Murad, M. Hassan

e24070 Background: We have maintained a living interactive systematic review (LISR) on the treatment of CAT ( CAT LISR ). Recent publications of CASTA-DIVA and CANVAS trials prompted this report of updated analysis. Methods: The approach to creating LISRs has been previously published and is available on our website. ( LIvE synthesis framework ). Patient important outcomes included venous thromboembolism (VTE) recurrence, major bleeding (MB), clinically relevant non-major bleeding (CRNMB), net clinical benefit (NCB) and all-cause mortality. Mantel-Haenszel method was used to pool treatment effect estimates. A Paul-Mendel random-effects meta-analysis was conducted to compare DOACs with LMWH. Mixed-treatment comparisons were computed using fixed-effect model within a Bayesian framework owing to a sparse and open network. Effect estimates were expressed as odds ratio (OR) with 95% confidence intervals (CI). Surface under the cumulative ranking curve (SUCRA) was used to assess relative treatment rankings. Results: This systematic review currently includes six RCTs with a total of 3690 patients and four unique treatment choices. Apixaban was assessed in two trials (ADAM-VTE, CARAVAGGIO), rivaroxaban in two (SELECT-D, CASTA-DIVA) and edoxaban in one (HOKUSAI-VTE). CANVAS trial reported efficacy of DOACs as a class and hence, was only included in direct comparisons with LMWH. Direct comparisons showed that DOACs as a class significantly decreased the odds of VTE recurrence (OR 0.63, 95% CI: 0.49-0.82) without significantly increasing major bleeding (OR 1.23, 95% CI: 0.84-1.79) when compared to LMWH. However, higher odds of CRNMB (OR 1.65, 95% CI: 1.18-2.31) was observed with DOACs when compared to LMWH. Mortality rates were not different between the two groups (OR: 1.03, 95% CI: 0.87-1.21). Mixed treatment comparisons showed decreased VTE recurrences with rivaroxaban (rank 1; OR 0.49, 95% CI: 0.23-0.99) and apixaban (rank 2; OR 0.58, 95% CI: 0.36-0.90) relative to LMWH (rank 4). No significant differences were observed between edoxaban (rank 3) and LMWH in terms of VTE risk reduction. Edoxaban (rank 4) increased the risk of major bleeding (OR 1.77, 95% CI: 1.05-3.15) compared to LMWH (rank 2); there were no significant differences among rivaroxaban (rank 3) apixaban (rank 1), and LMWH. Rivaroxaban (rank 4; OR 3.16; 95% CI: 1.61-6.68) and apixaban (rank 3; OR 1.51, 95% CI: 1.01-2.28) increased the risk of CRNMB compared to LMWH (rank 1). Significant net clinical benefit was observed with apixaban (rank 1; OR 0.66; 95% CI: 0.46-0.94) when compared to LMWH (rank 4). No significant differences were observed among other mixed treatment comparisons. Conclusions: Patients treated with DOACs have 31 fewer VTE events per 1000 CAT patients compared to LMWH. Amongst DOACs, apixaban offers the greatest net clinical benefit with 39 fewer VTE and MB events per 1000 patients compared to LMWH.

AbstractBackground and ObjectiveIntensive interdisciplinary pain treatment (IIPT) for youth with high impact chronic pain has been found to be effective in improving child symptoms and functioning. However, it remains unclear how these interventions impact the parents' own well‐being, as well as cognitions and behaviours which are known to influence child pain and functioning. Thus, the current study sought to determine the effect of IIPT on parent mental health, cognitions and behaviours in parents of youth attending IIPT with their child.Databases and Data TreatmentA search of the electronic databases CINAHL, Ovid EBM Reviews, Embase, Medline, APA PsychINFO, Scopus and web of Science was conducted. Studies were included if they comprised at least 10 parents of patients aged 9–22 with nonmalignant chronic pain attending an IIPT and were written in English.ResultsA random‐effects model was used to pool the standardized mean change (SMC) across seven prepost studies. At discharge, IIPT participation was associated with small to moderate improvements in direct parental outcomes (general mental health, anxiety, depression and parenting stress), a moderate improvement in pain catastrophizing and large improvements in psychological flexibility and parenting behaviours. Most improvements were maintained at follow‐up. The risk of bias of all studies was rated as serious and the certainty of the evidence as low, suggesting limited confidence in the estimates.ConclusionsAlthough parents appear to benefit from attending an IIPT with their child, RCTs are needed to substantiate the effect of these interventions on important aspects of parent well‐being and functioning.

