Project description:ObjectivesDevelop predictive models using an administrative healthcare database that provide information for Patient-Centred Medical Homes to proactively identify patients at risk of hospitalisation for conditions that may be impacted through improved patient care.DesignRetrospective healthcare utilisation analysis with multivariate logistic regression models.DataA population-based longitudinal database of residents served by the Emilia-Romagna, Italy, health service in the years 2004-2012 including demographic information and utilisation of health services by 3,726,380 people aged ?18 years.Outcome measuresModels designed to predict risk of hospitalisation or death in 2012 for problems that are potentially avoidable were developed and evaluated using the area under the receiver operating curve C-statistic, in terms of their sensitivity, specificity and positive predictive value, and for calibration to assess performance across levels of predicted risk.ResultsAmong the 3,726,380 adult residents of Emilia-Romagna at the end of 2011, 449,163 (12.1%) were hospitalised in 2012; 4.2% were hospitalised for the selected conditions or died in 2012 (3.6% hospitalised, 1.3% died). The C-statistic for predicting 2012 outcomes was 0.856. The model was well calibrated across categories of predicted risk. For those patients in the highest predicted risk decile group, the average predicted risk was 23.9% and the actual prevalence of hospitalisation or death was 24.2%.ConclusionsWe have developed a population-based model using a longitudinal administrative database that identifies the risk of hospitalisation for residents of the Emilia-Romagna region with a level of performance as high as, or higher than, similar models. The results of this model, along with profiles of patients identified as high risk are being provided to the physicians and other healthcare professionals associated with the Patient Centred Medical Homes to aid in planning for care management and interventions that may reduce their patients' likelihood of a preventable, high-cost hospitalisation.
Project description:The Delta variant of SARS-CoV-2 causes higher viral loads in infected hosts, increasing the risk of close proximity airborne transmission through breathing, speaking and coughing. We performed a Monte Carlo simulation using a social contact network and exponential dose-response model to quantify the close proximity reproduction number of both wild-type SARS-CoV-2 and the Delta variant. We estimate more than twice as many Delta variant cases will reproduce infection in their close proximity contacts (64%) versus the wild-type SARS-CoV-2 (29%). Occupational health guidelines must consider close proximity airborne transmission and recommend improved personal respiratory protection for high-risk workers. Graphical abstract Unlabelled Image
Project description:ObjectiveTo estimate the contribution of health insurance status to the risk of death among hospitalized neonates.Data sourcesKids' Inpatient Databases (KID) for 2003, 2006, and 2009.Study designKID 2006 subpopulation of neonatal discharges was analyzed by weighted frequency distribution and multivariable logistic regression analyses for the outcome of death, adjusted for insurance status and other variables. Multivariable linear regression analyses were conducted for the outcomes mean adjusted length of stay and hospital charges. The death analysis was repeated with KID 2003 and 2009.Principal findingsOf 4,318,121 estimated discharges in 2006, 5.4 percent were uninsured. There were 17,892 deaths; 9.5 percent were uninsured. The largest risks of death were five clinical conditions with adjusted odds ratios (AOR) of 13.7-3.1. Lack of insurance had an AOR of 2.6 (95 percent CI: 2.4, 2.8), greater than many clinical conditions; AOR estimates in alternate models were 2.1-2.7. Compared with insureds, uninsureds were less likely to have been admitted in transfer, more likely to have died in rural hospitals and to have received fewer resources. Similar death outcome results were observed for 2003 and 2009.ConclusionsUninsured neonates had decreased care and increased risk of dying.
Project description:The Delta variant has dominated SARS-CoV-2 infections in Tokyo, Japan from June 2021 to date. We conducted a retrospective cohort study to assess BNT162b2 vaccine effectiveness during the surge in Delta among 3,911 healthcare workers (HCWs) at a medical center of Tokyo with a high vaccination rate of 84.1%. With strict infection control protocols including universal masking, only a small number of cases among vaccinated and unvaccinated HCWs were identified before June. As Delta spread in Tokyo, 16 cases among 3,289 fully vaccinated HCWs and 11 cases among 574 unvaccinated HCWs were reported in July and August (case rate in August: 4.0 vs. 19.2 per 1,000). All breakthrough cases were confirmed as Delta. While our study confirms a robust vaccine effectiveness of BNT162b2 vaccine against Delta, rising breakthrough cases suggest that continued infection control measures are warranted in higher risk environments, even when high rates of vaccination coverage are achieved.
