Artificial intelligence-driven approach for patient-focused drug development.

Patients' increasing digital participation provides an opportunity to pursue patient-centric research and drug development by understanding their needs. Social media has proven to be one of the most useful data sources when it comes to understanding a company's potential audience to drive more targeted impact. Navigating through an ocean of information is a tedious task where techniques such as artificial intelligence and text analytics have proven effective in identifying relevant posts for healthcare business questions. Here, we present an enterprise-ready, scalable solution demonstrating the feasibility and utility of social media-based patient experience data for use in research and development through capturing and assessing patient experiences and expectations on disease, treatment options, and unmet needs while creating a playbook for roll-out to other indications and therapeutic areas.

Author Correction: Exploring the coronavirus pandemic with the WashU Virus Genome Browser.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Systematic review of raloxifene in postmenopausal Japanese women with osteoporosis or low bone mass (osteopenia).

PURPOSE: To systematically review the literature describing the efficacy, effectiveness, and safety of raloxifene for postmenopausal Japanese women with osteoporosis or low bone mass (osteopenia). MATERIALS AND METHODS: Medline via PubMed and Embase was systematically searched using prespecified terms. Retrieved publications were screened and included if they described randomized controlled trials or observational studies of postmenopausal Japanese women with osteoporosis or osteopenia treated with raloxifene and reported one or more outcome measures (change in bone mineral density [BMD]; fracture incidence; change in bone-turnover markers, hip structural geometry, or blood-lipid profile; occurrence of adverse events; and change in quality of life or pain). Excluded publications were case studies, editorials, letters to the editor, narrative reviews, or publications from non-peer-reviewed journals; multidrug, multicountry, or multidisease studies with no drug-, country-, or disease-level analysis; or studies of participants on dialysis. RESULTS: Of the 292 publications retrieved, 15 publications (seven randomized controlled trials, eight observational studies) were included for review. Overall findings were statistically significant increases in BMD of the lumbar spine (nine publications), but not the hip region (eight publications), a low incidence of vertebral fracture (three publications), decreases in markers of bone turnover (eleven publications), improved hip structural geometry (two publications), improved blood-lipid profiles (five publications), a low incidence of hot flushes, leg cramps, venous thromboembolism, and stroke (12 publications), and improved quality of life and pain relief (one publication). CONCLUSION: Findings support raloxifene for reducing vertebral fracture risk by improving BMD and reducing bone turnover in postmenopausal Japanese women with osteoporosis or osteopenia. Careful consideration of fracture risk and the risk-benefit profile of antiosteoporosis medications is required when managing patients with osteoporosis.

Bone fractures and feeling at risk for osteoporosis among women in Japan: patient characteristics and outcomes in the National Health and Wellness Survey.

UNLABELLED: Women aged 50 and older in Japan were compared according to perceived risk for osteoporosis and fracture history. Perceived risk was associated with family history of osteoporosis but few other risk factors. Few felt at risk, and perception was only loosely related to epidemiological risks, indicating a need for patient education. PURPOSE: Osteoporosis is prevalent but underdiagnosed and undertreated. This study was conducted to explore characteristics associated with history of fractures and feeling at risk for osteoporosis in women aged 50 and older in Japan. METHODS: Data were provided by a large annual survey representative of Japanese aged 18 and older. Women 50 and older without diagnosed osteoporosis were categorized into four mutually exclusive groups based on fracture history since age 50 and feeling at risk for developing osteoporosis. Sociodemographic and health characteristics were compared across groups using bivariate statistics, and health outcomes were compared using generalized linear models. RESULTS: A total of 16,801 women aged 50 and older were included in the analyses. Most (n = 12,798; 76.2 %) had no fracture since age 50 and did not feel at risk for osteoporosis, 12.9 % (n = 2170) felt at risk but had no fracture, 8.7 % (n = 1455) did not feel at risk despite having a fracture, and 2.2 % (n = 378) had a fracture and felt at risk for osteoporosis. Feeling at risk was slightly more common among those with than without a fracture since age 50 (20.6 vs. 14.5 %, p < 0.001). Feeling at risk was most associated with family history of osteoporosis, though known risk factors for fracture did not significantly differ across the fracture/perceived-risk group. CONCLUSIONS: Approximately 15 % of women in Japan aged 50 and older felt at risk for developing osteoporosis in the future, far fewer than expected by epidemiologists. Risk perception was only loosely related to epidemiological risks for fracture, indicating a need for patient education.

