Publications by authors named "Brittany B Dennis"

52 Publications

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

Liver Int 2021 Nov 24. Epub 2021 Nov 24.

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, United States.

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 (1) estimate the trends in the national prevalence of HCV infection based on the type of health insurance coverage and (2) 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 analyzed 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 [CI], 0.71%-1.19%) in the US non-institutionalized civilian population. While 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.
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http://dx.doi.org/10.1111/liv.15113DOI Listing
November 2021

Sex-specific Risk Factors and Health Disparity Among Hepatitis C Positive Patients Receiving Pharmacotherapy for Opioid Use Disorder: Findings From a Propensity Matched Analysis.

J Addict Med 2021 Nov 18. Epub 2021 Nov 18.

Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada (BBD, LJM, AW, TO); Department of Family Medicine, Michael DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada (LN); Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford University, CA (BBD, GC, DK, AA); Department of Medicine, University of British Columbia, Vancouver Costal Health, Vancouver, Canada (DA); Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada (NS, AH, CC, AD, BP, ZS); Department of Health Research Evaluation and Impact (Formerly Department of Clinical Epidemiology and Biostatistics), McMaster University, Hamilton, ON, Canada (LN, AW, LT, ZS); Northern Ontario School of Medicine, Sudbury ON, Canada (DCM); Canadian Addiction Treatment Centres, Markham ON, Canada (DCM); Guys and St. Thomas Hospital NHS Trust, London, United Kingdom (MB); Centre for Evaluation of Medicine, Hamilton, ON, Canada (LT); System Linked Research Unit, Hamilton, ON, Canada (LT); Population Genomics Program, Chanchlani Research Centre, McMaster University, Hamilton, ON, Canada (ZS).

Background: The incidence of opioid-related fatality has reached unparalleled levels across North America. Patients with comorbid hepatitis C virus (HCV) remain the most vulnerable and difficult to treat. Considering the unique challenges associated with this population, we aimed to re-examine the impact of HCV on response to medication assistant treatment for opioid use disorder and establish sex-specific risk factors affecting care.

Methods: This study employs a multi-center prospective cohort design, with 1-year follow-up. Patients aged ≥18, receiving methadone for opioid use disorder were recruited from a network of out-patient opioid addiction treatment centers across Southern Ontario, Canada. Patients with ≥50% positive opioid urine screens over 1 year of follow-up were classified as poor responders. The prognostic impact of HCV on response was established using a propensity score matched analysis. Sex-specific regression models were constructed to evaluate risk factors for treatment response.

Results: Among participants eligible for inclusion (n = 1234), HCV was prevalent in 25% (n = 307). HCV patients exhibited significantly higher rates of high-risk opioid consumption patterns 35.29% (standard deviation 0.478). Sex-specific examination revealed females with HCV incur a 2 times increased risk for high-risk opioid consumption behaviors (female odds ratio: 1.95, 95% confidence interval 1.23, 3.10; P = 0.01).

Conclusions: Findings from this study establish the link between HCV and poor treatment response, with differentially higher risk among female patients. In light of the high potential for overdose among this population, concerted efforts are required for distinguishing the source for sex-based disparities, in addition to establishing trauma and gender informed treatment protocols.
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http://dx.doi.org/10.1097/ADM.0000000000000937DOI Listing
November 2021

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

J Clin Gastroenterol 2021 10;55(9):747-756

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA.

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.
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http://dx.doi.org/10.1097/MCG.0000000000001555DOI Listing
October 2021

New hope for hepatitis C virus: Summary of global epidemiologic changes and novel innovations over 20 years.

World J Gastroenterol 2021 Aug;27(29):4818-4830

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94304, United States.

Hepatitis C virus (HCV) is a global health concern associated with significant morbidity and mortality. Before the approval of second-generation direct-acting antiviral agents (DAAs), interferon therapy and liver transplantation constituted the mainstay of treatment. The introduction of well-tolerated oral DAAs in late 2013 has revolutionized HCV management with over 95% cure rates. The predominance of HCV-related liver transplantations has declined following the widespread approval of DAAs. Despite the unparallel efficacy observed among these novel therapies, pharmaceutical costs continue to limit equitable access to healthcare and likely contribute to the differential HCV infection rates observed globally. To reduce the burden of disease worldwide, essential agenda items for all countries must include the prioritization of integrated care models and access to DAAs therapies. Through transparent negotiations with the pharmaceutical industry, the consideration for compassionate release of medications to promote equitable division of care is paramount. Here we provide a literature review of HCV, changes in epidemiologic trends, access issues for current therapies, and global inequities in disease burden.
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http://dx.doi.org/10.3748/wjg.v27.i29.4818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371499PMC
August 2021

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

J Hepatol 2021 Dec 8;75(6):1284-1291. Epub 2021 Aug 8.

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, 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.
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http://dx.doi.org/10.1016/j.jhep.2021.07.035DOI Listing
December 2021

Community implementation of the 3 Wishes Project: an observational study of a compassionate end-of-life care initiative for critically ill patients.

