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The Cochrane Database of Systematic... Oct 2016This is an updated version of the original Cochrane review published in Issue 12, 2011. Phantom limb pain (PLP) is pain that arises in the missing limb after amputation... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of the original Cochrane review published in Issue 12, 2011. Phantom limb pain (PLP) is pain that arises in the missing limb after amputation and can be severe, intractable, and disabling. Various medications have been studied in the treatment of phantom pain. There is currently uncertainty in the optimal pharmacologic management of PLP.
OBJECTIVES
This review aimed to summarise the evidence of effectiveness of pharmacologic interventions in treating PLP.
SEARCH METHODS
For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library), MEDLINE, and Embase for relevant studies. We ran the searches for the original review in September 2011 and subsequent searches for this update up to April 2016. We sought additional studies from clinical trials databases and reference lists of retrieved papers.
SELECTION CRITERIA
We included randomised and quasi-randomised trials studying the effectiveness of pharmacologic interventions compared with placebo, another active treatment, or no treatment, in established PLP. We considered the following outcomes: change in pain intensity, function, sleep, depression or mood, quality of life, adverse events, treatment satisfaction, and withdrawals from the study.
DATA COLLECTION AND ANALYSIS
We independently assessed issues of study quality and extracted efficacy and adverse event data. Due to the wide variability in the studies, we did not perform a meta-analysis for all the interventions and outcomes, but attempted to pool the results of some studies where possible. We prepared a qualitative description and narrative summary of results. We assessed clinical heterogeneity by making qualitative comparisons of the populations, interventions, outcomes/outcome measures, and methods.
MAIN RESULTS
We added only one new study with 14 participants to this updated review. We included a 14 studies (10 with low risk of bias and 4 with unclear risk of bias overall) with a total of 269 participants. We added another drug class, botulinum neurotoxins (BoNTs), in particular botulinum toxin A (BoNT/A), to the group of medications reviewed previously. Our primary outcome was change in pain intensity. Most studies did not report our secondary outcomes of sleep, depression or mood, quality of life, treatment satisfaction, or withdrawals from the study.BoNT/A did not improve phantom limb pain intensity during the six months of follow-up compared with lidocaine/methylprednisolone.Compared with placebo, morphine (oral and intravenous) was effective in decreasing pain intensity in the short term with reported adverse events being constipation, sedation, tiredness, dizziness, sweating, voiding difficulty, vertigo, itching, and respiratory problems.The N-methyl D-aspartate (NMDA) receptor antagonists ketamine (versus placebo; versus calcitonin) and dextromethorphan (versus placebo), but not memantine, had analgesic effects. The adverse events of ketamine were more serious than placebo and calcitonin and included loss of consciousness, sedation, hallucinations, hearing and position impairment, and insobriety.The results for gabapentin in terms of pain relief were conflicting, but combining the results favoured treatment group (gabapentin) over control group (placebo) (mean difference -1.16, 95% confidence interval -1.94 to -0.38; 2 studies). However, gabapentin did not improve function, depression score, or sleep quality. Adverse events experienced were somnolence, dizziness, headache, and nausea.Compared with an active control benztropine mesylate, amitriptyline was not effective in PLP, with dry mouth and dizziness as the most frequent adverse events based on one study.The findings for calcitonin (versus placebo; versus ketamine) and local anaesthetics (versus placebo) were variable. Adverse events of calcitonin were headache, vertigo, drowsiness, nausea, vomiting, and hot and cold flushes. Most of the studies were limited by their small sample sizes.
AUTHORS' CONCLUSIONS
Since the last version of this review, we identified another study that added another form of medical therapy, BoNTs, specifically BoNT/A, to the list of pharmacologic interventions being reviewed for clinical efficacy in phantom limb pain. However, the results of this study did not substantially change the main conclusions. The short- and long-term effectiveness of BoNT/A, opioids, NMDA receptor antagonists, anticonvulsants, antidepressants, calcitonins, and local anaesthetics for clinically relevant outcomes including pain, function, mood, sleep, quality of life, treatment satisfaction, and adverse events remain unclear. Based on a small study, BoNT/A (versus lidocaine/methylprednisolone) does not decrease phantom limb pain. Morphine, gabapentin, and ketamine demonstrate favourable short-term analgesic efficacy compared with placebo. Memantine and amitriptyline may not be effective for PLP. However, results must be interpreted with caution, as they were based mostly on a small number of studies with limited sample sizes that varied considerably and also lacked long-term efficacy and safety outcomes. The direction of efficacy of calcitonin, local anaesthetics, and dextromethorphan needs further clarification. Overall, the efficacy evidence for the reviewed medications is thus far inconclusive. Larger and more rigorous randomised controlled trials are needed for us to reach more definitive conclusions about which medications would be useful for clinical practice.
