Adverse infant outcomes following low-risk pregnancies in England: a retrospective cohort study.

BACKGROUND: There are limited data describing adverse infant outcomes in infants born to women with a low risk of complications during pregnancy, such as those who may be enrolled in maternal immunization trials. This retrospective study estimated incidence proportions of infant outcomes in different cohorts of liveborn infants in England between 2005 and 2017. METHODS: The incidence proportions of 10 infant outcomes were calculated for liveborn infants from pregnancies represented in the Clinical Practice Research Datalink (CPRD) Mother-Baby Link (MBL) and linkage to Hospital Episode Statistics (HES). Three infant cohorts were designed: (1) the all pregnancies infants cohort (N = 185,119), (2) the all pregnancies with a gestational age (GA) ≥ 24 weeks infants cohort (N = 183,869), and (3) the low-risk pregnancies infants cohort (LR infants cohort, N = 121,871), which included pregnancies with a GA ≥ 24 weeks and no diagnosis of predefined high-risk medical conditions until 24 weeks GA. RESULTS: The most common adverse infant outcome in the three infant cohorts was macrosomia (e.g., 1,085.9/10,000 live births in the LR infants cohort), followed by minor congenital anomalies (e.g., 800.6/10,000 in the LR infants cohort), very low/low birth weight (e.g., 400.6/10,000 in the LR infants cohort), and major congenital anomalies (e.g., 270.4/10,000 in the LR infants cohort). The incidence proportions for early-onset sepsis, very low/low birth weight, and minor and major congenital anomalies were lower in the LR infants than in the other cohorts (non-overlapping confidence intervals [CIs]). The incidence proportions of neonatal death, infant death, late-onset sepsis, macrosomia, small for GA, and large for GA were similar between cohorts (overlapping CIs). CONCLUSIONS: This study generated background rates of adverse infant outcomes from liveborn infants of all and low-risk pregnancies represented in the CPRD Pregnancy Register MBL and linkage to HES. The results indicate lower incidence proportions of several adverse infant outcomes in infants from low-risk pregnancies compared to all pregnancies, illustrating the importance of considering maternal risk factors. These background rates may facilitate the interpretation of safety data from maternal immunization trials and of pharmacovigilance data from maternal vaccines. They may also be of interest for other interventions studied in pregnant women.

Strategies to Address Current Challenges in Real-World Evidence Generation in Japan.

The generation of real-world evidence (RWE), which describes patient characteristics or treatment patterns using real-world data (RWD), is rapidly growing more popular as a tool for decision-making in Japan. The aim of this review was to summarize challenges to RWE generation in Japan related to pharmacoepidemiology, and to propose strategies to address some of these challenges. We first focused on data-related issues, including the lack of transparency of RWD sources, linkage across different care settings, definitions of clinical outcomes, and the overall assessment framework of RWD when used for research purposes. Next the study reviewed methodology-related challenges. As lack of design transparency impairs study reproducibility, transparent reporting of study design is critical for stakeholders. For this review, we considered different sources of biases and time-varying confounding, along with potential study design and methodological solutions. Additionally, the implementation of robust assessment of definition uncertainty, misclassification, and unmeasured confounders would enhance RWE credibility in light of RWD source-related limitations, and is being strongly considered by task forces in Japan. Overall, the development of guidance for best practices on data source selection, design transparency, and analytical methods to address different sources of biases and robustness in the process of RWE generation will enhance credibility for stakeholders and local decision-makers.

Burden of Pertussis in Adults Aged 50 Years and Older: A Retrospective Database Study in England.

INTRODUCTION: Pertussis, a highly infectious respiratory disease caused by Bordetella pertussis, affects people of all ages. Older adults are particularly susceptible to its severe outcomes and complications. METHODS: In this retrospective cohort study, the incidence rate of pertussis among individuals aged ≥ 50 years was assessed during 2009-2018 using Clinical Practice Research Datalink and Hospital Episode Statistics databases, United Kingdom. Health care resource utilisation (HCRU) and direct medical costs (DMCs) were compared between patients with a pertussis diagnosis and propensity score-matched controls (matched on demographic and clinical variables). RESULTS: Among 5,222,860 individuals, 1638 had a pertussis diagnosis (incidence rate: 5.8 per 100,000 person-years; 95% confidence interval 5.5-6.0). Baseline (- 18 to - 6 months) HCRU and DMC were similar among 1480 pertussis patients and 1480 matched controls. However, there were increases in HCRU in the pertussis vs. matched cohort around the pertussis diagnosis (from months - 6 to - 1 to 5-11). The most notable increases (pertussis vs. controls) were in the rates of general practitioner (GP)/nurse visits (4.7-fold), clinical assessments (4.1-fold), and accident and emergency visits (3.0-fold) during the month before diagnosis and GP/nurse visits during the 2 months after diagnosis (2.5-fold) (all p < 0.001). DMCs were significantly higher in the pertussis cohort (p < 0.001). Total excess DMC in the pertussis cohort during months - 1 to + 11 was £318 per patient. CONCLUSION: A pertussis diagnosis among adults aged ≥ 50 years resulted in significant increases in HCRU and DMC across several months around diagnosis. These results highlight the need for increased awareness of pertussis infection among adults aged ≥ 50 years and suggest that pertussis booster doses among this population should be considered.