CMAJ Open 2021 Jul-Sep;9(3):E757-E764. Epub 2021 Jul 20.

Department of Critical Care (Reeve, Dechert, Longo, Scholes, Arthur), Brantford General Hospital, Brantford, Ont.; Department of Medicine (Dennis, Cook), McMaster University, Hamilton, Ont.; Department of Health Research Methods, Evaluation, and Impact (Dennis, Heels-Ansdell, Clarke, Cook), McMaster University, Hamilton, Ont.; Department of Critical Care (Dechert, Clarke, Cook), St. Joseph's Healthcare Hamilton, Ont.

Background: The 3 Wishes Project (3WP) promotes a personalized dying experience by eliciting and facilitating individualized terminal wishes for patients, families and the clinicians caring for them. We aimed to evaluate the adaptability of the 3WP to a community intensive care unit (ICU), and to describe the patients cared for with this palliative approach, as well as local implementation strategies.

Methods: The 3WP was implemented in a 15-bed community hospital ICU in southern Ontario from 2017 to 2019. In this observational, descriptive study, we invited adult patients (≥ 18 yr) whose risk of death was deemed to be 95% or greater by the attending physician, or patients undergoing withdrawal of life-support to participate. We abstracted patient data from medical records, as well as the type, timing and cost of each wish, which person or service made and facilitated each wish, and if and why wishes were completed or not. We summarized data both narratively and quantitatively.

Results: The 3WP helped to realize 479 (99.2%) of 483 terminal wishes for 101 dying patients. This initiative was introduced as an interprofessional intervention and championed by nursing staff who were responsible for most patient enrolment and wish facilitation. Wishes included humanizing the ICU environment for the patient with belongings and blankets, musical performances, smudging and bathing ceremonies, and keepsakes. The cost was $5.39 per patient (standard deviation $22.40), with 430 (89.8%) wishes incurring no cost. Wishes made directly by patients accounted for 30 (6.2%) of wishes; those from family members and ICU staff accounted for 236 (48.9%) and 238 (49.3%) of wishes, respectively. The program comforted patients and their loved ones, motivating clinicians to sustain this end-of-life intervention.

Interpretation: We documented successful implementation of the 3WP in a community hospital, showing program adaptability and uptake outside of academic centres at relatively low cost. The lack of strict protocolization and personalized design of this intervention underscores its inherent flexibility, with potential to promote individualized end-of-life care in nonacademic hospital wards, homes or hospice.
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http://dx.doi.org/10.9778/cmajo.20200273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313093PMC
August 2021

Are patients' goals in treatment associated with expected treatment outcomes? Findings from a mixed-methods study on outpatient pharmacological treatment for opioid use disorder.

BMJ Open 2021 01 12;11(1):e044017. Epub 2021 Jan 12.

Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, Ontario, Canada

Objectives: Existing methods of measuring effectiveness of pharmacological treatment for opioid use disorder (OUD) are highly variable. Therefore, understanding patients' treatment goals is an integral part of patient-centred care. Our objective is to explore whether patients' treatment goals align with a frequently used clinical outcome, opioid abstinence.

Design: Triangulation mixed-methods design.

Setting And Participants: We collected prospective data from 2030 participants who were receiving methadone or buprenorphine-naloxone treatment for a diagnosis of OUD in order to meet study inclusion criteria. Participants were recruited from 45 centrally-managed outpatient opioid agonist therapy clinics in Ontario, Canada. At study entry, we asked, 'What are your goals in treatment?' and used NVivo software to identify common themes.

Primary Outcome Measure: Urine drug screens (UDS) were collected for 3 months post-study enrolment in order to identify abstinence versus ongoing opioid use (mean number of UDS over 3 months=12.6, SD=5.3). We used logistic regression to examine the association between treatment goals and opioid abstinence.

Results: Participants had a mean age of 39.2 years (SD=10.7), 44% were women and median duration in treatment was 2.6 years (IQR 5.2). Six overarching goals were identified from patient responses, including 'stop or taper off of treatment' (68%), 'stay or get clean' (37%) and 'live a normal life' (14%). Participants reporting the goal 'stay or get clean' had lower odds of abstinence at 3 months than those who did not report this goal (OR=0.73, 95% CI 0.59 to 0.91, p=0.005). Although the majority of patients wanted to taper off or stop medication, this goal was not associated with opioid abstinence, nor were any of their other goals.

Conclusions: Patient goals in OUD treatment do not appear to be associated with programme measures of outcome (ie, abstinence from opioids). Future studies are needed to examine outcomes related to patient-reported treatment goals found in our study; pain management, employment, and stopping/tapering treatment should all be explored.
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http://dx.doi.org/10.1136/bmjopen-2020-044017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805377PMC
January 2021

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

Ann Intern Med 2021 04 8;174(4):493-500. Epub 2020 Dec 8.

McMaster University, Hamilton, Ontario, Canada (A.T., M.S., F.J.C., D.H., B.B.D., M.V.).

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.
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http://dx.doi.org/10.7326/M20-6943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747669PMC
April 2021

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

Dig Dis Sci 2021 05 13;66(5):1461-1476. Epub 2020 Jun 13.

