Risk for Congenital Anomalies in Children Conceived With Medically Assisted Fertility Treatment : A Population-Based Cohort Study.

BACKGROUND: More than 2 million children are conceived annually using assisted reproductive technologies (ARTs), with a similar number conceived using ovulation induction and intrauterine insemination (OI/IUI). Previous studies suggest that ART-conceived children are at increased risk for congenital anomalies (CAs). However, the role of underlying infertility in this risk remains unclear, and ART clinical and laboratory practices have changed drastically over time, particularly there has been an increase in intracytoplasmic sperm injection (ICSI) and cryopreservation. OBJECTIVE: To investigate the role of underlying infertility and fertility treatment on CA risks in the first 2 years of life. DESIGN: Propensity score-weighted population-based cohort study. SETTING: New South Wales, Australia. PARTICIPANTS: 851 984 infants (828 099 singletons and 23 885 plural children) delivered between 2009 and 2017. MEASUREMENTS: Adjusted risk difference (aRD) in CAs of infants conceived through fertility treatment compared with 2 naturally conceived (NC) control groups-those with and without a parental history of infertility (NC-infertile and NC-fertile). RESULTS: The overall incidence of CAs was 459 per 10 000 singleton births and 757 per 10 000 plural births. Compared with NC-fertile singleton control infants (n = 747 018), ART-conceived singleton infants (n = 31 256) had an elevated risk for major genitourinary abnormalities (aRD, 19.0 cases per 10 000 births [95% CI, 2.3 to 35.6]); the risk remained unchanged (aRD, 22 cases per 10 000 births [CI, 4.6 to 39.4]) when compared with NC-infertile singleton control infants (n = 36 251) (that is, after accounting for parental infertility), indicating that ART remained an independent risk. After accounting for parental infertility, ICSI in couples without male infertility was associated with an increased risk for major genitourinary abnormalities (aRD, 47.8 cases per 10 000 singleton births [CI, 12.6 to 83.1]). There was some suggestion of increased risk for CAs after fresh embryo transfer, although estimates were imprecise and inconsistent. There were no increased risks for CAs among OI/IUI-conceived infants (n = 13 574). LIMITATIONS: This study measured the risk for CAs only in those children who were born at or after 20 weeks' gestation. Observational study design precludes causal inference. Many estimates were imprecise. CONCLUSION: Patients should be counseled on the small increased risk for genitourinary abnormalities after ART, particularly after ICSI, which should be avoided in couples without problems of male infertility. PRIMARY FUNDING SOURCE: Australian National Health and Medical Research Council.

Childbirth timing and completed family size by the mode of conception-the role of medically assisted reproduction: a population-based cohort study in Australia.

Background: With declining total fertility rates to below replacement levels amongst all high-, middle- and low-income countries, coupled with increasing use of medically assisted reproduction (MAR) treatments globally, we describe the impact of these treatments on completed family size and childbearing timing in a country with unlimited publicly funded access to MAR. Methods: We utilised a unique longitudinal propensity score-weighted population-based birth cohort that included nulliparous mothers who gave birth after all major forms of MAR treatments (assisted reproductive technologies [ART], ovulation induction [OI], and intrauterine insemination [IUI]) and after natural conception (reference category) in Australia, 2003-2017. We followed first-time mothers over their reproductive lifespan (15-50 years). The primary outcome was completed family size (i.e., the mean cumulative number of children per mother of our cohort) and the fertility gap (i.e., adjusted difference in completed family size between MAR conceptions and the reference). Findings: Our cohort includes 481,866 first-time mothers, mean follow-up of 13.8 years. ART mothers (n = 25,296) were six years older (mean age: 34.6 years) than mothers who conceived naturally (28.7 years (reference)) while OI/IUI mothers were only 2.2 years older (31.0 years) than the reference. ART mothers had up to 27% smaller completed family size (2.54 children) compared to OI/IUI mothers (2.98 children) and natural conception mothers (3.23 children). ART mothers who resided in the lower socioeconomic areas were less likely to reach a similar family size to the natural conception mothers (fertility gap of 0.83 fewer children per ART mother compared to natural conception mothers) than ART mothers who resided in the higher socioeconomic areas (0.43 fewer children). Interpretation: Greater awareness of the limitations of MAR treatment to resolve childlessness and achieve desired family size is needed. Furthermore, with policymakers increasingly turning to MAR treatment as a tool to reverse declining fertility rates, their potential impact should not be overestimated. Funding: Australian National Health and Medical Research Council.

