Osama Altayar

Drugs Commonly Associated With Weight Change: A Systematic Review and Meta-analysis

CONTEXT Various drugs affect body weight as a side effect. OBJECTIVE We conducted this systematic review and meta-analysis to summarize the evidence about commonly prescribed drugs and their association with weight change. DATA SOURCES MEDLINE, DARE, and the Cochrane Database of Systematic Reviews were searched to identify published systematic reviews as a source for trials. STUDY SELECTION We included randomized trials that compared an a priori selected list of drugs to placebo and measured weight change. DATA EXTRACTION We extracted data in duplicate and assessed the methodological quality using the Cochrane risk of bias tool. RESULTS We included 257 randomized trials (54 different drugs; 84 696 patients enrolled). Weight gain was associated with the use of amitriptyline (1.8 kg), mirtazapine (1.5 kg), olanzapine (2.4 kg), quetiapine (1.1 kg), risperidone (0.8 kg), gabapentin (2.2 kg), tolbutamide (2.8 kg), pioglitazone (2.6 kg), glimepiride (2.1 kg), gliclazide (1.8 kg), glyburide (2.6 kg), glipizide (2.2 kg), sitagliptin (0.55 kg), and nateglinide (0.3 kg). Weight loss was associated with the use of metformin (1.1 kg), acarbose (0.4 kg), miglitol (0.7 kg), pramlintide (2.3 kg), liraglutide (1.7 kg), exenatide (1.2 kg), zonisamide (7.7 kg), topiramate (3.8 kg), bupropion (1.3 kg), and fluoxetine (1.3 kg). For many other remaining drugs (including antihypertensives and antihistamines), the weight change was either statistically nonsignificant or supported by very low-quality evidence. CONCLUSIONS Several drugs are associated with weight change of varying magnitude. Data are provided to guide the choice of drug when several options exist and institute preemptive weight loss strategies when obesogenic drugs are prescribed.

Charged particle therapy versus photon therapy for paranasal sinus and nasal cavity malignant diseases: a systematic review and meta-analysis

BACKGROUND Malignant tumours arising within the nasal cavity and paranasal sinuses are rare and composed of several histological types, rendering controlled clinical trials to establish the best treatment impractical. We undertook a systematic review and meta-analysis to compare the clinical outcomes of patients treated with charged particle therapy with those of individuals receiving photon therapy. METHODS We identified studies of nasal cavity and paranasal sinus tumours through searches of databases including Embase, Medline, Scopus, and the Cochrane Collaboration. We included treatment-naive cohorts (both primary and adjuvant radiation therapy) and those with recurrent disease. Primary outcomes of interest were overall survival, disease-free survival, and locoregional control, at 5 years and at longest follow-up. We used random-effect models to pool outcomes across studies and compared event rates of combined outcomes for charged particle therapy and photon therapy using an interaction test. FINDINGS 43 cohorts from 41 non-comparative observational studies were included. Median follow-up for the charged particle therapy group was 38 months (range 5-73) and for the photon therapy group was 40 months (14-97). Pooled overall survival was significantly higher at 5 years for charged particle therapy than for photon therapy (relative risk 1·51, 95% CI 1·14-1·99; p=0·0038) and at longest follow-up (1·27, 1·01-1·59; p=0·037). At 5 years, disease-free survival was significantly higher for charged particle therapy than for photon therapy (1·93, 1·36-2·75, p=0·0003) but, at longest follow-up, this event rate did not differ between groups (1·51, 1·00-2·30; p=0·052). Locoregional control did not differ between treatment groups at 5 years (1·06, 0·68-1·67; p=0·79) but it was higher for charged particle therapy than for photon therapy at longest follow-up (1·18, 1·01-1·37; p=0·031). A subgroup analysis comparing proton beam therapy with intensity-modulated radiation therapy showed significantly higher disease-free survival at 5 years (relative risk 1·44, 95% CI 1·01-2·05; p=0·045) and locoregional control at longest follow-up (1·26, 1·05-1·51; p=0·011). INTERPRETATION Compared with photon therapy, charged particle therapy could be associated with better outcomes for patients with malignant diseases of the nasal cavity and paranasal sinuses. Prospective studies emphasising collection of patient-reported and functional outcomes are strongly encouraged. FUNDING Mayo Foundation for Medical Education and Research.

