Publications by authors named "Thomas D Brothers"

32 Publications

Unhealthy alcohol use in a 65-year-old man awaiting surgery.

CMAJ 2021 Aug;193(32):E1250-E1252

Division of General Internal Medicine, Department of Medicine, Faculty of Medicine (Brothers, Kaulbach, Tran), Dalhousie University; Clinician-Investigator Program, Faculty of Medicine (Brothers), Dalhousie University, Halifax, NS; UCL Collaborative Centre for Inclusion Health (Brothers), Institute of Epidemiology and Health Care, University College London, UK.

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http://dx.doi.org/10.1503/cmaj.202128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386484PMC
August 2021

Social and structural determinants of injecting-related bacterial and fungal infections among people who inject drugs: protocol for a mixed studies systematic review.

BMJ Open 2021 08 9;11(8):e049924. Epub 2021 Aug 9.

Department of Public Health, Environments and Society, London School of Hygiene & Tropical Medicine, London, UK.

Introduction: Injecting-related bacterial and fungal infections are a common complication among people who inject drugs (PWID), associated with significant morbidity and mortality. Invasive infections, including infective endocarditis, appear to be increasing in incidence. To date, preventive efforts have focused on modifying individual-level risk behaviours (eg, hand-washing and skin-cleaning) without much success in reducing the population-level impact of these infections. Learning from successes in HIV prevention, there may be great value in looking beyond individual-level risk behaviours to the social determinants of health. Specifically, the risk environment conceptual framework identifies how social, physical, economic and political environmental factors facilitate and constrain individual behaviour, and therefore influence health outcomes. Understanding the social and structural determinants of injecting-related bacterial and fungal infections could help to identify new targets for prevention efforts in the face of increasing incidence of severe disease.

Methods And Analysis: This is a protocol for a systematic review. We will review studies of PWID and investigate associations between risk factors (both individual-level and social/structural-level) and the incidence of hospitalisation or death due to injecting-related bacterial infections (skin and soft-tissue infections, bacteraemia, infective endocarditis, osteomyelitis, septic arthritis, epidural abscess and others). We will include quantitative, qualitative and mixed methods studies. Using directed content analysis, we will code risk factors for these infection-related outcomes according to their contributions to the risk environment in type (social, physical, economic or political) and level (microenvironmental or macroenvironmental). We will also code and present risk factors at each stage in the process of drug acquisition, preparation, injection, superficial infection care, severe infection care or hospitalisation, and outcomes after infection or hospital discharge.

Ethics And Dissemination: As an analysis of the published literature, no ethics approval is required. The findings will inform a research agenda to develop and implement social/structural interventions aimed at reducing the burden of disease.

Prospero Registration Number: CRD42021231411.
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http://dx.doi.org/10.1136/bmjopen-2021-049924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354281PMC
August 2021

Uptake of slow-release oral morphine as opioid agonist treatment among hospitalised patients with opioid use disorder.

Drug Alcohol Rev 2021 Aug 4. Epub 2021 Aug 4.

Department of Medicine, Faculty of Medicine, Dalhousie University, Halifax, Canada.

Introduction: Buprenorphine and methadone are highly effective first-line medications for opioid agonist treatment (OAT) but are not acceptable to all patients. We aimed to assess the uptake of slow-release oral morphine (SROM) as second-line OAT among medically ill, hospitalised patients with opioid use disorder who declined buprenorphine and methadone.

Methods: This study included consecutive hospitalised patients with untreated moderate-to-severe opioid use disorder referred to an inpatient addiction medicine consultation service, between June 2018 and September 2019, in Nova Scotia, Canada. We assessed the proportion of patients initiating first-line OAT (buprenorphine or methadone) in-hospital, and the proportion initiating SROM after declining first-line OAT. We compared rates of outpatient OAT continuation (i.e., filling outpatient OAT prescription or attending first outpatient OAT clinic visit) by medication type, and compared OAT selection between patients with and without chronic pain, using χ tests.

Results: Thirty-four patients were offered OAT initiation in-hospital; six patients (18%) also had chronic pain. Twenty-one patients (62%) initiated first-line OAT with buprenorphine or methadone. Of the 13 patients who declined first-line OAT, seven (54%) initiated second-line OAT with SROM in-hospital. Rates of outpatient OAT continuation after hospital discharge were high (>80%) and did not differ between medications (P = 0.4). Patients with co-existing chronic pain were more likely to choose SROM over buprenorphine or methadone (P = 0.005).

Discussion And Conclusions: The ability to offer SROM (in addition to buprenorphine or methadone) increased rates of OAT initiation among hospitalised patients. Increasing access to SROM would help narrow the opioid use disorder treatment gap of unmet need.
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http://dx.doi.org/10.1111/dar.13365DOI Listing
August 2021

Les soins hospitaliers aux personnes qui consomment des drogues injectables.