Department of Medicine, St. Luke's Hospital, St. Louis, MO, 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.
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http://dx.doi.org/10.1007/s10620-020-06402-3DOI Listing
May 2021

Feasibility of behavioral activation group therapy in reducing depressive symptoms and improving quality of life in patients with depression: the BRAVE pilot trial.

Pilot Feasibility Stud 2020 7;6:61. Epub 2020 May 7.

1Department of Psychiatry and Behavioural Neuroscience, McMaster University, 100 West 5th Street, Hamilton, ON Canada.

Background: Depression impacts the lives of millions of people worldwide. Behavioral activation (BA), derived from cognitive behavioral therapy, has the potential for improving depressive symptoms in patients with depression. Studies evaluating the effectiveness of BA specifically in the context of group therapy programs in a hospital setting for patients with depression are limited. In this study, we report findings from a pilot trial evaluating group BA for major depressive disorder.

Objective: The objectives of this pilot trial are to assess the potential of a full trial of BA group therapy in a large-scale tertiary care setting and to provide preliminary information about possible results regarding mood symptoms and quality of life in adults with depression.

Methods: Using a parallel single-cohort pragmatic pilot randomized controlled trial design, we evaluated the potential of conducting a large trial of BA effectiveness among adults with depression. Participants were randomized to the intervention (BA in addition to usual care) or control (support group in addition to usual care) groups and were assessed weekly for 18 consecutive weeks. Participants randomized to intervention underwent 28 2-h group BA therapy visits administered by trained therapists and completed assessments to examine treatment outcomes. Feasibility was measured in terms of enrollment rates (min. 20%), completion rates of study (min. 80%), and completion rates of weekly measurement scales (min. 80%). The reporting of this pilot trial is in accordance with the CONSORT extension for randomized pilot and feasibility trials.

Results: We randomized 20 individuals of mean age of 48.8 years (standard deviation = 9.7) with a DSM-5 diagnosis of major depressive disorder to intervention ( = 10) or control ( = 10) groups. Based on our feasibility criteria, our recruitment rate was excellent (20/27; 74%), study completion was found to be a moderate (80% of the total participants in both arms completed the study; BA = 100%, control = 60%), and completeness of measurements on a weekly basis was adequate overall (82%; BA = 86%, control = 79%).

Conclusions: The study has demonstrated the potential feasibility to perform a larger scale trial upon modifications to the control group to avoid the low rate of study completion (60%) in this group.

Trial Registration: ClinicalTrials NCT02045771, Registered January 22, 2014.
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http://dx.doi.org/10.1186/s40814-020-00596-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206724PMC
May 2020

The impact of chronic liver disease in patients receiving active pharmacological therapy for opioid use disorder: One-year findings from a prospective cohort study.

Drug Alcohol Depend 2020 04 20;209:107917. Epub 2020 Feb 20.

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address:

Introduction: Despite the demonstrated benefit of methadone, the incidence opioid-related overdose, and its associated mortality continues to rise at an alarming rate. The impact of high prevalence comorbid features such as chronic liver disease (CLD) on methadone treatment response remain unclear.

Aim: To determine whether CLD is associated with poor response to methadone treatment.

Methods: Using a well-established multi-center cohort from the Genetics of Opioid Addiction Study (GENOA), we evaluated if presence of CLD among 1234 eligible patients with opioid use disorder receiving methadone treatment impacted health and behavioural responses to treatment. CLD was classified as any liver disorder/dysfunction present for a minimum period of six months. Serial urine toxicology assessments were used to determine treatment response. The effect of CLD was determined using a multi-variable logistic regression model.

Results: CLD was present in 25 % (n = 314) of the population. On average, patients with CLD were found to be older (mean age 44 vs 36 years, p < 0.0001), unemployed (81.8 % vs 61 %, p < 0.0001), and receiving government disability benefits at significantly higher rates (21.9 % vs 11 %, p < 0.0001). Increased levels of physical craving, emotional stress, as well as health risk behaviors were noted in CLD patients. Findings from the multi-variable model demonstrate a 68 % increased risk for dangerous opioid consumption behaviors (Odds Ration [OR]: 1.68, 95 % Confidence Interval [CI] 1.22, 2.31, p = 0.001) among patients with CLD. Methadone dose (OR: 0.76, 95 % CI 0.70, 0.81, p < 0.0001) was shown to be protective with a significant risk reduction of 24 % per 20 mg increase in methadone. Duration in treatment was also found to be protective (OR: 0.99, 95 % CI 0.97, 0.99, p < 0.0001).

Conclusion: CLD poses a distinct risk for patients with opioid addiction. Closer drug monitoring, and substance use contingency management should be considered to reduce mortality risk in these patients.
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http://dx.doi.org/10.1016/j.drugalcdep.2020.107917DOI Listing
April 2020

Recent advances in liver transplantation with HCV seropositive donors.

F1000Res 2019 30;8. Epub 2019 Dec 30.

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA.