Rectal Nonsteroidal Anti-inflammatory Drugs Are Superior to Pancreatic Duct Stents in Preventing Pancreatitis After Endoscopic Retrograde Cholangiopancreatography: A Network Meta-analysis

BACKGROUND & AIMS Placement of pancreatic duct (PD) stents prevents pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). There is evidence that rectal administration of nonsteroidal anti-inflammatory drugs (NSAIDs) also prevents post-ERCP pancreatitis, but the 2 approaches alone have not been compared directly. We conducted a network meta-analysis to indirectly compare the efficacies of these procedures. METHODS PubMed and Embase were searched by 2 independent reviewers to identify full-length clinical studies, published in English, investigating use of PD stent placement and rectal NSAIDs to prevent post-ERCP pancreatitis. We identified 29 studies (22 of PD stents and 7 of NSAIDs). We used network meta-analysis to compare rates of post-ERCP pancreatitis among patients who received only rectal NSAIDs, only PD stents, or both. RESULTS Placement of PD stents and rectal administration of NSAIDs were each superior to placebo in preventing post-ERCP pancreatitis. The combination of rectal NSAIDs and stents was not superior to either approach alone. Pooled results showed that rectal NSAIDs alone were superior to PD stents alone in preventing post-ERCP pancreatitis (odds ratio, 0.48; 95% confidence interval, 0.26-0.87). CONCLUSIONS Based on a network meta-analysis, rectal NSAIDs alone are superior to PD stents alone in preventing post-ERCP pancreatitis, and should be considered first-line therapy for selected patients. However, these findings were limited by the small number of studies assessed (only 29 studies), potential publication bias, and the indirect nature of the comparison. High-quality, randomized, controlled trials are needed to compare these 2 interventions and confirm these findings.

Accuracy of urea breath test in Helicobacter pylori infection: Meta-analysis

AIM To quantitatively summarize and appraise the available evidence of urea breath test (UBT) use to diagnose Helicobacter pylori (H. pylori) infection in patients with dyspepsia and provide pooled diagnostic accuracy measures. METHODS We searched MEDLINE, EMBASE, Cochrane library and other databases for studies addressing the value of UBT in the diagnosis of H. pylori infection. We included cross-sectional studies that evaluated the diagnostic accuracy of UBT in adult patients with dyspeptic symptoms. Risk of bias was assessed using QUADAS (Quality Assessment of Diagnostic Accuracy Studies)-2 tool. Diagnostic accuracy measures were pooled using the random-effects model. Subgroup analysis was conducted by UBT type (13C vs 14C) and by measurement technique (Infrared spectrometry vs Isotope Ratio Mass Spectrometry). RESULTS Out of 1380 studies identified, only 23 met the eligibility criteria. Fourteen studies (61%) evaluated 13C UBT and 9 studies (39%) evaluated 14C UBT. There was significant variation in the type of reference standard tests used across studies.Pooled sensitivity was 0.96 (95%CI: 0.95-0.97) andpooled specificity was 0.93 (95%CI: 0.91-0.94). Likelihood ratio for a positive test was 12 and for a negative test was 0.05 with an area under thecurve of 0.985. Meta-analyses were associated with a significant statistical heterogeneity that remained unexplained after subgroup analysis. The included studies had a moderate risk of bias. CONCLUSION UBT has high diagnostic accuracy for detecting H. pylori infection in patients with dyspepsia. The reliability of diagnostic meta-analytic estimates however is limited by significant heterogeneity.

Comparative systematic review and meta-analysis of compression modalities for the promotion of venous ulcer healing and reducing ulcer recurrence

OBJECTIVE This was a systematic review of the literature to determine which compression method is superior in promoting ulcer healing and reducing recurrence in patients with lower extremity venous ulcer disease. METHODS We conducted a comprehensive search of multiple databases for randomized and nonrandomized comparative studies from 1990 to December 2013. RESULTS We identified 36 studies and two Cochrane systematic reviews. Many studies had moderate risk of bias. We found no overall difference between compression stockings vs compression bandages with respect to ulcer healing, time to ulcer healing, or ulcer recurrence outcomes. When we compared stockings vs short stretch bandages, stockings were superior with respect to ulcer healing. However, stockings compared with four-layer systems showed no difference in ulcer healing outcomes. When four-layer systems were compared with compression with less than four layers, there was also no significant difference in ulcer healing outcomes. Similarly, short stretch bandages were not superior to long stretch bandages with respect to ulcer healing, time to ulcer healing, or ulcer recurrence. One Cochrane review presented many additional comparisons and reported increased wound healing with compression compared with no compression, with multicomponent systems over single component systems, and compression systems with an elastic component over no elastic component. Another Cochrane review demonstrated a reduction in recurrence with compression in patients with healed ulcers. CONCLUSIONS At least moderate-quality evidence supports compression over no compression, multicomponent systems over single component systems, and systems with an elastic component over those without. We did not find significant differences with respect to ulcer healing outcomes for other comparisons. Low-quality evidence supports the effect of compression on ulcer recurrence.

