Protocol implementation during the COVID-19 pandemic: experiences from a randomized trial of stress ulcer prophylaxis.

BACKGROUND: During the COVID-19 pandemic, many intensive care units (ICUs) halted research to focus on COVID-19-specific studies. OBJECTIVE: To describe the conduct of an international randomized trial of stress ulcer prophylaxis (Re-Evaluating the Inhibition of Stress Erosions in the ICU [REVISE]) during the pandemic, addressing enrolment patterns, center engagement, informed consent processes, data collection, a COVID-specific substudy, patient transfers, and data monitoring. METHODS: REVISE is a randomized trial among mechanically ventilated patients, comparing pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important upper gastrointestinal bleeding and the primary safety outcome of 90-day mortality. We documented protocol implementation status from March 11th 2020-August 30th 2022. RESULTS: The Steering Committee did not change the scientific protocol. From the first enrolment on July 9th 2019 to March 10th 2020 (8 months preceding the pandemic), 267 patients were enrolled in 18 centers. From March 11th 2020-August 30th 2022 (30 months thereafter), 41 new centers joined; 59 were participating by August 30th 2022 which enrolled 2961 patients. During a total of 1235 enrolment-months in the pandemic phase, enrolment paused for 106 (8.6%) months in aggregate (median 3 months, interquartile range 2;6). Protocol implementation involved a shift from the a priori consent model pre-pandemic (188, 58.8%) to the consent to continue model (1615, 54.1%, p < 0.01). In one new center, an opt-out model was approved. The informed consent rate increased slightly (80.7% to 85.0%, p = 0.05). Telephone consent encounters increased (16.6% to 68.2%, p < 0.001). Surge capacity necessitated intra-institutional transfers; receiving centers continued protocol implementation whenever possible. We developed a nested COVID-19 substudy. The Methods Centers continued central statistical monitoring of trial metrics. Site monitoring was initially remote, then in-person when restrictions lifted. CONCLUSION: Protocol implementation adaptations during the pandemic included a shift in the consent model, a sustained high consent rate, and launch of a COVID-19 substudy. Recruitment increased as new centers joined, patient transfers were optimized, and monitoring methods were adapted.

Does This Patient Have Alcohol Use Disorder?: The Rational Clinical Examination Systematic Review.

Importance: The accuracy of screening tests for alcohol use disorder (defined as a problematic pattern of alcohol use leading to clinically significant impairment or distress) requires reassessment to align with the latest definition in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5). Objective: To assess the diagnostic accuracy of screening tools in identifying individuals with alcohol use disorder as defined in the DSM-5. Data Sources and Study Selection: The databases of MEDLINE and Embase were searched (January 2013-February 2023) for original studies on the diagnostic accuracy of brief screening tools to identify alcohol use disorder according to the DSM-5 definition. Because diagnosis of alcohol use disorder does not include excessive alcohol use as a criterion, studies of screening tools that identify excessive or high-risk drinking among younger (aged 9-18 years), older (aged ≥65 years), and pregnant persons also were retained. Data Extraction and Synthesis: Sensitivity, specificity, and likelihood ratios (LRs) were calculated. When appropriate, a meta-analysis was performed to calculate a summary LR. Results: Of 4303 identified studies, 35 were retained (N = 79 633). There were 11 691 individuals with alcohol use disorder or a history of excessive drinking. Across all age categories, a score of 8 or greater on the Alcohol Use Disorders Identification Test (AUDIT) increased the likelihood of alcohol use disorder (LR, 6.5 [95% CI, 3.9-11]). A positive screening result using AUDIT identified alcohol use disorder better among females (LR, 6.9 [95% CI, 3.9-12]) than among males (LR, 3.8 [95% CI, 2.6-5.5]) (P = .003). An AUDIT score of less than 8 reduced the likelihood of alcohol use disorder similarly for both males and females (LR, 0.33 [95% CI, 0.20-0.52]). The abbreviated AUDIT-Consumption (AUDIT-C) has sex-specific cutoff scores of 4 or greater for males and 3 or greater for females, but was less useful for identifying alcohol use disorder (males: LR, 1.8 [95% CI, 1.5-2.2]; females: LR, 2.0 [95% CI, 1.8-2.3]). The AUDIT-C appeared useful for identifying measures of excessive alcohol use in younger people (aged 9-18 years) and in those older than 60 years of age. For those younger than 18 years of age, the National Institute on Alcohol Abuse and Alcoholism age-specific drinking thresholds were helpful for assessing the likelihood of alcohol use disorder at the lowest risk threshold (LR, 0.15 [95% CI, 0.11-0.21]), at the moderate risk threshold (LR, 3.4 [95% CI, 2.8-4.1]), and at the highest risk threshold (LR, 15 [95% CI, 12-19]). Among persons who were pregnant and screened within 48 hours after delivery, an AUDIT score of 4 or greater identified those more likely to have alcohol use disorder (LR, 6.4 [95% CI, 5.1-8.0]), whereas scores of less than 2 for the Tolerance, Worried, Eye-Opener, Amnesia and Cut-Down screening tool and the Tolerance, Annoyed, Cut-Down and Eye-Opener screening tool identified alcohol use disorder similarly (LR, 0.05 [95% CI, 0.01-0.20]). Conclusions and Relevance: The AUDIT screening tool is useful to identify alcohol use disorder in adults and in individuals within 48 hours postpartum. The National Institute on Alcohol Abuse and Alcoholism youth screening tool is helpful to identify children and adolescents with alcohol use disorder. The AUDIT-C appears useful for identifying various measures of excessive alcohol use in young people and in older adults.

