Normal liver stiffness and influencing factors in healthy children: An individual participant data meta-analysis.

BACKGROUND & AIMS: Although transient elastography (TE) is used to determine liver stiffness as a surrogate to hepatic fibrosis, the normal range in children is not well defined. We performed a systematic review and individual participant data (IPD) meta-analysis to determine the range of liver stiffness in healthy children and evaluate the influence of important biological parameters. METHODS: We pooled data from 10 studies that examined healthy children using TE. We divided 1702 children into two groups: ≥3 years (older group) and < 3 years of age (younger group). Univariate and multivariate linear regression models predicting liver stiffness were conducted. RESULTS: After excluding children with obesity, diabetes, or abnormal liver tests, 652 children were analysed. Among older children, mean liver stiffness was 4.45 kPa (95% confidence interval 4.34-4.56), and increased liver stiffness was associated with age, sedation status, and S probe use. In the younger group, the mean liver stiffness was 4.79 kPa (95% confidence interval 4.46-5.12), and increased liver stiffness was associated with sedation status and Caucasian race. In a subgroup analysis, hepatic steatosis on ultrasound was significantly associated with increased liver stiffness. We define a reference range for normal liver stiffness in healthy children as 2.45-5.56 kPa. CONCLUSIONS: We have established TE-derived liver stiffness ranges for healthy children and propose an upper limit of liver stiffness in healthy children to be 5.56 kPa. We have identified increasing age, use of sedation, probe size, and presence of steatosis on ultrasound as factors that can significantly increase liver stiffness.

Immune checkpoint inhibitor-induced Type 1 diabetes: a systematic review and meta-analysis.

AIM: To conduct a systematic review and meta-analysis to understand the timing and factors associated with anti-programmed cell death protein-1 (PD-1)/anti-programmed cell death protein-1 ligand (PD-L1) inhibitor-induced Type 1 diabetes. METHODS: We searched MEDLINE, EMBASE, SCOPUS and Cochrane databases (August 2000-2018) for studies of any design on immune checkpoint inhibitors. A total of 71 cases were reviewed from 56 publications. Comparisons were made using Fisher's exact and Student's t-tests. RESULTS: The mean ± sd age at Type 1 diabetes presentation was 61.7±12.2 years, 55% of cases were in men, and melanoma (53.5%) was the most frequent cancer. The median time to Type 1 diabetes onset was 49 (5-448) days with ketoacidosis in 76% of cases. The average ± sd HbA1c concentration was 62 ± 0.3 mmol/mol (7.84±1.0%) at presentation. All cases had insulin deficiency and required permanent exogenous insulin treatment. Half of the cases had Type 1 diabetes-associated antibodies at presentation, and those with antibodies had a more rapid onset (P=0.005) and higher incidence of diabetic ketoacidosis (P=0.02) compared to people without antibodies. CONCLUSIONS: Many people developed Type 1 diabetes within 3 months of initial PD-1/PD-L1 inhibitor exposure. People presenting with Type 1 diabetes-associated antibodies had a more rapid onset and higher incidence of ketoacidosis than those without antibodies. Healthcare providers caring for people receiving these state-of-the-art therapies need to be aware of this potential severe adverse event.

Late boosting phenomenon in TST conversion among health care workers.

BACKGROUND: Available information is insufficient to guide determination of whether tuberculin skin test (TST) conversions of health care workers (HCWs) within 2 years of two-step testing are related to occupational exposures or to other causes, including late boosting. AIMS: To describe the epidemiologic factors of TST conversion in HCWs, comparing early TST conversion (≤2 years after two-step testing) with late conversion to possibly distinguish late boosting phenomenon from occupational TST conversion. METHODS: Retrospective analysis of a database of TSTs of HCWs from 1 January 1998, through 31 May 2014, in the United States Midwest. RESULTS: In total, 40142 HCWs had 197932 tests over the 16 years, with 123 conversions (conversion rate: 0.3%; 95% CI 0.3-0.4%). Among 61 HCWs with a negative two-step TST, 30 (49%) were found to have early TST conversion within 2 years; 31 (51%) had late conversion, with likely occupational exposure but no identifiable community risks. Persons with early conversion were more likely to be born outside the USA (89% versus 57%; P < 0.05), had a higher rate of prior bacille Calmette-Guérin (BCG) vaccination (89% versus 52%; P < 0.05) and had no identifiable risk factors for conversion (63% versus 58%; P < 0.05). CONCLUSIONS: Early conversions among HCWs after negative two-step TST are associated with various nonoccupational factors, including international birth and BCG vaccination history. Therefore, conversion is not a reliable indicator of recent tuberculosis contact in this population, and two-step TST is insufficient to discount a delayed boosting response for HCWs.