The paradigm shift from interferon-based to direct-acting antiviral (DAA) therapy for the treatment of hepatitis C virus (HCV) infection has revolutionized the field of liver transplantation. These advances in effective HCV treatment, along with the persistent shortage in available liver grafts, have encouraged investigators to assess the need for adopting more inclusive donor policies. Owing to the poor outcomes following liver transplantation with recurrent HCV infection, liver transplantation using HCV seropositive donors (non-viremic and viremic) had been restricted. However, as a result of the growing supply of HCV seropositive donors from the recent opioid epidemic along with the advent of efficacious DAA therapy to treat HCV recurrence, there has been an increasing trend to use HCV seropositive donors for both HCV seropositive and seronegative recipients. The review aims to discuss recent advances and associated outcomes related to the use of HCV seropositive grafts for liver transplantation.
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http://dx.doi.org/10.12688/f1000research.20387.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944251PMC
June 2020

Pathogenesis of Insulin Resistance and Atherogenic Dyslipidemia in Nonalcoholic Fatty Liver Disease.

J Clin Transl Hepatol 2019 Dec 29;7(4):362-370. Epub 2019 Nov 29.

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the developed world, with a global prevalence of around 25%. NAFLD is considered to be the hepatic manifestation of metabolic syndrome and is strongly associated with obesity, insulin resistance and dyslipidemia. Insulin resistance plays a pivotal role in the development of NAFLD-related dyslipidemia, which ultimately increases the risk of premature cardiovascular diseases, a leading cause of morbidity and mortality in patients with NAFLD. Insulin affects hepatic glucose and lipid metabolism by hepatic or extrahepatic pathways. Aside from insulin resistance, several other factors also contribute to the pathogenesis of atherogenic dyslipidemia in patients with NAFLD. These include diet composition, gut microbiota and genetic factors, to name a few. The identification of potentially modifiable risk factors of NAFLD is of importance, so as to target those who may benefit from lifestyle changes and to help develop targeted therapies that decrease the risk of cardiovascular diseases in patients with NAFLD.
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http://dx.doi.org/10.14218/JCTH.2019.00028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943204PMC
December 2019

A call for consensus in defining efficacy in clinical trials for opioid addiction: combined results from a systematic review and qualitative study in patients receiving pharmacological assisted therapy for opioid use disorder.

Trials 2020 Jan 6;21(1):30. Epub 2020 Jan 6.

Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.

Background: Given the complex nature of opioid addiction treatment and the rising number of available opioid substitution and antagonist therapies (OSAT), there is no 'gold standard' measure of treatment effectiveness, and each successive trial measures a different set of outcomes which reflect success in arbitrary or opportune terms. We sought to describe the variation in current outcomes employed across clinical trials for opioid addiction, as well as determine whether a discrepancy exists between the treatment targets that patients consider important and how treatment effectiveness is measured in the literature.

Methods: We searched nine commonly used databases (e.g., EMBASE, MEDLINE) from inception to August 1, 2015. Outcomes used across trials were extracted and categorized according to previously established domains. To evaluate patient-reported goals of treatment, semi-structured interviews were conducted with 18 adults undergoing methadone treatment.

Results: We identified 60 trials eligible for inclusion. Once outcomes were categorized into eight broad domains (e.g., abstinence/substance abuse), we identified 21 specific outcomes with furthermore 53 subdomains and 118 measurements. Continued opioid use and treatment retention were the most commonly reported measures (46%, n = 28). The majority of patients agreed that abstinence from opioids was a primary goal in their treatment, although they also stressed goals under-reported in clinical trials.

Conclusions: There is inconsistency in the measures used to evaluate the effectiveness of OSATs. Individual and population level decision making is being guided by a standard of effect considered useful to researchers yet in direct conflict with what patients deem important.

Trial Registration: PROSPERO, CRD42013006507.
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http://dx.doi.org/10.1186/s13063-019-3995-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945391PMC
January 2020

Regional Trends in Mortality from Alcohol-Induced Causes in the United States, 2000-2017.

J Gen Intern Med 2020 08 2;35(8):2495-2498. Epub 2019 Dec 2.

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA.

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http://dx.doi.org/10.1007/s11606-019-05442-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403270PMC
August 2020

Public, health professional and legislator perspectives on the concept of psychiatric disease: a population-based survey.

BMJ Open 2019 06 4;9(6):e024265. Epub 2019 Jun 4.

Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.

Objective: To assess which mental health-related states of being are perceived as diseases by psychiatrists, non-psychiatric physicians, nurses, parliament members and laypeople.

Design And Setting: A population-based, mailed survey in Finland.

Participants: Respondents from a random sample of 3000 laypeople, 1500 physicians, 1500 nurses and all 200 members of the parliament (MPs) of Finland.

Primary Outcome Measures: Respondents' perspectives on 20 mental health-related states of being as diseases, measuring the extent of agreement with the claim: '[This state of being] is a disease'.