Gallstone Disease and Its Association With Nonalcoholic Fatty Liver Disease, All-Cause and Cause-Specific Mortality.

BACKGROUND & AIMS: Presence of gallstone disease may influence outcomes in patients with nonalcoholic fatty liver disease (NAFLD). We studied the impact of gallstone disease on mortality in individuals with and without NAFLD. METHODS: Prospective cohort study used the Third National Health and Nutrition Examination Survey (1988-1994) with mortality data through 2015. Gallstone disease was defined as ultrasonographic evidence of gallstones or absence of the gallbladder (prior cholecystectomy). NAFLD was defined using standardized ultrasonographic criteria. RESULTS: Gallstone disease and cholecystectomy were independently associated with NAFLD (odds ratio [OR], 1.75; 95% confidence interval [CI], 1.43-2.15 for gallstone disease and OR, 2.77; 95% CI, 2.01-3.83 for cholecystectomy compared with no gallstone disease). During the median follow-up of 23 years, gallstone disease was associated with a higher risk of all-cause mortality (hazard ratio [HR], 1.19; 95% CI, 1.05-1.37) and cause-specific mortality. Gallstone disease was associated with a higher risk of all-cause mortality in non-NAFLD sub-cohort (HR, 1.42; 95% CI, 1.23-1.64) but not in NAFLD (HR, 1.03; 95% CI, 0.87-1.22). Gallstone disease was associated with a higher risk of cardiovascular-related (HR, 1.40; 95% CI, 1.10-1.78) and cancer-related (HR, 1.71; 95% CI, 1.18-2.48) mortality in non-NAFLD sub-cohort. Gallstone disease was associated with increased cardiovascular mortality (HR, 1.36; 95% CI, 1.05-1.77) in NAFLD. CONCLUSIONS: Gallstone disease is an independent risk factor for NAFLD, but gallstone disease is not associated with all-cause mortality in individuals with NAFLD. Screening for gallstone disease in individuals at risk for developing NAFLD may help with risk stratification for all-cause mortality related to gallstone disease.

Enhancing end of life care on general internal medical wards: the 3 Wishes Project.

