Prevalence and Incidence Rates of Dementia: A Nationwide Population-Based Study of Electronic Health Records in Israel1

Background: Data on the rate of dementia is essential for planning and developing appropriate services at the national level. Objective: We report the prevalence and incidence of dementia, based on electronic health records available for the whole population. Methods: This national dementia dataset was established as a part of the National Program to Address Alzheimer’s and Other Types of Dementia. Data from medical health records for all persons aged 45+ in Israel, for 2016, were extracted from the databases of the four health maintenance organizations. Dementia cases were identified based on either recorded dementia diagnosis, through International Classification of Diseases (ICD-9 and ICD-10) or dispensation of anti-dementia drugs. The date of first diagnosis was determined by the earliest recording. Results: A total of 65,951 persons with dementia, aged 45+, were identified from electronic health data. Based on both ICD codes and anti-dementia drugs, the prevalence rates of dementia among individuals aged 45+ and 65+ in 2016 were 2.5%and 6.4%, respectively, and the incidence rates were 0.49%and 1.3%, respectively. Based on ICD codes alone, the prevalence rates of dementia among individuals aged 45+ and 65+ in 2016 were 2.1%and 5.4%respectively, and the incidence rates were 0.36%and 0.96%respectively. The rates were higher among females compared to males and paradoxically lower in lower socioeconomic status compared to higher statuses. Conclusion: This data collection reflects the present access of dementia patients to medical care resources and provides the basis for service planning and future dementia policies.

HIV Pre-Exposure Prophylaxis (PrEP) purchase patterns and STI occurrence among Israeli men: A cohort analysis

Background HIV Pre-exposure prophylaxis (PrEP) is the regular use of antiretroviral medication by people who are not infected with HIV to prevent seroconversion. Israel approved PrEP for continuous use in 2017, and Israeli Health Maintenance Organizations (HMO) offered PrEP with a copayment to eligible members. Methodology This retrospective cohort study included all people who were dispensed PrEP between September 2017 to June 2019 in the second largest HMO in Israel. Statistical analysis, including Kaplan Meier, was conducted to evaluate user PrEP purchase, adherence to medical follow-up, and clinical outcomes. Results In total, a cohort of 757 PrEP users were followed for 657.8 person-years. All but one user were male; median age was 35 years. At baseline, 0.8% had gonorrhea and 1.5% had chlamydia infections and 4.4% had recent syphilis infection. Continuous use of PrEP (without interruption/discontinuation) was observed in 29.9%, while 39.9% interrupted and 30.3% discontinued use. Median time to first interruption/discontinuation was 4.0 months. At 6–12 months after initiation, 79.8% of users had a documented HIV test, 77.3% a Chlamydia-Gonorrhea panel, and 78.9% a creatinine test. There was one new case of HIV among the cohort, five months after PrEP discontinuation. Estimated first-year infection rates were 5.0%, 8.6% and 6.8% for gonorrhea, chlamydia and first-time syphilis, respectively. Conclusions This study shows heterogeneous PrEP purchase patterns and required medical follow-up, and an increase in STIs among consistent PrEP users. Improving adherence to recommended medical follow-up during PrEP use is essential in PrEP’s integration into Israel’s national HIV prevention strategy.

Determinants of total end-of-life healthcare costs of Medicare beneficiaries: A quantile regression forests analysis

Background To identify and rank the importance of key determinants of end-of-life (EOL) healthcare costs, and to understand how the key factors impact different percentiles of the distribution of healthcare costs. Methods We applied a principled, machine learning based variable selection algorithm, using Quantile Regression Forests, to identify key determinants for predicting the 10 th (low), 50 th (median) and 90 th (high) quantiles of EOL healthcare costs, including costs paid for by Medicare, Medicaid, Medicare Health Maintenance Organizations (HMO), private HMO, and patient’s out-of-pocket expenditures. Results Our sample included 7,539 Medicare beneficiaries who died between 2002 and 2017. The 10 th, 50 th and 90 th quantiles of EOL healthcare cost are $5,244, $35,466 and $87,241 respectively. Regional characteristics, specifically, the EOL-expenditure index, a measure for regional variation in Medicare spending driven by physician practice, and the number of total specialists in the hospital referral region, were the top two influential determinants for predicting the 50 th and 90 th quantiles of EOL costs, but were not determinants of the 10 th quantile. Black race and Hispanic ethnicity were associated with lower EOL healthcare costs among decedents with lower total EOL healthcare costs but were associated with higher costs among decedents with the highest total EOL healthcare costs. Conclusions Factors associated with EOL healthcare costs varied across different percentiles of the cost distribution. Regional characteristics and decedent race/ethnicity exemplified factors that did not impact EOL costs uniformly across its distribution, suggesting the need to use a “higher-resolution” analysis for examining the association between risk factors and healthcare costs.