Topics: Analgesics, Opioid; Anesthetics; Anticonvulsants; Antidepressive Agents; Botulinum Toxins, Type A; Calcitonin; Humans; Neurotoxins; Phantom Limb; Randomized Controlled Trials as Topic; Receptors, N-Methyl-D-Aspartate
PubMed: 27737513
DOI: 10.1002/14651858.CD006380.pub3 -
The Journal of Dermatological Treatment Jun 2022Endocrine mucin-producing sweat gland carcinoma is a rare, under-reported cutaneous adnexal tumor that is often misdiagnosed and has an unknown incidence of metastasis. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Endocrine mucin-producing sweat gland carcinoma is a rare, under-reported cutaneous adnexal tumor that is often misdiagnosed and has an unknown incidence of metastasis.
OBJECTIVE
To determine the incidence of metastasis and tumor recurrence, as well as diagnostic accuracy and current trends in treatment modality.
METHODS
A search was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Tumor pathology and clinical data concerning demographics, presentation, diagnosis, treatment and follow-up were assessed.
RESULTS
A total of 36 publications with 110 cases were identified. Initial pathological diagnosis was incorrect in 45.5% of cases. One case of metastatic disease was reported. The incidence of locoregional recurrence was 10.6% over a mean follow-up period of 21.3 months. Of cases with known methods of resection, 34.6% were resected by excisional biopsy, 42.8% were resected by wide surgical excision, and 31.3% were cleared by Mohs micrographic surgery.
LIMITATIONS
The low reported incidence and level of evidence was suboptimal with only case reports and retrospective case studies being reported.
CONCLUSION
Reported cases of this pathology demonstrate poor diagnostic accuracy. High rates of misdiagnosis and inadequate definitive treatment suggest the need for more comprehensive work-up and management of lesions suspicious for this pathology.
Topics: Adenocarcinoma, Mucinous; Eyelid Neoplasms; Humans; Mucins; Neoplasm Recurrence, Local; Retrospective Studies; Sweat Gland Neoplasms; Sweat Glands
PubMed: 34057875
DOI: 10.1080/09546634.2021.1937479 -
The Cochrane Database of Systematic... Nov 2023A panic attack is a discrete period of fear or anxiety that has a rapid onset and reaches a peak within 10 minutes. The main symptoms involve bodily systems, such as... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A panic attack is a discrete period of fear or anxiety that has a rapid onset and reaches a peak within 10 minutes. The main symptoms involve bodily systems, such as racing heart, chest pain, sweating, shaking, dizziness, flushing, churning stomach, faintness and breathlessness. Other recognised panic attack symptoms involve fearful cognitions, such as the fear of collapse, going mad or dying, and derealisation (the sensation that the world is unreal). Panic disorder is common in the general population with a prevalence of 1% to 4%. The treatment of panic disorder includes psychological and pharmacological interventions, including antidepressants and benzodiazepines.
OBJECTIVES
To compare, via network meta-analysis, individual drugs (antidepressants and benzodiazepines) or placebo in terms of efficacy and acceptability in the acute treatment of panic disorder, with or without agoraphobia. To rank individual active drugs for panic disorder (antidepressants, benzodiazepines and placebo) according to their effectiveness and acceptability. To rank drug classes for panic disorder (selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), mono-amine oxidase inhibitors (MAOIs) and benzodiazepines (BDZs) and placebo) according to their effectiveness and acceptability. To explore heterogeneity and inconsistency between direct and indirect evidence in a network meta-analysis.
SEARCH METHODS
We searched the Cochrane Common Mental Disorders Specialised Register, CENTRAL, CDSR, MEDLINE, Ovid Embase and PsycINFO to 26 May 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of people aged 18 years or older of either sex and any ethnicity with clinically diagnosed panic disorder, with or without agoraphobia. We included trials that compared the effectiveness of antidepressants and benzodiazepines with each other or with a placebo.