BACKGROUND: Initially developed in the intensive care unit (ICU) at St. Joseph's Healthcare Hamilton (SJHH) the 3 Wishes Project (3WP) provides personalized, compassionate care to dying patients and their families. The objective of this study was to develop and evaluate 3WP expansion strategies for patients cared for on General Internal Medicine (GIM) wards in our hospital. METHODS: From January 2020-November 2021, we developed a phased, multicomponent approach for program expansion. We enrolled patients on the GIM wards who had a high probability of dying in hospital, then elicited, implemented, and documented wishes for them or their families. Data were analyzed descriptively. RESULTS: From March 2020 to November 2020, we implemented staff education and engagement activities, created an Expansion Coordinator position, held strategic consultations, and offered enabling resources. From March 2020 to November 2021, we enrolled 62 patients and elicited 281 wishes (median [1st, 3rd quartiles] 4 [4, 5] wishes/patient). The most common wish categories were personalizing the environment (67 wishes, 24%), rituals and spiritual support (42 wishes, 15%), and facilitating connections (39 wishes, 14%). The median [1st, 3rd] cost/patient was $0 [0, $10.00] (range $0 to $86); 91% of wishes incurred no cost to the program. CONCLUSIONS: The formal expansion of the 3WP on GIM wards has been successful despite COVID-19 pandemic disruptions. While there is still work ahead, these data suggest that implementing the 3WP on the GIM wards is feasible and affordable. Increased engagement of the clinical team during the pandemic suggests that it is positively received.

Trends in Etiology-based Mortality From Chronic Liver Disease Before and During COVID-19 Pandemic in the United States.

BACKGROUND & AIMS: During the global coronavirus disease 2019 (COVID-19) pandemic, patients with pre-existing chronic liver disease may represent a vulnerable population. We studied the etiology-based temporal trends in mortality of chronic liver disease and the underlying cause of death in the United States before and during the COVID-19 pandemic. METHODS: Population-based analyses were performed on United States national mortality records (2017-2020). Temporal trends in quarterly age-standardized mortality were obtained by joinpoint analysis with estimates of quarterly percentage change (QPC). RESULTS: Quarterly age-standardized all-cause mortality due to alcohol-related liver disease (ALD) initially increased at a quarterly rate of 1.1% before the COVID-19 pandemic, followed by a sharp increase during the COVID-19 pandemic at a quarterly rate of 11.2%. Likewise, steady increase in mortality of nonalcoholic fatty liver disease before the COVID-19 pandemic (QPC, 1.9%) accelerated during the COVID-19 pandemic (QPC, 6.6%). Although ALD-related mortality increased steeply compared with viral hepatitis-related mortality during the COVID-19 pandemic, the proportion of mortality due to COVID-19 among individuals with ALD was the lowest at 2.5%; more than 50% lower than viral hepatitis. The significant decline in all-cause mortality due to viral hepatitis before the COVID-19 pandemic plateaued during the COVID-19 pandemic due to increase in COVID-19-related mortality in individuals with viral hepatitis. Mortality due to cirrhosis increased markedly during the COVID-19 pandemic, mainly attributable to ALD. CONCLUSION: All-cause mortality for ALD and nonalcoholic fatty liver disease rapidly accelerated during the COVID-19 pandemic compared with the pre-COVID-19 era. There has been a significant decline in viral hepatitis; however, a significant increase in COVID-related death in this population.

Trends in the Prevalence of Hepatitis C Virus Infection based on the Insurance Status in the United States from 2013 to 2018.

BACKGROUND & AIMS: With the recent improvement in the treatment of hepatitis C virus (HCV) infection, a better understanding of the infection burden is needed. We aimed to (a) estimate the trends in the national prevalence of HCV infection based on the type of health insurance coverage and (b) identify at-risk populations for HCV infection in the United States (US) general population. METHODS: Population-based analyses using the National Health and Nutrition Examination Survey (2013-2018) were performed with a focus on HCV infection. We analysed the prevalence of HCV infection based on the health insurance status before the direct-acting antiviral (DAA) era (2013-2014) and during the DAA era (2015-2018). RESULTS: The age-adjusted prevalence of active HCV infection (HCV RNA [+]) was 0.92% (95% confidence interval, 0.71%-1.19%) in the US non-institutionalized civilian population. Although the prevalence of active HCV infection has remained stable, the prevalence of resolved HCV infection has increased after the introduction of DAA. In terms of health insurance coverage, the prevalence of active HCV infection decreased, and the prevalence of resolved HCV infection increased among individuals who had health insurance, especially private health insurance. The independent risk factors of active HCV infection were 40-69 years group, male, less than high school education, unmarried, below poverty status, being born in the US, history of blood transfusion and not having private health insurance. CONCLUSION: The burden of active HCV infection has decreased among individuals who had health insurance, especially private health insurance, during the DAA era.