Lista de pacientes

Este artigo discute o tema da lista de pacientes como modelo de vinculação da população às equipes de Atenção Primária à Saúde (APS). Objetivo: evidenciar as características da lista de pacientes enquanto modelo de pagamento. Método: ensaio teórico sobre modelos de pagamento que analisa o piloto de lista de pacientes da Secretaria Municipal de Saúde (SMS) de Florianópolis-SC. Para fundamentar os princípios da lista de pacientes apresenta-se sua aplicação em dois contextos diferentes: (a) em sistemas fechados de saúde, como nas Health Maintenance Organizations (HMO) nos Estados Unidos; e (b) em sistemas universais de saúde, utilizando o sistema de saúde britânico como modelo. Discussão: o projeto piloto de lista de pacientes da SMS/Florianópolis enfrenta dois problemas estruturais: (a) o sistema de saúde universal que caracteriza a APS brasileira; e (b) o modelo de pagamento salarial. Esses dois componentes impõem o desafio de se estabelecer um teto real para as listas de pacientes. Sem um limite no número de pacientes não é possível adequar a carga de trabalho dos profissionais de saúde. Adicionalmente, uma lista de pacientes construída com base na utilização repetida e no atendimento de casos agudos não fidelizados tende a aumentar a carga de trabalho dos profissionais com o passar do tempo. Entretanto, a proposta da lista de pacientes confere maior visibilidade da carga de trabalho para a gestão, facilitando o monitoramento da pressão assistencial e a redistribuição interna dos usuários entre as equipes de saúde da APS. Permite também justificar a expansão das equipes de ESF de acordo com dados mais fidedignos da realidade dos serviços e implementar programas de melhoria de qualidade. Conclusão: a implantação da modalidade de vinculação flexível em Florianópolis não traz impactos positivos diretos na carga de trabalho das equipes, mas talvez de forma indireta por meio de uma gestão inteligente da rede da APS.

P616 Sustainability of thiopurines monotherapy in ulcerative colitis: a nationwide analysis from the epi-IIRN cohort

Background Thiopurines have been long used to maintain remission in ulcerative colitis (UC) but are also associated with toxicity and therapeutic failure. We aimed to assess the sustainability rate of thiopurines commenced as monotherapy in UC, and to explore predictors of sustainability. Methods This study was performed on data from four Health Maintenance Organizations (HMOs), covering 98% of the Israeli population. We included all biologic-naïve UC patients diagnosed after 2005 and treated with thiopurines monotherapy for at least three months. Treatment with 5- aminosalicylic acid (ASA) was allowed if initiated prior to or during the first three months from initiation of thiopurines. Sustainability was defined as continued thiopurines treatment without switching therapy, adding biologics or requiring surgery. At most one short steroid course was allowed. Cox regression model was used to explore estimated predictors to sustainability. Results A total of 1,897 (370 [20%] pediatric-onset and 1,527 [80%] adults) thiopurines-treated patients were included with a 15,033 person-years of follow-up. The median time from UC diagnosis to initiation of thiopurines was 12.7 months (IQR 4.6–30.9), and the median treatment duration was 13.0 months (6.3–28.4). Sustainability rate was evident in 92% of patients after 6 months from initiation of thiopurines and 83%, 65% and 42% at one, three and five years, thereafter. Sustainability was associated with early initiation of thiopurines during disease course (HR 0.99 [95%CI 0.985–0.995]) and lack of 5-ASA at initiation of thiopurines (HR 0.7 [95%CI 0.6–0.8]). Conclusion As many as two thirds of biologic-naïve UC patients treated with thiopurines monotherapy sustain this treatment after five years, especially when initiated early and without 5-ASA.

DOP45 Utilization and sustainability of biologics in CD - A nationwide study from the epi-IIRN