DATA COLLECTION AND ANALYSIS
Two authors independently screened titles/abstracts and full texts, extracted data and assessed risk of bias. We analysed dichotomous data and continuous data as risk ratios (RRs), mean differences (MD) or standardised mean differences (SMD): response to treatment (i.e. substantial improvement from baseline as defined by the original investigators: dichotomous outcome), total number of dropouts due to any reason (as a proxy measure of treatment acceptability: dichotomous outcome), remission (i.e. satisfactory end state as defined by global judgement of the original investigators: dichotomous outcome), panic symptom scales and global judgement (continuous outcome), frequency of panic attacks (as recorded, for example, by a panic diary; continuous outcome), agoraphobia (dichotomous outcome). We assessed the certainty of evidence using threshold analyses.
MAIN RESULTS
Overall, we included 70 trials in this review. Sample sizes ranged between 5 and 445 participants in each arm, and the total sample size per study ranged from 10 to 1168. Thirty-five studies included sample sizes of over 100 participants. There is evidence from 48 RCTs (N = 10,118) that most medications are more effective in the response outcome than placebo. In particular, diazepam, alprazolam, clonazepam, paroxetine, venlafaxine, clomipramine, fluoxetine and adinazolam showed the strongest effect, with diazepam, alprazolam and clonazepam ranking as the most effective. We found heterogeneity in most of the comparisons, but our threshold analyses suggest that this is unlikely to impact the findings of the network meta-analysis. Results from 64 RCTs (N = 12,310) suggest that most medications are associated with either a reduced or similar risk of dropouts to placebo. Alprazolam and diazepam were associated with a lower dropout rate compared to placebo and were ranked as the most tolerated of all the medications examined. Thirty-two RCTs (N = 8569) were included in the remission outcome. Most medications were more effective than placebo, namely desipramine, fluoxetine, clonazepam, diazepam, fluvoxamine, imipramine, venlafaxine and paroxetine, and their effects were clinically meaningful. Amongst these medications, desipramine and alprazolam were ranked highest. Thirty-five RCTs (N = 8826) are included in the continuous outcome reduction in panic scale scores. Brofaromine, clonazepam and reboxetine had the strongest reductions in panic symptoms compared to placebo, but results were based on either one trial or very small trials. Forty-one RCTs (N = 7853) are included in the frequency of panic attack outcome. Only clonazepam and alprazolam showed a strong reduction in the frequency of panic attacks compared to placebo, and were ranked highest. Twenty-six RCTs (N = 7044) provided data for agoraphobia. The strongest reductions in agoraphobia symptoms were found for citalopram, reboxetine, escitalopram, clomipramine and diazepam, compared to placebo. For the pooled intervention classes, we examined the two primary outcomes (response and dropout). The classes of medication were: SSRIs, SNRIs, TCAs, MAOIs and BDZs. For the response outcome, all classes of medications examined were more effective than placebo. TCAs as a class ranked as the most effective, followed by BDZs and MAOIs. SSRIs as a class ranked fifth on average, while SNRIs were ranked lowest. When we compared classes of medication with each other for the response outcome, we found no difference between classes. Comparisons between MAOIs and TCAs and between BDZs and TCAs also suggested no differences between these medications, but the results were imprecise. For the dropout outcome, BDZs were the only class associated with a lower dropout compared to placebo and were ranked first in terms of tolerability. The other classes did not show any difference in dropouts compared to placebo. In terms of ranking, TCAs are on average second to BDZs, followed by SNRIs, then by SSRIs and lastly by MAOIs. BDZs were associated with lower dropout rates compared to SSRIs, SNRIs and TCAs. The quality of the studies comparing antidepressants with placebo was moderate, while the quality of the studies comparing BDZs with placebo and antidepressants was low.
AUTHORS' CONCLUSIONS
In terms of efficacy, SSRIs, SNRIs (venlafaxine), TCAs, MAOIs and BDZs may be effective, with little difference between classes. However, it is important to note that the reliability of these findings may be limited due to the overall low quality of the studies, with all having unclear or high risk of bias across multiple domains. Within classes, some differences emerged. For example, amongst the SSRIs paroxetine and fluoxetine seem to have stronger evidence of efficacy than sertraline. Benzodiazepines appear to have a small but significant advantage in terms of tolerability (incidence of dropouts) over other classes.