Changing trends in aetiology-based hospitalizations with end-stage liver disease in the United States from 2016 to 2019.

BACKGROUNDS AND AIMS: A potent and safe antiviral agent may impact chronic hepatitis C (HCV)-related end-stage liver disease (ESLD). We assess aetiology-based hospitalizations for ESLD in the United States, 2016-2019. METHODS: We utilized the National Inpatient Sample (NIS) from 2016 to 2019. We defined ESLD as either decompensated cirrhosis or hepatocellular carcinoma, criteria obtained from the International Classification of Diseases, Tenth Revision. RESULTS: National hospitalization rates for non-alcoholic fatty liver disease (NAFLD) increased significantly from 67.1/100 000 persons in 2016 to 93.6 in 2019 with an average annual percentage change (AAPC) of 12.1%, while chronic hepatitis C (HCV) decreased significantly from 71.2/100 000 persons in 2016 to 58.5 in 2019 (-6.5% AAPC). Hospitalizations for ESLD in alcohol-related liver disease (ALD) increased as well. CONCLUSIONS: Hospitalization rates for NAFLD- and ALD-related ESLD increased steadily, while those for HCV-related ESLD decreased during the direct-acting antivirals era.

Experiences and disease self-management in individuals living with chronic kidney disease: qualitative analysis of the National Kidney Foundation's online community.

BACKGROUND: Self-management of chronic kidney disease (CKD) is one of the keys in improving CKD outcomes and quality of life. There has been an increased use of online health communities to share the experiences of those living with CKD. By analyzing the CKD online forum data, this study aims to: 1) understand the experiences and challenges of individuals living with CKD, and 2) explore how online communities may help CKD patients in improving CKD self-management. METHODS: Publicly available posts of peer interactions on the National Kidney Foundation's online community for individuals affected by CKD were extracted in April 2021 using computer programming. A total of 20,436 posts were collected, of which 400 posts were analyzed using inductive thematic analysis, and saturation was reached. Two researchers coded each post independently, and discrepancies were discussed to reach consensus. RESULTS: The analysis identified seven themes: 1) Dynamics of CKD status, 2) CKD comorbidities, 3) Managing CKD and symptoms, 4) Life participation and outlook; 5) Navigating healthcare and clinical needs, 6) Medical tests and results; and 7) Support on the forum. The results revealed that comorbidities were common in CKD patients and early-stage CKD was not communicated in a timely manner to patients by the health care community; living with CKD challenged both CKD and caregivers; some common challenges included but were not limited to the management of a diet for CKD and co-morbidities (especially co-morbid diabetes), CKD dynamics and symptoms, and fear of/ways to prevent progression. Individuals living with CKD primarily used the online forum to share and seek information and emotional support for managing CKD (including co-morbidities). CONCLUSIONS: Challenges of living with CKD were found not only in those with advanced kidney disease and those on dialysis, but also in those with early and middle stages. Information and emotional support from the online forum serve as a platform to empower CKD individuals with the knowledge, skills and confidence for CKD self-management. Proactive and innovative strategies with a combination of virtual and real settings to improve self-management for individuals with all-stage CKD needs to be explored and tailored.