Population-wide contribution of medically assisted reproductive technologies to overall births in Australia: temporal trends and parental characteristics.

STUDY QUESTION: In a country with supportive funding for medically assisted reproduction (MAR) technologies, what is the proportion of MAR births over-time? SUMMARY ANSWER: In 2017, 6.7% of births were conceived by MAR (4.8% ART and 1.9% ovulation induction (OI)/IUI) with a 55% increase in ART births and a stable contribution from OI/IUI births over the past decade. WHAT IS KNOWN ALREADY: There is considerable global variation in utilization rates of ART despite a similar infertility prevalence worldwide. While the overall contribution of ART to national births is known in many countries because of ART registries, very little is known about the contribution of OI/IUI treatment or the socio-demographic characteristics of the parents. Australia provides supportive public funding for all forms of MAR with no restrictions based on male or female age, and thus provides a unique setting to investigate the contribution of MAR to national births as well as the socio-demographic characteristics of parents across the different types of MAR births. STUDY DESIGN, SIZE, DURATION: This is a novel population-based birth cohort study of 898 084 births using linked ART registry data and administrative data including birth registrations, medical services, pharmaceuticals, hospital admissions and deaths. Birth (a live or still birth of at least one baby of ≥400 g birthweight or ≥20 weeks' gestation) was the unit of analysis in this study. Multiple births were considered as one birth in our analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study included a total of 898 084 births (606 488 mothers) in New South Wales and the Australian Capital Territory, Australia 2009-2017. We calculated the prevalence of all categories of MAR-conceived births over the study period. Generalized estimating equations were used to examine the association between parental characteristics (parent's age, parity, socio-economic status, maternal country of birth, remoteness of mother's dwelling, pre-existing medical conditions, smoking, etc.) and ART and OI/IUI births relative to naturally conceived births. MAIN RESULTS AND THE ROLE OF CHANCE: The proportion of MAR births increased from 5.1% of all births in 2009 to 6.7% in 2017, representing a 30% increase over the decade. The proportion of OI/IUI births remained stable at around 2% of all births, representing 32% of all MAR births. Over the study period, ART births conceived by frozen embryo-transfer increased nearly 3-fold. OI/IUI births conceived using clomiphene citrate decreased by 39%, while OI/IUI births conceived using letrozole increased 56-fold. Overall, there was a 55% increase over the study period in the number of ART-conceived births, rising to 56% of births to mothers aged 40 years and older. In 2017, almost one in six births (17.6%) to mothers aged 40 years and over were conceived using ART treatment. Conversely, the proportion of OI/IUI births was similar across different mother's age groups and remained stable over the study period. ART children, but not OI/IUI children, were more likely to have parents who were socio-economically advantaged compared to naturally conceived children. For example, compared to naturally conceived births, ART births were 16% less likely to be born to mothers who live in the disadvantaged neighbourhoods after accounting for other covariates (adjusted relative risk (aRR): 0.84 [95% CI: 0.81-0.88]). ART- or OI/IUI-conceived children were 25% less likely to be born to immigrant mothers than births after natural conception (aRR: 0.75 [0.74-0.77]). LIMITATIONS, REASONS FOR CAUTION: The social inequalities that we observed between the parents of children born using ART and naturally conceived children may not directly reflect disparities in accessing fertility care for individuals seeking treatment. WIDER IMPLICATIONS OF THE FINDINGS: With the ubiquitous decline in fertility rates around the world and the increasing trend to delay childbearing, this population-based study enhances our understanding of the contribution of different types of MARs to population profiles among births in high-income countries. The parental socio-demographic characteristics of MAR-conceived children differ significantly from naturally conceived children and this highlights the importance of accounting for such differences in studies investigating the health and development of MAR-conceived children. STUDY FUNDING/COMPETING INTEREST(S): This study was funded through Australian National Health and Medical Research Council (NHMRC) grant: APP1127437. G.M.C. is an employee of The University of New South Wales (UNSW) and Director of the National Perinatal Epidemiology and Statistics Unit (NPESU), UNSW. The NPESU manages the Australian and New Zealand Assisted Reproduction Database with funding support from the Fertility Society of Australia and New Zealand. C.V. is an employee of The University of New South Wales (UNSW), Director of Clinical Research of IVFAustralia, Member of the Board of the Fertility Society of Australia and New Zealand, and Member of Research Committee of School of Women's and Children's Health, UNSW. C.V. reports grants from Australian National Health and Medical Research Council (NHMRC), and Merck KGaA. C.V. reports consulting fees, and payment or honoraria for lectures, presentations, speakers, bureaus, manuscript, writing or educational events or attending meeting or travel from Merck, Merck Sparpe & Dohme, Ferring, Gedon-Richter and Besins outside this submitted work. C.V. reported stock or stock options from Virtus Health Limited outside this submitted work. R.J.N. is an employee of The University of Adelaide, and Chair DSMC for natural therapies trial of The University of Hong Kong. R.J.N. reports grants from NHMRC. R.J.N. reports lecture fees and support for attending or travelling for lecture from Merck Serono which is outside this submitted work. L.R.J. is an employee of The UNSW and Foundation Director of the Centre for Big Data Research in Health at UNSW Sydney. L.R.J. reports grants from NHMRC. The other co-authors have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Comparison of Cardiovascular Safety for Smoking Cessation Pharmacotherapies in a Population-Based Cohort in Australia.