History of Respiratory Events Prior to a First COPD Diagnosis and Future Exacerbations: A Longitudinal Observational Cohort Database Study in Japan.

Background: Little is known about the association between respiratory events prior to diagnosis of chronic obstructive pulmonary disease (COPD) and future clinical outcomes in Japan. We investigated the association between pre-COPD diagnosis respiratory events and the incidence of exacerbations in a cohort of newly diagnosed COPD patients in Japan. Patients and Methods: Data were retrieved from the JMDC claims database. Patients ≥40 years old with a first COPD diagnosis (≥1 hospitalization or ≥2 outpatient claims for COPD) between 2010 and 2016 were included. The incidence rate (IR) of exacerbations in patients with or without any respiratory event (including lower respiratory tract infection and respiratory failure) in the year preceding diagnosis was compared. A negative binomial model explored the association between pre-diagnosis respiratory event and IR ratio (IRR) of exacerbations. Results: A total of 20,212 patients newly diagnosed with COPD were identified: 61% male, mean age 55 years (SD 9); of these, 955 (4.7%) had experienced ≥1 respiratory event in the year preceding diagnosis. Median duration of follow-up was 3.3 years during which the IR of exacerbations was 0.31 per patient-year (95% confidence interval [CI] 0.29-0.33) in patients with respiratory event, and 0.11 (95% CI 0.10-0.13) in patients without. The IR for severe exacerbation was nearly 10 times greater in patients with respiratory event versus without. Experiencing respiratory event pre-diagnosis was independently associated with an increased IRR of future moderate-to-severe exacerbation (adjusted IRR, 2.7; 95% CI 2.3-3.1). Conclusion: Patients experiencing respiratory events in the year preceding COPD diagnosis should be considered at-risk of worse clinical COPD outcomes.

Comorbidities and clinical outcomes in adult- and juvenile-onset Huntington's disease: a study of linked Swedish National Registries (2002-2019).

BACKGROUND: Huntington's disease (HD) is a rare, neurodegenerative disease and its complex motor, cognitive and psychiatric symptoms exert a lifelong clinical burden on both patients and their families. OBJECTIVE: To describe the clinical burden and natural history of HD. METHODS: This longitudinal cohort study used data from the linked Swedish national registries to describe the occurrence of comorbidities (acute and chronic), symptomatic treatments and mortality in an incident cohort of individuals who either received the first diagnosis of HD above (adult onset HD; AoHD) or below (juvenile-onset HD; JoHD) 20 years of age, compared with a matched cohort without HD from the general population. Disease burden of all individuals alive in Sweden was described during a single calendar year (2018), including the occurrence of key symptoms, treatments and hospitalizations. RESULTS: The prevalence of HD in 2018 was approximately 10.2 per 100,000. Of 1492 individuals with a diagnosis of HD during 2002 and 2018, 1447 had AoHD and 45 had JoHD. Individuals with AoHD suffered a higher incidence of obsessive-compulsive disorder, acute psychotic episodes, pneumonia, constipation and fractures compared with matched controls. Individuals with JoHD had higher incidence rates of epilepsy, constipation and acute respiratory symptoms. Median time to all-cause mortality in AoHD was 12.1 years from diagnosis. Patients alive with HD in Sweden in 2018 displayed a pattern of increased clinical burden for a number of years since diagnosis. CONCLUSIONS: This study demonstrates the significant and progressive clinical burden in individuals with HD and presents novel insights into the natural history of JoHD.

Facilitating safety evaluation in maternal immunization trials: a retrospective cohort study to assess pregnancy outcomes and events of interest in low-risk pregnancies in England.

