Chaitanya Undavalli

Risk Factors for Low Bone Mass-Related Fractures in Men: A Systematic Review and Meta-Analysis

CONTEXT Testing men at increased risk for osteoporotic fractures has been recommended. OBJECTIVE The aim of this study was to estimate the magnitude of association and quality of supporting evidence linking multiple risk factors with low bone mass-related fractures in men. DATA SOURCES We searched MEDLINE, EMBASE, Web of Science, SCOPUS and Cochrane CENTRAL through February 2010. We identified further studies by reviewing reference lists from selected studies and reviews. STUDY SELECTION Eligible studies had to enroll men and quantitatively evaluate the association of risk factors with low bone density-related fractures. DATA EXTRACTION Reviewers working independently and in duplicate determined study eligibility and extracted study description, quality, and outcome data. DATA SYNTHESIS Fifty-five studies provided data sufficient for meta-analysis. The quality of these observational studies was moderate with fair levels of multivariable adjustment and adequate exposure and outcome ascertainment. Statistically significant associations were established for age, low body mass index, current smoking, excessive alcohol use, chronic corticosteroid use, history of prior fractures, history of falls, history of hypogonadism, history of stroke, and history of diabetes. Statistical heterogeneity of the meta-analytic estimates of all associations was significant except for chronic corticosteroid use. None of these associations were of large magnitude (i.e. adjusted odds ratios were generally <2). No evidence supporting a particular effective testing or screening strategy was identified. CONCLUSIONS Multiple risk factors for fractures in men were identified, but their usefulness for stratifying and selecting men for bone density testing remains uncertain.

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.

The natural history of untreated severe or critical limb ischemia

OBJECTIVE Critical limb ischemia (CLI) is associated with high morbidity and mortality. Because most patients with CLI will eventually undergo some type of revascularization, the natural history of CLI is not well defined, although it is important to know when patients decide to pursue treatment. METHODS We systematically searched multiple databases for controlled and uncontrolled studies of patients with CLI who did not receive revascularization with a minimum follow-up of ≥1 year. Predefined outcomes of interest were mortality, major amputation, and wound healing. Random-effects meta-analysis was used to pool cumulative incidence across studies. RESULTS We identified 13 studies enrolling 1527 patients. During a median follow-up of 12 months, all-cause mortality rate was 22% (confidence interval [CI], 12%-33%) and major amputation rate was 22% (CI, 2%-42%). Worsened wound or ulcer was found at 35% (CI, 10%-62%). There was a trend toward improvement in mortality and amputation rate in studies done after 1997. The quality of evidence was low because of increased risk of bias and inconsistency. CONCLUSIONS Mortality and major amputations are common in patients who have untreated CLI during a median follow-up of 1 year, although these outcomes have improved in recent times.

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.

Testing for germline mutations in sporadic pheochromocytoma/paraganglioma: a systematic review

The presence of germline mutations in sporadic pheochromocytomas and paragangliomas (SPPs) may change the clinical management of both index patients and their family members. However, the frequency of germline mutations in SPPs is unknown.

Pretransplant frailty is associated with decreased survival after lung transplantation

BACKGROUND Frailty is a condition of increased vulnerability to adverse health outcomes. Although frailty is an important prognostic factor for many conditions, the effect of frailty on mortality in lung transplantation is unknown. Our objective was to assess the association of frailty with survival after lung transplantation. METHODS We performed a retrospective cohort analysis of all adult lung transplant recipients at our institution between 2002 and 2013. Frailty was assessed using the frailty deficit index, a validated instrument that assesses cumulative deficits for up to 32 impairments and measures the proportion of deficits present (with frailty defined as >0.25). We examined the association between frailty and survival, adjusting for age, sex, and bilateral (vs single) lung transplant using Cox proportional hazard regression models. RESULTS Among 144 lung transplant patients, 102 (71%) completed self-reported questionnaires necessary to assess the frailty deficit index within 1 year before lung transplantation. Frail patients (n = 46) had an increased risk of death, with an adjusted hazard ratio (HR) of 2.24 (95% confidence interval [CI], 1.22-4.19; p = 0.0089). Frailty was not associated with an increased duration of mechanical ventilation (median, 2 vs 2 days; p = 0.26), intensive care unit length of stay (median, 7.5 vs 6 days; p = 0.36) or hospital length of stay after transplantation (median, 14 vs 10.5 days; p = 0.26). CONCLUSIONS Pre-transplant frailty was independently associated with decreased survival after lung transplantation. Pre-transplant frailty may represent an important area for intervention to improve candidate selection and lung transplant outcomes.

Bypass surgery versus endovascular interventions in severe or critical limb ischemia

OBJECTIVE Critical limb ischemia is associated with a significant morbidity and mortality. We systematically reviewed the evidence to compare bypass surgery with endovascular revascularization in patients with critical limb ischemia. METHODS We systematically searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, CINAHL, and Scopus through October 2014 for comparative studies (randomized and nonrandomized). Predefined outcomes of interest were mortality, major amputation, patency, and wound healing. We pooled odds ratios (ORs) of the outcomes of interest using the random-effects model. RESULTS Nine studies that enrolled 3071 subjects were included. There was no significant difference in mortality (OR, 0.72; 95% confidence interval [CI], 0.44-1.16) or amputation (OR, 1.2; 95% CI, 0.87-1.65). Bypass surgery was associated with higher primary patency (OR, 2.50; 95% CI, 1.25-4.99) and assisted primary patency (OR, 3.39; 95% CI, 1.53-7.51). The quality of evidence was low for mortality and amputation outcomes and moderate for patency outcomes. CONCLUSIONS Low quality of evidence due to imprecision and heterogeneity suggests that bypass surgery and endovascular approaches may have similar effect on mortality and major amputations. However, better primary and primary assisted patency can be expected with surgery.

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.