CMAJ 2021 May;193(22):E829-E830

Division de médecine interne générale et du programme de clinicien-chercheur (Brothers), Division des maladies infectieuses (Webster), Département de médecine, Université Dalhousie; Services de santé mobiles de rue (Fraser), Centre de santé communautaire North End, Halifax, N.-É.; Centre collaboratif pour la santé inclusive UCL (Brothers), Institut d'épidémiologie et de soins de santé, Collège universitaire de Londres, Londres, G.-B.; Division des maladies infectieuses (Webster), Hôpital régional Saint John, Saint John, N.-B.

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http://dx.doi.org/10.1503/cmaj.202124-fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177935PMC
May 2021

Caring for people who inject drugs when they are admitted to hospital.

CMAJ 2021 Mar;193(12):E423-E424

Division of General Internal Medicine and Clinician Investigator Program (Brothers), and Division of Infectious Diseases (Webster), Department of Medicine, Dalhousie University; Mobile Outreach Street Health (Fraser), North End Community Health Centre, Halifax, NS; UCL Collaborative Centre for Inclusion Health (Brothers), Institute of Epidemiology & Health Care, University College London, London, UK; Division of Infectious Diseases (Webster), Saint John Regional Hospital, Saint John, NB.

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http://dx.doi.org/10.1503/cmaj.202124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096383PMC
March 2021

Patients with infective endocarditis deserve evidence-based addiction treatment.

Ann Thorac Surg 2021 Mar 19. Epub 2021 Mar 19.

Department of Psychiatry, Cumming School of Medicine, University of Calgary.

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http://dx.doi.org/10.1016/j.athoracsur.2021.01.085DOI Listing
March 2021

Linking opioid use disorder treatment from hospital to community.

Addiction 2021 08 18;116(8):2244-2245. Epub 2021 Mar 18.

Division of Addiction Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

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http://dx.doi.org/10.1111/add.15460DOI Listing
August 2021

"The Times They Are a-Changin'": Addressing Common Misconceptions About the Role of Safe Supply in North America's Overdose Crisis.

J Stud Alcohol Drugs 2021 01;82(1):158-160

School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.

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January 2021

Implementation and evaluation of a novel, unofficial, trainee-organized hospital addiction medicine consultation service.

Subst Abus 2020 Dec 17:1-8. Epub 2020 Dec 17.

Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.

Background: To evaluate a novel, unofficial, trainee-organized, hospital addiction medicine consultation service (AMCS), we aimed to assess whether it was (1) acceptable to hospital providers and patients, (2) feasible to organize and deliver, and (3) impacted patient care. : We performed a retrospective descriptive study of all AMCS consultations over the first 16 months. We determined acceptability via the number of referrals received from admitting services, and the proportion of referred patients who consented to consultation. We evaluated feasibility via continuation/growth of the service over time, and the proportion of referrals successfully completed before hospital discharge. As most referrals related to opioid use disorder, we determined impact through the proportion of eligible patients offered and initiated on opioid agonist therapy (OAT) in hospital, and the proportion of patients who filled their outpatient prescription or attended their first visit with their outpatient OAT prescriber. : The unofficial AMCS grew to involve six hospital-based residents and five supervising community-based addiction physicians. The service received 59 referrals, primarily related to injection opioid use, for 50 unique patients from 12 different admitting services. 90% of patients were seen before discharge, and 98% agreed to addiction medicine consultation. Among 34 patients with active moderate-severe opioid use disorder who were not already on OAT, 82% initiated OAT in hospital and 89% of these patients continued after discharge. : Established in response to identified gaps in patient care and learning opportunities, a novel, unofficial, trainee-organized AMCS was acceptable, feasible, and positively impacted patient care over the first 16 months. This trainee-organized, unofficial AMCS could be used as a model for other hospitals that do not yet have an official AMCS.
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http://dx.doi.org/10.1080/08897077.2020.1856291DOI Listing
December 2020

Addressing the Syndemic of HIV, Hepatitis C, Overdose, and COVID-19 Among People Who Use Drugs: The Potential Roles for Decriminalization and Safe Supply.

J Stud Alcohol Drugs 2020 09;81(5):556-560

School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.

People who use drugs (PWUD) face concurrent public health emergencies from overdoses, HIV, hepatitis C, and COVID-19, leading to an unprecedented syndemic. Responses to PWUD that go beyond treatment--such as decriminalization and providing a safe supply of pharmaceutical-grade drugs--could reduce impacts of this syndemic. Solutions already implemented for COVID-19, such as emergency safe-supply prescribing and providing housing to people experiencing homelessness, must be sustained once COVID-19 is contained. This pandemic is not only a public health crisis but also a chance to develop and maintain equitable and sustainable solutions to the harms associated with the criminalization of drug use.
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September 2020

Epidemiology, Microbiology, and Clinical Outcomes Among Patients With Intravenous Drug Use-Associated Infective Endocarditis in New Brunswick.

CJC Open 2020 Sep 23;2(5):379-385. Epub 2020 May 23.

Medical School, Dalhousie Medicine New Brunswick, Saint John, New Brunswick, Canada.

Background: Within the context of Canada's opioid crisis, medical complications associated with intravenous drug use (IVDU) are increasing. Infective endocarditis (IE) is a serious complication of IVDU, and understanding the characteristics of these patients could aid health systems, clinicians, and patients in the optimization of treatment and prevention of IVDU-IE.