The Benefits and Harms of Systemic Dehydroepiandrosterone (DHEA) in Postmenopausal Women With Normal Adrenal Function: A Systematic Review and Meta-analysis

CONTEXT Exogenous dehydroepiandrosterone (DHEA) therapy has been proposed to replenish the depletion of endogenous DHEA and its sulfate form, which occurs with advancing age and is thought to be associated with loss of libido and menopausal symptoms. OBJECTIVE We conducted a systematic review and meta-analysis to summarize the evidence supporting the use of systemic DHEA in postmenopausal women with normal adrenal function. METHODS We searched MEDLINE, EMBASE, PsycInfo, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus through January 2014. Pairs of reviewers, working independently, selected studies and extracted data from eligible randomized controlled trials (RCTs). We used the random-effects model to pool across studies and evaluated heterogeneity using the I(2) statistic. RESULTS We included 23 RCTs with moderate to high risk of bias enrolling 1188 women. DHEA use was not associated with significant improvement in libido or sexual function (standardized mean difference, 0.35; 95% confidence interval, -0.02 to 0.73; P value = .06; I(2) = 62%). There was also no significant effect of DHEA on serious adverse effects, serum lipids, serum glucose, weight, body mass index, or bone mineral density. This evidence warranted low confidence in the results, mostly due to imprecision, risk of bias, and inconsistency across RCTs. CONCLUSIONS Evidence warranting low confidence suggests that DHEA administration does not significantly impact sexual symptoms or selected metabolic markers in postmenopausal women with normal adrenal function.

The Benefits and Harms of Systemic Testosterone Therapy in Postmenopausal Women With Normal Adrenal Function: A Systematic Review and Meta-analysis

CONTEXT The use of T has been suggested to improve womens health during the postmenopausal period. OBJECTIVE We conducted a systematic review and meta-analysis of randomized trials to summarize the best available evidence regarding the benefits and harms of systemic T in postmenopausal women with normal adrenal function. METHODS A comprehensive search of MEDLINE, EMBASE, PsycInfo, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, EBSCO CINAHL, and Scopus was conducted through January 2014. We conducted study selection, data extraction, and appraisal in duplicate. Random-effects meta-analysis was used to pool results. RESULTS We identified 35 randomized trials (n = 5053) at a moderate risk of bias. T use was associated with statistically significant improvement in various domains of sexual function and personal distress in postmenopausal women, although the majority of the trials did not have specific or contemporary diagnostic criteria for androgen deficiency in women. T use was also associated with a reduction in total cholesterol, triglyceride, and high-density lipoprotein and an increase in low-density lipoprotein and in the incidence of acne and hirsutism. No significant effect was noted on anthropometric measures and bone density. Long-term safety data were sparse, and the quality of such evidence was low. CONCLUSION Despite the improvement in sexual function associated with T use in postmenopausal women, long-term safety data are lacking.

Systematic review and meta-analysis of surgical interventions versus conservative therapy for venous ulcers

OBJECTIVE This goal of this study was to systematically review the literature to determine if surgical intervention (open or endovascular) is superior to compression alone with respect to ulcer healing, ulcer recurrence, and time to ulcer healing in patients with lower extremity venous ulcer disease. METHODS We conducted a comprehensive search of multiple databases for randomized controlled trials (RCTs) and comparative observational studies from 1990 to December 2013. The interventions of interest were any open or endovascular surgical interventions on the venous system in the lower extremity compared with compression alone. RESULTS We included 11 studies (seven RCTs and four observational studies) with moderate to increased risk of bias. The meta-analysis of all studies demonstrated increased healing rate (pooled risk ratio [RR], 1.06; 95% confidence interval [CI], 1.00-1.13; I(2) = 10%) and lower risk of recurrence (RR, 0.54; 95% CI, 0.34-0.85; I(2) = 27%) with open surgical procedures compared with compression. However, the meta-analysis of only RCTs showed no difference, possibly due to imprecision. The meta-analysis of three RCTs showed no difference in time to ulcer healing, -0.41 (95% CI, -0.89 to 0.07). Two studies of endovascular surgical procedures compared with compression showed no significant difference in ulcer healing (RR, 1.65; 95% CI, 0.43-6.32). One study of open surgical venous ligation and stripping compared with endovenous laser also showed no significant difference in ulcer recurrence (RR, 0.83; 95% CI, 0.21-3.27). CONCLUSIONS Open surgical interventions may improve lower extremity venous ulcer healing. The quality of this evidence is low because the analysis was dominated by the results of observational studies. The current evidence does not definitively support the superiority of endovascular surgical interventions compared with compression alone.