Treatment for Osteoporosis among Women in Japan: Associations with Patient Characteristics and Patient-Reported Outcomes in the 2008-2011 Japan National Health and Wellness Surveys.

This study was conducted to identify characteristics associated with treatment for osteoporosis among women aged 50 years and older in Japan and to explore differences among patients according to treatment regimen. Data were provided by a large annual survey representative of Japanese aged 18 and older; all measures were by self-report. Women aged 50 and older who reported diagnosed osteoporosis (N = 900) were compared based on current treatment status using bivariate statistics and logistic regression. Approximately 1 in 3 women in this study reporting diagnosed osteoporosis were currently untreated. Factors associated with current treatment for osteoporosis included having ≥1 physician visit in the prior 6 months (OR = 5.4, P < 0.001), self-rated moderate or severe osteoporosis (OR = 2.8, P < 0.001), completion of menopause (OR = 1.6, P < 0.05), and family history of osteoporosis (OR = 1.5, P < 0.05), while longer duration of osteoporosis diagnosis (OR = 0.9, P < 0.05) and arthritis (OR = 0.7, P < 0.05) were associated with lower odds of treatment. These findings suggest that diagnosed patients are not being actively managed in the longer term, and efforts need to be made to ensure that patients stay engaged with their healthcare providers.

The Health Technology Assessment Environment in Mainland China, Japan, South Korea, and Taiwan-Implications for the Evaluation of Diabetes Mellitus Therapies.

BACKGROUND: Diabetes mellitus (DM) is associated with a significant global economic and humanistic burden. The condition presents a real challenge in Asia, which accounts for more than 60% of individuals with DM globally. Health technology assessment (HTA) is a field of scientific research used to inform policy and clinical decision making relating to the introduction and diffusion of health technologies. OBJECTIVES: This article, examines the present use and predicted evolution of HTA with respect to pricing and reimbursement of drugs in mainland China, Japan, South Korea, and Taiwan. It makes specific reference to important assessment considerations for DM therapies, which should assist key stakeholders in choosing which data to capture, and what approaches to use, to help quantify the value of treatment. METHODS: The findings are informed by two Advisory Board discussions, a literature review, and the authors' personal experience. RESULTS: HTA already has a key role in South Korea and Taiwan, with current systems undergoing important changes. In contrast, in mainland China and Japan, HTA is not yet formally utilized, although this appears likely to change. Several elements are important for HTA to be meaningful and impactful for DM therapies, including a clear, transparent analytical framework for HTA that includes all relevant costs and outcomes; availability of local DM epidemiologic, economic, and quality-of-life data; acceptance of modeling as a core methodology; availability of real-life patient data; and recognition of specific evidence requirements associated with biosimilars. HTA has the potential to assist payors in making informed decisions about the coverage of DM medications.

Osteoporosis and treatments in Japan: management for preventing subsequent fractures.

Prevalent fractures are major contributors to an increased risk of subsequent fractures, particularly in people with osteoporosis. While many studies have been conducted to assess the incidence of fracture in Japanese people with osteoporosis, far fewer have been conducted to assess the risk of subsequent fractures. This article reviews the morbidity, mortality, and risk of fracture in patients who are at high risk of subsequent fracture in Japan and the current treatment options available for these patients. Osteoporotic fractures in Japan are associated with high morbidity and mortality that result in significant financial and social costs. The rise in the proportion of elderly women in the Japanese population is contributing to a greater proportion of people with osteoporotic fractures and the high cost of osteoporosis. Although hip fractures have a significant effect on costs, a greater proportion of the Japanese population experience vertebral fractures. An increase in the incidence of vertebral fractures is concerning because preexisting vertebral fractures in older patients are associated with an increased risk of subsequent fractures. Hence, there is a clear rationale for pharmacological treatment of patients with prevalent vertebral fractures, or for those who are hospitalized or undergo surgery for osteoporotic fractures. Several pharmacological therapies are now available in Japan for the treatment of patients with osteoporosis. Understanding the consequences of subsequent fractures and the treatment options available for patients at high risk of subsequent fractures may contribute to clinical decision-making and improved outcomes for patients with osteoporosis.