Methods: At a tertiary care hospital in southern New Brunswick, we conducted a retrospective chart review to identify patients with IVDU-IE admitted between January 1, 2013, and December 31, 2017. We collected data related to the epidemiology, microbiology, clinical manifestations, echocardiography, complications during hospital admission, and outcomes.

Results: Forty-two cases of IVDU-IE met inclusion criteria. The rate of IVDU-IE increased from 2.28 per 100,000 population in 2014 to 4.00 in 2017, which, although not statistically significant, reflects patterns in other jurisdictions. Most patients (72.4%) were male, and the mean age was 38.3 (±11.5) years. Most patients (79.3%) injected opioids. The most common clinical sign was fever (90.5%), and 61.9%) was the most common microorganism. The tricuspid valve was most commonly infected (58.5%), 50% of cases had heart failure as a complication during admission, and 45.2% of cases required valve replacement or repair. The 2-year survival rate after admission for initial IVDU-IE episode was 62.0% (95% confidence interval: 36.5-79.7).

Conclusion: IVDU-IE is common in New Brunswick and may be increasing. Despite the relatively young age of this patient population, IVDU-IE is associated with significant morbidity and mortality. Expanding effective harm reduction and addiction treatment strategies for this cohort is recommended.
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http://dx.doi.org/10.1016/j.cjco.2020.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499377PMC
September 2020

Challenges in Prediction and Diagnosis of Alcohol Withdrawal Syndrome and Wernicke Encephalopathy-Reply.

JAMA Intern Med 2020 Dec;180(12):1716-1717

Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada.

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http://dx.doi.org/10.1001/jamainternmed.2020.3561DOI Listing
December 2020

Patient-centred care in opioid agonist treatment could improve outcomes.

CMAJ 2019 04;191(17):E460-E461

Department of Medicine (Brothers), Dalhousie University; Halifax Area Network of Drug Using People (HANDUP) (Bonn); Hepatitis Outreach Society of Nova Scotia (Bonn), Halifax, NS.

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http://dx.doi.org/10.1503/cmaj.190430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488477PMC
April 2019

Challenges in Prediction, Diagnosis, and Treatment of Alcohol Withdrawal in Medically Ill Hospitalized Patients: A Teachable Moment.

JAMA Intern Med 2020 06;180(6):900-901

Department of Medicine, University of British Columbia, Vancouver, Canada.

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http://dx.doi.org/10.1001/jamainternmed.2020.1091DOI Listing
June 2020

Case Series: Limited Opioid Withdrawal With Use of Transdermal Buprenorphine to Bridge to Sublingual Buprenorphine in Hospitalized Patients.

Am J Addict 2020 01 18;29(1):73-76. Epub 2019 Oct 18.

Mental Health and Addictions Service, St. Michael's Hospital, Toronto, Ontario, Canada.

Background: Prerequisite opioid withdrawal symptoms prior to buprenorphine induction are unacceptable to many patients. We assessed whether transdermal buprenorphine minimized withdrawal while bridging to sublingual therapy among hospital inpatients.

Methods: Retrospective chart review of (n = 23) inpatients with opioid use disorder or opioid dependence due to chronic pain.

Results: Of 23 inpatients, 65% transitioned without symptoms, while 35% experienced mild withdrawal. Ninety-six percent completed planned hospitalizations, with 83% engaged in treatment 4 weeks post-discharge.

Discussion And Conclusions: Bridging to sublingual therapy with transdermal buprenorphine patches was feasible without withdrawal symptoms.

Scientific Significance: This strategy may facilitate buprenorphine therapy in hospital inpatients. (Am J Addict 2019;00:1-4).
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http://dx.doi.org/10.1111/ajad.12964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7134509PMC
January 2020

Predictors of transitions in frailty severity and mortality among people aging with HIV.

PLoS One 2017 5;12(10):e0185352. Epub 2017 Oct 5.

Division of Geriatric Medicine, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.

Background: People aging with HIV show variable health trajectories. Our objective was to identify longitudinal predictors of frailty severity and mortality among a group aging with HIV.

Methods: Exploratory analyses employing a multistate transition model, with data from the prospective Modena HIV Metabolic Clinic Cohort Study, based in Northern Italy, begun in 2004. Participants were followed over four years from their first available visit. We included all 963 participants (mean age 46.8±7.1; 29% female; 89% undetectable HIV viral load; median current CD4 count 549, IQR 405-720; nadir CD4 count 180, 81-280) with four-year data. Frailty was quantified using a 31-item frailty index. Outcomes were frailty index score or mortality at four-year follow-up. Candidate predictor variables were baseline frailty index score, demographic (age, sex), HIV-disease related (undetectable HIV viral load, current CD4+ T-cell count, nadir CD4 count, duration of HIV infection, and duration of antiretroviral therapy [ARV] exposure), and behavioral factors (smoking, injection drug use (IDU), and hepatitis C virus co-infection).