Results: Of the 6200 people approached, we received 3259 eligible responses (53%). Two conditions (schizophrenia and autism) were considered to be diseases by at least 75% and two states (grief and homosexuality) were considered not to be diseases by at least 75% in each group. A majority (at least 50% in each group) considered seven states as diseases (anorexia, attention deficit hyperactivity disorder, bulimia, depression, generalised anxiety disorder, panic disorder and personality disorder) and three not to be diseases (absence of sexual desire, premature ejaculation and transsexualism). In six states, there was a wide divergence of opinion (alcoholism, drug addiction, gambling addiction, insomnia, social anxiety disorder and work exhaustion). Psychiatrists were significantly more inclined to considering states of being as diseases relative to other groups, followed by non-psychiatric physicians, nurses, MPs and laypeople.

Conclusions: Respondents agreed that some conditions, such as schizophrenia and autism, are diseases and other states, such as grief and homosexuality, are not; for others, there was considerable disagreement. Psychiatrists are more inclined to consider mental health-related states of being as diseases compared with other physicians, who, in turn, are more inclined than other constituencies. Understanding notions of disease may underlie important debates in public policy and practice in areas of mental health and behaviour, and have implications for resource allocation and stigma.
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http://dx.doi.org/10.1136/bmjopen-2018-024265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561450PMC
June 2019

Pre-Operative Delta-MELD is an Independent Predictor of Higher Mortality following Liver Transplantation.

Sci Rep 2019 06 5;9(1):8312. Epub 2019 Jun 5.

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA.

Clinical decompensation immediately prior to liver transplantation may affect post-liver transplant (LT) outcomes. Using the serial Model for End-Stage Liver Disease (MELD) scores recorded in the United Network for Organ Sharing national registry (2010-2017), we analyzed post-LT mortality among adult LT recipients based on the degree of fluctuation in MELD score during the 30-day period prior to LT surgery. Delta-MELD (D-MELD) was defined as recipient MELD score at LT minus lowest MELD score within the preceding 30 days. Impact of D-MELD as a continuous and categorical variable (D-MELD 0-4, 5-10, >10) on early, 30-day post-LT mortality was assessed. Overall, a total of 12,785 LT recipients were analyzed, of which 8,862 (67.9%) had a pre-operative D-MELD 0-4; 2,574 (20.1%) with a D-MELD 5-10; and 1,529 (12.0%) with a D-MELD > 10. One-point incremental increase in pre-operative D-MELD (adjusted HR, 1.07, 95% CI: 1.04-1.10) was associated with higher 30-day post-LT mortality. Moreover, pre-operative D-MELD > 10 was associated with nearly a two-fold increased risk for 30-day post-LT mortality (adjusted HR, 1.89, 95% CI: 1.30-2.77) compared to D-MELD 0-4. The increased risk of pre-LT mortality associated with severity of clinical decompensation assessed by the magnitude of pre-operative D-MELD persists in the early post-LT period.
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http://dx.doi.org/10.1038/s41598-019-44814-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549161PMC
June 2019

Use of anti-platelet agents in the prevention of hepatic fibrosis in patients at risk for chronic liver disease: a systematic review and meta-analysis.

Hepatol Int 2019 Jan 12;13(1):84-90. Epub 2018 Dec 12.

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA.

Background And Aims: While the association between platelet activation and hepatic fibrosis has been previously demonstrated in animal studies; the utility of anti-platelet agents in reversing the progression of hepatic fibrosis requires further review. Utilizing systematic review methods, we provide to our knowledge the first meta-analysis combining evidence from all studies aimed to establish the effect of anti-platelet agents in the prevention of hepatic fibrosis.

Methods: We searched Medline, EMBASE and PubMed databases from inception to October 2018 to identify all studies aimed at evaluating the role of anti-platelet agents in the prevention of hepatic fibrosis. The primary outcome was hepatic fibrosis. The initial title, abstract, and full-text screening were performed in duplicate. Risk of bias was evaluated using the Newcastle-Ottawa Scale. A fixed-effect generic inverse variance method was used to create a pooled estimate of the odds of hepatic fibrosis in patients with anti-platelet agents versus without anti-platelet agents.

Results: Among the 2310 unique articles identified during the title screening, 4 studies with a combined population of 3141 patients were deemed eligible for inclusion into the meta-analysis establishing the effect of anti-platelet agents on hepatic fibrosis. One study failed to report their findings in the entire cohort, electing to instead summarize the effects of anti-platelets within subgroups categorized by fibrotic risk factors. Use of anti-platelets was associated with 32% decreased odds of hepatic fibrosis, (adjusted pooled OR 0.68; CI 0.56-0.82, p ≤ 0.0001). The statistical heterogeneity among the studies was insignificant.

Conclusion: Use of anti-platelet agents is associated with the decreased odds of hepatic fibrosis. Due to limited evidence, future high-quality randomized controlled trials with larger comparative samples are required to further delineate the potential beneficial effects of these drugs in preventing hepatic fibrosis.
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http://dx.doi.org/10.1007/s12072-018-9918-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6675411PMC
January 2019

Identifying patient-important outcomes in medication-assisted treatment for opioid use disorder patients: a systematic review protocol.

BMJ Open 2018 12 4;8(12):e025059. Epub 2018 Dec 4.

Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada.

Introduction: Illicit opioid use has become a national crisis in Canada, with over 65 000 people seeking treatment for opioid use disorder (OUD) in Ontario and British Columbia alone. Medication-assisted treatment (MAT) is a common treatment for OUD. There is substantial variability in treatment outcomes used to evaluate effectiveness of MAT, making it difficult to establish clinically and scientifically relevant treatment effect. Furthermore, patients are often excluded from the process of determining these outcomes. The primary objective of this review is to examine outcomes currently used to measure MAT effectiveness and to identify patient-relevant outcomes to enhance effectiveness of treatment options. This review refers to patient-important outcomes as those outcomes patients consider important to or markers of treatment success.

Methods And Analysis: MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Cochrane Library, Cochrane Clinical Trials Registry, National Institutes for Health Clinical Trials Registry and WHO International Clinical Trials Registry Platform databases will be searched. We will search databases from inception to the date the search is ran. Studies of interest include those evaluating the effectiveness of MAT for patients with OUD, with or without consultation with patients regarding what they consider to be important as an indicator of treatment success. Results will be analysed using thematic analysis and qualitative analysis where possible. This will result in comprehensive synthesis of all outcomes and measures found related to OUD treatment effectiveness.

Ethics And Dissemination: We are collaborating with Canadian Addiction Treatment Centres which provide MAT to patients with OUD who will participate in disseminating study results. Dissemination strategies will involve sharing study results through workshops, presentations, peer-reviewed publications, study reports, community presentations and resources in primary care settings.

Prospero Registration Number: CRD42018095553.
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http://dx.doi.org/10.1136/bmjopen-2018-025059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286642PMC
December 2018

Temporal Trends Associated With the Rise in Alcoholic Liver Disease-related Liver Transplantation in the United States.

Transplantation 2019 01;103(1):131-139

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA.

Background: In the United States, alcoholic liver disease (ALD) has recently become the leading indication for liver transplantation.

Methods: Using the United Network for Organ Sharing registry, we examined temporal trends in adult liver transplant waitlist (WL) registrants and recipients with chronic liver disease (CLD) due to ALD from 2007 to 2016.

Results: From 2007 to 2016, ALD accounted for 20.4% (18 399) of all CLD WL additions. The age-standardized ALD WL addition rate was 0.459 per 100 000 US population in 2007; nearly doubled to 0.872 per 100 000 US population in 2016 and increased with an average annual percent change of 47.56% (95% confidence interval, 30.33% to 64.72%).The ALD WL addition rate increased over twofold among young (18-39 years) and middle-aged (40-59 years) adults during the study period. Young adult ALD WL additions presented with a higher severity of liver disease including Model for End-Stage Liver Disease score compared to middle aged and older adults (≥60 years). The number of annual ALD WL deaths readily rose from 2014 to 2016, despite an overall annual decline in all CLD WL deaths. Severe hepatic encephalopathy, low body mass index (<18.5) and diabetes mellitus were significant predictors for 1-year WL mortality.

Conclusions: Alcoholic liver disease-related WL registrations and liver transplantation have increased over the past decade with a disproportionate increase in young and middle-aged adults. These subpopulations within the ALD cohort need to be evaluated in future studies to improve our understanding of factors associated with these alarming trends.
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http://dx.doi.org/10.1097/TP.0000000000002471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6709987PMC
January 2019

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

Arthroscopy 2019 01 5;35(1):262-274.e6. Epub 2018 Oct 5.

MedSport, Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, U.S.A.. Electronic address:

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.
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http://dx.doi.org/10.1016/j.arthro.2018.07.027DOI Listing
January 2019

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

Clin Gastroenterol Hepatol 2019 07 27;17(8):1634-1636. Epub 2018 Sep 27.

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California. Electronic address:

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. 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. Subsequently, a case was reported in which an HCV-V liver was transplanted into a HCV-seronegative recipient. In collaboration with OPTN/UNOS, we identified cases in which HCV-V deceased donor livers were transplanted into HCV-seronegative recipients.
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http://dx.doi.org/10.1016/j.cgh.2018.09.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470034PMC
July 2019

The utility of drug reaction assessment trials for inhaled therapies in patients with chronic lung diseases.

Respir Med 2018 07 8;140:122-126. Epub 2018 Jun 8.

Royal Brompton and Harefield NHS Foundation Trust, London, UK; National Heart and Lung Institute, Imperial College London, London, UK. Electronic address:

Background: Current guidelines recommend a Drug Reaction Assessment (DRA) before beginning inhaled therapies to assess for bronchoconstriction and tolerability. There is limited evidence to support this recommendation.

Methods: In this study we aimed to establish the predictors of successful DRAs in different patient groups using a cohort of all DRAs performed in adults between 2011 and 2016 at the Royal Brompton Hospital. Spirometry, age, gender, height, and underlying lung disease were recorded. A multivariable logistic regression model was constructed to ascertain variables associated with successful DRAs.

