Murad, M. Hassan

Abstract Background Abdominal pain is a debilitating symptom affecting ∼80% of pancreatic cancer (PC) patients. Pancreatic duct (PD) decompression has been reported to alleviate this pain, although this practice has not been widely adopted. We aimed to evaluate the role, efficacy, and safety of endoscopic PD decompression for palliation of PC post-prandial obstructive-type pain. Methods A systematic review until 7 October 2020 was performed. Two independent reviewers selected studies, extracted data, and assessed the methodological quality. Results We identified 12 publications with a total of 192 patients with PC presenting with abdominal pain, in whom PD decompression was attempted, and was successful in 167 patients (mean age 62.5 years, 58.7% males). The use of plastic stents was reported in 159 patients (95.2%). All included studies reported partial or complete improvement in pain levels after PD stenting, with an improvement rate of 93% (95% confidence interval, 79%–100%). The mean duration of pain improvement was 94 ± 16 days. Endoscopic retrograde cholangiopancreatography (ERCP)-related adverse events (AEs) were post-sphincterotomy bleeding (1.8%), post-ERCP pancreatitis (0.6%), and hemosuccus pancreaticus (0.6%). AEs were not reported in two patients who underwent endoscopic ultrasound-guided PD decompression. In the 167 patients with technical success, the stent-migration and stent-occlusion rates were 3.6% and 3.0%, respectively. No AE-related mortality was reported. The methodological quality assessment showed the majority of the studies having low or unclear quality. Conclusion In this exploratory analysis, endoscopic PD drainage may be an effective and safe option in selected patients for the management of obstructive-type PC pain. However, a randomized–controlled trial is needed to delineate the role of this invasive practice.

Background The reported prevalence of chronic pain after spinal cord injury (SCI) varies widely due, in part, to differences in the taxonomy of chronic pain. A widely used classification system is available to describe subcategories of chronic pain in SCI, but the prevalence of chronic pain in SCI based on this system is unknown. Objective The primary objective of this systematic review and meta-analysis is to determine the prevalence of chronic pain after SCI based on the International Spinal Cord Injury Pain (ISCIP) classification system. Evidence review A comprehensive search of databases from January 1980 to August 2019 was conducted. The risk of bias was assessed using a modified tool developed for uncontrolled studies. The Grading of Recommendations, Assessment, Development and Evaluation approach was used to assess certainty in prevalence estimates. Findings A total of 1305 records were screened, and 37 studies met inclusion criteria. The pooled prevalence of overall chronic pain was 68% (95% CI 63% to 73%). The pooled prevalence of neuropathic pain in 13 studies was 58% (95% CI 49% to 68%); the pooled prevalence of musculoskeletal pain in 11 studies was 56% (95% CI 41% to 70%); the pooled prevalence of visceral pain in 8 studies was 20% (95% CI 11% to 29%) and the pooled prevalence of nociceptive pain in 2 studies was 45% (95% CI 13% to 78%). Meta-regression of risk of bias (p=0.20), traumatic versus non-traumatic etiology of injury (p=0.59), and studies where pain was a primary outcome (p=0.32) demonstrated that these factors were not significant moderators of heterogeneity. Certainty in prevalence estimates was judged to be low due to unexplained heterogeneity. Conclusion This systematic review and meta-analysis extends the findings of previous studies by reporting the prevalence of chronic pain after SCI based on the ISCIP classification system, thereby reducing clinical heterogeneity in the reporting of pain prevalence related to SCI.

Background There has been limited research on the positive aspects of physician wellness and to our knowledge there have been no validity studies on measures of resilience and grit among internal medicine (IM) residents. Objectives To investigate the validity of resilience (10 items Connor-Davidson Resilience Scale (CD-RISC 10)) and grit (Short Grit Scale (GRIT-S)) scores among IM residents at a large academic centre, and assess potential associations with previously validated measures of medical knowledge, clinical performance and professionalism. Methods We evaluated CD-RISC 10 and GRIT-S instrument scores among IM residents at the Mayo Clinic Rochester, Minnesota between July 2017 and June 2019. We analysed dimensionality, internal consistency reliability and criterion validity in terms of relationships between resilience and grit, with standardised measures of residents’ medical knowledge (in-training examination (ITE)), clinical performance (faculty and peer evaluations and Mini-Clinical Evaluation Examination (mini-CEX)) and professionalism/dutifulness (conference attendance and evaluation completion). Results A total of 213 out of 253 (84.2%) survey-eligible IM residents provided both CD-RISC 10 and GRIT-S survey responses. Internal consistency reliability (Cronbach alpha) was excellent for CD-RISC 10 (0.93) and GRIT-S (0.82) overall, and for the GRIT subscales of consistency of interest (0.84) and perseverance of effort (0.71). CD-RISC 10 scores were negatively associated with ITE percentile (β=−3.4, 95% CI −6.2 to −0.5, p=0.02) and mini-CEX (β=−0.2, 95% CI −0.5 to −0.02, p=0.03). GRIT-S scores were positively associated with evaluation completion percentage (β=2.51, 95% CI 0.35 to 4.67, p=0.02) and conference attendance (β=2.70, 95% CI 0.11 to 5.29, p=0.04). Conclusions This study revealed favourable validity evidence for CD-RISC 10 and GRIT-S among IM residents. Residents demonstrated resilience within a competitive training environment despite less favourable test performance and grittiness that was manifested by completing tasks. This initial validity study provides a foundation for further research on resilience and grit among physicians in training.