Results: Four-year mortality was 3.0% (n = 29). In multivariable analyses, independent predictors of frailty index at follow-up were baseline frailty index (RR 1.06, 95% CI 1.05-1.07), female sex (RR 0.93, 95% CI 0.87-0.98), nadir CD4 cell count (RR 0.96, 95% CI 0.93-0.99), duration of HIV infection (RR 1.06, 95% CI 1.01-1.12), duration of ARV exposure (RR 1.08, 95% CI 1.02-1.14), and smoking pack-years (1.03, 1.01-1.05). Independent predictors of mortality were baseline frailty index (OR 1.19, 1.02-1.38), current CD4 count (0.34, 0.20-0.60), and IDU (2.89, 1.30-6.42).

Conclusions: Demographic, HIV-disease related, and social and behavioral factors appear to confer risk for changes in frailty severity and mortality among people aging with HIV.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0185352PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5628822PMC
October 2017

A frailty index predicts post-liver transplant morbidity and mortality in HIV-positive patients.

AIDS Res Ther 2017 Aug 5;14(1):37. Epub 2017 Aug 5.

Department of Medical and Surgical Sciences for Adults and Children, Liver and Multivisceral Transplant Center, University of Modena and Reggio Emilia, Modena, Italy.

Background: We hypothesized that frailty acts as a measure of health outcomes in the context of LT. The aim of this study was to explore frailty index across LT, as a measure of morbidity and mortality. This was a retrospective observational study including all consecutive 47 HIV+patients who received LT in Modena, Italy from 2003 to June 2015.

Methods: frailty index (FI) was constructed from 30 health variables. It was used both as a continuous score and as a categorical variable, defining 'most frail' a FI > 0.45. FI change across transplant (deltaFI, ΔFI) was calculated as the difference between year 1 FI (FI-Y1) and pre-transplant FI (FI-t0). The outcomes measures were mortality and "otpimal LT" (defined as being alive without multi-morbidity).

Results: Median value of FI-t0 was 0.48 (IQR 0.42-0.52), FI-Y1 was 0.31 (IQR 0.26-0.41). At year five mortality rate was 45%, "optimal transplant" rate at year 1 was 38%. All the patients who died in the post-LT were most frail in the pre-LT. ΔFI was a predictor of mortality after correction for age and MELD (HR = 1.10, p = 0.006) and was inversely associated with optimal transplant after correction for age (HR = 1.04, p = 0.01).

Conclusions: We validated FI as a valuable health measure in HIV transplant. In particular, we found a relevant correlation between FI strata at baseline and mortality and a statistically significant correlation between, ΔFI and survival rate.
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http://dx.doi.org/10.1186/s12981-017-0163-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5545092PMC
August 2017

Late presentation increases risk and costs of non-infectious comorbidities in people with HIV: an Italian cost impact study.

AIDS Res Ther 2017 Feb 16;14(1). Epub 2017 Feb 16.

Department of Medical and Surgical Sciences for Adults and Children, Clinic of Infectious Diseases, University of Modena and Reggio Emilia, Emilia-Romagna, Modena, Italy.

Background: Late presentation (LP) at the time of HIV diagnosis is defined as presentation with AIDS whatever the CD4 cell count or with CD4 <350 cells/mm. The objective of our study was to assess the prevalence of non-infectious comorbidities (NICM) and multimorbidity among HIV-positive individuals with and without a history of LP (HIV + LP and HIV + EP, respectively), and compare them to matched HIV-negative control participants from a community-based cohort. The secondary objective was to provide estimates and determinants of direct cost of medical care in HIV patients.

Methods: We performed a matched cohort study including HIV + LP and HIV + EP among people attending the Modena HIV Metabolic Clinic (MHMC) in 2014. HIV-positive participants were matched in a 1:3 ratio with HIV-negative participants from the CINECA ARNO database. Multimorbidity was defined as the concurrent presence of ≥2 NICM. Logistic regression models were constructed to evaluate associated predictors of NICM and multimorbidity.

Results: We analyzed 452 HIV + LP and 73 HIV + EP participants in comparison to 1575 HIV-negative controls. The mean age was 46 ± 9 years, 27.5% were women. Prevalence of NICM and multimorbidity were fourfold higher in the HIV + LP compared to the general population (p < 0.001), while HIV + EP present an intermediate risk. LP was associated with increased total costs in all age strata, but appear particularly relevant in patients above 50 years of age, after adjusting for age, multimorbidity, and antiretroviral costs.

Conclusions: LP with HIV infection is still very frequent in Italy, is associated with higher prevalence of NICM and multimorbidity, and contributes to higher total care costs. Encouraging early testing and access to care is still urgently needed.
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http://dx.doi.org/10.1186/s12981-016-0129-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5311843PMC
February 2017

Foot Conditions among Homeless Persons: A Systematic Review.

PLoS One 2016 9;11(12):e0167463. Epub 2016 Dec 9.

Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.

Introduction: Foot problems are common among homeless persons, but are often overlooked. The objectives of this systematic review are to summarize what is known about foot conditions and associated interventions among homeless persons.