Importance: Although concerns exist regarding a potential increased risk of cardiovascular events for smoking cessation pharmacotherapies, there is general consensus that any increased risk associated with their use would be outweighed by the benefits of smoking cessation; thus, clinical guidelines recommend that such pharmacotherapies be offered to everyone who wants to quit smoking. In the interest of minimizing risk to patients, prescribers need evidence indicating how these pharmacotherapies compare with one another in terms of cardiovascular safety. Objective: To compare the risk of major adverse cardiovascular events (MACE) among individuals initiating varenicline, nicotine replacement therapy (NRT) patches, or bupropion. Design, Setting, and Participants: This retrospective, population-based cohort study using linked pharmaceutical dispensing, hospital admissions, and death data was conducted in New South Wales, Australia. Participants included adults who were dispensed a prescription smoking cessation pharmacotherapy between 2008 and 2015 or between 2011 and 2015, depending on the availability of the pharmacotherapies being compared. Pairwise comparisons were conducted for risk of MACE among 122 932 varenicline vs 92 148 NRT initiators; 342 064 varenicline vs 10 457 bupropion initiators; and 102 817 NRT vs 6056 bupropion initiators. Exposure: First course of the smoking cessation pharmacotherapy of interest. Main Outcomes and Measures: The primary outcome was MACE, defined as a composite of acute coronary syndrome, stroke, and cardiovascular death. Secondary outcomes were the individual components of MACE. Inverse probability of treatment weighting with high-dimensional propensity scores was used to account for potential confounding. Cox proportional hazards regression models with robust variance were used to estimate hazard ratios (HRs) and 95% CIs. Data were analyzed January 24, 2019, to September 1, 2021. Results: The mean (SD) age of included individuals ranged from 41.9 (14.2) to 49.8 (14.9) years, and the proportion of women ranged from 42.8% (52 702 of 123 128) to 52.2% (53 693 of 102 913). The comparison of 122 932 varenicline initiators and 92 148 NRT patch initiators showed no difference in the risk of MACE (HR, 0.87; 95% CI, 0.72-1.07) nor in the risk of the secondary outcomes of acute coronary syndrome (HR, 0.96; 95% CI, 0.76-1.21) and stroke (HR, 0.72; 95% CI, 0.45-1.14). However, decreased risk of cardiovascular death was found among varenicline initiators (HR, 0.49; 95% CI, 0.30-0.79). The results of comparisons involving bupropion were inconclusive owing to wide confidence intervals (eg, risk of MACE: 342 064 varenicline vs 10 457 bupropion initiators, HR, 0.87 [95% CI, 0.53-1.41]; 102 817 NRT patch vs 6056 bupropion initiators, HR, 0.79 [95% CI, 0.39-1.62]). Conclusions and Relevance: The finding of this cohort study that varenicline and NRT patch use have similar risk of MACE suggests that varenicline, the most efficacious smoking cessation pharmacotherapy, may be prescribed instead of NRT patches without increasing risk of major cardiovascular events. Further large-scale studies of the cardiovascular safety of varenicline and NRT relative to bupropion are needed.

