Alexandra Cernat’s research while affiliated with McMaster University and other places

Treatment-resistant depression (TRD) occurs when depressive symptoms persist after a patient has tried at least two antidepressants at an appropriate dose for an adequate length of time, as judged by their clinician. Understanding what it is like to live with and seek care for TRD can inform treatment planning and contribute to health technology assessments for depression-related therapies. Our objective was to systematically review this evidence through an investigation of qualitative literature about the experiences of people who have TRD. We searched MEDLINE, CINAHL, PsycINFO, and the Web of Science Core Collection. Publications eligible for inclusion were English-language primary empirical qualitative studies or the qualitative component of mixed methods studies examining adults’ experiences with TRD or with specific treatment options for TRD. Two reviewers independently screened and extracted data, as well as critically appraised included studies using the Standards for Reporting Qualitative Research (SRQR) instrument. This review was guided by integrative meta-synthesis. Data analysis consisted of a staged coding process similar to grounded theory. The protocol was registered in PROSPERO prior to the search (record ID: CRD42022356813). Sixteen studies were included from screening 18,568 results. Two studies focused on the overall experience of TRD and 14 explored experiences of specific treatments such as ketamine. Patients described the depressive symptoms they experienced, a sense of futility and desperation to find an effective treatment, and their experiences with new, sometimes experimental, therapies including deriving benefits beyond the clinical. Overall, few studies have examined the patient experience of TRD, reflecting the clinical complexity of this patient population. As most literature coalesced around experiences of specific treatments, greater examination of the overall experience of TRD is needed to inform clinical practice, and administrative and funding policy decisions for interventions that may be effective for this patient population. PROSPERO registration number: CRD42022356813.

Objective Screening for lung cancer with low dose computed tomography aims to reduce lung cancer mortality, but there is a lack of knowledge about how target populations consider its potential benefits and harms. Methods We conducted a systematic review of primary empirical studies published in any jurisdiction since 2002 using an integrative meta-synthesis technique. We searched six health and social science databases. Two reviewers independently screened titles, abstracts, and potentially eligible full-text studies. Quantitative assessments and open-ended perspectives on benefits and harms were extracted and convergently integrated at analysis using a narrative approach. Study quality was assessed. Results The review included 26 quantitative, 18 qualitative, and 5 mixed methods studies. Study quality was acceptable. Lung cancer screening was widely perceived to be personally beneficial for early detection and reassurance. Radiation exposure and screening accuracy were recognised as harms, but these were frequently considered to be justified by early detection of lung cancer. Stigma, anxiety, and fear related to screening procedures and results were pervasive among current smokers. People with low incomes reported not participating in screening because of potential out-of-pocket costs and geographic access. Conclusions Populations targeted for lung cancer screening tended to consider screening as personally beneficial and rationalised physical, but not psychological, harms. Screening programmes should be clear about benefits, use non-stigmatising design, and consider equity as a guiding principle.

Introduction Legalization in many jurisdictions has increased the prevalence of cannabis use, including during pregnancy and lactation. Accordingly, clinicians providing perinatal and infant care are increasingly required to counsel about this topic, even if they do not feel comfortable or prepared for this conversation. The aim of this research was to explore how prenatal clinicians and pregnant and lactating women interact with cannabis consumption. Methods Using qualitative description, we conducted semi‐structured interviews with 75 individuals in Canada: 23 clinicians who provide pregnancy and lactation care, and 52 individuals who made cannabis consumption decisions during pregnancy and/or lactation. Data were analyzed using inductive content analysis. Results Three phases of the clinical encounter influenced decision‐making about cannabis consumption: initiation of a discussion about cannabis, sense‐making, and the outcome of the encounter. Patients and clinicians described similar ideals for a counseling encounter about cannabis consumption during pregnancy or lactation: open, patient‐centered conversation grounded in an informed decision‐making model to explore the benefits, risks, and alternatives to cannabis. While clinicians described these values as reflecting real clinical interactions, patients reported that in their experience, actual interactions did not live up to these ideals. Conclusion Clinicians and pregnant and lactating people report desiring the same things from a counseling interaction about cannabis: sharing of information, identification of values, and facilitation of a decision. Both groups endorse an open, nonjudgemental counseling approach that explores the reasons why a patient is considering cannabis consumption and reflects these reasons against available evidence and alternatives known to be safe.

Many patients with major depressive disorder (MDD) try multiple antidepressants before finding one that works well and is tolerable. Pharmacogenomic (PGx) testing was developed to facilitate more efficacious prescribing. This technology has not been robustly implemented clinically. Patient perspectives are critical to policy decisions, but the views of patients with MDD about the use of PGx testing to guide antidepressant prescribing have not been extensively examined, particularly in publicly funded healthcare systems. The purpose of this qualitative description study was to produce actionable patient perspectives evidence to inform future technology assessment of PGx testing. We conducted semi-structured interviews with 21 adults with MDD for which antidepressants were indicated in Ontario, Canada, and used the Ontario Decision Determinants Framework to conduct an unconstrained deductive content analysis. Patients expressed views about the overall clinical benefit of PGx testing in depression care, preferences for deployment of testing, perspectives on ethical considerations, opinions about equity and patient care, and beliefs regarding the feasibility of adopting PGx testing into the healthcare system. They also worried about the possibility of conflicts of interest between PGx test manufacturers and pharmaceutical companies. This study provides policymakers with patient priorities to facilitate the development of patient-centred policies. It highlights that formal adoption of PGx testing into the healthcare system requires a focus on equity of access and health outcomes.