Background: Dermatofibromas are common skin tumors that typically occur on the extremities and trunk and demonstrate benign behavior, frequent recurrences, and very rare metastasis. Facial dermatofibromas are rare and not well studied. We analyzed clinicopathologic features of facial dermatofibromas. Design: Considering the rarity of the condition, we conducted a cohort study and a systematic review. We queried medical records of a single tertiary care center for dermatofibromas from January 1, 2000, to July 1, 2021. A systematic review of multiple databases was conducted through October 27, 2021, to include studies reporting facial dermatofibromas. Random-effects meta-analysis was used to estimate pooled odds ratio and proportions with associated 95% confidence interval (CI). Results: The cohort study identified 2858 cases of dermatofibromas, of which, 23 cases from 18 patients were on the face (1%). The mean age was 52.7 ± 17.8 years. Fifty-six percent of the cases were women. The most common location was the forehead (6 cases). The mean follow-up was 54 months. Forty-four percent of the cases had subcutaneous involvement, and 39% were the cellular type. Margins were positive in 89% of the cases, recurrence rate was 22%, and no metastases were observed. The systematic review included 10 studies (119 patients). Meta-analyses showed that facial dermatofibromas were 2% of all dermatofibromas (95% CI: 1%–3%). The local recurrence rate was 14% (95% CI: 6%–26%). Facial dermatofibromas with subcutaneous involvement were more likely to recur [odds ratio 4.53 (95% CI: 1.12–18.24)]. Before histopathologic examination, clinical differential diagnosis included dermatofibromas in only 9% of the cases (95% CI: 2%–19%). Conclusion: Facial dermatofibromas are rare and are difficult to fully excise. Cellular type and subcutaneous or muscular involvement are common in these cases and tend to have higher local recurrence rate than other nonfacial dermatofibromas. Wider excisions might be necessary for complete excision.

Slow deep breathing (SDB) may help patients with acute pain. The primary aim of this systematic review and meta-analysis is to investigate the effects of SDB on acute pain. Secondary aims include investigating the effects of SDB on acute pain-related physical and emotional functioning. An a priori protocol was registered and a database search was conducted by a reference librarian. Randomized controlled trials (RCT) were eligible for inclusion and exclusion criteria included studies of SDB for non-pain indications and studies that applied SDB as a component of an encompassing intervention. The risk or bias was assessed using the Cochrane Collaboration's revised tool for assessing risk of bias in randomized trials. Meta-analysis was conducted using the random effects model. A total of 11 968 studies were screened and seven RCTs met inclusion criteria; five were judged to have low risk of bias. Meta-analysis of post-intervention pain scores demonstrated that SDB was associated with significantly lower pain scores compared with a control group, but with high levels of heterogeneity. Subgroup analyzes demonstrated that trials of burn pain were associated with a larger reduction in pain which partially explains the heterogeneity. Very low certainty evidence suggests that SDB may reduce acute pain intensity. Further research is needed to identify patients who are candidates for SDB and determine the best approach to deliver this therapy.

INTRODUCTION: Observational studies have suggested an increased risk of pancreatic ductal adenocarcinoma (PDAC) in patients with acute and chronic pancreatitis. We conducted a systematic review and meta-analysis to evaluate the magnitude of this association and summarize the published epidemiological evidence. METHODS: We searched electronic databases (MEDLINE, Embase, Web of Science, Cochrane, and Scopus) and reference lists until January 18, 2021. Studies reporting quantitative association between pancreatitis and PDAC were included and assessed for eligibility, data abstraction, and risk of bias. Standardized incidence ratios (SIRs) were pooled using the random-effects model. RESULTS: Twenty-five cohort and case-control studies met inclusion criteria. Meta-analysis of 12 chronic pancreatitis (CP) studies demonstrated an increased risk of PDAC in patients with CP (SIR: 22.61, 95% confidence interval [CI]: 14.42–35.44). This elevated risk persisted in subgroup analysis of studies that excluded patients diagnosed with PDAC within 2 years of CP diagnosis (SIR: 21.77, 95% CI: 14.43–32.720). The risk was higher in hereditary pancreatitis (SIR: 63.36, 95% CI: 45.39–88.46). The cumulative incidence rates of PDAC in CP increased with follow-up duration. Limited evidence in acute pancreatitis indicates higher PDAC risk in the subset of patients eventually diagnosed with CP. PDAC seems to be uncommon in patients with autoimmune pancreatitis, with 8 reported cases in 358 patients with autoimmune pancreatitis across 4 studies. DISCUSSION: There is an increased risk of PDAC in patients with CP, and incidence rates increase with CP disease duration. Our results indicate that PDAC surveillance may be considered in individuals with long-standing CP.

