Murad, M Hassan

We aimed to develop tools that can facilitate uptake of evidence summarised in systematic reviews by clinical decision makers in health systems. After conducting a systematic review on the management of anxiety in children, we interviewed health system representatives, clinicians and patients to ask about additional information needed for decision-making. Using stakeholders’ feedback and literature searches for contextual and implementation information, we developed two tools (decision aids (DAs)), one for the health system and the second for the clinical encounter. This information mapped to factors of the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) Evidence to Decision Framework. The health system DAs provided information on which patients are candidate for treatment, values and preferences, costs and resources, acceptability, impact on health equity, feasibility, drug dosing, alternative therapies, remission rates and prognosis. Health system stakeholders found the DA useful for clinical decision-making and generalisable to other conditions. The encounter DA was produced as cards containing information on issues that drive treatment decisions (effect on symptoms, effect on function, treatment burden, side effects and cost). Patients and parents prioritised the cards and chose the order in which these issues were discussed with clinician. The encounter DA was found to be helpful by patients, parents and clinicians. We conclude that the uptake of evidence summaries by health systems can be enhanced by developing tools that provide contextual and implementation information about clinical care. A dual approach addressing health system stakeholders as well as clinicians and patients is likely feasible and helpful.

Aims Dupuytren’s contracture is a benign, myoproliferative condition affecting the palmar fascia that results in progressive contractures of the fingers. Despite increased knowledge of the cellular and connective tissue changes involved, neither a cure nor an optimum form of treatment exists. The aim of this systematic review was to summarize the best available evidence on the management of this condition. Materials and Methods A comprehensive database search for randomized controlled trials (RCTs) was performed until August 2017. We studied RCTs comparing open fasciectomy with percutaneous needle aponeurotomy (PNA), collagenase clostridium histolyticum (CCH) with placebo, and CCH with PNA, in addition to adjuvant treatments aiming to improve the outcome of open fasciectomy. A total of 20 studies, involving 1584 patients, were included. Results PNA tended to provide higher patient satisfaction with fewer adverse events, but had a higher rate of recurrence compared with limited fasciectomy. Although efficacious, treatment with CCH had notable recurrence rates and a high rate of transient adverse events. Recent comparative studies have shown no difference in clinical outcome between patients treated with PNA and those treated with CCH. Conclusion Currently there remains limited evidence to guide the management of patients with Dupuytren’s contracture. Cite this article: Bone Joint J 2018;100-B:1138–45.

We performed a systematic review with network meta‐analysis (NMA) to compare the efficacy of different approaches in primary prevention of esophageal variceal bleeding and overall survival in patients with cirrhosis with large varices. Thirty‐two randomized clinical trials (RCTs) with 3,362 adults with cirrhosis with large esophageal varices and no prior history of bleeding, with a minimum of 12 months of follow‐up, were included. Nonselective beta‐blockers (NSBB), isosorbide‐mononitrate (ISMN), carvedilol, and variceal band ligation (VBL), alone or in combination, were compared with each other or placebo. Primary outcomes were reduction of all‐cause mortality and prevention of esophageal variceal bleeding. Random‐effects NMA was performed and summary estimates were expressed as odds ratio and 95% confidence intervals (OR; CI). Quality of evidence was critically appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. Moderate quality evidence supports NSBB monotherapy (0.70; 0.49‐1.00) or in combination with VBL (0.49; 0.23‐1.02) or ISMN (0.44; 0.21‐0.93) for decreasing mortality in patients with cirrhosis with large esophageal varices and no prior history of bleeding. Moderate‐quality evidence supports carvedilol (0.21; 0.08‐0.56) and VBL monotherapy (0.33; 0.19‐0.55) or in combination with NSBB (0.34; 0.14‐0.86), and low‐quality evidence supports NSBB monotherapy (0.64; 0.38‐1.07) for primary prevention of variceal bleeding. VBL carries a higher risk of serious adverse events compared with NSBB.Conclusion:NSBB monotherapy may decrease all‐cause mortality and the risk of first variceal bleeding in patients with cirrhosis with large esophageal varices. Additionally, NSBB carries a lower risk of serious complications compared with VBL. Therefore, NSBB may be the preferred initial approach for primary prophylaxis of esophageal variceal bleeding.