Project description:Bone fractures may have an impact on prognosis of breast cancer. The long-term risks of bone fracture in breast cancer patients have not been thoroughly studied.Poisson regression was used to investigate the incidence of hospitalisation due to bone fracture comparing women with and without breast cancer based on Swedish National registers. Cox regression was used to investigate the risk of being hospitalised with bone fracture, and subsequent risk of death, in a regional cohort of breast cancer patients.For breast cancer patients, the 5-year risk of bone fracture hospitalisation was 4.8% and the 30-day risk of death following a bone fracture hospitalisation was 2.0%. Compared with the general population, breast cancer patients had incidence rate ratios of 1.25 (95% CI: 1.23-1.28) and 1.18 (95% CI: 1.14-1.22) for hospitalisation due to any bone fracture and hip fracture, respectively. These ratios remained significantly increased for 10 years. Comorbidities (Charlson Comorbidity Index ?1) were associated with the risk of being hospitalised with bone fracture. Women taking aromatase inhibitors were at an increased risk as compared with women taking tamoxifen (HR=1.48; 95% CI: 0.98-2.22). Breast cancer patients hospitalised for a bone fracture showed a higher risk of death (HR=1.83; 95% CI: 1.50-2.22) compared with those without bone fracture.Women with a previous breast cancer diagnosis are at an increased risk of hospitalisation due to a bone fracture, particularly if they have other comorbidities.
Project description:The KRAS-variant is a biologically functional, microRNA binding site variant, which predicts increased cancer risk especially for women. Because external exposures, such as chemotherapy, differentially impact the effect of this mutation, we evaluated the association of estrogen exposures, breast cancer (BC) risk and tumor biology in women with the KRAS-variant. Women with BC (n = 1712), the subset with the KRAS-variant (n = 286) and KRAS-variant unaffected controls (n = 80) were evaluated, and hormonal exposures, KRAS-variant status, and pathology were compared. The impact of estrogen withdrawal on transformation of isogenic normal breast cell lines with or without the KRAS-variant was studied. Finally, the association and presentation characteristics of the KRAS-variant and multiple primary breast cancer (MPBC) were evaluated. KRAS-variant BC patients were more likely to have ovarian removal pre-BC diagnosis than non-variant BC patients (p = 0.033). In addition, KRAS-variant BC patients also appeared to have a lower estrogen state than KRAS-variant unaffected controls, with a lower BMI (P < 0.001). Finally, hormone replacement therapy (HRT) discontinuation in KRAS-variant patients was associated with a diagnosis of triple negative BC (P < 0.001). Biologically confirming our clinical findings, acute estrogen withdrawal led to oncogenic transformation in KRAS-variant positive isogenic cell lines. Finally, KRAS-variant BC patients had greater than an 11-fold increased risk of presenting with MPBC compared to non-variant patients (45.39% vs 6.78%, OR 11.44 [3.42-37.87], P < 0.001). Thus, estrogen withdrawal and a low estrogen state appear to increase BC risk and to predict aggressive tumor biology in women with the KRAS-variant, who are also significantly more likely to present with multiple primary breast cancer.
Project description:Bipolar disorder is a highly heritable mental illness, but the relevant genetic variants and molecular mechanisms are largely unknown. Recent GWASs have identified an intergenic region associated with both cognitive performance and bipolar disorder. This region contains dozens of putative fetal brain-specific enhancers and is located ~0.7 Mb upstream of the neuronal transcription factor POU3F2. We identified a candidate causal variant, rs77910749, that falls within a highly conserved putative enhancer, LC1. This human-specific variant is a single-base deletion in a PAX6 binding site and is predicted to be functional. We hypothesized that rs77910749 alters LC1 activity and hence POU3F2 expression during neurodevelopment. Indeed, transgenic reporter mice demonstrated LC1 activity in the developing cerebral cortex and amygdala. Furthermore, ex vivo reporter assays in embryonic mouse brain and human iPSC-derived cerebral organoids revealed increased enhancer activity conferred by the variant. To probe the in vivo function of LC1, we deleted the orthologous mouse region, which resulted in amygdala-specific changes in Pou3f2 expression. Lastly, ‘humanized’ rs77910749 knock-in mice displayed behavioral defects in sensory gating, an amygdala-dependent endophenotype seen in patients with bipolar disorder. Our study suggests a molecular mechanism underlying the long-speculated link between enhanced cognitive performance and neuropsychiatric disease.