Clinician Perspectives on Caring for Dying Patients During the Pandemic : A Mixed-Methods Study.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has affected the hospital experience for patients, visitors, and staff. OBJECTIVE: To understand clinician perspectives on adaptations to end-of-life care for dying patients and their families during the pandemic. DESIGN: Mixed-methods embedded study. (ClinicalTrials.gov: NCT04602520). SETTING: 3 acute care medical units in a tertiary care hospital from 16 March to 1 July 2020. PARTICIPANTS: 45 dying patients, 45 family members, and 45 clinicians. INTERVENTION: During the pandemic, clinicians continued an existing practice of collating personal information about dying patients and "what matters most," eliciting wishes, and implementing acts of compassion. MEASUREMENTS: Themes from semistructured clinician interviews that were summarized with representative quotations. RESULTS: Many barriers to end-of-life care arose because of infection control practices that mandated visiting restrictions and personal protective equipment, with attendant practical and psychological consequences. During hospitalization, family visits inside or outside the patient's room were possible for 36 patients (80.0%); 13 patients (28.9%) had virtual visits with a relative or friend. At the time of death, 20 patients (44.4%) had a family member at the bedside. Clinicians endeavored to prevent unmarked deaths by adopting advocacy roles to "fill the gap" of absent family and by initiating new and established ways to connect patients and relatives. LIMITATION: Absence of clinician symptom or wellness metrics; a single-center design. CONCLUSION: Clinicians expressed their humanity through several intentional practices to preserve personalized, compassionate end-of-life care for dying hospitalized patients during the SARS-CoV-2 pandemic. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research and Canadian Critical Care Trials Group Research Coordinator Fund.

Metabolic dysfunction-associated fatty liver disease is associated with increased all-cause mortality in the United States.

BACKGROUND & AIMS: Recently, international experts proposed redefining non-alcoholic fatty liver disease (NAFLD) as metabolic dysfunction-associated fatty liver disease (MAFLD), based on modified criteria. It is suspected that outcomes such as mortality may differ for these clinical entities. We studied the impact of MAFLD and NAFLD on all-cause and cause-specific mortality in US adults. METHODS: We analyzed data from 7,761 participants in the Third National Health and Nutrition Examination Survey and their linked mortality through 2015. NAFLD was diagnosed by ultrasonographic evidence of hepatic steatosis without other known liver diseases. MAFLD was defined based on the criteria proposed by an international expert panel. The Cox proportional hazard model was used to study all-cause mortality and cause-specific mortality between MAFLD and NAFLD, with adjustments for known risk factors. RESULTS: During a median follow-up of 23 years, individuals with MAFLD had a 17% higher risk of all-cause mortality (hazard ratio [HR] 1.17; 95% CI 1.04-1.32). Furthermore, MAFLD was associated with a higher risk of cardiovascular mortality. NAFLD per se did not increase the risk of all-cause mortality. Individuals who met both definitions had a higher risk of all-cause mortality (HR 1.13, 95% CI 1.00-1.26), while individuals who met the definition for MAFLD but not NAFLD had a 1.7-fold higher risk of all-cause mortality (HR 1.66, 95% CI 1.19-2.32). Estimates for all-cause mortality were higher for those with advanced fibrosis and MAFLD than for those with advanced fibrosis and NAFLD. CONCLUSIONS: In this US population-based study, MAFLD was associated with an increased risk of all-cause mortality, while NAFLD demonstrated no association with all-cause mortality after adjusting for metabolic risk factors. LAY SUMMARY: Our findings provide further support for the idea that non-alcoholic fatty liver disease (NAFLD) is a part of a broader multi-system disease that also includes obesity, diabetes, high blood pressure, and high cholesterol. Therefore, re-defining NAFLD as metabolic dysfunction-associated fatty liver disease (MAFLD) may help improve our understanding of predictors that increase the risk of death.

Management of Cardiometabolic Complications in Patients With Nonalcoholic Fatty Liver Disease: A Review of the Literature With Recommendations.

Nonalcoholic fatty liver disease (NAFLD) comprises a spectrum of liver conditions characterized by significant lipid deposition within hepatocytes. As an overarching diagnosis, NAFLD contains a continuum of progressive liver diseases ranging from isolated liver steatosis to necroinflammatory states leading to end-stage liver disease. Nonalcoholic fatty liver and nonalcoholic steatohepatitis are distinguished by their histologic patterns, with the former exhibiting steatosis without fibrosis or inflammation. This important distinction provides clinicians a timeline within the NAFLD staging to target appropriate interventions against modifiable risk factors. NAFLD is likely formed in response to metabolic imbalances that damage the livers adaptive capacity. Metabolic conditions leading to steatosis mirror common cardiovascular risk factors, including dyslipidemia, diabetes mellitus, and obesity. Acknowledging the common risk factors for development and progression of NAFLD, it is unsurprising the first-line management focuses on the treatment of metabolic syndrome with an emphasis on weight reduction in obese populations. The purpose of this review is to provide a detailed summary of the literature as well as outline the current treatment recommendations for patients with NAFLD with a detailed focus on pharmacologic antiobesity interventions.