Neuraxial vs general anaesthesia for total hip and total knee arthroplasty: a systematic review of comparative-effectiveness research.

BACKGROUND: This systematic review evaluated the evidence comparing patient-important outcomes in spinal or epidural vs general anaesthesia for total hip and total knee arthroplasty. METHODS: MEDLINE, Ovid EMBASE, EBSCO CINAHL, Thomson Reuters Web of Science, and the Cochrane Central Register of Controlled Trials from inception until March 2015 were searched. Eligible randomized controlled trials or prospective comparative studies investigating mortality, major morbidity, and patient-experience outcomes directly comparing neuraxial (spinal or epidural) with general anaesthesia for total hip arthroplasty, total knee arthroplasty, or both were included. Independent reviewers working in duplicate extracted study characteristics, validity, and outcomes data. Meta-analysis was conducted using the random-effects model. RESULTS: We included 29 studies involving 10 488 patients. Compared with general anaesthesia, neuraxial anaesthesia significantly reduced length of stay (weighted mean difference -0.40 days; 95% confidence interval -0.76 to -0.03; P=0.03; I2 73%; 12 studies). No statistically significant differences were found between neuraxial and general anaesthesia for mortality, surgical duration, surgical site or chest infections, nerve palsies, postoperative nausea and vomiting, or thromboembolic disease when antithrombotic prophylaxis was used. Subgroup analyses failed to find statistically significant interactions (P>0.05) based on risk of bias, type of surgery, or type of neuraxial anaesthesia. CONCLUSION: Neuraxial anaesthesia for total hip or total knee arthroplasty, or both appears equally effective without increased morbidity when compared with general anaesthesia. There is limited quantitative evidence to suggest that neuraxial anaesthesia is associated with improved perioperative outcomes. Future investigations should compare intermediate and long-term outcome differences to better inform anaesthesiologists, surgeons, and patients on importance of anaesthetic selection.

Screening for depression in the occupational health setting.

BACKGROUND: The cost of workplace absenteeism and presenteeism due to depression in the USA is substantial. AIMS: To assess the frequency of depression and its impact at the point of care in an occupational health (OH) practice. METHODS: Patients presenting to an OH practice completed a standardized depression screening tool and were compared to an unscreened group in the same clinic. Respondents with a nine-item Patient Health Questionnaire (PHQ-9) score >15 and untreated for depression were referred for further evaluation per usual practice. A comparison group of unscreened patients were selected from the same clinic from 1 year prior and records were reviewed for evidence of prior depression, treatment and outcomes. After 1 year, frequency of depression, PHQ-9 scoring for screened patients, days absent from work, days on restricted duties and permanent restrictions were recorded for both groups. RESULTS: Two hundred and five patients were screened for depression. Screening was associated with increased frequency of a diagnosis of current depression (30 versus 4%; P < 0.05). Screening was associated with similar rates of absenteeism but lower number of days on restricted duties (97 versus 159 days; P < 0.001). After adjusting for age, sex, history of and treatment for depression, screening was associated with lower odds of being on work restrictions [odds ratio (OR) 0.55; 95% confidence interval (CI) 0.38-0.78] or permanent restrictions (OR 0.35; 95% CI 0.23-0.52). CONCLUSIONS: Depression was common in this OH practice. Screening for depression, with appropriate recognition and referral, may reduce time for employed patients on restricted duties and permanent restrictions.