Topics: Adult; Humans; Panic Disorder; Selective Serotonin Reuptake Inhibitors; Paroxetine; Fluoxetine; Venlafaxine Hydrochloride; Serotonin and Noradrenaline Reuptake Inhibitors; Alprazolam; Clomipramine; Reboxetine; Clonazepam; Desipramine; Network Meta-Analysis; Antidepressive Agents; Antidepressive Agents, Tricyclic; Benzodiazepines; Diazepam
PubMed: 38014714
DOI: 10.1002/14651858.CD012729.pub3 -
Pediatric Allergy, Immunology, and... Dec 2015The measurement of sweat chloride concentration (sweat test) remains the gold standard for the diagnosis of cystic fibrosis (CF). For infants with a positive newborn... (Review)
Review
The measurement of sweat chloride concentration (sweat test) remains the gold standard for the diagnosis of cystic fibrosis (CF). For infants with a positive newborn screening test for CF, the sweat test is the next step to confirm the diagnosis. However, there are several reports in the literature regarding conditions that are known to be associated with false positive or false negative sweat tests. This systematic review of the literature summarizes the evidence available regarding these conditions. Interpretation of sweat test results should be done in the context of patient's clinical presentation and associated comorbidities. Additional research is needed for conditions that may affect sweat chloride concentrations.
PubMed: 35923002
DOI: 10.1089/ped.2015.0552 -
Journal of Environmental and Public... 2012Arsenic, cadmium, lead, and mercury exposures are ubiquitous. These toxic elements have no physiological benefits, engendering interest in minimizing body burden. The... (Review)
Review
Arsenic, cadmium, lead, and mercury exposures are ubiquitous. These toxic elements have no physiological benefits, engendering interest in minimizing body burden. The physiological process of sweating has long been regarded as "cleansing" and of low risk. Reports of toxicant levels in sweat were sought in Medline, Embase, Toxline, Biosis, and AMED as well as reference lists and grey literature, from inception to March 22, 2011. Of 122 records identified, 24 were included in evidence synthesis. Populations, and sweat collection methods and concentrations varied widely. In individuals with higher exposure or body burden, sweat generally exceeded plasma or urine concentrations, and dermal could match or surpass urinary daily excretion. Arsenic dermal excretion was severalfold higher in arsenic-exposed individuals than in unexposed controls. Cadmium was more concentrated in sweat than in blood plasma. Sweat lead was associated with high-molecular-weight molecules, and in an interventional study, levels were higher with endurance compared with intensive exercise. Mercury levels normalized with repeated saunas in a case report. Sweating deserves consideration for toxic element detoxification. Research including appropriately sized trials is needed to establish safe, effective therapeutic protocols.
Topics: Arsenic; Body Burden; Cadmium; Environmental Exposure; Environmental Monitoring; Environmental Pollutants; Humans; Lead; Mercury; Metals, Heavy; Sweat
PubMed: 22505948
DOI: 10.1155/2012/184745 -
Sports Medicine (Auckland, N.Z.) Feb 2018Although the acquisition of heat acclimation (HA) is well-documented, less is known about HA decay (HAD) and heat re-acclimation (HRA). The available literature suggests... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although the acquisition of heat acclimation (HA) is well-documented, less is known about HA decay (HAD) and heat re-acclimation (HRA). The available literature suggests 1 day of HA is lost following 2 days of HAD. Understanding this relationship has the potential to impact upon the manner in which athletes prepare for major competitions, as a HA regimen may be disruptive during final preparations (i.e., taper).
OBJECTIVE
The aim of this systematic review and meta-analysis was to determine the rate of HAD and HRA in three of the main physiological adaptations occurring during HA: heart rate (HR), core temperature (T ), and sweat rate (SR).
DATA SOURCES
Data for this systematic review were retrieved from Scopus and critical review of the cited references.
STUDY SELECTION
Studies were included when they met the following criteria: HA, HAD, and HRA (when available) were quantified in terms of exposure and duration. HA had to be for at least 5 days and HAD for at least 7 days for longitudinal studies. HR, T , or SR had to be monitored in human participants.