Methods: A literature search was conducted on MEDLINE (1966-2016), EMBASE (1947-2016), and CINAHL (1982-2016) and complemented by manual searches of reference lists. Articles that described foot conditions in homeless persons or associated interventions were included. Data were independently extracted on: general study characteristics; participants; foot assessment methods; foot conditions and associated interventions; study findings; quality score assessed using the Downs and Black checklist.

Results: Of 333 articles screened, 17 articles met criteria and were included in the study. Prevalence of any foot problem ranged from 9% to 65% across study populations. Common foot-related concerns were corns and calluses, nail pathologies, and infections. Foot pathologies related to chronic diseases such as diabetes were identified. Compared to housed individuals across studies, homeless individuals were more likely to have foot problems including tinea pedis, foot pain, functional limitations with walking, and improperly-fitting shoes.

Discussion: Foot conditions were highly prevalent among homeless individuals with up to two thirds reporting a foot health concern, approximately one quarter of individuals visiting a health professional, and one fifth of individuals requiring further follow-up due to the severity of their condition. Homeless individuals often had inadequate foot hygiene practices and improperly-fitting shoes. These findings have service provision and public health implications, highlighting the need for evidence-based interventions to improve foot health in this population. An effective interventional approach could include optimization of foot hygiene and footwear, provision of comprehensive medical treatment, and addressing social factors that lead to increased risk of foot problems. Targeted efforts to screen for and treat foot problems could result in improved health and social outcomes for homeless individuals.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0167463PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5147925PMC
July 2017

Lower Frailty Is Associated with Successful Cognitive Aging Among Older Adults with HIV.

AIDS Res Hum Retroviruses 2017 02 3;33(2):157-163. Epub 2017 Jan 3.

2 Department of Medical and Surgical Sciences for Adults and Children, Clinic of Infectious Diseases, University of Modena and Reggio Emilia , Modena, Italy .

Aging with HIV poses unique and complex challenges, including avoidance of neurocognitive disorder. Our objective here is to identify the prevalence and predictors of successful cognitive aging (SCA) in a sample of older adults with HIV. One hundred three HIV-infected individuals aged 50 and older were recruited from the Modena HIV Metabolic Clinic in Italy. Participants were treated with combination antiretroviral therapy for at least 1 year and had suppressed plasma HIV viral load. SCA was defined as the absence of neurocognitive impairment (as defined by deficits in tasks of episodic learning, information processing speed, executive function, and motor skills) depression, and functional impairment (instrumental activities of daily living). In cross-sectional analyses, odds of SCA were assessed in relation to HIV-related clinical data, HIV-Associated Non-AIDS (HANA) conditions, multimorbidity (≥2HANA conditions), and frailty. A frailty index was calculated as the number of deficits present out of 37 health variables. SCA was identified in 38.8% of participants. Despite no differences in average chronologic age between groups, SCA participants had significantly fewer HANA conditions, a lower frailty index, and were less likely to have hypertension. In addition, hypertension (odds ratio [OR] = 0.40, p = .04), multimorbidity (OR = 0.35, p = .05), and frailty (OR = 0.64, p = .04) were significantly associated with odds of SCA. Frailty is associated with the likelihood of SCA in people living with HIV. This defines an opportunity to apply knowledge from geriatric population research to people aging with HIV to better appreciate the complexity of their health status.
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http://dx.doi.org/10.1089/AID.2016.0189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5335777PMC
February 2017

A frailty index predicts survival and incident multimorbidity independent of markers of HIV disease severity.

AIDS 2015 Aug;29(13):1633-41

aDepartment of Medical and Surgical Sciences for Adults and Children, Clinic of Infectious Diseases, University of Modena and Reggio Emilia, Modena, Italy bFaculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada cDepartment of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy dDepartment of Community Health and Epidemiology, Dalhousie University, Halifax, Nova Scotia eChronic Viral Illness Service, McGill University Hospital Center, Montreal, Quebec fDepartment of Medicine (Geriatric Medicine and Neurology), Dalhousie University, Halifax, Nova Scotia, Canada.

Objectives: Aging with HIV is associated with multisystem vulnerability that might be well characterized by frailty. We sought to construct a frailty index based on health deficit accumulation in a large HIV clinical cohort and evaluate its validity including the ability to predict mortality and incident multimorbidity.

Design And Methods: This is an analysis of data from the prospective Modena HIV Metabolic Clinic cohort, 2004-2014. Routine health variables were screened for potential inclusion in a frailty index. Content, construct, and criterion validity of the frailty index were assessed. Multivariable regression models were built to investigate the ability of the frailty index to predict survival and incident multimorbidity (at least two chronic disease diagnoses) after adjusting for known HIV-related and behavioral factors.

Results: Two thousand, seven hundred and twenty participants (mean age 46 ± 8; 32% women) provided 9784 study visits; 37 non-HIV-related variables were included in a frailty index. The frailty index exhibited expected characteristics and met validation criteria. Predictors of survival were frailty index (0.1 increment, adjusted hazard ratio 1.63, 95% confidence interval 1.05-2.52), current CD4 cell count (0.48, 0.32-0.72), and injection drug use (2.51, 1.16-5.44). Predictors of incident multimorbidity were frailty index (adjusted incident rate ratio 1.98, 1.65-2.36), age (1.07, 1.05-1.09), female sex (0.61, 0.40-0.91), and current CD4 cell count (0.71, 0.59-0.85).