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

UNLABELLED: The 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. INTRODUCTION: Paget'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. METHODS: We 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. RESULTS: We 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). CONCLUSION: The 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.

A survey of physicians' perceptions of their health care needs.

BACKGROUND: Physicians may face unique challenges in accessing health care and managing their own health. AIMS: To evaluate physicians' perceptions of their health care needs and desired services. METHODS: A written survey, distributed and collected anonymously among attendees at a large primary care continuing medical education conference. RESULTS: The survey was given to 346 physicians and 141 (41%) responded. The majority of physicians (53%) reported having difficulty accessing health care and reverting to self-diagnosis and treatment (63%). Over 83% reported having or knowing a colleague who had a career-threatening illness and 42% had experienced concern about a colleague's ability to practise safely. CONCLUSIONS: Physicians as an occupational group have challenges in accessing health care, very commonly suffer career-limiting illnesses and revert to self-diagnosis and treatment. Programmes tailored to providing health care to physicians are needed.

Pioglitazone and risk of bladder cancer: a meta-analysis of controlled studies.

AIMS: Pioglitazone, a thiazolidinedione, was approved for treatment of Type 2 diabetes. However, several observational studies suggest an association of pioglitazone with an increased risk of bladder cancer in patients with diabetes. Therefore, we sought to perform a systematic review and meta-analysis to evaluate the magnitude of this association and the quality of the supporting evidence. METHODS: Electronic databases were queried to identify controlled studies of pioglitazone that measured the risk of bladder cancer. RESULTS: Six studies involving 215 142 patients using pioglitazone were included, with a median period of follow-up of 44 months. The hazard of developing bladder cancer was significantly higher in patients using pioglitazone (hazard ratio 1.23; 95% CI 1.09-1.39; I² = 0%) compared with control groups. The risk of bias was moderate across the six studies. Considering an incidence rate of 20.8 per 100 000 person years, the number needed to harm was five additional cases of bladder cancer per 100 000 person years. CONCLUSIONS: Patients treated with pioglitazone have a slight increased risk of bladder cancer compared to general population. Patient involvement and weighing treatment benefits versus risks should be discussed with patient toward shared decision. Patients with type 2 diabetes with risk factors, such as family history, smoking, or exposure to certain forms of chemotherapy may need to consider other anti-hyperglycemic agents. Also, pioglitazone should be discontinued in type 2 diabetes patients with newly diagnosed bladder cancer.

Within-Person Blood Pressure Variability During Hospitalization and Clinical Outcomes Following First-Ever Acute Ischemic Stroke.

BACKGROUND: Uncertainty remains over the relationship between blood pressure (BP) variability (BPV), measured in hospital settings, and clinical outcomes following acute ischemic stroke (AIS). We examined the association between within-person systolic blood pressure (SBP) variability (SBPV) during hospitalization and readmission-free survival, all-cause readmission, or all-cause mortality 1 year after AIS. METHODS: In a cohort of 862 consecutive patients (age [mean ± SD] 75 ± 15 years, 55% women) with AIS (2005-2018, follow-up through 2019), we measured SBPV as quartiles of standard deviations (SD) and coefficient of variation (CV) from a median of 16 SBP readings obtained throughout hospitalization. RESULTS: In the cumulative cohort, the measured SD and CV of SBP in mmHg were 16 ± 6 and 10 ± 5, respectively. The hazard ratios (HR) for readmission-free survival between the highest vs. lowest quartiles were 1.44 (95% confidence interval [CI] 1.04-1.81) for SD and 1.29 (95% CI 0.94-1.78) for CV after adjustment for demographics and comorbidities. Similarly, incident readmission or mortality remained consistent between the highest vs. lowest quartiles of SD and CV (readmission: HR 1.29 [95% CI 0.90-1.78] for SD, HR 1.29 [95% CI 0.94-1.78] for CV; mortality: HR 1.15 [95% CI 0.71-1.87] for SD, HR 0.86 [95% CI 0.55-1.36] for CV). CONCULSIONS: In patients with first AIS, SBPV measured as quartiles of SD or CV based on multiple readings throughout hospitalization has no independent prognostic implications for the readmission-free survival, readmission, or mortality. This underscores the importance of overall patient care rather than a specific focus on BP parameters during hospitalization for AIS.