Gender and Racial Differences in Hospitalizations for Primary Biliary Cholangitis in the USA.

BACKGROUND/AIM: The prevalence, characteristics, burden and trends of primary biliary cholangitis (PBC) hospitalizations in the USA remain unclear. METHOD: We identified primary PBC hospitalizations from the National Inpatient Sample (NIS) 2007 through 2014 using ICD-9-CM codes. We calculated the rates and trends of hospitalization for PBC per 100,000 US population among each gender (males and females) and racial categories (Whites, Blacks, Hispanics and other racial minorities), and measured the predictors of hospitalization, and of mortality, charges and length of stay (LOS) among PBC hospitalizations. RESULT: There were 8460 (weighted: 41,191) PBC hospitalizations between 2007 and 2014. The mean national PBC hospitalization rate was 2.2 cases per 100,000 population (2.2/100,000), increasing from 1.7/100,000 (2007) to 2.5/100,000 (2014). From 2007 to 2014, the in-hospital mortality and LOS were unchanged while the charges increased from $65,993 to $73,093 ($225 million to $447 million overall expenses). Compared to Whites, the PBC hospitalization rate was 12% higher among Hispanics (RR: 1.12 [1.09-1.16]), 53% lower in Blacks (RR: 0.47 [0.45-0.49]) and 5% lower among other racial minorities (0.95 [0.91-0.99]). The rate was higher among females (RR:4.02 [3.93-4.12]) compared to males. On multivariate analysis, Blacks and other racial minorities, respectively, had higher odds of mortality (AOR: 1.47 [1.03-2.10] and 1.33 [0.96-1.84]), while other racial minorities had longer LOS (7.0 vs. 5.6 days) and higher hospital charges ($48,984 vs. $41,495) when compared to Whites. CONCLUSION: The hospitalization rate and burden of PBC in the USA have increased disproportionately among females and Hispanics with higher mortality in Blacks.

A meta-analysis of level I evidence comparing tenotomy vs tenodesis in the management of long head of biceps pathology.

BACKGROUND: The ideal surgical treatment of long head of biceps pathology is unclear. This review evaluates Level I studies comparing tenotomy and tenodesis for the management of long head of biceps pathology. METHODS: Medline, EMBASE, and the Cochrane Library databases were searched from database inception though April 17, 2020. Clinical outcomes including Constant-Murley Shoulder Outcome Score, American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) shoulder score, pain on visual analog scale, postoperative strength, and Popeye deformity were evaluated. Dichotomous outcomes were pooled into relative risk ratios whereas continuous outcomes were pooled into weighted mean differences using random effects meta-analysis. RESULTS: A total of 5 studies (227 tenotomy and 227 tenodesis patients) met the final inclusion criteria. Postoperative improvement across all outcomes was observed regardless of surgical treatment. Pooled analysis demonstrated no statistically significant difference for Constant-Murley Shoulder Outcome Score, ASES, pain, or flexion strength. Tenodesis was superior to tenotomy in reducing the risk of Popeye deformity (relative risk ratio 3.07, confidence interval 1.87, 5.02; P < .001). CONCLUSION: Tenotomy and tenodesis of the long head of the biceps results in comparable postoperative clinical and functional outcomes. Tenodesis is superior to tenotomy in preventing Popeye deformity postoperatively.

Assessing acceptability and patient experience of a behavioral lifestyle intervention using fitbit technology in older adults to manage type 2 diabetes amid COVID-19 pandemic: A focus group study.