Conclusion: Among people aging with HIV in northern Italy, a frailty index based on deficit accumulation predicted survival and incident multimorbidity independently of HIV-related and behavioral risk factors. The frailty index holds potential value in quantifying vulnerability among people aging with HIV.
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http://dx.doi.org/10.1097/QAD.0000000000000753DOI Listing
August 2015

Social equity in health care.

CMAJ 2015 Jul;187(10):758

Dalhousie University (Brothers, To, Van Zoost), Halifax, NS; The Ottawa Hospital (Turnbull), Ottawa Ont.

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http://dx.doi.org/10.1503/cmaj.1150046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500704PMC
July 2015

Aging with HIV vs. HIV seroconversion at older age: a diverse population with distinct comorbidity profiles.

PLoS One 2015 13;10(4):e0118531. Epub 2015 Apr 13.

McGill University Health Center, Montreal, Canada.

Objective: People aging with HIV might have different health conditions compared with people who seroconverted at older ages. The study objective was to assess the prevalence of, and risk factors for, individual co-morbidities and multimorbidity (MM) between HIV-positive patients with a longer duration of HIV infection, and patients who seroconverted at an older age. We compared estimates across both groups to a matched community-based cohort sampled from the general population.

Methods: We performed a case-control study including antiretroviral therapy (ART)-experienced patients who were HIV seropositive for ≥ 20.6 years ("HIV-Aging"), or who were seropositive for < 11.3 years ("HIV-Aged") having access in 2013 at the Modena HIV Metabolic Clinic. Patients were matched in a 1:3 ratio with controls from the CINECA ARNO database. MM was defined as the concurrent presence of >2 NICM. Logistic regression models were constructed to evaluate associated predictors of NICM and MM.

Results: We analysed 404 HIV-Aging and 404 HIV-Aged participants in comparison to 2424 controls. The mean age was 46.7 ± 6.2 years, 28.9% were women. Prevalence of HIV co-morbidities and MM were significantly higher in the HIV-positive groups compared to the general population (p<0.001) and a trend towards higher rates of MM was found in aging vs aged group. This difference turned to be significant in patients above the age of 45 years old (p<0.001).

Conclusions: People aging with HIV display heterogeneous health conditions. Host factors and duration of HIV infection are associated with increased risk of MM compared to the general population.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0118531PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4395353PMC
April 2016

Modifications to the frailty phenotype criteria: Systematic review of the current literature and investigation of 262 frailty phenotypes in the Survey of Health, Ageing, and Retirement in Europe.

Ageing Res Rev 2015 May 4;21:78-94. Epub 2015 Apr 4.

Department of Medicine, Dalhousie University, Veterans' Memorial Building, 5955 Veterans' Memorial Lane, Halifax, Nova Scotia, Canada; Centre for Health Care of the Elderly, QEII Health Sciences Centre, Capital District Health Authority, Veterans' Memorial Building, 5955 Veterans' Memorial Lane, Halifax, Nova Scotia, Canada.

We conducted a systematic review to determine variability in how the criteria of the frailty phenotype (grip strength, weight loss, exhaustion, walking speed, physical activity) were assessed. We then evaluated the impact on estimating prevalence and mortality of modifying the criteria, using the Survey of Health, Ageing, & Retirement in Europe (SHARE). Five databases were searched for original research articles published after 2000, which evaluated frailty using the phenotypic criteria. Among the 264 included studies, 24 studies provided enough information to demonstrate that all criteria were assessed as proposed in the original frailty phenotype study by Fried et al. (2001). Physical inactivity and weight loss were the criteria most often modified. We then created 262 phenotypes from SHARE based on common modifications found in the review. Among these phenotypes, frailty prevalence ranged from 12.7% to 28.2%. Agreement with the primary frailty phenotype ranged from 0.662 to 0.967 and internal consistency ranged from 0.430 to 0.649. Women had 2.1-16.3% higher frailty prevalence than men. Areas under receiver operating characteristic curves for discriminating five-year mortality ranged from 0.607 (95% CI: 0.583-0.630) to 0.668 (0.645-0.691). The frailty phenotype often has been modified, and these modifications have important impact on its classification and predictive ability.
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http://dx.doi.org/10.1016/j.arr.2015.04.001DOI Listing
May 2015

Do Performance-based Health Measures Reflect Differences in Frailty Among Immigrants Age 50+ in Europe?

Can Geriatr J 2014 Sep 5;17(3):103-7. Epub 2014 Sep 5.

Geriatric Medicine Research, Department of Medicine, Dalhousie University, Halifax, NS; ; Centre for Health Care of the Elderly, Capital District Health Authority, Halifax, NS.

Background: Life course influences, including country of residence and country of birth, are associated with frailty index scores. We investigated these associations using performance-based health measures.