Background Real-world studies demonstrate that ~33% of CD patients fail to respond to induction therapy with biologics. In this nationwide study we aimed to evaluate trends in biologics utilization and sustainability in CD during the last 15 years. Methods This study was performed on data from the four Israeli Health Maintenance Organizations, covering 98% of the population. Sustainability was defined as continuous treatment without IBD-related surgeries and at most one short steroid course. Sustainability was compared across different biologics utilizing a propensity score (PS) weighted analysis, estimated by generalized boosted modeling (GBM). Results 16,936 patients were diagnosed with CD in Israel since 2005 (2,932 [17%] pediatric-onset, 14,004 [83%] adult-onset), of whom 5,804 (34%) were ever treated with biologics (1,659 [57%] pediatric-onset, 4,145 adults [30%], OR 3.1 [95%CI 2.9–3.4]) with a median of 6.4 years follow up (IQR 3.4–9.9). Infliximab was the most common first-line treatment in children (58%, p<0.001), while adalimumab was the most common in adults (63%, p<0.001). However, in recent years there was an increase in adalimumab and vedolizumab utilization in parallel with a decrease in infliximab (Figure). The rate of initiating biologics in the first year of diagnosis increased from 20% among all biologics users during 2005–2010 through 36% during 2011–2014 and 74% since 2015 (p<0.001). The use of combination therapy with immunomodulators is becoming less common in last years and decreased in infliximab from 38% until 2010 to 21% in 2018 (P<0.001) and in adalimumab from 22% to 7%, respectively (p<0.001). The sustainability rate in those treated with infliximab was 65% at one year from initiation of biologics, and 46% and 42% at three and five years, thereafter; compared to 72%, 61% and 57% with adalimumab and 84% and 80% after one and two years in vedolizumab. The rate of primary non-response was 21% with infliximab, 17% with adalimumab and 12% with vedolizumab. Sustainability was associated with male sex (HR 0.9 [95%CI 0.8–0.95]) and earlier initiation of biologics (HR 0.92 [95%CI 0.9–0.95]). In the PS-adjusted model the sustainability of both infliximab (HR 0.7 [95%CI 0.6–0.8]) and vedolizumab (HR 0.8 [95%CI 0.7–0.95]) were lower than adalimumab. Compared with monotherapy, combination therapy did not change significantly the sustainability rate of all three biologics (adalimumab: HR 1.3 [95%CI 0.8–2.1], infliximab: HR 1.2 [95%CI 0.7–1.9], and vedolizumab: HR 0.8 [95%CI 0.5–1.3]). Conclusion Biologics are being increasingly used in CD and earlier during the disease course, but most patients do not sustain treatment at five years. Sustainability rate was higher with adalimumab compared with either infliximab or vedolizumab

DOP44 Long term outcomes of patients with untreated IBD - A population-based analysis from the epi-IIRN

Background Therapy in IBD is recommended in order to treat or prevent complications. In this nationwide study we aimed to assess the incidence of patients with IBD who were not receiving maintenance treatment after diagnosis and the duration of non-treatment. Methods This study was performed on data from four Health Maintenance Organizations (HMOs), covering 98% of the Israeli population. We included all patients with IBD diagnosed from 2005 to 2019. Non-treatment was defined as lack of drug prescription of maintenance medication for at least six months from diagnosis. Sustainability was defined as lack of maintenance medications and without IBD-related surgeries. Cox regression model was used to explore estimated predictors of sustainability. Results A total of 30,168 patients were diagnosed with IBD in Israel since 2005 (16,936 [56%] Crohn’s disease [CD] and 13,231 [44%] ulcerative colitis [UC]). A total of 5,448 (32%) patients with CD were untreated, compared to 5,158 (39%) with UC (OR 1.35 [95%CI 1.3–1.4]; p<0.001). Non-treatment was more likely in adult compared to pediatric-onset (34% vs 21%, respectively, p<0.001 in CD; and 41%% vs 22%, respectively, in UC; p<0.001) (Figure 1). Sustainability rate in CD was 72%, 46%, 36% and 28% after one, two, five and ten years from diagnosis, while in UC the corresponding rates were 59%, 39%, 24% and 16%. In CD, sustainability was associated with older age at diagnosis (HR 0.996 [95%CI 0.994–0.998]) and no induction therapy (HR 0.7 [95%CI 0.6–0.9] compared to steroids). In UC, sustainability was associated only with female sex (HR 0.9 [95%CI 0.88–0.98]). Conclusion Most patients with IBD eventually require maintenance therapy. Lack of maintenance treatment is more common in UC. Nevertheless, a third of patients with CD and one quarter with UC who had no medical treatment at six months from diagnosis remained untreated for five years, especially in older patients with CD and those who did not require induction therapy, suggesting milder disease.