AbstractContextLymphocytic hypophysitis (LyHy) is characterized by inflammation of the pituitary and or neuroinfundibulum and is uncommon. Treatment options include observation, high-dose glucocorticoids (HD-GCs) or surgery. Optimal first-line management strategy, however, remains unknown.ObjectiveThis work aimed to assess response to first-line treatment options (observation, HD-GCs, or surgery) of clinically relevant outcomes (symptomatic, hormonal, and radiographic improvement) among patients with LyHy.MethodsA systematic review was conducted in 6 databases through 2020. Meta-analysis was conducted when feasible using a random-effects model.ResultsWe included 33 studies reporting on 591 patients (423 women, 72%) with LyHy. Improvement/resolution of anterior pituitary dysfunction was highest when HD-GCs was first-line treatment. Surgery was associated with the greatest proportion of patients who had regression on imaging. Subgroup analysis comparing HD-GCs to observation showed the odds of anterior pituitary hormone recovery (OR 3.41; 95% CI, 1.68-6.94) or radiographic regression (OR 3.13; 95% CI, 1.54-6.36) were higher with HD-GCs, but so was the need for additional forms of treatment (OR 4.37; 95% CI, 1.70-11.22). No statistically significant difference was seen in recovery of diabetes insipidus (OR 0.9; 95% CI, 0.26-3.10). Certainty in these estimates was very low.ConclusionObservation and use of HD-GCs both are successful first-line management strategies in LyHy. Although use of HD-GCs was associated with increased recovery of anterior pituitary hormone deficit, it also was associated with greater likelihood of additional treatment after withdrawal. Optimal dosing and duration of HD-GCs remains unknown.

BACKGROUND Complete removal of melanoma is a primary goal of excision, and local recurrence is one measure to evaluate the efficacy of surgical technique. OBJECTIVE To compare published local recurrence rates for melanoma treated with Mohs micrographic surgery (MMS) or staged excision versus wide local excision (WLE). METHODS AND MATERIALS Search of 6 databases identified comparative and noncomparative studies that reported local recurrence rates after MMS, staged excision, or WLE for melanoma. Random-effects meta-analysis was used to estimate odds ratios and 95% confidence interval (CI) from comparative studies and event rates from noncomparative studies. RESULTS Of the 71 studies included (16,575 patients), 12 were comparative studies (2,683 patients) and 56 were noncomparative studies (13,698 patients). Comparative studies showed increased recurrence after WLE compared with MMS or staged excision (odds ratio [OR], 2.5; 95% CI, 1.4–4.6) and compared with MMS alone (OR, 3.3; 95% CI, 1.8–5.9). Pooled data from comparative and noncomparative studies showed a local recurrence rate of 7% after WLE (95% CI, 5%–11%), 3% after staged excision (95% CI, 2%–4%), and less than 1% after MMS (95% CI, 0%–1%). Statistical heterogeneity was moderate to high. CONCLUSION Local recurrence of melanoma is significantly lower after MMS (<1%) and staged excision (3%) compared with WLE (7%).

There is no clear consensus regarding the optimal approach for secondary prophylaxis of gastric variceal bleeding (GVB) in patients with cirrhosis. We conducted a systematic review and network meta‐analysis (NMA) to compare the efficacy of available treatments. A comprehensive search of several databases from each database's inception to March 23, 2021, was conducted to identify relevant randomized controlled trials (RCTs). Outcomes of interest were rebleeding and mortality. Results were expressed as relative risk (RR) and 95% confidence interval (CI). We followed the Grading of Recommendations Assessment, Development, and Evaluation approach to rate the certainty of evidence. We included 9 RCTs with 647 patients who had histories of GVB and follow‐ups >6 weeks. A total of 9 interventions were included in the NMA. Balloon‐occluded retrograde transvenous obliteration (BRTO) was associated with a lower risk of rebleeding when compared with β‐blockers (RR, 0.04; 95% CI, 0.01‐0.26; low certainty), and endoscopic injection sclerotherapy (EIS)–cyanoacrylate (CYA) (RR, 0.18; 95% CI, 0.04‐0.77; low certainty). β‐blockers were associated with a higher risk of rebleeding compared with most interventions and with increased mortality compared with EIS‐CYA (RR, 4.12, 95% CI, 1.50‐11.36; low certainty), and EIS‐CYA + nonselective β‐blockers (RR, 5.61; 95% CI, 1.91‐16.43; low certainty). Analysis based on indirect comparisons suggests that BRTO may be the best intervention in preventing rebleeding, whereas β‐blocker monotherapy is likely the worst in preventing rebleeding and mortality. Head‐to‐head RCTs are needed to validate these results.