Recurrence and mortality rates with different treatment approaches of Merkel cell carcinoma: a systematic review and meta-analysis.

BACKGROUND: Comprehensive treatment recommendations for Merkel cell carcinoma are complex. We aimed to systematically review the published data on recurrence and mortality rates associated with various treatment approaches for Merkel cell carcinoma. METHODS: Search of MEDLINE, Embase, Web of Science, and Scopus from inception to August 2015. Studies were included that reported comparative survival and recurrence data for two or more treatment modalities. Two reviewers independently reviewed and abstracted recurrence and mortality rates. Event rates for individual treatment arms in each study were pooled and meta-analyzed across studies using a random-effects model. RESULTS: Fifty-two retrospective studies met inclusion criteria, revealing a total of 1,804 patients with primary Merkel cell carcinoma with data available for analyses. The recurrence rate was higher for surgery alone (55.0%) versus a combination of surgery and radiotherapy (39.0%) (odds ratio, 2.089; 95% CI, 1.374-3.177; P < 0.001). Combination therapy including surgery, radiotherapy, and chemotherapy had a higher mortality rate (44.6%) than did combined surgery and radiotherapy (23.2%) (odds ratio, 2.688; 95% CI, 1.196-6.037; P = 0.02). CONCLUSIONS: The treatment of Merkel cell carcinoma with surgery plus adjuvant radiotherapy may produce lower recurrence rates.

Long-Term Rupture Risk in Patients with Unruptured Intracranial Aneurysms Treated with Endovascular Therapy: A Systematic Review and Meta-Analysis.

BACKGROUND: Surveillance imaging of previously unruptured, coiled aneurysms remains routine even though reports of rupture of these aneurysms are extremely rare. PURPOSE: We performed meta-analysis to examine long-term rupture risk over ≥1-year follow-up duration in patients with unruptured intracranial aneurysm who underwent endovascular therapy. DATA SOURCES: Multiple databases were searched for relevant publications between 1995 and 2018. STUDY SELECTION: Studies reporting outcome of long-term rupture risk over ≥1-year follow-up in treated patients with unruptured intracranial aneurysms were included. DATA ANALYSIS: Random effects meta-analysis was used, and results were expressed as long-term rupture rate per 100 patient-year with respective 95% CIs. For ruptured aneurysms during follow-up, data were collected on size and completeness of initial Treatment. DATA SYNTHESIS: Twenty-four studies were identified. Among 4842 patients with a mean follow-up duration of 3.2 years, a total of 12 patients (0.25%) experienced rupture of previous unruptured intracranial aneurysms after endovascular treatment. Nine of these 12 patients harbored aneurysms that were large, incompletely treated, or both. A total of 2 anterior circulation, small, completely coiled aneurysms subsequently ruptured. The long-term rupture rate per 100 patient-year for unruptured intracranial aneurysms treated with endovascular therapy was 0.48 (95% CI, 0.45-0.51). Retreatment was carried out in 236 (4.9%) of these 4842 patients. LIMITATIONS: A limitation of the study is that a lack of systematic nature of follow-up and mean follow-up duration of 3.2 years are not sufficient to make general recommendations about aneurysm followup paradigms. CONCLUSIONS: Given a 5% retreatment rate, postcoil embolization spontaneous rupture of previously unruptured, small- and medium-sized, well-treated aneurysms is exceedingly rare.

American Society of Hematology 2020 guidelines for sickle cell disease: prevention, diagnosis, and treatment of cerebrovascular disease in children and adults.

