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      Healthcare utilisation and costs associated with adherence to antipsychotics among people living with HIV/AIDS and schizophrenia: a population-based cohort study in British Columbia, Canada


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          Non-adherence to antipsychotics is the greatest obstacle to treating schizophrenia. We assessed the economic and clinical impacts of adherence to antipsychotics among people living with HIV/AIDS (PLWH) and schizophrenia in British Columbia, Canada.

          Design and setting

          A population-based cohort study in British Columbia, Canada.


          Eligible PLWH were enrolled in the Seek and Treat for Optimal Prevention HIV/AIDS population-based cohort during 2001–2016, diagnosed with schizophrenia, on antipsychotics for ≥1 day, and followed for ≥1 year from schizophrenia diagnosis date or 1 January 2001, whichever occurred last.

          Primary and secondary outcome measures

          A two-part model assessed the marginal effect of adherence on healthcare costs (in 2016 Canadian dollar), while logistic regression examined the effect on virological failure, and generalised linear mixed models examined the effect on hospital readmissions within 30 days and length of hospital stay.


          Among 726 PLWH with schizophrenia, ≥80% adherence to antipsychotics increased from 25% (50/198) in 2001 to 41% (225/554) in 2016. In most years, we observed no difference in adherence to antipsychotics among those who used only injectables, only non-injectables, and a combination of both, or among those who have ever consumed typical/first-generation antipsychotics and who consumed only atypical/second-generation antipsychotics. Overall healthcare costs were higher in the non-adherent group ($C2185), driven by the average annual hospitalisation costs ($C5517), particularly among women ($C8806) and people who ever injected drugs (PWID) ($C5985). Non-adherent individuals also experienced higher hospital readmissions (adjusted odds ratio (aOR) 1.48, 95% CI 1.23 to 1.77), and longer hospital stays (adjusted mean ratio 1.23, 95% CI 1.13 to 1.35) in comparison to adherent individuals. We found no difference in virological failure by adherence groups, except when we stratified by gender where the aOR for women was 2.48 (95% CI 1.06 to 5.82).


          Our results showed that implementing strategies and interventions to increase antipsychotic adherence, particularly among women and PWID, will be critical in addressing this public health challenge.

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          Most cited references35

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          A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation

          The objective of this study was to develop a prospectively applicable method for classifying comorbid conditions which might alter the risk of mortality for use in longitudinal studies. A weighted index that takes into account the number and the seriousness of comorbid disease was developed in a cohort of 559 medical patients. The 1-yr mortality rates for the different scores were: "0", 12% (181); "1-2", 26% (225); "3-4", 52% (71); and "greater than or equal to 5", 85% (82). The index was tested for its ability to predict risk of death from comorbid disease in the second cohort of 685 patients during a 10-yr follow-up. The percent of patients who died of comorbid disease for the different scores were: "0", 8% (588); "1", 25% (54); "2", 48% (25); "greater than or equal to 3", 59% (18). With each increased level of the comorbidity index, there were stepwise increases in the cumulative mortality attributable to comorbid disease (log rank chi 2 = 165; p less than 0.0001). In this longer follow-up, age was also a predictor of mortality (p less than 0.001). The new index performed similarly to a previous system devised by Kaplan and Feinstein. The method of classifying comorbidity provides a simple, readily applicable and valid method of estimating risk of death from comorbid disease for use in longitudinal studies. Further work in larger populations is still required to refine the approach because the number of patients with any given condition in this study was relatively small.
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            Suicide and schizophrenia: a systematic review of rates and risk factors

            Risk assessment is a core skill in psychiatry. Risk prediction for suicide in schizophrenia is known to be complex. We undertook a systematic review of all original studies concerning suicide in schizophrenia published since 2004. We found 51 data-containing studies (from 1281 studies screened) that met our inclusion criteria, and ranked these by standardized quality criteria. Estimates of rates of suicide and risk factors associated with later suicide were identified, and the risk factors were grouped according to type and strength of association with suicide. Consensus on the lifetime risk of suicide was a rate of approximately 5%. Risk factors with a strong association with later suicide included being young, male, and with a high level of education. Illness-related risk factors were important predictors, with number of prior suicide attempts, depressive symptoms, active hallucinations and delusions, and the presence of insight all having a strong evidential basis. A family history of suicide, and comorbid substance misuse were also positively associated with later suicide. The only consistent protective factor for suicide was delivery of and adherence to effective treatment. Prevention of suicide in schizophrenia will rely on identifying those individuals at risk, and treating comorbid depression and substance misuse, as well as providing best available treatment for psychotic symptoms.
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              Non-adherence to medication in patients with psychotic disorders: epidemiology, contributing factors and management strategies.