Type 2 diabetes (T2D) contributes to reduced quality of life in older adults, especially in those with comorbidities such as being overweight or obese. Personal fitness technology (Fitbit ®) has the potential to improve the management of T2D. Using a semi-structured interview guide, focus groups were conducted to explore participants' acceptability and experiences following a behavioral lifestyle intervention that integrated Fitbit in overweight/obese older adults with T2D amid the COVID-19 pandemic which began during the time of this study. Focus group transcripts were transcribed and analyzed using thematic analysis. Eighteen (18) of the 20 participants completed the program and focus group interviews. Overall, we observed high acceptability of the program, and participants reported favorable experiences such as increased knowledge of health behaviors, improved diabetes management, and improved quality of life following the behavioral lifestyle intervention, even under stressful life circumstances from COVID-19.

Increasing Trends in Transplantation of HCV-Positive Livers Into Uninfected Recipients.

The introduction of direct-acting antiviral (DAA) agents and the opioid epidemic have resulted in an increased interest in liver transplantation (LT) of organs from donors with hepatitis C virus (HCV)-related viremia.1 In March of 2015, the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) implemented a policy to perform HCV nucleic acid testing (NAT) in all HCV-seropositive donors. An open-label, single-center experience with 10 patients using a multistep informed consent reported successful transplantation of HCV-seropositive viremic (HCV-V) kidneys into HCV-seronegative recipients.2 Subsequently, a case was reported in which an HCV-V liver was transplanted into a HCV-seronegative recipient.3 In collaboration with OPTN/UNOS, we identified cases in which HCV-V deceased donor livers were transplanted into HCV-seronegative recipients.

Influence of Graft Source on Postoperative Activity and Joint Laxity in Posterior Cruciate Ligament Reconstruction: A Systematic Review.

PURPOSE: To compare the clinical and functional outcomes of allograft and autograft reconstruction in patients with posterior cruciate ligament (PCL) deficiency. METHODS: The MEDLINE, Embase, and Cochrane Library databases were used to identify all relevant articles. Clinical outcomes including International Knee Documentation Committee, Tegner, and Lysholm scores; joint laxity; and posterior tibial displacement were evaluated. RESULTS: Among the 145 unique articles identified during the title screening, 25 studies published between 2002 and 2016 with a combined population of 900 patients were deemed eligible for inclusion in the review. Of the 900 patients, 603 were treated with autograft and 297 were treated with allograft PCL reconstruction. Five of the included studies directly compared autograft and allograft PCL reconstruction. Most studies found postoperative functional outcomes and joint laxity to improve postoperatively regardless of graft source. With only 1 exception, the included comparative studies found no significant postoperative difference in any of the functional outcome scores between patients treated with allograft and those treated with autograft. Two comparative studies found autograft reconstruction to result in significantly less posterior laxity than in the allograft group, whereas 2 comparative studies found no significant difference in posterior laxity between the 2 groups. CONCLUSIONS: PCL reconstruction results in improved functional outcome scores and joint laxity regardless of graft source. Current studies suggest there is no significant difference in postoperative functional outcomes between patients treated with autograft and those treated with allograft. Patients treated with autograft have donor-site morbidity that is not associated with allograft reconstruction. Some evidence suggests that autograft reconstruction may result in reduced posterior laxity relative to allograft reconstruction. The magnitude of this finding, however, may not be clinically significant. Our review found that decision making based on the current literature is at high risk of potential bias. LEVEL OF EVIDENCE: Level IV, systematic review of Level I to IV studies.

Digital Rectal Examination for Prostate Cancer Screening in Primary Care: A Systematic Review and Meta-Analysis.

PURPOSE: Although the digital rectal examination (DRE) is commonly performed to screen for prostate cancer, there is limited data to support its use in primary care. This review and meta-analysis aims to evaluate the diagnostic accuracy of DRE in screening for prostate cancer in primary care settings. METHODS: We searched MEDLINE, Embase, DARE (Database of Abstracts of Reviews of Effects), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) from their inception to June 2016. Six reviewers, in pairs, independently screened citations for eligibility and extracted data. Pooled estimates were calculated for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of DRE in primary care settings using an inverse-variance meta-analysis. We used QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) and GRADE (Grades of Recommendation Assessment, Development, and Evaluation) guidelines to assess study risk of bias and quality. RESULTS: Our search yielded 8,217 studies, of which 7 studies with 9,241 patients were included after the screening process. All patients analyzed underwent both DRE and biopsy. Pooled sensitivity of DRE performed by primary care clinicians was 0.51 (95% CI, 0.36-0.67; I2 = 98.4%) and pooled specificity was 0.59 (95% CI, 0.41-0.76; I2 = 99.4%). Pooled PPV was 0.41 (95% CI, 0.31-0.52; I2 = 97.2%), and pooled NPV was 0.64 (95% CI, 0.58-0.70; I2 = 95.0%). The quality of evidence as assessed with GRADE was very low. CONCLUSION: Given the considerable lack of evidence supporting its efficacy, we recommend against routine performance of DRE to screen for prostate cancer in the primary care setting.