STUDY APPRAISAL
The level of bias in each study was assessed using the McMaster critical review form. Multiple linear regression techniques were used to determine the dependency of HAD in HR, T , and SR from the number of HA and HAD days, daily HA exposure duration, and intensity.
RESULTS
Twelve studies met the criteria and were systematically reviewed. HAD was quantified as a percentage change relative to HA (0% = HA, 100% = unacclimated state). Adaptations in end-exercise HR decreased by 2.3% (P < 0.001) for every day of HAD. For end-exercise T , the daily decrease was 2.6% (P < 0.01). The adaptations in T during the HA period were more sustainable when the daily heat exposure duration was increased and heat exposure intensity decreased. The decay in SR was not related to the number of decay days. However, protracted HA-regimens seem to induce longer-lasting adaptations in SR. High heat exposure intensities during HA seem to evoke more sustained adaptations in SR than lower heat stress. Only eight studies investigated HRA. HRA was 8-12 times faster than HAD at inducing adaptations in HR and T , but no differences could be established for SR.
LIMITATIONS
The available studies lacked standardization in the protocols for HA and HAD.
CONCLUSIONS
HAD and HRA differ considerably between physiological systems. Five or more HA days are sufficient to cause adaptations in HR and T ; however, extending the daily heat exposure duration enhances T adaptations. For every decay day, ~ 2.5% of the adaptations in HR and T are lost. For SR, longer HA periods are related to better adaptations. High heat exposure intensities seem beneficial for adaptations in SR, but not in T . HRA induces adaptations in HR and T at a faster rate than HA. HRA may thus provide a practical and less disruptive means of maintaining and optimizing HA prior to competition.
Topics: Acclimatization; Body Temperature Regulation; Cross-Sectional Studies; Exercise; Heart Rate; Heat Stress Disorders; Hot Temperature; Humans; Male; Oxygen Consumption; Physical Exertion
PubMed: 29129022
DOI: 10.1007/s40279-017-0808-x -
The Cochrane Database of Systematic... Jun 2013Premenstrual syndrome (PMS) is a common cause of physical, psychological and social problems in women of reproductive age. The key characteristic of PMS is the timing of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Premenstrual syndrome (PMS) is a common cause of physical, psychological and social problems in women of reproductive age. The key characteristic of PMS is the timing of symptoms, which occur only during the two weeks leading up to menstruation (the luteal phase of the menstrual cycle). Selective serotonin reuptake inhibitors (SSRIs) are increasingly used as first line therapy for PMS. SSRIs can be taken either in the luteal phase or else continuously (every day). SSRIs are generally considered to be effective for reducing premenstrual symptoms but they can cause adverse effects.
OBJECTIVES
The objective of this review was to evaluate the effectiveness and safety of SSRIs for treating premenstrual syndrome.
SEARCH METHODS
Electronic searches for relevant randomised controlled trials (RCTs) were undertaken in the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, PsycINFO, and CINAHL (February 2013). Where insufficient data were presented in a report, attempts were made to contact the original authors for further details.
SELECTION CRITERIA
Studies were considered in which women with a prospective diagnosis of PMS, PMDD or late luteal phase dysphoric disorder (LPDD) were randomised to receive SSRIs or placebo for the treatment of premenstrual syndrome.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected the studies, assessed eligible studies for risk of bias, and extracted data on premenstrual symptoms and adverse effects. Studies were pooled using random-effects models. Standardised mean differences (SMDs) with 95% confidence intervals (CIs) were calculated for premenstrual symptom scores, using separate analyses for different types of continuous data (that is end scores and change scores). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for dichotomous outcomes. Analyses were stratified by type of drug administration (luteal or continuous) and by drug dose (low, medium, or high). We calculated the number of women who would need to be taking a moderate dose of SSRI in order to cause one additional adverse event (number needed to harm: NNH). The overall quality of the evidence for the main findings was assessed using the GRADE working group methods.