ObjectivePsoriatic arthritis (PsA) and ankylosing spondylitis (AS) are chronic inflammatory diseases associated with a higher risk of cardiometabolic comorbidities compared to the general population. Individual studies examining mortality in these patients have produced conflicting results. The present study was undertaken to perform a systematic review and meta‐analysis to analyze the all‐cause and cause‐specific mortality in PsA and AS from the available literature.MethodsA comprehensive database search was performed for studies reporting all‐cause or cause‐specific mortality in patients with PsA and AS compared with the general population. Pooled relative risks (RRs) were calculated using a random‐effects model.ResultsWe included 19 studies (11 of PsA, 7 of AS, 1 of both). In PsA studies, there was no increased mortality compared to the general population (RR 1.12 [95% confidence interval (95% CI) 0.96–1.30]; n = 10 studies). We found a higher all‐cause mortality in female (RR 1.19 [95% CI 1.04–1.36]) but not in male (RR 1.02 [95% CI 0.66–1.59]) PsA patients. Cardiovascular‐, respiratory‐, and infection‐specific mortality risks were significantly higher for PsA patients (RR 1.21 [95% CI 1.06–1.38], RR 3.37 [95% CI 1.30–8.72], and RR 2.43 [95% CI 1.01–5.84], respectively), but not cancer‐related mortality (RR 1.01 [95% CI 0.91–1.11]). In AS, we found a higher risk of death from all causes (RR 1.64 [95% CI 1.49–1.80]; n = 6 studies) and cardiovascular causes (RR 1.35 [95% CI 1.01–1.81]; n = 3 studies) compared to the general population. All‐cause mortality was high in both male (RR 1.56 [95% CI 1.43–1.71]) and female (RR 1.85 [95% CI 1.56–2.18]) AS patients. The included AS studies did not report mortality data for non‐cardiovascular causes.ConclusionThis systematic review and meta‐analysis showed a significantly increased risk of overall mortality in AS but not PsA. Cardiovascular‐specific mortality was higher for both PsA and AS, which emphasizes the importance of early screening and management of cardiovascular risk factors.

Abstract Background Since its emergence in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose a risk to healthcare personnel (HCP) and patients in healthcare settings. Although all clinical interactions likely carry some risk of transmission, human actions, such as coughing, and care activities, such as aerosol-generating procedures, likely have a higher risk of transmission. The rapid emergence and global spread of SARS-CoV-2 continues to create significant challenges in healthcare facilities, particularly with shortages of the personal protective equipment (PPE) used by HCP. Evidence-based recommendations for what PPE to use in conventional, contingency, and crisis standards of care continue to be needed. Where evidence is lacking, the development of specific research questions can help direct funders and investigators. The purpose of the current study was to develop evidence-based rapid guidelines intended to support HCP in their decisions about infection prevention when caring for patients with suspected or known coronavirus disease 2019 (COVID-19). Methods The Infectious Diseases Society of America (IDSA) formed a multidisciplinary guideline panel including frontline clinicians, infectious disease specialists, experts in infection control, and guideline methodologists, with representation from the disciplines of public health, medical microbiology, pediatrics, critical care medicine and gastroenterology. The process followed a rapid recommendation checklist. The panel prioritized questions and outcomes. Then a systematic review of the peer-reviewed and gray literature was conducted. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of evidence and make recommendations. Results The IDSA guideline panel agreed on 8 recommendations, including 2 updated recommendations and 1 new recommendation added since the first version of the guideline. Narrative summaries of other interventions undergoing evaluations are also included. Conclusions Using a combination of direct and indirect evidence, the panel was able to provide recommendations for 8 specific questions on the use of PPE by HCP providing care for patients with suspected or known COVID-19. Where evidence was lacking, attempts were made to provide potential avenues for investigation. There remain significant gaps in the understanding of the transmission dynamics of SARS-CoV-2, and PPE recommendations may need to be modified in response to new evidence. These recommendations should serve as a minimum for PPE use in healthcare facilities and do not preclude decisions based on local risk assessments or requirements of local health jurisdictions or other regulatory bodies.