A bespoke data linkage of an IVF clinical quality registry to population health datasets; methods and performance.

INTRODUCTION: Assisted reproductive technologies (ART), such as in-vitro fertilisation (IVF), have revolutionised the treatment of infertility, with an estimated 8 million babies born worldwide. However, the long-term health outcomes for women and their offspring remain an area of concern. Linking IVF treatment data to long-term health data is the most efficient method for assessing such outcomes. OBJECTIVES: To describe the creation and performance of a bespoke population-based data linkage of an ART clinical quality registry to state-based and national administrative datasets. METHODS: The linked dataset was created by deterministically and probabilistically linking the Australia and New Zealand Assisted Reproduction Database (ANZARD) to New South Wales (NSW) and Australian Capital Territory (ACT) administrative datasets (performed by NSW Centre for Health Record Linkage (CHeReL)) and to national claims datasets (performed by Australian Institute of Health and Welfare (AIHW)). The CHeReL's Master Linkage Key (MLK) was used as a bridge between ANZARD's partially identifiable patient data (statistical linkage key) and NSW and ACT administrative datasets. CHeReL then provided personal identifiers to the AIHW to obtain national content data. The results of the linkage were reported, and concordance between births recorded in ANZARD and perinatal data collections (PDCs) was evaluated. RESULTS: Of the 62,833 women who had ART treatment in NSW or ACT, 60,419 could be linked to the CHeReL MLK (linkage rate: 96.2%). A reconciliation of ANZARD-recorded births among NSW residents found that 94.2% (95% CI: 93.9-94.4%) of births were also recorded in state/territory-based PDCs. A high concordance was found in plurality status and birth outcome ≥99% agreement rate, Cohen's kappa ranged: 0.78-0.98) between ANZARD and PDCs. CONCLUSION: The data linkage resource demonstrates that high linkage rates can be achieved with partially identifiable data and that a population spine, such as the CHeReL's MLK, can be successfully used as a bridge between clinical registries and administrative datasets.

The Comparative Effectiveness of Varenicline and Nicotine Patches for Smoking Abstinence During Pregnancy: Evidence From a Population-based Cohort Study.

INTRODUCTION: In the general population, varenicline is consistently shown to be more efficacious for smoking cessation than nicotine replacement therapy (NRT). Current clinical guidelines for the management of smoking during pregnancy recommend against the use of varenicline, whilst supporting the use of NRT. However, little is known about the comparative effectiveness of these smoking cessation therapies among pregnant women. AIMS AND METHODS: Routinely-collected records of all births in two Australian States during 2011 and 2012 were used to create a population-based cohort of women who smoked during the first half of pregnancy. Pharmaceutical dispensing data were used to identify varenicline and nicotine patch dispensings in the first half of pregnancy. Propensity score matching was used to account for the potentially different distribution of confounding factors between the treatment groups. The outcome was defined as smoking abstinence during the second half of pregnancy. RESULTS: After propensity score-matching, our cohort comprised 60 women who used varenicline and 60 who used nicotine patches during the first half of pregnancy. More varenicline users (33.3%, 95% CI: 21.7%-46.7%) quit smoking than nicotine patch users (13.3%, 95% CI: 5.9%-24.6%). The adjusted rate difference was 24.2% (95% CI: 10.2%-38.2%) and the adjusted relative risk was 2.8 (95% CI: 1.4-5.7). CONCLUSIONS: Varenicline was almost three times more effective than nicotine patches in assisting pregnant women to quit smoking. Further studies are needed to corroborate our results. Together with data on the safety of varenicline during pregnancy, evidence regarding the relative benefit of varenicline and NRT during pregnancy important for informing clinical decisions for pregnant smokers. IMPLICATIONS: This study is the first to measure the comparative effectiveness of varenicline and nicotine patches during pregnancy - women using varenicline were almost three times as likely to quit smoking than those using nicotine patches. This study addressed a clinically important question using an observational study, noting that there is an absence of evidence from randomized controlled trials because of the ethical issues associated with including pregnant women in clinical trials of medicines of unknown safety.