Direct-to-consumer (DTC) genetic testing exists largely outside of any regulatory schemes, and studies providing a comprehensive overview of the ethical, social, legal, and technological considerations for regulating these types of technologies are lacking. This paper uses the 3-I framework for policy analysis to analyze the ideas, interests, and institutions relevant to policy development for DTC genetic testing in North America and internationally. A scoping review was conducted. Citation databases were searched for papers addressing the ethical, social, legal, and technological implications of DTC genetic testing; stakeholder perspectives on and experiences with DTC genetic testing; or the effect of such testing on the healthcare system. Ninety-nine publications, organizational reports, governmental documents, or pieces of legislation were included. The ideas included are autonomy, informed decision making, privacy, and clinical validity and utility. The interests discussed are those of the public and healthcare providers. The institutions included are regulatory organizations such as the Food and Drug Administration in the United States, laws governing the implementation or delivery of genetic testing in general, and legislation created to protect against genetic discrimination. This analysis clarifies the ethical, social, legal, and technological issues of DTC genetic testing regulation. This information can be used by policy makers to develop or strengthen regulations for DTC genetic testing such as requiring an assessment of the clinical validity of tests before they become publicly available, controlling how tests are marketed, and stipulating requirements for healthcare provider involvement and informed consent.

Cascade genetic testing is the identification of individuals at risk for a hereditary condition by genetic testing in relatives of people known to possess particular genetic variants. Cascade testing has health system implications, however cascade costs and health effects are not considered in health technology assessments (HTAs) that focus on costs and health consequences in individual patients. Cascade health service use must be better understood to be incorporated in HTA of emerging genetic tests for children. The purpose of this review was to characterise published research related to patterns and costs of cascade health service use by relatives of children with any condition diagnosed through genetic testing. To this end, a scoping literature review was conducted. Citation databases were searched for English-language papers reporting uptake, costs, downstream health service use, or cost-effectiveness of cascade investigations of relatives of children who receive a genetic diagnosis. Included publications were critically appraised, and findings were synthesised. Twenty publications were included. Sixteen had a paediatric proband population; four had a combined paediatric and adult proband population. Uptake of cascade testing varied across diseases, from 37% for cystic fibrosis, 39% to 65% for hypertrophic cardiomyopathy, and 90% for rare monogenic conditions. Two studies evaluated costs. It was concluded that cascade testing in the child-to-parent direction has been reported in a variety of diseases, and that understanding the scope of cascade testing will aid in the design and conduct of HTA of emerging genetic technologies to better inform funding and policy decisions.

Cascade genetic testing is indicated for family members of individuals testing positive on a genetic test, and is particularly relevant for child health because of their vulnerability and the long-term health and economic implications. Cascade testing has patient- and health system-level implications; however cascade costs and health effects are not routinely considered in economic evaluation. The methodological challenges associated with incorporating cascade effects in economic evaluation require examination. The purpose of this scoping review was to identify published economic evaluations that considered cascade genetic testing. Citation databases were searched for English-language economic evaluations reporting on cascade genetic testing. Nineteen publications were included. In four, genetic testing was used to identify new index patients—cascade effects were also considered; thirteen assessed cascade genetic testing strategies for the identification of at-risk relatives; and two calculated the costs of cascade genetic testing as a secondary objective. Methodological challenges associated with incorporating cascade effects in economic evaluation are related to study design, costing, measurement and valuation of health outcomes, and modeling. As health economic studies may currently be underestimating both the cost and health benefits attributable to genetic technologies through omission of cascade effects, development of methods to address these difficulties is required.

Background/aims: Children with bilateral cataracts may undergo immediate sequential bilateral cataract surgery (ISBCS), which involves surgery on both eyes during the same general anaesthesia, or delayed sequential bilateral cataract surgery (DSBCS), which involves operating on each eye on separate days and requires a second anaesthesia. ISBCS is viewed with caution because of the risk of bilateral endophthalmitis. Proponents of ISBCS emphasise that the incidence of serious complications is low and is outweighed by benefits such as avoidance of multiple anaesthesia, faster visual rehabilitation and potential for decreased costs. However, there is a paucity of literature regarding the cost-effectiveness of ISBCS in children. We conducted a cost-effectiveness analysis to determine whether ISBCS is more cost-effective than DSBCS from the societal and health system perspectives in Ontario, Canada, which has a universal, single-payer system. Methods: A retrospective analysis of children who underwent ISBCS or DSBCS at a tertiary referral paediatric hospital was conducted. A decision tree was constructed using TreeAge Pro 2018 software. Clear visual axis was the measure of effectiveness. A time horizon of 8 weeks postoperatively was adopted. Both direct and indirect costs were included. Results: Fifty-three children were included, 37 in the ISBCS group and 16 in the DSBCS group. ISBCS and DSBCS were equally effective. ISBCS resulted in cost-savings of $3,776 (95$4,641 to $12,578) CAD, per patient, from the societal perspective and$2,200 (95% CI:−$5,615 to$10,373) CAD per patient from the health system perspective. Conclusion: ISBCS was less costly than DSBCS from both societal and health system perspectives while being equally effective.

The last decade has experienced unprecedented uptake of noninvasive prenatal testing (NIPT), creating significant changes in the way prenatal clinicians provide services. Through the lens of social shaping of technology, we examine the effects of the introduction of this technology on the health care system in Ontario, Canada. Using a qualitative descriptive approach, we conducted a cross-sectional study investigating clinicians’ perspectives of NIPT in 2014, 2016, and 2018. Through in-depth interviews ( n = 37), we explored their perspectives on the impact of NIPT on their referral practices, workload, coordination of testing modalities, education and counseling, and elicited their views on recent expansions of the test. Findings suggest that the introduction of NIPT has created unintended consequences with respect to clinician workload and wellness, clinician education, equity of access, and public system resources. Responsiveness from decision makers is key to ensuring the responsible use of NIPT in the health care system.