DOP46 Sustainability rate of immunomodulators monotherapy in patients with Crohn’s Diseases: A population-based analysis from the epi-IIRN cohort

Background Immunomodulators (IMM), including thiopurines and methotrexate (MTX), have been long used to maintain remission in Crohn’s disease (CD), both associated with remission, but also with toxicity and therapeutic failure. We aim to compare the sustainability of thiopurines and MTX commenced as monotherapy in patients with CD, and to explore predictors of sustainability. Methods This study was performed on data from four Health Maintenance Organizations (HMOs), covering 98% of the Israeli population. We included all biologic-naïve CD patients diagnosed after 2005 and treated with IMM monotherapy for at least three months. Sustainability was defined as continues IMM treatment without switching therapy, adding biologics or requiring surgery. In addition, at most one short steroid course was allowed. Cox regression model was used to explore estimated predictors to sustainability. To compare sustainability rate between thiopurines and MTX we used propensity score (PS) matching, and thereafter Cox regression model. Results A total of 4,891 (1,551 [32%] pediatric-onset and 3,340 [68%] adults) IMM-treated patients were included with 37,825 person-years of follow up, of whom 4,339 (89%) were treated with thiopurines and 552 (11%) with MTX. The median time from CD diagnosis to initiation of IMM was 6.1 months (IQR 1.7–19.7), and the median course duration was 11.9 months (6.1–25.3). Sustainability rate was recorded in 92% of patients after 6 months from initiation of IMM and 81%, 69% and 65% at one, three and five years, thereafter. The most common type of failure was escalation to biologics (67%), while 17% required repeated steroid courses and 15% underwent surgery. Sustainability was associated with earlier initiation of IMM during the disease course (HR 0.98 [95%CI 0.97–0.985]) and lack of steroids at initiation of IMM (HR 0.7 [95%CI 0.6–0.8]). A PS adjusted analysis that included 337 thiopurnes-treated patients individually matched with 337 MTX-treated patients, showed sustainability was significantly better with thiopurines (HR 0.7 [95%CI 0.5–0.8]). Conclusion Two thirds of biologic-naïve CD patients treated with IMM monotherapy sustain this treatment after five years, especially when initiated early during the disease course. Sustainability was more likely in those treated with thiopurines compared with MTX.

DOP39 Utilization and sustainability of biologics in UC - A nationwide study from the epi-IIRN

Background 25% of UC patients fail to respond to induction therapy with biologics. In this nationwide study we aimed to evaluate trends in biologics utilization and sustainability in UC during the last 15 years. Methods This study was performed on data from four the four Israeli Health Maintenance Organizations, covering 98% of the population. Sustainability was defined as continuous treatment without IBD-related surgeries and at most one short steroid course. Sustainability was compared across different biologics utilizing a propensity score (PS) weighted analysis, estimated by generalized boosted modeling (GBM). Results 13,231 patients were diagnosed with UC in Israel since 2005 (1,426 [11%] pediatric-onset,11,805 [89%] adult-onset), of whom 1,692 (13%) were ever treated with biologics (400 [24%] pediatric-onset, 1,292 adults [76%], OR 3.2 [95%CI 2.8–3.6]; p<0.001) with a median of 6.4 years follow up (IQR 3.4–9.9). Infliximab was the most common first-line treatment in both children and adults (75% and 54%, respectively, p<0.001). However, in recent years there was an increase in adalimumab and vedolizumab utilization in parallel with a decrease in infliximab (Figure). The rate of initiating biologics in the first year of diagnosis increased from from 11% during 2005–2010 to 25% during 2011–2014 and 61% since 2015 (p<0.001). The use of combination therapy with immunomodulators is becoming less common and decreased with infliximab: from 36% in 2010 to 17% in 2018 (p<0.001) and with adalimumab from 32% to 12%, respectively (p<0.001). The sustainability rate in those treated with infliximab was 52% at one year from initiation of biologics, and 37% and 34% at three and five years, thereafter; compared to 55%, 43% and 40% with adalimumab and 72% and 67% after one and two years with vedolizumab. The primary non-response rate was 30% with infliximab, 31% with adalimumab and 16% with vedolizumab. Sustainability was associated with earlier initiation of biologics during the disease course (HR 0.9 [95%CI 0.85–0.95]). In the PS-adjusted model where vedolizumab served as the reference, the sustainability of both infliximab (HR 0.7 [95%CI 0.6–0.95]) and adalimumab (HR 0.8 [95%CI 0.6–0.99]) were lower. Compared with monotherapy, combination therapy increased the sustainability rate with both adalimumab (HR 0.3 [95%CI 0.2–0.6]) and infliximab (HR 0.4 [95%CI 0.-0.6]), but not with vedolizumab (HR 1.4 [95%CI 0.98–2.1]). Conclusion Biologics are being increasingly used in UC but only half of patients sustain treatment at one year. Treatment is commenced earlier during the disease course, and this is associated with improved sustainability. Sustainability rate is higher with vedolizumab, and in combination therapy of IMM and infliximab or adalimumab.