Methods: Among 33,745 participants age 50+ (mean age 64.8 ± 10.1; 55% women) in the Survey of Health, Ageing, and Retirement in Europe, grip strength, delayed word recall, and semantic verbal fluency were assessed. Participants were grouped by country of residence (Northern/Western Europe or Southern/Eastern Europe), and by country of birth (native-born, immigrants born in low- and middle-income countries [LMICs], or immigrants born in high-income countries [HICs]).

Results: Participants in Southern/Eastern Europe had lower mean test scores than those in Northern/Western Europe, and their scores did not differ by country of birth group. In Northern/Western Europe, compared with native-born participants, LMIC-born immigrants demonstrated lower mean grip strength (32.8 ± 7.6 kg vs. 35.7 ± 7.7 kg), delayed recall (2.9 ± 1.9 vs. 3.6 ± 1.9), and verbal fluency scores (16.0 ± 6.9 vs. 20.3 ± 7.0). HIC-born immigrants had mean scores higher than LMIC-born immigrants, but lower than native-born participants (all p<.001).

Conclusions: Cognitive and motor performance, measured from late middle age, were associated with national income levels of both country of residence and country of birth. This was similar to previously observed differences in frailty index scores.
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http://dx.doi.org/10.5770/cgj.17.114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4164677PMC
September 2014

Frailty in people aging with human immunodeficiency virus (HIV) infection.

J Infect Dis 2014 Oct 5;210(8):1170-9. Epub 2014 Jun 5.

Division of Geriatric Medicine, Dalhousie University Centre for Health Care of the Elderly, Capital District Health Authority, Halifax, Nova Scotia, Canada.

The increasing life spans of people infected with human immunodeficiency virus (HIV) reflect enormous treatment successes and present new challenges related to aging. Even with suppression of viral loads and immune reconstitution, HIV-positive individuals exhibit excess vulnerability to multiple health problems that are not AIDS-defining. With the accumulation of multiple health problems, it is likely that many people aging with treated HIV infection may be identified as frail. Studies of frailty in people with HIV are currently limited but suggest that frailty might be feasible and useful as an integrative marker of multisystem vulnerability, for organizing care and for comprehensively measuring the impact of illness and treatment on overall health status. This review explains how frailty has been conceptualized and measured in the general population, critically reviews emerging data on frailty in people with HIV infection, and explores how the concept of frailty might inform HIV research and care.
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http://dx.doi.org/10.1093/infdis/jiu258DOI Listing
October 2014

Biologic aging, frailty, and age-related disease in chronic HIV infection.

Curr Opin HIV AIDS 2014 Jul;9(4):412-8

aGeriatric Medicine Research bFaculty of Medicine, Dalhousie University cCentre for Healthcare of the Elderly, QEII Health Sciences Centre, Capital District Health Authority, Halifax, Nova Scotia, Canada.

Purpose Of Review: Effective therapies have transformed HIV infection into a chronic disease, and new problems are arising related to aging. This article reviews the aging process, age-related deficit accumulation and frailty, and how these might be affected by chronic HIV infection.

Recent Findings: Aging is characterized by acceleration in the rate of unrepaired physiologic damage an organism accumulates. HIV infection is associated with many factors that might affect the aging process, including extrinsic behavioral risk factors and co-infections, and multiple intrinsic factors, including intercellular communication, inflammation, and coagulation pathways. Whether each factor affects the aging process, they likely result in an increase in the risk of adverse health outcomes, and so give rise to frailty, likely with several clinical manifestations.

Summary: Age-related deficit accumulation is influenced by both the background or environmental rate of insults an organism sustains and the efficacy of intrinsic damage control and repair mechanisms. Both processes are likely affected in people living with HIV infection.
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http://dx.doi.org/10.1097/COH.0000000000000070DOI Listing
July 2014

Identifying common characteristics of frailty across seven scales.

J Am Geriatr Soc 2014 May 2;62(5):901-6. Epub 2014 Apr 2.

Geriatric Medicine Research, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.

Objectives: To determine whether commonly used frailty scales exhibit shared characteristics when applied to a representative sample of middle-aged and older Europeans.

Design: Secondary analysis of the Survey of Health, Ageing, and Retirement in Europe (SHARE).

Setting: Eleven European countries.

Participants: Community-dwelling adults (N = 27,527; mean age 65.3 ± 10.5, 55% female).

Measurements: Frailty was assessed using SHARE-operationalized versions of seven frailty scales: Edmonton Frail Scale, FRAIL scale, Groningen Frailty Indicator, frailty phenotype, Tilburg Frailty Indicator, a 70-item frailty index (FI), and a 44-item frailty index based on Comprehensive Geriatric Assessment.

Results: All frailty scales demonstrated right-skewed density distributions. On all scales, frailty scores increased nonlinearly with age, between 1% (FRAIL) and 3.6% (FI) per year on a log scale. Frailty scores on all scales exhibited dose-response relationships with 5-year mortality. On all scales, women had higher frailty scores than men of the same age but demonstrated better survival than did men with the same frailty score. On all scales except the frailty phenotype, 99% of participants had scores below the scale's theoretical maximum.