BACKGROUND: Central nervous system (CNS) complications are among the most common, devastating sequelae of sickle cell disease (SCD) occurring throughout the lifespan. OBJECTIVE: These evidence-based guidelines of the American Society of Hematology are intended to support the SCD community in decisions about prevention, diagnosis, and treatment of the most common neurological morbidities in SCD. METHODS: The Mayo Evidence-Based Practice Research Program supported the guideline development process, including updating or performing systematic evidence reviews. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE evidence-to-decision frameworks, to assess evidence and make recommendations. RESULTS: The panel placed a higher value on maintaining cognitive function than on being alive with significantly less than baseline cognitive function. The panel developed 19 recommendations with evidence-based strategies to prevent, diagnose, and treat CNS complications of SCD in low-middle- and high-income settings. CONCLUSIONS: Three of 19 recommendations immediately impact clinical care. These recommendations include: use of transcranial Doppler ultrasound screening and hydroxyurea for primary stroke prevention in children with hemoglobin SS (HbSS) and hemoglobin Sß0 (HbSß0) thalassemia living in low-middle-income settings; surveillance for developmental delay, cognitive impairments, and neurodevelopmental disorders in children; and use of magnetic resonance imaging of the brain without sedation to detect silent cerebral infarcts at least once in early-school-age children and once in adults with HbSS or HbSß0 thalassemia. Individuals with SCD, their family members, and clinicians should become aware of and implement these recommendations to reduce the burden of CNS complications in children and adults with SCD.

Routine laboratory measures of heparin anticoagulation for children on extracorporeal membrane oxygenation: Systematic review and meta-analysis.

OBJECTIVE: Specific protocols for anticoagulation for children on ECMO vary across institutions, with most using a continuous infusion of unfractionated heparin. The goal of this study is to aid clinician's decision on the best measure of heparin anticoagulation test; which would be the one that correlates well with heparin activity and helps in predicting hemorrhagic and thrombotic complications. DATA SOURCES: A comprehensive search of MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Scopus was conducted from each database's inception to 07/13/2018. STUDY SELECTION: Studies evaluating children (<18 years) treated with ECMO and evaluating ACT, aPTT, TEG and Anti-Xa in any language were included. DATA EXTRACTION: Two reviewers selected and appraised studies independently, and abstracted data. RESULTS: We included 19 studies (759 patients, mean age 19.8 months). Meta-analysis showed strong correlation between heparin dosing and anti-Xa. Additionally, there was not a strong correlation between laboratory tests and complications (hemorrhagic and thrombosis), or mortality. CONCLUSION: Based on current evidence, Anti-Xa is the only laboratory test that shows strong correlation with heparin infusion dose and seems like the most suitable test for monitoring of anticoagulation with heparin in children on ECMO.

A case for clarity, consistency, and helpfulness: state-of-the-art clinical practice guidelines in endocrinology using the grading of recommendations, assessment, development, and evaluation system.

CONTEXT: The Endocrine Society, and a growing number of other organizations, have adopted the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to develop clinical practice guidelines and grade the strength of recommendations and the quality of the evidence. Despite the use of GRADE in several of The Endocrine Society's clinical practice guidelines, endocrinologists have not had access to a context-specific discussion of this system and its merits. EVIDENCE ACQUISITION: The authors are involved in the development of the GRADE standard and its application to The Endocrine Society clinical practice guidelines. Examples were extracted from these guidelines to illustrate how this grading system enhances the quality of practice guidelines. EVIDENCE SYNTHESIS: We summarized and described the components of the GRADE system, and discussed the features of GRADE that help bring clarity and consistency to guideline documents, making them more helpful to practicing clinicians and their patients with endocrine disorders. CONCLUSIONS: GRADE describes the quality of the evidence using four levels: very low, low, moderate, and high quality. Recommendations can be either strong ("we recommend") or weak ("we suggest"), and this strength reflects the confidence that guideline panel members have that patients who receive recommended care will be better off. The separation of the quality of the evidence from the strength of the recommendation recognizes the role that values and preferences, as well as clinical and social circumstances, play in formulating practice recommendations.

Systematic review with network meta-analysis: first- and second-line pharmacotherapy for moderate-severe ulcerative colitis.