An unusual case of infective pneumocephalus: case report of pneumocephalus exacerbated by continuous positive airway pressure.

BACKGROUND: Pneumocephalus, illustrated by air in the cranial vault is relatively infrequent and generally associated with neurosurgery, trauma, meningitis and barotrauma. However cases of spontaneous non-traumatic pneumocephalus remain rare. While the relationship between continuous positive airway pressure (CPAP) and atraumatic pneumocephalus has been previously reported, to our knowledge the rare presentation associated with sinus wall osteomyelitis has never been described. We summarize here the case of a 67-year-old woman's acute presentation of Streptococcus salvarius infection after a sudden drop in her consciousness. CASE PRESENTATION: The patient was brought to hospital by family reporting a one week history of sudden deterioration, cognitive decline, and lethargy. The patient presented with reduced arousal, cognitive function (Glasgow Coma Scale: 10, Abbreviated Mental Test Score:CS, 0 AMTS), and no history of trauma. Computed Tomography (CT) imaging was ordered and identified a significant pneumocephalus with no cranial defect. Further investigations acknowledged possible sinus or middle ear disease, which was highlighted by the discovery of S. salivarius by polymerase chain reaction (PCR) and potentially exacerbated by the use of nocturnal continuous positive airway pressure (CPAP). The patient made a complete recovery by eliminating likely causative factors and long term regimental antibiotics administration. CONCLUSION: This case highlights a rare neurological presentation of S. salivarius infection with a mixed aetiology of spontaneous pneumocephalus. This case features an atypical complication associated with CPAP use, and to our knowledge is the first case to be associated with sinus wall osteomyelitis. Recognition of the clinical features and risk factors for spontaneous pneumocephalus -while rare-serve to broaden our clinical index of suspicion when presented with patients experiencing neurological deficit. Information from this case may also aid in improving prevention, early diagnosis, and future management.

When is a meta-analysis conclusive? A guide to Trial Sequential Analysis with an example of remote ischemic preconditioning for renoprotection in patients undergoing cardiac surgery.

Regardless of whether a randomized trial finds a statistically significant effect for an intervention or not, readers often wonder if the trial was large enough to be conclusive. To answer this question, we can estimate the required sample size for a trial by considering how commonly the outcome occurs, the smallest effect of clinical importance and the acceptable risk of falsely detecting or rejecting that effect. But when is a meta-analysis conclusive? We explain and illustrate the interpretation of Trial Sequential Analysis (TSA), a method increasingly used to answer this question. We conducted a conventional meta-analysis which suggested that, in adults undergoing cardiac surgery, remote ischemic preconditioning does not provide a statistically significant reduction in acute kidney injury (AKI) [12 trials, 4230 patients; relative risk 0.87 (95% confidence interval 0.74-1.02); P = 0.08; I2= 35%] or the risk of receiving acute dialysis [5 trials, 2111 patients; relative risk 1.15 (95% confidence interval 0.42-3.19); P = 0.78; I2 = 59%]. TSA demonstrates that as little as a 20% relative risk reduction in AKI is unlikely. Reliably finding effects on acute dialysis and smaller effects on AKI would require much more evidence. Notably, conventional meta-analyses conducted at one of the two earlier time points may have prematurely declared a statistically significant reduction in AKI, even though at no point in the TSA was there sufficient evidence to support such an effect. With this and other examples, we demonstrate that the TSA can prevent premature conclusions from meta-analyses.