Summary Objective Surgery is a stressor that can be categorized by duration and severity and induces a systemic stress response that includes increased adrenal cortisol production. However, the precise impact of surgical stress on the cortisol response remains to be defined. Design We performed a systematic review and meta‐analysis to assess the cortisol stress response induced by surgery and to stratify this response according to different parameters. Methods We conducted a comprehensive search in several databases from 1990 to 2016. Pairs of reviewers independently selected studies, extracted data and evaluated the risk of bias. Cortisol concentrations were standardized, pooled in meta‐analysis and plotted over time. Results We included 71 studies reporting peri‐operative serum cortisol measurements in 2953 patients. The cortisol response differed substantially between moderately/highly invasive and minimally invasive surgical procedures. Minimally invasive procedures did not show a peri‐operative cortisol peak, whereas more invasive surgeries caused a cortisol surge that was more pronounced in older subjects, women and patients undergoing open surgery and general anaesthesia. The duration of the procedure and the use of etomidate for induction of anaesthesia did not affect the cortisol response. Conclusions The peri‐operative cortisol stress response is dynamic and influenced by patient‐specific, surgical and anaesthetic features. However, the available evidence is derived from highly heterogeneous studies, with only two of 71 studies measuring cortisol by mass spectrometry, which currently prevents a precise and reproducible definition of this response.

OBJECTIVE De novo aneurysms are rare entities periodically discovered during follow-up imaging. Little is known regarding the frequency with which these lesions form or the time course. This systematic review and meta-analysis was undertaken to estimate the incidence of de novo aneurysms and to determine risk factors for aneurysm formation. METHODS The authors searched multiple databases for studies of patients with unruptured and ruptured aneurysms describing the rate of de novo aneurysm formation. The primary outcome was incidence of de novo aneurysm formation. A meta-analysis was performed using a random-effects model. The authors examined the associations of multiple aneurysms, prior subarachnoid hemorrhage, smoking, sex, age at presentation, and hypertension with de novo aneurysm formation. RESULTS The meta-analysis included 14,968 aneurysm patients who received imaging follow-up from 35 studies. The overall incidence of de novo aneurysm formation was 2% (95% CI 2%–3%) over a mean follow-up time of 8.3 years. The estimated incidence density was 0.3%/patient-year. There was no statistically significant difference in rates of de novo aneurysm formation between patients who had ruptured aneurysms and those with unruptured aneurysms. In 8 studies, 11.2% of de novo aneurysms were found in patients with ≤ 5 years of follow-up and 88.8% were found at > 5 years. The mean time to rupture for de novo aneurysms was 10 years. CONCLUSIONS This systematic review demonstrates that formation of de novo aneurysms is rare. Overall, routine screening for de novo aneurysms is likely to be of low yield and could be performed at time intervals of at least 5 to 10 years.