Use of smoking cessation pharmacotherapies during pregnancy is not associated with increased risk of adverse pregnancy outcomes: a population-based cohort study.

BACKGROUND: Varenicline, bupropion and nicotine replacement therapy (NRT) are three effective pharmacotherapies for smoking cessation, but data about their safety in pregnancy are limited. We assessed the risk of adverse perinatal outcomes and major congenital anomalies associated with the use of these therapies in pregnancy in Australia. METHODS: Perinatal data for 1,017,731 deliveries (2004 to 2012) in New South Wales and Western Australia were linked to pharmaceutical dispensing, hospital admission and death records. We identified 97,875 women who smoked during pregnancy; of those, 233, 330 and 1057 were exposed to bupropion, NRT and varenicline in pregnancy, respectively. Propensity scores were used to match exposed women to those who were unexposed to any smoking therapy (1:10 ratio). Propensity scores and gestational age at exposure were used to match varenicline-exposed to NRT-exposed women (1:1 ratio). Time-dependent Cox proportional hazards models estimated hazard ratios (HR) with 95% confidence intervals (95% CI) for any adverse perinatal event (a composite of 10 unfavourable maternal and neonatal outcomes) and any major congenital anomaly. RESULTS: The risk of any adverse perinatal event was not significantly different between bupropion-exposed and unexposed women (39.2% versus 39.3%, HR 0.93, 95% CI 0.73-1.19) and between NRT-exposed and unexposed women (44.8% vs 46.3%, HR 1.02, 95% CI 0.84-1.23), but it was significantly lower in women exposed to varenicline (36.9% vs 40.1%, HR 0.86, 95% CI 0.77-0.97). Varenicline-exposed infants were less likely than unexposed infants to be born premature (6.5% vs 8.9%, HR 0.72, 95% CI 0.56-0.92), be small for gestational age (11.4% vs 15.4%, HR 0.68, 95% CI 0.56-0.83) and have severe neonatal complications (6.6% vs 8.2%, HR 0.74, 95% CI 0.57-0.96). Among infants exposed to varenicline in the first trimester, 2.9% had a major congenital anomaly (3.5% in unexposed infants, HR 0.91, 95% CI 0.72-1.15). Varenicline-exposed women were less likely than NRT-exposed women to have an adverse perinatal event (38.7% vs 51.4%, HR 0.58, 95% CI 0.33-1.05). CONCLUSIONS: Pregnancy exposure to smoking cessation pharmacotherapies does not appear to be associated with an increased risk of adverse birth outcomes. Lower risk of adverse birth outcomes in varenicline-exposed pregnancies is inconsistent with recommendations that NRT be used in preference to varenicline.

Adverse perinatal outcomes in immigrants: A ten-year population-based observational study and assessment of growth charts.

BACKGROUND: Maternity populations are becoming increasingly multiethnic. Conflicting findings exist regarding the risk of adverse perinatal outcomes among immigrant mothers from different world regions and which growth charts are most appropriate for identifying the risk of adverse outcomes. OBJECTIVE: To evaluate whether infant mortality and morbidity, and the categorisation of infants as small for gestational age or large for gestational age (SGA or LGA) vary by maternal country of birth, and to assess whether the choice of growth chart alters the risk of adverse outcomes in infants categorised as SGA and LGA. METHODS: A population cohort of 601 299 singleton infants born in Australia to immigrant mothers was compared with 1.7 million infants born to Australian-born mothers, 2004-2013. Infants were categorised as SGA and LGA according to a descriptive Australian population-based birthweight chart (Australia-2012 reference) and the prescriptive INTERGROWTH-21st growth standard. Propensity score reweighting was used for the analysis. RESULTS: Compared to Australian-born infants, infants of mothers from Africa, Philippines, India, other Asia countries, and the Middle East had between 15.4% and 48.1% elevated risk for stillbirth, preterm delivery, or low Apgar score. The association between SGA and LGA and perinatal mortality varied markedly by growth chart and country of birth. Notably, SGA infants from African-born mothers had a relative risk of perinatal mortality of 6.1 (95% CI 4.3, 6.7) and 17.3 (95% CI 12.0, 25.0) by the descriptive and prescriptive charts, respectively. LGA infants born to Australian-born mothers were associated with a 10% elevated risk of perinatal mortality by the descriptive chart compared to a 15% risk reduction by the prescriptive chart. CONCLUSIONS: Country-of-birth-specific variations are becoming increasingly important for providing ethnically appropriate and safe maternity care. Our findings highlight significant variations in risk of adverse perinatal outcomes in immigrant subgroups, and demonstrate how the choice of growth chart alters the quantification of risk associated with being born SGA or LGA.