BACKGROUND: There are limited data to inform positioning of agents for treating moderate-severe ulcerative colitis (UC). AIM: To assess comparative efficacy and safety of different therapies as first-line (biologic-naïve) and second-line (prior exposure to anti-tumour necrosis factor(TNF)-α) agents for moderate-severe UC, through a systematic review and network meta-analysis, and appraise quality of evidence (QoE) using grading of recommendations, assessment, development and evaluation (GRADE) approach. METHODS: We identified randomised controlled trials (RCTs) in adults with moderate-severe UC treated with anti-TNF agents, anti-integrin agents and janus kinase (JAK) inhibitors, as first-line or second-line agents, and compared with placebo or another active agent. Efficacy outcomes were induction/maintenance of remission and mucosal healing; and 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. RESULTS: In biologic-naïve patients (12 trials, no head-to-head comparisons), infliximab and vedolizumab were ranked highest for induction of clinical remission (infliximab: odds ratio [OR], 4.10 [95% confidence intervals [CI], 2.58-6.52]; SUCRA,0.85; vedolizumab:SUCRA,0.82) and mucosal healing (infliximab:SUCRA,0.91; vedolizumab:SUCRA,0.81) (moderate QoE). In patients with prior anti-TNF exposure (4 trials, no head-to-head comparisons), tofacitinib was ranked highest for induction of clinical remission (OR, 11.88 [2.32-60.89]; SUCRA, 0.96) and mucosal healing (moderate QoE). Differences in trial design limited comparability of trials of maintenance therapy for efficacy. Vedolizumab was ranked safest in terms of serious adverse events (SUCRA, 0.91), and infection (SUCRA, 0.75) in maintenance trials. CONCLUSIONS: Infliximab and vedolizumab are ranked highest as first-line agents, and tofacitinib is ranked highest as second-line agent, for induction of remission and mucosal healing in patients with moderate-severe UC, based on indirect comparisons. Head-to-head trials are warranted to inform clinical decision-making with greater confidence.

Systematic review and network meta-analysis: first- and second-line biologic therapies for moderate-severe Crohn's disease.

BACKGROUND: There are limited data to inform positioning of agents for treating moderate-severe Crohn's disease (CD). AIM: We 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. METHODS: We 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. RESULTS: No 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. CONCLUSION: Indirect 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.

Treatment of Dupuytren's contracture: a systematic review.

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.

Does natriuretic peptide monitoring improve outcomes in heart failure patients? A systematic review and meta-analysis.

BACKGROUND: Current guidelines do not support the use of serial natriuretic peptide (NP) monitoring for heart failure with preserved (HFpEF) or reduced ejection fraction (HFrEF) treatment, despite some studies showing benefit. We conducted an updated meta-analysis to address whether medical therapy in HFpEF or HFrEF should be titrated according to NP levels. METHODS: MEDLINE, Scopus and Cochrane CENTRAL databases were searched for randomized controlled trials (RCTs) comparing NP versus guideline directed titration in HF patients through December 2017. The key outcomes of interest were mortality, HF hospitalizations and all-cause hospitalizations. Risk ratios and 95% confidence intervals were pooled using random effects model. Sub-group analyses were performed for type of NP used, average age and acute or chronic HF. RESULTS: Eighteen trials including 5116 patients were included. Meta-analysis showed no significant difference between the NP-guided arm versus guideline directed titration in all-cause mortality (RR = 0.91 [0.81, 1.03]; p = 0.13), HF hospitalizations (RR = 0.81 [0.65, 1.01]; p = 0.06), and all cause hospitalizations (RR = 0.93 [0.86, 1.01]; p = 0.09). The results were consistent upon subgroup analysis by biomarker type (NT-proBNP or BNP) and type of heart failure (acute or chronic and HFrEF or HFpEF). Sub-group analysis suggested that NP-guided treatment was associated with decreased all-cause hospitalizations in patients younger than 72 years of age. CONCLUSION: The available evidence suggests that NP-guided therapy provides no additional benefit over guideline directed therapy in terms of all-cause mortality and HF-related hospitalizations in acute or chronic HF patients, regardless of their ejection fraction.

Endovascular Management of Acute Stroke in the Elderly: A Systematic Review and Meta-Analysis.

