.24); simultaneous pumping with no massage, 87.69 g (95% CI 96.80 to 78.57); simultaneous pumping with massage, 125.08 g (95% CI 140.43 to 109.74). The fat concentration in the milk was not affected by the increase in volume achieved by the interventions. CONCLUSIONS: The results are unequivocal and show that simultaneous pumping is more effective at producing milk than sequential pumping and that breast massage has an additive effect, improving milk production in both groups. As frequent and efficient milk removal is essential for continued production of milk, mothers of preterm infants wishing to express milk for their sick babies should be taught these techniques.

Determination of total menstrual blood loss.

OBJECTIVE: To develop and validate a simple method of measuring total menstrual blood loss using a pictorial representation of blood loss, the menstrual pictogram. DESIGN: A prospective evaluation of total menstrual blood loss measurement by the menstrual pictogram compared to the alkaline hematin technique. SETTING: Academic menorrhagia research clinic. PATIENT(S): One hundred twenty-one women; 62 women complaining of heavy menstrual blood loss, 59 women who considered their menstrual blood loss to be normal. INTERVENTION(S): Participants were asked to complete the menstrual pictogram through the period and collect their feminine hygiene products for an alkaline hematin assessment. MAIN OUTCOME MEASURE(S): Percentage agreement between blood loss measured by the gold standard alkaline hematin method and the menstrual pictogram. Extraneous blood loss was measured using a semiquantitative pictorial method. RESULT(S): The menstrual pictogram had a high level of agreement for blood collected on feminine hygiene products compared with the alkaline hematin method. Some women also lose a significantly large amount of extraneous blood, which is not proportional to the alkaline hematin blood loss assessment. CONCLUSION(S): The menstrual pictogram provides a simple means of measuring menstrual blood loss. It is no longer appropriate to ignore extraneous blood loss, particularly as there is no correlation between extraneous blood loss and that measured on feminine hygiene products.

Efficacy of selective serotonin-reuptake inhibitors in premenstrual syndrome: a systematic review.

BACKGROUND: Selective serotonin-reuptake inhibitors (SSRIs) are increasingly being used as first-line therapy for severe premenstrual syndrome (PMS). We undertook a meta-analysis on the efficacy of SSRIs in this disorder. METHODS: We searched medical and scientific databases, approached pharmaceutical companies, and reviewed citations of relevant articles to identify 29 studies of the use of SSRIs in PMS. 14 were excluded (no placebo group, preliminary report of included trial, or low quality). 15 randomised placebo-controlled trials were included. Information on study design, participants, drugs used and dosing regimens, outcome measures, side-effects, and sources of funding was extracted. Standardised mean differences between treatment and placebo groups were calculated to obtain an overall estimate of efficacy. The primary outcome measure was a reduction in overall PMS symptoms. FINDINGS: The primary analysis included data on 904 women (570 assigned active treatment and 435 assigned placebo, including 101 in crossover trials). The overall standardised mean difference was -1.066 (95% CI -1.381 to -0.750), which corresponds to an odds ratio of 6.91 (3.90 to 12.2) in favour of SSRIs. SSRIs were effective in treating physical and behavioural symptoms. There was no significant difference in symptom reduction between continuous and intermittent dosing or between trials funded by pharmaceutical companies and those independently funded. Withdrawal due to side-effects was 2.5 times more likely in the active-treatment group than in the placebo group. INTERPRETATION: SSRIs are an effective first-line therapy for severe PMS. The safety of these drugs has been demonstrated in trials of affective disorder, and the side-effects at low doses are generally acceptable.

Efficacy of vitamin B-6 in the treatment of premenstrual syndrome: systematic review.

OBJECTIVE: To evaluate the efficacy of vitamin B-6 in the treatment of premenstrual syndrome. DESIGN: Systematic review of published and unpublished randomised placebo controlled trials of the effectiveness of vitamin B-6 in the management of premenstrual syndrome. SUBJECTS: Nine published trials representing 940 patients with premenstrual syndrome. MAIN OUTCOME MEASURES: Proportion of women whose overall premenstrual symptoms showed an improvement over placebo. A secondary analysis was performed on the proportion of women whose premenstrual depressive symptoms showed an improvement over placebo. RESULTS: Odds ratio relative to placebo for an improvement in overall premenstrual symptoms was 2.32 (95% confidence interval 1.95 to 2.54). Odds ratio relative to placebo for an improvement in depressive symptoms was 1.69 (1.39 to 2.06) from four trials representing 541 patients. CONCLUSION: Conclusions are limited by the low quality of most of the trials included. Results suggest that doses of vitamin B-6 up to 100 mg/day are likely to be of benefit in treating premenstrual symptoms and premenstrual depression.