Impact of depression and recreational drug use on emergency department encounters and hospital admissions among people living with HIV in Ontario: A secondary analysis using the OHTN cohort study.

INTRODUCTION: Nearly half of HIV-positive patients experience mental health and substance use problems, but many do not receive adequate or ongoing mental health or addiction care. This lack of ongoing care can result in the use of costly acute care services. Prospective evaluations of the relationship between psychiatric and substance use disorders and acute care services use are lacking, and this information is needed to understand unmet needs and improve access to appropriate services. METHODS: We conducted a secondary data analysis from a multicenter, longitudinal, prospective cohort study (n = 3,482 adults) between October 1, 2007 and March 31, 2013. We used explanatory extended Cox proportional hazard regression models to examine the impact of current depression and recreational drug use on acute care services use, and to explore whether current depression and recreational drug use were associated with potentially avoidable acute care services use. RESULTS: Over our 5.5 year study period, HIV-positive participants with current depression-only (aHR [95% CI]:1.2[1.1-1.4]), recreational drug use-only (1.3[1.1-1.6]), or co-occurring depression and recreational drug use (1.4[1.2-1.7]) were associated with elevated hazard of emergency department (ED) encounters compared to participants without these conditions. Over half of ED encounters were potentially avoidable. Participants with current depression-only (1.3[1.1-1.5];1.3[1.03-1.6]), recreational drug use-only (1.3[1.04-1.6];1.5[1.1-1.9]), or co-occurring depression and recreational drug use (1.3[1.04-1.7];1.4[1.06-1.9]) were associated with elevated hazard of low-acuity or repeated ED encounters respectively. CONCLUSIONS: We found a significant increase in ED services use and potentially avoidable ED encounters (including low-acuity or repeated ED encounters), particularly among those with either current depression or recreational drug use. These findings emphasize the challenges in managing HIV and mental health/addiction co-morbidities in the current HIV care model. Future research should evaluate integrated and collaborative care programs for improving the coordination of care and effectively treat mental health and addiction problems among HIV-positive patients in Ontario.

The Cost-Effectiveness of Salpingectomies for Family Planning in the Prevention of Ovarian Cancer.

OBJECTIVE: Ovarian cancer is the most lethal gynaecologic cancer. Disease prevention may be the only method to reduce the incidence of ovarian cancer. The Society of Gynecologic Oncology advised that salpingectomies may be an appropriate and feasible strategy for ovarian cancer risk reduction. This study conducted an economic evaluation from a societal perspective of bilateral salpingectomies versus conventional sterilization techniques in the prevention of ovarian cancer. STUDY DESIGN: We performed a micro-cost analysis comparing laparoscopic tubal coagulation, tubal clips and bilateral salpingectomies at the Michael Garron Hospital, formerly the Toronto East General Hospital, from 2015 to 2016. A Markov model was used in the cost-effectiveness and cost-utility analyses on these surgical procedures in ovarian cancer prevention. Costs were derived for the number ovarian cancer cases observed per sterilization method, cancer treatment, and associated procedural costs over each cancer patient's lifetime. The number of bilateral salpingectomies required to prevent an additional ovarian cancer case with the recommended treatment was also estimated. RESULTS: Bilateral salpingectomies performed at the Michael Garron Hospital generated savings of $7823 per life-year gained (95% CI $3248-$10 190; incremental cost [ΔC] -$907, incremental effect [ΔE] 0.11 life-years gained) compared with tubal clips and savings of $6315 per life-year gained (95% CI -$6360 to $9342; ΔC -$755, ΔE 0.11 life-years gained) compared with tubal coagulation. Most importantly, for every 150 bilateral salpingectomies performed, one case of ovarian cancer may be prevented. CONCLUSION: Laparoscopic bilateral salpingectomy is the dominant, cost-effective surgical strategy when compared to tubal clips and tubal coagulation to prevent ovarian cancer. Laparoscopic bilateral salpingectomies reduce costs and enhance quality-adjusted life-years relative to the two alternative treatments.