MAIN RESULTS
Thirty-one RCTs were included in the review. They compared fluoxetine, paroxetine, sertraline, escitalopram and citalopram versus placebo. SSRIs reduced overall self-rated symptoms significantly more effectively than placebo. The effect size was moderate when studies reporting end scores were pooled (for moderate dose SSRIs: SMD -0.65, 95% CI -0.46 to -0.84, nine studies, 1276 women; moderate heterogeneity (I(2) = 58%), low quality evidence). The effect size was small when studies reporting change scores were pooled (for moderate dose SSRIs: SMD -0.36, 95% CI -0.20 to -0.51, four studies, 657 women; low heterogeneity (I(2)=29%), moderate quality evidence).SSRIs were effective for symptom relief whether taken only in the luteal phase or continuously, with no clear evidence of a difference in effectiveness between these modes of administration. However, few studies directly compared luteal and continuous regimens and more evidence is needed on this question.Withdrawals due to adverse effects were significantly more likely to occur in the SSRI group (moderate dose: OR 2.55, 95% CI 1.84 to 3.53, 15 studies, 2447 women; no heterogeneity (I(2) = 0%), moderate quality evidence). The most common side effects associated with a moderate dose of SSRIs were nausea (NNH = 7), asthenia or decreased energy (NNH = 9), somnolence (NNH = 13), fatigue (NNH = 14), decreased libido (NNH = 14) and sweating (NNH = 14). In secondary analyses, SSRIs were effective for treating specific types of symptoms (that is psychological, physical and functional symptoms, and irritability). Adverse effects were dose-related.The overall quality of the evidence was low to moderate, the main weakness in the included studies being poor reporting of methods. Heterogeneity was low or absent for most outcomes, though (as noted above) there was moderate heterogeneity for one of the primary analyses.
AUTHORS' CONCLUSIONS
SSRIs are effective in reducing the symptoms of PMS, whether taken in the luteal phase only or continuously. Adverse effects are relatively frequent, the most common being nausea and asthenia. Adverse effects are dose-dependent.
Topics: Adolescent; Adult; Female; Humans; Luteal Phase; Middle Aged; Premenstrual Syndrome; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Young Adult
PubMed: 23744611
DOI: 10.1002/14651858.CD001396.pub3 -
The Cochrane Database of Systematic... Oct 2016Tibolone is a synthetic steroid used for the treatment of menopausal symptoms, on the basis of short-term data suggesting its efficacy. We considered the balance between... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tibolone is a synthetic steroid used for the treatment of menopausal symptoms, on the basis of short-term data suggesting its efficacy. We considered the balance between the benefits and risks of tibolone.
OBJECTIVES
To evaluate the effectiveness and safety of tibolone for treatment of postmenopausal and perimenopausal women.
SEARCH METHODS
In October 2015, we searched the Gynaecology and Fertility Group (CGF) Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and PsycINFO (from inception), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and clinicaltrials.gov. We checked the reference lists in articles retrieved.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing tibolone versus placebo, oestrogens and/or combined hormone therapy (HT) in postmenopausal and perimenopausal women.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures of The Cochrane Collaboration. Primary outcomes were vasomotor symptoms, unscheduled vaginal bleeding and long-term adverse events. We evaluated safety outcomes and bleeding in studies including women either with or without menopausal symptoms.