A comparison of pulse oximetry and near infrared spectroscopy (NIRS) in the detection of hypoxaemia occurring with pauses in nasal airflow in neonates.

OBJECTIVE: The aim of this study was to compare the ability of NIRS and pulse oximetry to detect changes in cerebral oxygenation occurring in response to a pause in nasal airflow (PNA). METHODS: Twenty-one recordings of cerebral oxygenation index by NIRS together with oxyhemoglobin saturation by pulse oximetry were measured on 17 preterm infants with a history of apnoea. Photoplethysmography was used to confirm the accuracy of the pulse oximetry data. PNA events were defined as pauses of greater than 4 seconds in a thermistor trace measuring nasal air flow. RESULTS: Baseline variability in oxygenation index (Hbdiff) was found to be from -0.12 to +0.13 micromol 100 g brain(-1). A fall in Hbdiff or SpO2 was defined as a decrease of greater magnitude than 2 standard deviations from the baseline, i.e., -0.12 micromol 100 g brain(-1) and 3% respectively. In 68% of 468 PNA events a fall in oxyhemoglobin saturation (SpO2) was detected and in 56% a fall in Hbdiff was detected. In 20% of events there was no fall in cerebral oxygenation despite a fall in SpO2. In 8% of PNA episodes we recorded a fall in cerebral oxygenation but no fall in SpO2. When a fall in cerebral oxygenation was recorded, the fall was greater when the event was also associated with a fall in SpO2 (median (interquartile range (IQR)) 0.32 (0.21-0.69) vs. 0.25 (0.16-0.43) micromol 100 g brain(-1), p < 0.05). When all the PNA episodes were reviewed no close correlation was shown between the magnitude of change in cerebral oxygenation and the change in SpO2 for small changes in both indices. However, large falls (>1.5 micromol 100 g brain(-1)) in cerebral oxygenation were closely associated with large changes in SpO2. CONCLUSIONS: We conclude that both techniques are sensitive to changes in oxygenation during PNA. Small changes in cerebral Hbdiff and arterial SpO2 do not always correlate for physiological reasons. A change in Hbdiff of >0.3 micromol 100 g brain(-1) is likely to be physiologically significant and is associated with a change in SpO2 of 12%.

Name-calling and nicknames in a sample of primary school children.

BACKGROUND: Name-calling, unkind nicknames and other forms of verbal harassment represent some of the most prevalent forms of bullying in school but they have been little studied. Name-calling and nicknames in particular are ambiguous social events that can serve positive as well as negative goals, and their adverse consequences can be difficult to identify. AIMS: (i) To assess the incidence of nicknames and name calling as reported by a sample of primary school children; (ii) to examine the kinds of names reported by children, and to relate these to names reported in other social contexts; (iii) to explore the impact that name-calling and nicknames have on children. SAMPLE: Pupils (N = 60) from the top two classes in a British primary school completed a questionnaire; 20 of the children were subsequently interviewed. METHOD: Pupils completed a questionnaire that was constructed for this study. Pupils were asked to provide examples of nicknames and to report on the types and incidence of several forms of verbal harassment. The interview included questions which aimed to explore the children's reactions to harassment. RESULTS: Being called disliked nicknames, called names, teased, and other forms of verbal harassment were reported by most of the sample, with more than 20% of children experiencing nasty comments and unkind nicknames on a daily basis. Girls reported more disliked nicknames than boys. The most common nicknames referred to the child's appearance, whereas nasty comments and untrue stories contained a preponderance of sexual references. In the interview, nearly all children reported that being called names and nicknames were negative experiences that caused distress. CONCLUSIONS: Name-calling and the assignment of unkind nicknames are prevalent and hurtful++ features of school life. The kinds of names are similar to those reported in other studies of children, adolescents, and adults. It is proposed that these names are hurtful because they threaten the child's identity.