Prevalence, Recurrence, and Incidence of Current Depressive Symptoms among People Living with HIV in Ontario, Canada: Results from the Ontario HIV Treatment Network Cohort Study.

INTRODUCTION: Current studies of depression among people living with HIV focus on describing its point prevalence. Given the fluctuating nature of depression and its profound impacts on clinical and quality-of-life outcomes, this study aimed to examine the prevalence, recurrence and incidence of current depressive symptoms and its underlying catalysts longitudinally and systematically among these individuals. METHODS: We conducted a prospective cohort study between October 1, 2007 and December 31, 2012 using longitudinal linked data sources. Current depressive symptoms was identified using the Centre for Epidemiologic Studies Depression Scale or the Kessler Psychological Distress Scale, first at baseline and again during follow-up interviews. Multivariable regressions were used to characterize the three outcomes. RESULTS: Of the 3,816 HIV-positive participants, the point prevalence of depressive symptoms was estimated at 28%. Of the 957 participants who were identified with depressive symptoms at baseline and who had at least two years of follow-up, 43% had a recurrent episode. The cumulative incidence among 1,745 previously depressive symptoms free participants (at or prior to baseline) was 14%. During the five-year follow-up, our multivariable models showed that participants with greater risk of recurrent cases were more likely to feel worried about their housing situation. Participants at risk of developing incident cases were also likely to be younger, gay or bisexual, and unable to afford housing-related expenses. CONCLUSIONS: Depressive symptoms are prevalent and likely to recur among people living with HIV. Our results support the direction of Ontario's HIV/AIDS Strategy to 2026, which addresses medical concerns associated with HIV (such as depression) and the social drivers of health in order to enhance the overall well-being of people living with or at risk of HIV. Our findings reinforce the importance of providing effective mental health care and demonstrate the need for long-term support and routine management of depression, particularly for individuals at high risk.

Adequacy of Mental Health Services for HIV-Positive Patients with Depression: Ontario HIV Treatment Network Cohort Study.

BACKGROUND: Major depression can profoundly impact clinical and quality-of-life outcomes of people living with HIV, and this disease is underdiagnosed and undertreated in many HIV-positive individuals. Here, we describe the prevalence of publicly funded primary and secondary mental health service use and antidepressant use, as well as mental health care for depression in accordance with existing Canadian guidelines for HIV-positive patients with depression in Ontario, Canada. METHODS: We conducted a prospective cohort study linking data from the Ontario HIV Treatment Network Cohort Study with administrative health databases in the province of Ontario, Canada. Current depression was assessed using the Center for Epidemiologic Depression Scale or the Kessler Psychological Distress Scale. Multivariable regressions were used to characterize prevalence outcomes. RESULTS: Of 990 HIV-positive patients with depression, 493 (50%) patients used mental health services; 182 (18%) used primary services (general practitioners); 176 (18%) used secondary services (psychiatrists); and 135 (14%) used both. Antidepressants were used by 407 (39%) patients. Patients who identified as gay, lesbian, or bisexual, as having low income or educational attainment, or as non-native English speakers or immigrants to Canada were less likely to obtain care. Of 493 patients using mental health services, 250 (51%) received mental health care for depression in accordance with existing Canadian guidelines. CONCLUSIONS: Our results showed gaps in delivering publicly funded mental health services to depressed HIV-positive patients and identified unequal access to these services, particularly among vulnerable groups. More effective mental health policies and better access to mental health services are required to address HIV-positive patient needs and reduce depression's impact on their lives.