Adherence and persistence with once-daily teriparatide in Japan: a retrospective, prescription database, cohort study.

Adherence and persistence with osteoporosis treatments are essential for reducing fracture risk. Once-daily teriparatide is available in Japan for treating osteoporosis in patients with a high risk of fracture. The study objective was to describe real-world adherence and persistence with once-daily teriparatide 20 µg during the first year of treatment for patients who started treatment during the first eight months of availability in Japan. This prescription database study involved patients with an index date (first claim) between October 2010 and May 2011, a preindex period ≥6 months, and a postindex period ≥12 months and who were aged >45 years. Adherence (medication possession ratio (MPR)) and persistence (time from the start of treatment to discontinuation; a 60-day gap in supply) were calculated. A total of 287 patients started treatment during the specified time period; 123 (42.9%) were eligible for inclusion. Overall mean (standard deviation) adherence was 0.702 (0.366), with 61.0% of patients having high adherence (MPR > 0.8). The percentage of patients remaining on treatment was 65.9% at 180 days and 61.0% at 365 days. Our findings suggest that real-world adherence and persistence with once-daily teriparatide in Japan are similar to that with once-daily teriparatide in other countries and with other osteoporosis medications.

Antipsychotic monotherapy among outpatients with schizophrenia treated with olanzapine or risperidone in Japan: a health care database analysis.

PURPOSE: Antipsychotic monotherapy is often recommended over antipsychotic polypharmacy because of fewer adverse events, reduced treatment complexity, and lower medication cost. This study compared the rate and the duration of antipsychotic monotherapy following initiation of olanzapine or risperidone in the treatment of outpatients with schizophrenia in Japan. METHODS: Outpatients diagnosed with schizophrenia in the Japan Medical Data Center database were identified using International Statistical Classification of Diseases and Related Health Problems, 10th Revision, diagnosis codes. Patients were between 20 and 65 years old, initiated on olanzapine or risperidone therapy between August 2003 and July 2008, and continuously enrolled during the 6 months prior to and the 12 months following the initiation date. Antipsychotic polypharmacy was defined as concurrent use of two or more antipsychotics. The probability of monotherapy during the 12-month follow-up period was assessed using a propensity score-adjusted generalized estimating equation model. Duration of monotherapy was contrasted using a propensity score-adjusted bootstrapping model. RESULTS: After applying all inclusion and exclusion criteria, the final analytic sample consisted of 332 olanzapine- and 496 risperidone-treated outpatients. At treatment initiation, 61.5% of the olanzapine-treated patients and 45.6% of the risperidone-treated patients received antipsychotic monotherapy (P < 0.001). After correcting for background differences, monotherapy was more common among olanzapine-treated patients (P = 0.001). In addition, olanzapine was used as monotherapy for a longer duration (P = 0.006). CONCLUSION: Consistent with prior global research, this retrospective naturalistic study of schizophrenia outpatients in Japan found that olanzapine is more likely to be used as monotherapy and to be used as monotherapy for a longer duration than risperidone.

Predictors of antipsychotic monotherapy with olanzapine during a 1-year naturalistic study of schizophrenia patients in Japan.