Results: There were 1492 DRA trials using hypertonic saline (32%), antimicrobials (63%), or rhDNase (5%). The majority of patients (94%, n = 1408) passed the DRA. Mean FEV% predicted was 58.03 (SD 23.36). Female sex, type of inhaled product, and FEV% predicted were established as significant predictors for DRA success. An FEV% predicted > 55% was associated with greater probability of DRA success (Odds Ratio [OR]: 2.96 (1.80,4.86) p < 0.0001). Those receiving dry powder, inhaled antibiotics were more likely to pass the DRA compared to nebulised antibiotics (OR: 3.99 (1.38,11.51) p = 0.01)).

Conclusion: This study classifies distinct patient groups with varying baseline risks which can be used to predict tolerability when adding an inhaled product to their management plan. Some "low risk" patients may in future be able to self-assess their tolerability for inhaled therapies at home to avoid unneeded hospital monitoring.
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http://dx.doi.org/10.1016/j.rmed.2018.06.008DOI Listing
July 2018

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

BMC Emerg Med 2018 01 18;18(1). Epub 2018 Jan 18.

Department of Medicine, Korle Bu Teaching Hospital, P.O. Box KB77, Accra, Ghana.

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.
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http://dx.doi.org/10.1186/s12873-018-0154-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774152PMC
January 2018

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

BMC Emerg Med 2018 01 18;18(1). Epub 2018 Jan 18.

Department of Medicine, Korle Bu Teaching Hospital, P.O. Box KB77, Accra, Ghana.

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.
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http://dx.doi.org/10.1186/s12873-018-0154-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774152PMC
January 2018

Agreement in reporting between trial publications and current clinical trial registry in high impact journals: A methodological review.

Contemp Clin Trials 2018 02 26;65:144-150. Epub 2017 Dec 26.

Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada.

Objectives: The primary objective of this systematic survey was to examine the percentage of studies in which there was agreement in the reporting of the primary outcome between the currently updated version of the clinical trial registry and the published paper. We also investigated the factors associated with agreement in reporting of the primary outcome.

Methods: We searched PubMed for all randomized control trials (RCT)s published in 2012-2015 in the top five general medicine journals (based on the 2014 impact factor). Two hundred abstracts (50 from each year) were randomly selected for data extraction. Agreement in reporting of 11 key study conduct items (e.g., sample size) and study characteristics (e.g., funding, number of sites) were extracted by two independent reviewers.

Analysis: Descriptive analyses were conducted to determine the proportion of studies on which there was agreement in reporting of key study conduct items. Generalized estimating equations were used to explore factors associated with agreement in reporting of the primary outcome.

Results: Of the 200 included studies, 87% had agreement in reporting of the primary outcome. After adjusting for other covariates, having greater than 50 sites was associated with an increased likelihood of agreement in reporting of the primary outcome (odds ratio=7.1, 95% confidence interval=1.39, 36.27, p=0.018).

Conclusions: We identified substantive disagreement in reporting between publications and current clinical trial registry, which were associated with several study characteristics. Further measures are needed to improve reporting given the potential threats to the quality and integrity of scientific research.
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http://dx.doi.org/10.1016/j.cct.2017.12.011DOI Listing
February 2018

The impact of comorbid psychiatric disorders on methadone maintenance treatment in opioid use disorder: a prospective cohort study.

Neuropsychiatr Dis Treat 2017 24;13:1399-1408. Epub 2017 May 24.

Biostatistics Unit, Research Institute, St Joseph's Healthcare.

Objective: There is a significant interindividual variability in treatment outcomes in methadone maintenance treatment (MMT) for opioid use disorder (OUD). This prospective cohort study examines the impact of comorbid psychiatric disorders on continued illicit opioid use in patients receiving MMT for OUD.

Methods: Data were collected from 935 patients receiving MMT in outpatient clinics between June 2011 and June 2015. Using linear regression analysis, we evaluated the impact of having a comorbid psychiatric disorder on continued illicit opioid use during MMT, adjusting for important confounders. The main outcome measure was percentage of opioid-positive urine screens for 6 months. We conducted a subgroup analysis to determine the influence of specific comorbid psychiatric disorders, including substance use disorders, on continued illicit opioid use.

Results: Approximately 80% of participants had at least one comorbid psychiatric disorder in addition to OUD, and 42% of participants had a comorbid substance use disorder. There was no significant association between having a psychiatric comorbidity and continuing opioid use (=0.248). Results from subgroup analysis, however, suggest that comorbid tranquilizer (β=20.781, <0.001) and cocaine (β=6.344, =0.031) use disorders are associated with increased rates of continuing opioid use.

Conclusion: Results from our study may serve to guide future MMT guidelines. Specifically, we find that cocaine or tranquilizer use disorder, comorbid with OUD, places patients at high risk for poor MMT outcomes. Treatment centers may choose to gear more intensive therapy toward such populations.
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http://dx.doi.org/10.2147/NDT.S129480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5449137PMC
May 2017

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.

Nephrol Dial Transplant 2017 04;32(suppl_2):ii23-ii30

Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.