Economic Evaluation of Community-Based HIV Prevention Programs in Ontario: Evidence of Effectiveness in Reducing HIV Infections and Health Care Costs.

Investments in community-based HIV prevention programs in Ontario over the past two and a half decades are assumed to have had an impact on the HIV epidemic, but they have never been systematically evaluated. To help close this knowledge gap, we conducted a macro-level evaluation of investment in Ontario HIV prevention programs from the payer perspective. Our results showed that, from 1987 to 2011, province-wide community-based programs helped to avert a total of 16,672 HIV infections, saving Ontario's health care system approximately $6.5 billion Canadian dollars (range 4.8-7.5B). We also showed that these community-based HIV programs were cost-saving: from 2005 to 2011, every dollar invested in these programs saved about $5. This study is an important first step in understanding the impact of investing in community-based HIV prevention programs in Ontario and recognizing the impact that these programs have had in reducing HIV infections and health care costs.

Validation of Six Short and Ultra-short Screening Instruments for Depression for People Living with HIV in Ontario: Results from the Ontario HIV Treatment Network Cohort Study.

OBJECTIVE: Major depression affects up to half of people living with HIV. However, among HIV-positive patients, depression goes unrecognized 60-70% of the time in non-psychiatric settings. We sought to evaluate three screening instruments and their short forms to facilitate the recognition of current depression in HIV-positive patients attending HIV specialty care clinics in Ontario. METHODS: A multi-centre validation study was conducted in Ontario to examine the validity and accuracy of three instruments (the Center for Epidemiologic Depression Scale [CESD20], the Kessler Psychological Distress Scale [K10], and the Patient Health Questionnaire depression scale [PHQ9]) and their short forms (CESD10, K6, and PHQ2) in diagnosing current major depression among 190 HIV-positive patients in Ontario. Results from the three instruments and their short forms were compared to results from the gold standard measured by Mini International Neuropsychiatric Interview (the "M.I.N.I."). RESULTS: Overall, the three instruments identified depression with excellent accuracy and validity (area under the curve [AUC]>0.9) and good reliability (Kappa statistics: 0.71-0.79; Cronbach's alpha: 0.87-0.93). We did not find that the AUCs differed in instrument pairs (p-value>0.09), or between the instruments and their short forms (p-value>0.3). Except for the PHQ2, the instruments showed good-to-excellent sensitivity (0.86-1.0) and specificity (0.81-0.87), excellent negative predictive value (>0.90), and moderate positive predictive value (0.49-0.58) at their optimal cut-points. CONCLUSION: Among people in HIV care in Ontario, Canada, the three instruments and their short forms performed equally well and accurately. When further in-depth assessments become available, shorter instruments might find greater clinical acceptance. This could lead to clinical benefits in fast-paced speciality HIV care settings and better management of depression in HIV-positive patients.

Food insufficiency, housing and health-related quality of life: results from the Positive Spaces, Healthy Places study.

Studies of people living with HIV who are homeless or unstably housed show a high prevalence of food insufficiency (>50%) and associated poor health outcomes; however, most evidence is in the form of cross-sectional studies. To better understand this issue, we conducted a longitudinal study to examine the impact of food insufficiency and housing instability on overall physical and mental health-related quality of life (HRQoL) among people living with HIV in Ontario. Six hundred and two adults living with HIV were enrolled in the Positive Spaces, Healthy Places study and followed from 2006 to 2009. Interviewer-administered questionnaires were used, and generalized linear mixed-effects models constructed to examine longitudinal associations between food insufficiency, housing instability and physical and mental HRQoL. At baseline, 57% of participants were classified as food insufficient. After adjusting for potential confounders, longitudinal analyses revealed a significant, negative association between food insufficiency and physical and mental HRQoL outcomes, respectively [effect size (ES) with 95% confidence interval (CI): (ES = -2.1, CI = -3.9,-0.3); (ES = -3.5, CI = -6.1,-1.5)]. Furthermore, difficulties meeting housing costs were shown to have additional negative impacts on mental HRQoL. Food insufficiency is highly prevalent among people living with HIV in Ontario, particularly for those with unstable housing. This vulnerable group of individuals is in urgent need of changes to current housing programmes, services and policies, as well as careful consideration of their unmet nutritional needs.