PURPOSE: Although expert guidelines for the treatment of schizophrenia recommend antipsychotic monotherapy, the use of antipsychotic polypharmacy is common. This study identified characteristics that differentiate patients with schizophrenia who are treated with olanzapine monotherapy versus polypharmacy in usual care in Japan. PATIENTS AND METHODS: In a large (N = 1850) prospective, observational study, Japanese patients with schizophrenia who initiated treatment with olanzapine were followed for 1 year. Consistent with past research, antipsychotic polypharmacy was defined as the concurrent use of olanzapine and another antipsychotic for at least 60 days. Switching was defined as discontinuing a prior antipsychotic therapy rather than augmenting the medication regimen. Predictors of antipsychotic monotherapy were based on information available at the time of olanzapine initiation. Baseline characteristics were compared using t-tests and χ(2) tests. Stepwise logistic regression was used to identify independent predictors of monotherapy. RESULTS: Patients treated with olanzapine monotherapy (43.2%) differed from those treated with antipsychotic polypharmacy (56.8%) on demographics, treatment history, baseline symptom levels, functional levels, and treatment-emergent adverse events. Stepwise logistic regression identified multiple variables that significantly predicted monotherapy: older age, shorter duration of schizophrenia, outpatient status, comorbid medical conditions, lower body mass index, no prior anticholinergic use, no prior mood stabilizer use, and switching from a previous antipsychotic (typical or atypical). CONCLUSION: Consistent with prior research in Japan, antipsychotic polypharmacy appears to be common in the treatment of schizophrenia. Patients treated with monotherapy could be differentiated from those treated with antipsychotic polypharmacy based on a specific set of demographic and baseline clinical characteristics.

Social instability stress in adolescent male rats alters hippocampal neurogenesis and produces deficits in spatial location memory in adulthood.

The ongoing development of the hippocampus in adolescence may be vulnerable to stressors. The effects of social instability stress (SS) in adolescence (daily 1 h isolation and change of cage partner postnatal days 30-45) on cell proliferation in the dentate gyrus (DG) in adolescence (on days 33 and 46, experiment 1) and in adulthood (experiment 2) was examined in Long Evans male rats and compared to nonstressed controls (CTL). Additionally, in experiment 2, a separate group of SS and CTL rats was tested on either a spatial (hippocampal-dependent) or nonspatial (nonhippocampal dependent) version of an object memory test and also were used to investigate hippocampal expression of markers of synaptic plasticity. No memory impairment was evident until the SS rats were adults, and the impairment was only on the spatial test. SS rats initially (postnatal day 33) had increased cell proliferation based on counts of Ki67 immunoreactive (ir) cells and greater survival of immature neurons based on counts of doublecortin ir cells on day 46 and in adulthood, irrespective of behavioral testing. Counts of microglia in the DG did not differ by stress group, but behavioral testing was associated with reduced microglia counts compared to nontested rats. As adults, SS and CTL rats did not differ in hippocampal expression of synaptophysin, but compared to CTL rats, SS rats had higher expression of basal calcium/calmodulin-dependent kinase II (CamKII), and lower expression of the phosphorylated CamKII subunit threonine 286, signaling molecules related to synaptic plasticity. The results are contrasted with those from previous reports of chronic stress in adult rats, and we conclude that adolescent stress alters the ongoing development of the hippocampus leading to impaired spatial memory in adulthood, highlighting the heightened vulnerability to stressors in adolescence.

Predictors of continuation with olanzapine during the 1-year naturalistic treatment of patients with schizophrenia in Japan.

PURPOSE: Treatment continuation is considered an important measure of antipsychotic effectiveness in schizophrenia, reflecting the medication's efficacy, safety, and tolerability from both patients' and clinicians' perspectives. This study identified characteristics of patients with schizophrenia who continue olanzapine therapy for a 1-year period in Japan. METHODS: In a large (N = 1850), prospective, observational study, Japanese patients with schizophrenia who initiated treatment with olanzapine were followed for 1 year. Baseline characteristics were compared using t-tests and chi-square tests. Stepwise logistic regression was used to identify independent baseline predictors of treatment continuation. RESULTS: Most patients (68.2%) continued with olanzapine therapy for the full 1-year study period, with an average duration of 265.5 ± 119.4 days. At baseline, patients who continued were significantly more likely to be male, older, and inpatients; have longer illness duration, higher negative and cognitive symptoms, better health-related quality of life, and prior anticholinergic use. Continuers were significantly less likely to engage in social activities, live independently, work for pay, or have prior antidepressant use. Continuers showed significantly greater early (3-month) improvement in global symptom severity. Logistic regression found that continuation was significantly predicted by longer illness duration, lower positive symptoms, higher negative symptoms, and better health-related quality of life. CONCLUSIONS: In this large naturalistic study in Japan, most patients with schizophrenia stayed on olanzapine therapy for the full 1-year study period. Treatment completion with olanzapine was independently predicted by longer illness duration, lower positive symptoms, higher negative symptoms, and better health-related quality of life.