Conclusion: On each frailty scale, frailty score increased nonlinearly with age, mortality risk increased with frailty score, and women had higher scores than men but demonstrated better survival. Each scale except the frailty phenotype demonstrated an upper limit to frailty below the scale's theoretical maximum. Across commonly used frailty scales, these characteristics are common in nature but differ in magnitude.
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http://dx.doi.org/10.1111/jgs.12773DOI Listing
May 2014

Comparison of alternate scoring of variables on the performance of the frailty index.

BMC Geriatr 2014 Feb 24;14:25. Epub 2014 Feb 24.

Geriatric Medicine Research, Dalhousie University, Halifax, NS, Canada.

Background: The frailty index (FI) is used to measure the health status of ageing individuals. An FI is constructed as the proportion of deficits present in an individual out of the total number of age-related health variables considered. The purpose of this study was to systematically assess whether dichotomizing deficits included in an FI affects the information value of the whole index.

Methods: Secondary analysis of three population-based longitudinal studies of community dwelling individuals: Nova Scotia Health Survey (NSHS, n = 3227 aged 18+), Survey of Health, Ageing and Retirement in Europe (SHARE, n = 37546 aged 50+), and Yale Precipitating Events Project (Yale-PEP, n = 754 aged 70+). For each dataset, we constructed two FIs from baseline data using the deficit accumulation approach. In each dataset, both FIs included the same variables (23 in NSHS, 70 in SHARE, 33 in Yale-PEP). One FI was constructed with only dichotomous values (marking presence or absence of a deficit); in the other FI, as many variables as possible were coded as ordinal (graded severity of a deficit). Participants in each study were followed for different durations (NSHS: 10 years, SHARE: 5 years, Yale PEP: 12 years).

Results: Within each dataset, the difference in mean scores between the ordinal and dichotomous-only FIs ranged from 0 to 1.5 deficits. Their ability to predict mortality was identical; their absolute difference in area under the ROC curve ranged from 0.00 to 0.02, and their absolute difference between Cox Hazard Ratios ranged from 0.001 to 0.009.

Conclusions: Analyses from three diverse datasets suggest that variables included in an FI can be coded either as dichotomous or ordinal, with negligible impact on the performance of the index in predicting mortality.
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http://dx.doi.org/10.1186/1471-2318-14-25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3938909PMC
February 2014

Operationalization of frailty using eight commonly used scales and comparison of their ability to predict all-cause mortality.

J Am Geriatr Soc 2013 Sep 26;61(9):1537-51. Epub 2013 Aug 26.

Geriatric Medicine Research, Dalhousie University, Halifax, Nova Scotia, Canada.

Objectives: To operationalize frailty using eight scales and to compare their content validity, feasibility, prevalence estimates of frailty, and ability to predict all-cause mortality.

Design: Secondary analysis of the Survey of Health, Ageing and Retirement in Europe (SHARE).

Setting: Eleven European countries.

Participants: Individuals aged 50 to 104 (mean age 65.3 ± 10.5, 54.8% female, N = 27,527).

Measurements: Frailty was operationalized using SHARE data based on the Groningen Frailty Indicator, the Tilburg Frailty Indicator, a 70-item Frailty Index (FI), a 44-item FI based on a Comprehensive Geriatric Assessment (FI-CGA), the Clinical Frailty Scale, frailty phenotype (weighted and unweighted versions), the Edmonton Frail Scale, and the FRAIL scale.

Results: All scales had fewer than 6% of cases with at least one missing item, except the SHARE-frailty phenotype (11.1%) and the SHARE-Tilburg (12.2%). In the SHARE-Groningen, SHARE-Tilburg, SHARE-frailty phenotype, and SHARE-FRAIL scales, death rates were 3 to 5 times as high in excluded cases as in included ones. Frailty prevalence estimates ranged from 6% (SHARE-FRAIL) to 44% (SHARE-Groningen). All scales categorized 2.4% of participants as frail. Of unweighted scales, the SHARE-FI and SHARE-Edmonton scales most accurately predicted mortality at 2 (SHARE-FI area under the receiver operating characteristic curve (AUC) = 0.77, 95% confidence interval (CI) = 0.75-0.79); SHARE-Edmonton AUC = 0.76, 95% CI = 0.74-0.79) and 5 (both AUC = 0.75, 95% CI = 0.74-0.77) years. The continuous score of the weighted SHARE-frailty phenotype (AUC = 0.77, 95% CI = 0.75-0.78) predicted 5-year mortality better than the unweighted SHARE-frailty phenotype (AUC = 0.70, 95% CI = 0.68-0.71), but the categorical score of the weighted SHARE-frailty phenotype did not (AUC = 0.70, 95% CI = 0.68-0.72).

Conclusion: Substantive differences exist between scales in their content validity, feasibility, and ability to predict all-cause mortality. These frailty scales capture related but distinct groups. Weighting items in frailty scales can improve their predictive ability, but the trade-off between specificity, predictive power, and generalizability requires additional evaluation.
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http://dx.doi.org/10.1111/jgs.12420DOI Listing
September 2013
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