              Although non-adherence is common across all branches of medicine, psychotic disorders pose additional challenges that increase its risk. Despite the importance of non-adherence, clinicians generally spend too little time on assessing and addressing adherence attitudes and behaviors. Importantly, how adherence is measured significantly impacts the findings, and the most frequently employed methods of asking patients or judging adherence indirectly based on efficacy or tolerability information have poor validity. Novel technologies are being developed that directly assess adherence and that can also be used to both provide real-time feedback to clinicians and serve as an intervention with patients. Several treatments are available that can positively impact adherence. Among psychosocial interventions, those combining multiple approaches and involving multiple domains seem to be most effective. Although long-acting injectable antipsychotics are theoretically a very powerful tool to assure adherence and signal non-adherence, recent results from randomized controlled trials failed to show superiority compared to oral antipsychotics. These data are in contrast to nationwide cohort studies and mirror-image studies, which arguably include more representative patients receiving long-acting antipsychotics in clinical practice. This disconnect suggests that traditional randomized controlled trials are not necessarily the best way to study interventions that are thought to work via reducing non-adherence. Clearly, non-adherence is likely to remain a major public health problem despite treatment advances. However, increasing knowledge about factors affecting adherence and leveraging novel technologies can enhance its early assessment and adequate management, particularly in patients with psychotic disorders.

                Author and article information

                BMJ Open
                BMJ Open
                BMJ Open
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                19 April 2023
                : 13
                : 4
                : e070680
                [1 ]Ringgold_198129British Columbia Centre for Excellence in HIV/AIDS , Vancouver, British Columbia, Canada
                [2 ]departmentDivision of Infectious Diseases, Department of Medicine, Faculty of Medicine , Ringgold_12358The University of British Columbia , Vancouver, British Columbia, Canada
                [3 ]departmentDepartment of Psychiatry , Ringgold_12358The University of British Columbia , Vancouver, British Columbia, Canada
                [4 ]departmentDepartment of Psychiatry , St Paul’s Hospital , Vancouver, British Columbia, Canada
                [5 ]departmentDepartment of Psychiatry , Ringgold_8784University of California San Diego , La Jolla, California, USA
                Author notes
                [Correspondence to ] Dr Viviane D Lima; vlima@ 123456bccfe.ca
                Author information
                © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:  http://creativecommons.org/licenses/by-nc/4.0/.

                : 01 December 2022
                : 04 April 2023
                Funded by: FundRef http://dx.doi.org/10.13039/501100000008, Health Canada;
                Award ID: N/A
                Funded by: FundRef http://dx.doi.org/10.13039/501100008002, Vancouver Coastal Health Research Institute;
                Award ID: N/A
                Funded by: British Columbia Ministry of Health;
                Award ID: N/A
                Funded by: FundRef http://dx.doi.org/10.13039/501100000024, Canadian Institutes of Health Research;
                Award ID: PJT-148595
                Funded by: FundRef http://dx.doi.org/10.13039/100008220, Canadian Foundation for AIDS Research;
                Award ID: CANFAR Innovation Grant – 30-101
                Funded by: Vancouver General Hospital Foundation;
                Award ID: N/A
                Funded by: FundRef http://dx.doi.org/10.13039/100011094, Public Health Agency of Canada;
                Award ID: N/A
                Original research
                Custom metadata

                hiv & aids,schizophrenia & psychotic disorders,epidemiology,public health,therapeutics
                hiv & aids, schizophrenia & psychotic disorders, epidemiology, public health, therapeutics


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