Health service utilization among Alzheimer's disease patients: evidence from managed care.

BACKGROUND: The objective of this study was to assess the disease burden of Alzheimer's disease (AD) in a commercial managed care setting by comparing direct health care costs and adverse event outcomes between patients with AD and without AD. METHODS: The study design used eligibility, medical, and pharmacy claims data from a large, national, geographically diverse, fee-for-service U.S. managed health plan. Commercially insured patients aged 65 years and older with a pharmacy benefit with evidence of AD (n = 4,450) and a control group without AD (n = 13,650) were matched by age, gender, plan location, and length of enrollment. Adverse event outcomes, comorbid conditions, and annualized health care costs were compared. Incremental costs were calculated by using a two-part model to estimate the burden of illness; incremental cost confidence intervals were estimated by bootstrap analysis. RESULTS: Patients with AD had generally higher health care costs and higher risk of acute adverse outcomes than the control cohort. Annual adjusted total health care costs per patient were approximately $1,418 greater for the AD cohort. Patients with AD had an unadjusted fracture risk of 14.6% versus 6.2% in the matched cohort and accidental injury/falls risk of 27.4% versus 11.4%. CONCLUSIONS: Few studies have examined the disease burden of AD in commercial managed care settings. Similar to results of comparative studies with Medicare data, the disease burden is greater for patients with AD compared with a matched control cohort, with a different mix and a greater number of comorbid health care conditions partially accounting for this difference. As membership in commercial and Medicare managed care plans increases, plans will need to develop effective mechanisms to manage the health care of high-risk, high-cost patients with AD.

Burden of illness among commercially insured patients with Alzheimer's disease.

BACKGROUND: The purpose of this study was to examine the direct costs of care for patients newly diagnosed with Alzheimer's disease (AD) by using retrospective healthcare claims data. METHODS: Patients aged 65 years or older with >or=1 claims containing a listed diagnosis of AD between January 1999 and November 2003 were selected. The first observed AD claim was deemed the index date. Control patients with no evidence of AD or dementia also were identified. Patients had a 12-month pre-index period and minimum 30-day follow-up. AD patients were matched to control patients on the basis of age, gender, and follow-up duration. Annualized utilization and costs were calculated; generalized linear models (GLM) were undertaken, controlling for demographic and clinical characteristics. Analyses focused on differences in costs among AD patients and controls. RESULTS: The average age of AD and control patients was 82 years; 38% were men (n = 2,475 AD; 4,950 controls). Average total costs for AD patients were more than five-fold higher compared with controls ($28,263 vs $5,880; P < .001), driven primarily by inpatient costs. Total costs were significantly higher (P < .001) for AD patients in GLM modeling, with diagnosis group (AD vs control) as the most important predictor. Adjusted annual costs per patient were also five-fold higher ($21,150 vs $4,053 for AD vs control, respectively) during the follow-up period. CONCLUSIONS: The annual economic burden of AD to third-party payers is more substantial than previously estimated ($3,805 to $8,200).

Impact of cognitive impairment on mild dementia patients and mild cognitive impairment patients and their informants.