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.
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http://dx.doi.org/10.1093/ndt/gfw219DOI Listing
April 2017

Behavioral activation group therapy for reducing depressive symptoms and improving quality of life: a feasibility study.

Pilot Feasibility Stud 2016 29;2:22. Epub 2016 Apr 29.

Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main St. W, Hamilton, ON Canada ; Biostatistics Unit, Centre for Evaluation of Medicine, ON, Canada ; System-Linked Research Unit, McMaster University, 1280 Main St. W, Hamilton, ON Canada ; Department of Anaesthesia, McMaster University, 1280 Main St. W, Hamilton, ON Canada ; Department of Paediatrics, McMaster University, 1280 Main St. W, Hamilton, ON Canada.

Background: Depression is associated with a loss of productivity and noticeable personal, social, and economic decline; it affects more than 350 million people worldwide. Behavioral activation (BA), derived from cognitive behavioral therapy, has drawn increasingly more interest as a means of treatment for major depressive disorder due to its relative cost-effectiveness and efficacy. In this study, we disseminate findings from a feasibility study evaluating barriers to implementing a group BA program for major depressive disorder. The purpose of this feasibility study is to assess both patient and clinician perceptions on components of a group-based behavioral activation (BA) program. In particular, this feasibility study provides in-depth evaluation of the acceptability of BA prior to the design and implementation of a randomized trial to investigate BA effectiveness. Findings from this study directly informed decisions regarding the design and implementation of BA during the pilot trial. Specific components of BA were assessed and modified based on the results of this study.

Methods: This qualitative study was completed through the Mood Disorders Program at St. Joseph's Healthcare Hamilton. The authors of this study used data from two focus group sessions, one consisting of an interdisciplinary group of clinicians working in the Mood Disorders Program, and the other of registered outpatients of the Mood Disorders Program with a confirmed clinical diagnosis of depression. The benefits of offering this program in a group format, mainly social skill development opportunities and the use of technology such as activity tracking device, smart phones, and tablets during the therapy sessions, are a major focus of both the clinician and patient groups. Both groups emphasized the importance of offering sustainable activation.

Results: Differences in opinions existed between staff and patient groups regarding the use of technology in the program, though ultimately it was agreed upon that technology could be useful as a therapeutic aid. All participants agreed that behavioral activation was essential to the development of positive habits and routines necessary for recovery from depression. Patients agreed the program looked sustainable and stressed the potential benefit for improving depressive symptoms.

Conclusions: Discussions from clinician and patient-centered focus groups directly informed decisions regarding the design and implementation of BA during the pilot trial. Specific components of BA were assessed and modified based on the results of this study. These findings provide insight for clinicians providing behavioral activation programming, and will serve as a framework for the development of the Out of the Blues program, a group-based BA program to be piloted in the Mood Disorders Program at St. Joseph's Healthcare Hamilton.

Trial Registration: Clinical Trials registration number NCT02045771.
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http://dx.doi.org/10.1186/s40814-016-0064-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5154036PMC
April 2016

Reporting quality of stepped wedge design randomized trials: a systematic review protocol.

Clin Epidemiol 2016 8;8:261-6. Epub 2016 Jul 8.

Department of Anesthesia, McMaster University Hamilton ON; Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton ON, Canada; Population Health Research Institute, Hamilton Health Sciences; Department of Pediatrics, McMaster University, Hamilton, ON, Canada; Centre for Evaluation of Medicine; Biostatistics Unit, Father Sean O'Sullivan Research Centre, St Joseph's Healthcare, Hamilton, ON, Canada.

Background: Stepped wedge design (SWD) is a cluster randomized controlled trial (RCT) design that sequentially rolls out intervention to all clusters at varying time points. Being a relatively new design method, reporting quality has yet to be explored, and this review will seek to fill this gap in knowledge.

Objectives: The objectives of this review are: 1) to assess the quality of SWD trial reports based on the CONSORT guidelines or CONSORT extension to cluster RCTs; 2) to assess the completeness of reporting of SWD trial abstracts using the CONSORT extension for abstracts; 3) to assess the reporting of sample size details in SWD trial reports or protocols; 4) to assess the completeness of reporting of SWD trial protocols according to SPIRIT guidelines; 5) to assess the consistency between the trial registration information and final SWD trial reports; and 6) to assess the consistency of what is reported in the abstracts and main text of the SWD trial reports. We will also explore factors that are associated with the completeness of reporting.

Methods: We will search MEDLINE, EMBASE, Web of Science, CINAHL, and PsycINFO for all randomized controlled trials utilizing SWD. Details from eligible papers will be extracted in duplicate. Demographic statistics obtained from the data extraction will be analyzed to answer the primary objectives pertaining to the reporting quality of several aspects of a published paper, as well as to explore possible temporal trends and consistency between abstracts, trial registration information, and final published articles.

Discussion: Findings from this review will establish the reporting quality of SWD trials and inform academics and clinicians on their completeness and consistency. Results of this review will influence future trials and improve the overall quality and reporting of SWD trials.
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http://dx.doi.org/10.2147/CLEP.S103098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944926PMC
July 2016
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