MAIN RESULTS
We included 46 RCTs (19,976 women). Most RCTs evaluated tibolone for treating menopausal vasomotor symptoms. Some had other objectives, such as assessment of bleeding patterns, endometrial safety, bone health, sexuality and safety in women with a history of breast cancer. Two included women with uterine leiomyoma or lupus erythematosus. Tibolone versus placebo Vasomotor symptomsTibolone was more effective than placebo (standard mean difference (SMD) -0.99, 95% confidence interval (CI) -1.10 to -0.89; seven RCTs; 1657 women; moderate-quality evidence), but removing trials at high risk of attrition bias attenuated this effect (SMD -0.61, 95% CI -0.73 to -0.49; odds ratio (OR) 0.33, 85% CI 0.27 to 0.41). This suggests that if 67% of women taking placebo experience vasomotor symptoms, between 35% and 45% of women taking tibolone will do so. Unscheduled bleedingTibolone was associated with greater likelihood of bleeding (OR 2.79, 95% CI 2.10 to 3.70; nine RCTs; 7814 women; I = 43%; moderate-quality evidence). This suggests that if 18% of women taking placebo experience unscheduled bleeding, between 31% and 44% of women taking tibolone will do so. Long-term adverse eventsMost of the studies reporting these outcomes provided follow-up of two to three years (range three months to three years). Breast cancerWe found no evidence of differences between groups among women with no history of breast cancer (OR 0.52, 95% CI 0.21 to 1.25; four RCTs; 5500 women; I= 17%; very low-quality evidence). Among women with a history of breast cancer, tibolone was associated with increased risk (OR 1.5, 95% CI 1.21 to 1.85; two RCTs; 3165 women; moderate-quality evidence). Cerebrovascular eventsWe found no conclusive evidence of differences between groups in cerebrovascular events (OR 1.74, 95% CI 0.99 to 3.04; four RCTs; 7930 women; I = 0%; very low-quality evidence). We obtained most data from a single RCT (n = 4506) of osteoporotic women aged 60 to 85 years, which was stopped prematurely for increased risk of stroke. Other outcomesEvidence on other outcomes was of low or very low quality, with no clear evidence of any differences between the groups. Effect estimates were as follows:• Endometrial cancer: OR 2.04, 95% CI 0.79 to 5.24; nine RCTs; 8504 women; I = 0%.• Cardiovascular events: OR 1.38, 95% CI 0.84 to 2.27; four RCTs; 8401 women; I = 0%.• Venous thromboembolic events: OR 0.85, 95% CI 0.37 to 1.97; 9176 women; I = 0%.• Mortality from any cause: OR 1.06, 95% CI 0.79 to 1.41; four RCTs; 8242 women; I = 0%. Tibolone versus combined HT Vasomotor symptomsCombined HT was more effective than tibolone (SMD 0.17, 95% CI 0.06 to 0.28; OR 1.36, 95% CI 1.11 to 1.66; nine studies; 1336 women; moderate-quality evidence). This result was robust to a sensitivity analysis that excluded trials with high risk of attrition bias, suggesting a slightly greater disadvantage of tibolone (SMD 0.25, 95% CI 0.09 to 0.41; OR 1.57, 95% CI 1.18 to 2.10). This suggests that if 7% of women taking combined HT experience vasomotor symptoms, between 8% and 14% of women taking tibolone will do so. Unscheduled bleedingTibolone was associated with a lower rate of bleeding (OR 0.32, 95% CI 0.24 to 0.41; 16 RCTs; 6438 women; I = 72%; moderate-quality evidence). This suggests that if 47% of women taking combined HT experience unscheduled bleeding, between 18% and 27% of women taking tibolone will do so. Long-term adverse eventsMost studies reporting these outcomes provided follow-up of two to three years (range three months to three years). Evidence was of very low quality, with no clear evidence of any differences between the groups. Effect estimates were as follows:• Endometrial cancer: OR 1.47, 95% CI 0.23 to 9.33; five RCTs; 3689 women; I = 0%.• Breast cancer: OR 1.69, 95% CI 0.78 to 3.67; five RCTs; 4835 women; I = 0%.• Venous thromboembolic events: OR 0.44, 95% CI 0.09 to 2.14; four RCTs; 4529 women; I = 0%.• Cardiovascular events: OR 0.63, 95% CI 0.24 to 1.66; two RCTs; 3794 women; I = 0%.• Cerebrovascular events: OR 0.76, 95% CI 0.16 to 3.66; four RCTs; 4562 women; I = 0%.• Mortality from any cause: only one event reported (two RCTs; 970 women).
AUTHORS' CONCLUSIONS
Moderate-quality evidence suggests that tibolone is more effective than placebo but less effective than HT in reducing menopausal vasomotor symptoms, and that tibolone is associated with a higher rate of unscheduled bleeding than placebo but with a lower rate than HT.Compared with placebo, tibolone increases recurrent breast cancer rates in women with a history of breast cancer, and may increase stroke rates in women over 60 years of age. No evidence indicates that tibolone increases the risk of other long-term adverse events, or that it differs from HT with respect to long-term safety.Much of the evidence was of low or very low quality. Limitations included high risk of bias and imprecision. Most studies were financed by drug manufacturers or failed to disclose their funding source.