BACKGROUND: The aim of this study was to identify key aspects of the impact of cognitive impairment on patients with mild cognitive impairment (MCI) and mild probable Alzheimer disease (AD) and their informants, and identify overlap and differences between the groups. METHODS: Structured focus group discussions were conducted with MCI patients, AD patients, MCI informants, and AD informants. Participants were recruited from memory clinics in the U.K. and the U.S.A. A total of 20 AD and 20 MCI patients and 16 AD and 11 MCI informants participated. Sessions were content reviewed to identify key impacts of cognitive impairment; results were compared across diagnostic groups and for patients and informants. RESULTS: Seven key themes emerged: uncertainty of diagnosis, skill loss, change in social and family roles, embarrassment and shame, emotionality, insight, and burden. Patients were able to discuss the impact of cognitive impairment on their lives and reported frustration with recognized memory problems, diminished self-confidence, fear of embarrassment, concerns about changing family roles due to cognitive impairment, and anxiety. Informants reported more symptoms and more impairment than did patients and indicated increased dependence on others among patients. CONCLUSION: MCI and mild AD exert substantial burden on patients' lives and the lives of those close to them.

Validation of a new symptom impact questionnaire for mild to moderate cognitive impairment.

BACKGROUND: Patient-reported outcomes assessment enhances the understanding of disease impact in a range of disorders. At mild levels of cognitive impairment the patient perspective on functioning, behavior and symptoms can be particularly valuable for syndrome characterization when clinical and neuropsychological findings are limited. We have evaluated the psychometric performance of the 55-item Patient-Reported Outcomes in Cognitive Impairment (PROCOG), a new patient-reported measure, to measure mild to moderate cognitive impairment symptoms and their impact from the perspective of patients with dementia of the Alzheimer's type (DAT) and mild cognitive impairment (MCI). METHODS: The sample of 75 DAT patients, 78 MCI patients and 33 cognitively intact control subjects (> 64 years) was recruited through medical centers in the U.SA. Validity was assessed through correlation to the Quality of Life--Alzheimer's Disease (QOL-AD) and Centers for Epidemiologic Studies--Depression Scale (CES-D) and neuropsychological assessments (WAIS subscales and MMSE). RESULTS: PROCOG scores for MCI patients were generally intermediate between DAT and control subjects. Internal consistency and test-retest reliability were acceptable. Correlations with the CES-D and QOL-AD were in the moderate to high range; correlations with the neuropsychological measures were low to moderate. CONCLUSIONS: The PROCOG demonstrated good to excellent psychometric properties among a sample of older adults with MCI and DAT as well as cognitively intact older adult control subjects and provides a method for collecting unique information on the patient experience of cognitive impairment. Subscales permit focused evaluation of domains relevant to the patient's experience of cognitive impairment.

The impact of severe respiratory syncytial virus on the child, caregiver, and family during hospitalization and recovery.

OBJECTIVE: To quantify the magnitude of child, caregiver, and family distress associated with hospitalization for severe respiratory syncytial virus (RSV) and the posthospitalization recovery period. DESIGN: A prospective study of 46 RSV-hospitalized infants and children < or =30 months of age with a history of prematurity (gestational age of < or =35 weeks) and 45 age-matched control subjects was performed. RSV group data were gathered during hospitalization and on days 4, 14, 21, and 60 after discharge; control group data were collected at the end of the RSV season and 60 days thereafter. MAIN OUTCOME MEASURES: RSV severity; caregiver's rating of the child's health (100-point rating) and functional status (Functional Status IIR); caregiver health, stress (7-point rating), and anxiety (Spielberger State Anxiety Inventory); and family health and functioning (Family Adaptability and Cohesion Evaluation Scale II) were recorded. RESULTS: The mean age of the sample was 10.2 months; 51% of the subjects were male. The average duration of hospital stay for the RSV group was 5.8 +/- 8 days. Most patients received supplemental oxygen (76%) and were monitored for apnea (60%). The mean age of the caregivers (93% mothers) was 29 years. During hospitalization, the RSV-infected patients' health and functional status were significantly poorer than those of control subjects. Caregivers of RSV-infected children reported more stress, greater anxiety, poorer health, and poorer family health and functioning. As long as 60 days after discharge, caregivers of RSV-infected children reported the children's health as significantly poorer and were personally more anxious, compared with control subjects. CONCLUSIONS: RSV-related hospitalization creates significant distress for infants and children, caregivers, and families, with some effects extending as long as 60 days after discharge.