Background: Assessment of heterogeneity in meta-analyses is critical to ensure the consistency of pooled results. Therefore, we sought to assess the evaluation and reporting of heterogeneity in heart failure (HF) meta-analyses. Methods: Study level meta-analyses pertaining to HF were selected from January 2009 to July 2019, published in 11 high impact factor journals. We tabulated the overall proportion of the meta-analyses reporting statistical heterogeneity and specific metrics and methods employed to quantify and explore heterogeneity. Results: Of 126 HF meta-analyses (612 outcomes), heterogeneity was reported for 422 outcomes (68.9 %) in 108 meta-analyses. Out of the 422 outcomes reporting statistical heterogeneity, 137 outcomes (32.5%) had no observable heterogeneity: ( I 2 =0%), 40 outcomes (9.5%) had low heterogeneity ( I 2 <25%), 76 outcomes (18%) had moderate heterogeneity ( I 2 =25%–50%), and 169 outcomes (40%) had high heterogeneity ( I 2 >50%). Reporting of statistical heterogeneity was not significantly associated with year of publication, funding source, disclosure information, or the type of studies pooled. Sensitivity analysis (n=68) was the most common statistical technique employed to evaluate the source of heterogeneity followed by subgroup analyses (n=59) and meta-regression (n=40). Conclusions: Despite being an essential component of meta-analyses, heterogeneity was not reported for nearly 30% of outcomes and variably handled in contemporary HF meta-analyses. As meta-analyses increase across HF science, interpreting and handling of heterogeneity should be standardized.

Abstract Background The current standard of care for the management of patients with newly diagnosed glioblastoma (GBM) includes maximal safe resection followed by radiotherapy (RT) with concurrent and adjuvant temozolomide (TMZ). While it is well established that TMZ has better efficacy in patients with MGMT promoter methylation, it remains an area of debate whether TMZ should be omitted when treating GBM patients with unmethylated MGMT. Methods We conducted a systematic review and meta-analysis to provide separate estimates of median overall survival (OS) and progression-free survival (PFS) for patients with methylated and unmethylated GBM treated with RT with or without TMZ. We searched multiple databases from inception to January 13, 2020. Results The median OS for patients with unmethylated GBM treated with RT/TMZ pooled from 5 phase III studies (N = 655) was 14.11 months (95% confidence interval [CI], 13.18–15.04) with a median PFS of 4.99 months (95% CI, 4.25–5.72). In contrast, the median OS for patients with methylated GBM pooled from 6 studies (N = 753) was 24.59 months (95% CI, 22.19–26.99) with a median PFS pooled from 7 studies (N = 805) of 9.51 months (95% CI, 7.41–11.61). There is a paucity of prospective data pertaining to OS/PFS in unmethylated patients treated with RT only and therefore a direct comparison was not possible. Conclusions This meta-analysis provides estimates of survival for patients with MGMT methylated or unmethylated GBM treated with RT/TMZ. Further research is needed to delineate whether TMZ should be withheld for patients with unmethylated GBM outside of the setting of clinical trials.

While numerous guidelines for the prescription of physical activity are released each year, the quality and practicability of these guidelines is unknown. We assessed the quality of 95 guidance documents published since 2000 that included recommendations about physical activity for the promotion of general health and prevention of cardiometabolic disease. We used 3 tools: Appraisal of Guidelines for Research and Evaluation (AGREE II), the National Academy of Medicine’s (NAM) Standards for Trustworthy Clinical Practice Guidelines, and the Frequency, Intensity, Time, and Type (FITT) score. Average AGREE II domain scores ranged from 38%−84%, and the portion of criteria fulfilled per NAM domain ranged from 7%–39%. The average FITT score for all recommendations was 2.48 out of 4. While guidelines improved according to both AGREE II and the NAM standards over time, their practicability as assessed by FITT score did not improve. Guidelines produced by governmental agencies or other nonprofit organizations, using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, or fulfilling a higher number of NAM criteria tended to be of higher quality. Organizations producing physical activity guidelines can improve their quality by establishing and reporting processes for public representation, external review, and conflict of interest (COI) management. Future recommendations about physical activity should be more specific and include strategies to improve implementation. Registration no.: PROSPERO CRD42019126364. Novelty: Most physical activity recommendations are not sufficiently specific to be practically implemented. The overall quality of guidelines has improved over time, but the specificity of recommendations has not. Improved public representation, external review, and COI disclosure and management processes would improve guideline quality.

AbstractBackground & AimsAlthough 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.MethodsWe 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.ResultsAfter 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.ConclusionsWe 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.