BACKGROUND: Acute ischemic stroke occurs more frequently, presents with more severe symptoms, and has worse outcomes in elderly patients. The safety and efficacy of endovascular therapy for acute stroke in this age group has not been fully established. PURPOSE: We present the results of a systematic review and meta-analysis examining clinical, procedural, and radiologic outcomes of endovascular therapy for acute stroke in patients older than 80 years of age. DATA SOURCES: We searched PubMed, MEDLINE, and EMBASE from 1992 to week 35 of 2017 for studies evaluating endovascular therapy for acute stroke in the elderly. STUDY SELECTION: Two independent reviewers selected studies and abstracted data. The primary end point was good functional outcome at 3 months defined as modified Rankin Scale score of ≤2. DATA ANALYSIS: Data were analyzed using random-effects meta-analysis. DATA SYNTHESIS: Seventeen studies reporting on 860 patients were included. The rate of good functional outcome at 3 months was 27% (95% CI, 21%-32%). Mortality at 3 months was 34% (95% CI, 23%-44%). Successful recanalization was achieved in 78% of patients (95% CI, 72%-85%). Procedure-related complications occurred in 11% (95% CI, 4%-17%). The incidence of intracranial hemorrhage was 24% (95% CI, 15%-32%), and for symptomatic intracranial hemorrhage, it was 8% (95% CI, 5%-10%). The mean time to groin was 251 minutes (95% CI, 224-278 minutes). Procedure time was 99 minutes (95% CI, 67-131 minutes). LIMITATIONS: I2 values were above 50% for all outcomes, indicating substantial heterogeneity. CONCLUSIONS: Good functional recovery in octogenarians treated with endovascular therapy for acute stroke can be achieved in a high proportion of patients despite the higher incidence of comorbidity in this cohort. Outcomes are inferior to those reported for younger patients; however, endovascular therapy can allow at least 1 in 4 patients older than 80 years of age to regain independent function at 3 months. More research is required to improve patient selection in the elderly, but age should not be a discriminator when deciding to offer endovascular therapy for patients with acute stroke.

Endovascular Treatment of Vein of Galen Malformations: A Systematic Review and Meta-Analysis.

BACKGROUND: Outcomes after endovascular embolization of vein of Galen malformations remain relatively poorly described. PURPOSE: We performed a systematic review of the literature to determine outcomes and predictors of good outcomes following endovascular treatment of vein of Galen malformations. DATA SOURCES: We used Ovid MEDLINE, Ovid Embase, and the Web of Science. STUDY SELECTION: Our study consisted of all case series with ≥4 patients receiving endovascular treatment of vein of Galen malformations published through January 2017. DATA ANALYSIS: We studied the following outcomes: complete/near-complete occlusion rates, technical complications, perioperative stroke, perioperative hemorrhage, technical mortality, all-cause mortality, poor neurologic outcomes, and good neurologic outcomes. Outcomes were stratified by age-group (neonate, infant, child). A random-effects meta-analysis was performed. DATA SYNTHESIS: A total of 27 series with 578 patients were included; 41.9% of patients were neonates, 45.0% of patients were infants, and 13.1% of patients were children. All-cause mortality was 14.0% (95% CI, 8.0%-22.0%). Overall good neurologic outcome rates were 62.0% (95% CI, 57.0%-67.0%). Overall poor neurologic outcome rates were 21.0% (95% CI, 17.0%-26.0%). Neonates were significantly less likely to have good neurologic outcomes than infants (48.0%; 95% CI, 35.0%-62.0% versus 77.0%; 95% CI, 70.0%-84.0%; P < .01). Treatment indications following the Bicêtre neonatal evaluation score resulted in significantly higher rates of good neurologic outcome (P = .04). Patients with congestive heart failure had significantly lower rates of good neurologic outcome (OR, 0.50; 95% CI, 0.28-0.88; P = .01). LIMITATIONS: Limitations were selection and publication biases. CONCLUSIONS: Patients receiving endovascular embolization of vein of Galen malformations experienced good long-term clinical outcomes in >60% of cases. Appropriate patient selection is key as treatment guided by the Bicêtre neonatal evaluation score was associated with improved neurologic outcomes.