Bone turnover markers in Paget’s disease of the bone: A Systematic review and meta-analysis

SummaryThe aim of this systematic review and meta-analysis is to study the utility of the commonly used bone turnover markers in evaluating disease activity in patients with Paget’s disease of bone before and after treatment with bisphosphonates. We found good correlation between the bone turnover marker concentrations and disease activity assessed by bone scintigraphy.IntroductionPaget’s disease of bone is a common skeletal disorder of the elderly. Bone turnover marker concentrations are used for diagnosis and follow-up. We aimed to compare the available bone turnover markers and determine their utility in assessing disease activity when compared to quantitative bone scintigraphy.MethodsWe conducted a systematic review and meta-analysis searching MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus. We evaluated total alkaline phosphatase (total ALP), bone-specific alkaline phosphatase (bone ALP), procollagen type 1 amino-terminal propeptide (P1NP), serum, and urine C-terminal telopeptide (uCTx and sCTx, respectively), and urine N-terminal telopeptide (uNTx). The main outcome of interest was the correlation of disease activity with concentrations of bone turnover markers in Paget’s disease patients before and after treatment with bisphosphonates. Correlation coefficients were pooled across studies using the random effects model.ResultsWe included 17 observational studies and one trial reporting on 953 patients. Prior to treatment, all studied bone turnover markers had moderate to strong correlation with scintigraphic indices (correlation coefficients ranging from 0.58 to 0.80) with no statistically significant difference between the bone turnover markers overall (p = 0.08). P1NP, uNTx, and bone ALP tend to have higher correlation with scintigraphy. After starting treatment with bisphosphonate, there was moderate to strong correlation with disease activity with all markers except bone ALP (correlation coefficients ranging from 0.43 to 0.70).ConclusionThe findings of this meta-analysis suggest the Paget’s disease activity is best monitored by following P1NP levels. However, total ALP, bone ALP, and uNTx are good alternatives as markers of disease activity in untreated patients. Total ALP and uNTx can be useful in following patients with Paget’s disease after treatment if P1NP is not available. Clinicians, however, should take availability, cost, and the presence of liver disease into consideration when deciding which bone turnover marker is most appropriate when evaluating patients with Paget’s disease.

Treatment Options for Hirsutism: A Systematic Review and Network Meta-Analysis

Background Several pharmacologic treatments for hirsutism are used in practice; however, their relative efficacy is unclear. Methods We searched MEDLINE, EMBASE, and CENTRAL through January 2017 for randomized controlled trials (RCTs) with follow-up of at least 6 months that evaluated antiandrogens, insulin sensitizers, and oral contraceptives in women with hirsutism. Independent pairs of reviewers selected and appraised trials. Random-effects network meta-analysis was used to compare individual drugs and classes. Results We included 43 trials. Estrogen-progestin oral contraceptives pills (OCPs), antiandrogens, and insulin sensitizers were superior to placebo, with standardized mean reductions (95% confidence intervals) of -0.94 (-1.49 to -0.38), -1.29 (-1.80 to -0.79), and -0.62 (-1.00 to -0.23), respectively. Antiandrogen monotherapy, the combination of OCP and antiandrogen, the combination of OCPs and insulin sensitizer, and the combination of antiandrogen and insulin sensitizer were superior to insulin sensitizer monotherapy. The combination of OCPs and antiandrogen was superior to OCPs. Antiandrogen monotherapy with flutamide, finasteride, and spironolactone were each superior to placebo but similar to each other in efficacy. OCPs containing levonorgestrel, cyproterone acetate, or drospirenone were similar in effectiveness to other OCPs or had trivial differences. The certainty in comparisons with placebo was moderate and for head-to-head comparisons was low. Conclusions Estrogen-progestin OCPs, antiandrogens, and insulin sensitizers are superior to placebo for the treatment of hirsutism.