Abstract Background GH deficiency (GHD) is common among childhood cancer survivors (CCSs) with history of tumors, surgery, and/or radiotherapy involving the hypothalamus-pituitary region. We aimed to evaluate the effects of GH therapy (GHT) in CCSs on adult height, risk of diabetes mellitus, abnormal lipids, metabolic syndrome, quality of life, secondary tumors, and disease recurrence. Methods We searched multiple databases for randomized and observational studies. Pairs of reviewers independently selected studies and collected data. Random effects meta-analysis was used to pool outcomes across the studies. Results We included 29 observational studies at moderate to high risk of bias. Sixteen studies compared CCSs on GHT with those not on GHT (512 patients, GH dose: 0.3 to 0.9 IU/kg/week). GHT was significantly associated with height gain [standard deviation score, 0.61; 95% CI, 0.08 to 1.13] and was not significantly associated with the occurrence of secondary tumors [odds ratio (OR), 1.10; 95% CI, 0.72 to 1.67] or tumor recurrence (OR, 0.57; 95% CI, 0.31 to 1.02). Thirteen studies compared CCSs on GHT with normal age- or sex-matched controls or controls with idiopathic GHD or short stature. GHT was associated with either improved or unchanged risk of diabetes, lipid profiles, and metabolic syndrome. GHT was associated with improvements in quality of life. Conclusion CCSs treated with GHT gain height compared with the untreated controls. GHT may improve lipid profiles and quality of life and does not appear to increase the risk of diabetes or the development of secondary tumors, although close monitoring for such complications remains warranted due to uncertainty in the current evidence.

Abstract Objective To formulate clinical practice guidelines for the endocrine treatment of hypothalamic–pituitary and growth disorders in survivors of childhood cancer. Participants An Endocrine Society–appointed guideline writing committee of six medical experts and a methodologist. Conclusions Due to remarkable improvements in childhood cancer treatment and supportive care during the past several decades, 5-year survival rates for childhood cancer currently are >80%. However, by virtue of their disease and its treatments, childhood cancer survivors are at increased risk for a wide range of serious health conditions, including disorders of the endocrine system. Recent data indicate that 40% to 50% of survivors will develop an endocrine disorder during their lifetime. Risk factors for endocrine complications include both host (e.g., age, sex) and treatment factors (e.g., radiation). Radiation exposure to key endocrine organs (e.g., hypothalamus, pituitary, thyroid, and gonads) places cancer survivors at the highest risk of developing an endocrine abnormality over time; these endocrinopathies can develop decades following cancer treatment, underscoring the importance of lifelong surveillance. The following guideline addresses the diagnosis and treatment of hypothalamic–pituitary and growth disorders commonly encountered in childhood cancer survivors.

SummaryBackgroundThere are limited data to inform positioning of agents for treating moderate‐severe Crohn's disease (CD).AimWe assessed comparative efficacy and safety of first‐line (biologic‐naïve) and second‐line (prior exposure to anti‐tumour necrosis factor [TNF]‐α) agents) biologic therapy for moderate‐severe CD, through a systematic review and network meta‐analysis, and appraised quality of evidence (QoE) using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.MethodsWe identified randomised controlled trials (RCTs) in adults with moderate‐severe CD treated with approved anti‐TNF agents, anti‐integrin agents and anti‐IL12/23 agents, first‐line or second‐line, and compared with placebo or another active agent. Efficacy outcomes were induction and maintenance of clinical remission; safety outcomes were serious adverse events and infections. Network meta‐analyses were performed, and ranking was assessed using surface under the cumulative ranking (SUCRA) probabilities.ResultsNo head‐to‐head trials were identified. In biologic‐naïve patients, infliximab (SUCRA,0.93) and adalimumab (SUCRA,0.75) were ranked highest for induction of clinical remission (moderate QoE). In patients with prior anti‐TNF exposure, adalimumab (SUCRA, 0.91; low QoE, in patients with prior response or intolerance to anti‐TNF agents) and ustekinumab (SUCRA, 0.71) were ranked highest for induction of clinical remission. In patients with response to induction therapy, adalimumab (SUCRA, 0.97) and infliximab (SUCRA, 0.68) were ranked highest for maintenance of remission. Ustekinumab had lowest risk of serious adverse events (SUCRA, 0.72) and infection (SUCRA, 0.71; along with infliximab, SUCRA, 0.83) in maintenance trials.ConclusionIndirect comparisons suggest that infliximab or adalimumab may be preferred first‐line agents, and ustekinumab a preferred second‐line agent, for induction of remission in patients with moderate‐severe CD. Head‐to‐head trials are warranted.