Topics: Aged; Breast Neoplasms; Dyspareunia; Estrogen Receptor Modulators; Estrogen Replacement Therapy; Female; Hot Flashes; Humans; Middle Aged; Neoplasm Recurrence, Local; Norpregnenes; Postmenopause; Randomized Controlled Trials as Topic; Stroke; Sweating; Uterine Hemorrhage
PubMed: 27733017
DOI: 10.1002/14651858.CD008536.pub3 -
Clinical Autonomic Research : Official... Aug 2021Hyperhidrosis (i.e. excessive sweating) is diagnosed from patient medical history and physical examination. In addition, focal sweat measurements can substantiate the... (Review)
Review
PURPOSE
Hyperhidrosis (i.e. excessive sweating) is diagnosed from patient medical history and physical examination. In addition, focal sweat measurements can substantiate the hyperhidrosis diagnosis. Likewise, the impact of living with hyperhidrosis can be assessed with patient-reported outcome measures. However, no consensus exists on how to diagnose hyperhidrosis, how to quantify the disease, or how to measure the impact hyperhidrosis has on patients. Therefore, the objective of this review was to summarize the literature on diagnostic criteria, focal sweat measurement methods, and patient-reported outcome measures of hyperhidrosis.
METHODS
A literature search of Cochrane Library, Embase, and PubMed was conducted. Studies that included and aimed at developing or validating hyperhidrosis diagnostic criteria, focal sweat measurement methods, or patient-reported outcome measures for individuals with hyperhidrosis were eligible for inclusion. The methodological quality of diagnostic accuracy studies about focal sweat measurement methods was determined using the Quality Assessment of Diagnostic Accuracy Studies-2.
RESULTS
Overall, 33 studies were included. We identified two sets of hyperhidrosis diagnostic criteria, one scale for assessment of severity of hyperhidrosis sweating, four focal sweat measurement methods, and 15 patient-reported outcome measures.
CONCLUSION
The algorithm for diagnosing hyperhidrosis and focal sweat measurement methods needs validation in large cohorts. Most patient-reported outcome measures for hyperhidrosis are not adequately validated. A potential solution is to develop a core outcome set that can standardize outcomes reported in clinical trials.
Topics: Humans; Hyperhidrosis; Sweat; Sweating
PubMed: 33772671
DOI: 10.1007/s10286-021-00794-6 -
Archives of Dermatological Research Oct 2023Sweating is a physiologic mechanism of human thermoregulation. Hyperhidrosis is defined as a somatic disorder where the sweating is exaggerated in an exact area because... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sweating is a physiologic mechanism of human thermoregulation. Hyperhidrosis is defined as a somatic disorder where the sweating is exaggerated in an exact area because the sweat glands are hyperfunctioning. It negatively affects the quality of life of the patients. We aim to investigate patient satisfaction and the effectiveness of oxybutynin in treating hyperhidrosis.
METHODS
We prospectively registered the protocol of this systematic review and meta-analysis on PROSPERO (CRD 42022342667). This systematic review and meta-analysis were reported according to the PRISMA statement guidelines. We searched three electronic databases (PubMed, Scopus, Web of Science) from inception until June 2, 2022, using MeSH terms. We include studies comparing patients with hyperhidrosis who received oxybutynin or a placebo. We assessed the risk of bias using the Cochrane risk of bias assessment tool (ROB2) for randomized controlled trials. The risk ratio was calculated for categorical variables, and the mean difference was calculated for continuous variables using the random effect model with 95% confidence intervals (CI).
RESULTS
Six studies were included in the meta-analysis, with a total of 293 patients. In all studies, patients were assigned to receive either Oxybutynin or Placebo. Oxybutynin represented an HDSS improvement (RR = 1.68 95% CI [1.21, 2.33], p = 0.002). It also can improve the quality of life. There is no difference between oxybutynin and placebo regarding dry mouth (RR = 1.68 95% CI [1.21, 2.33], p = 0.002).
CONCLUSION
Our study suggests that using oxybutynin as a treatment for hyperhidrosis is significant and needs to be highlighted for clinicians. However, more clinical trials are needed to grasp the optimum benefit.
Topics: Humans; Treatment Outcome; Quality of Life; Randomized Controlled Trials as Topic; Hyperhidrosis
PubMed: 36869926
DOI: 10.1007/s00403-023-02587-5