BACKGROUND: Maternal characteristics like medical history and health-related risk factors can influence the incidence of pregnancy outcomes and pregnancy-related events of interest (EIs). Data on the incidence of these endpoints in low-risk pregnant women are needed for appropriate external safety comparisons in maternal immunization trials. To address this need, this study estimated the incidence proportions of pregnancy outcomes and pregnancy-related EIs in different pregnancy cohorts (including low-risk pregnancies) in England, contained in the Clinical Practice Research Datalink (CPRD) Pregnancy Register linked to Hospital Episode Statistics (HES) between 2005 and 2017. METHODS: The incidence proportions of 7 pregnancy outcomes and 15 EIs were calculated for: (1) all pregnancies (AP) represented in the CPRD Pregnancy Register linked to HES (AP cohort; N = 298 155), (2) all pregnancies with a gestational age (GA) ≥ 24 weeks (AP24+ cohort; N = 208 328), and (3) low-risk pregnancies (LR cohort; N = 137 932) with a GA ≥ 24 weeks and no diagnosis of predefined high-risk medical conditions until 24 weeks GA. RESULTS: Miscarriage was the most common adverse pregnancy outcome in the AP cohort (1 379.5 per 10 000 pregnancies) but could not be assessed in the other cohorts because these only included pregnancies with a GA ≥ 24 weeks, and miscarriages with GA ≥ 24 weeks were reclassified as stillbirths. Preterm delivery (< 37 weeks GA) was the most common adverse pregnancy outcome in the AP24+ and LR cohorts (742.9 and 680.0 per 10 000 pregnancies, respectively). Focusing on the cohorts with a GA ≥ 24 weeks, the most common pregnancy-related EIs in the AP24+ and LR cohorts were fetal/perinatal distress or asphyxia (1 824.3 and 1 833.0 per 10 000 pregnancies), vaginal/intrauterine hemorrhage (799.2 and 729.0 per 10 000 pregnancies), and labor protraction/arrest disorders (752.4 and 774.5 per 10 000 pregnancies). CONCLUSIONS: This study generated incidence proportions of pregnancy outcomes and pregnancy-related EIs from the CPRD for different pregnancy cohorts, including low-risk pregnancies. The reported incidence proportions of pregnancy outcomes and pregnancy-related EIs are largely consistent with external estimates. These results may facilitate the interpretation of safety data from maternal immunization trials and the safety monitoring of maternal vaccines. They may also be of interest for any intervention studied in populations of pregnant women.

Burden of Pertussis in Individuals with a Diagnosis of Asthma: A Retrospective Database Study in England.

PURPOSE: The impact of pertussis in individuals with asthma is not fully understood. We estimated the incidence, health care resource utilization (HCRU), and direct medical costs (DMC) of pertussis in patients with asthma. PATIENTS AND METHODS: In this retrospective cohort study, the incidence rate of pertussis (identified using diagnostic codes) among individuals aged ≥50 years with an asthma diagnosis was assessed during 2009-2018 using Clinical Practice Research Datalink and Hospital Episode Statistics databases. HCRU and DMC were compared - between patients with diagnoses of asthma and pertussis (asthma+/pertussis+) and propensity score-matched patients with a diagnosis of asthma without pertussis (asthma+/pertussis-) - in the months around the pertussis diagnosis (-6 to +11). RESULTS: Among 687,105 individuals, 346 had a reported pertussis event (incidence rate: 9.6/100,000 person-years of follow-up; 95% confidence interval: 8.6-10.7). HCRU and DMC were assessed among 314 asthma+/pertussis+ patients and 1256 matched asthma+/pertussis- controls. Baseline HCRU was similar in both cohorts, but increases were observed in the asthma+/pertussis+ cohort from -6 to -1 month before to 2-5 months after diagnosis. Rates of accident and emergency visits, general practitioner (GP)/nurse visits, and GP prescriptions were 4.3-, 3.1-, and 1.3-fold, respectively, in the asthma+/pertussis+ vs asthma+/pertussis- cohorts during the month before diagnosis; GP/nurse visit rates were 2.0- and 1.2-fold during 0-2 and 2-5 months after diagnosis, respectively (all p<0.001). DMC was 1.9- and 1.6-fold during the month before and 2 months from diagnosis, respectively, in the asthma+/pertussis+ vs asthma+/pertussis- cohorts (both p<0.001). During months -1 to +11, DMC in the asthma+/pertussis+ cohort was £370 higher than in the asthma+/pertussis- controls. CONCLUSION: A pertussis diagnosis among adults aged ≥50 years with asthma resulted in significant increases in HCRU and DMC across several months around diagnosis, suggesting lengthy diagnosis times and highlighting the need for prevention strategies.

Extended dual antiplatelet therapy with ticagrelor 60 mg in patients with prior myocardial infarction: The design of ALETHEIA, a multi-country observational study.

INTRODUCTION: Clinical guidelines recommend extended treatment with dual antiplatelet therapy (DAPT) with ticagrelor 60 mg (twice daily) beyond 12 months in high-risk patients with a history of myocardial infarction (MI) who have previously tolerated DAPT and are not at heightened bleeding risk. However, evidence on patterns of use and associated clinical outcomes in routine clinical practice is limited. METHODS: ALETHEIA is an observational, multi-country study, designed to describe characteristics, treatment persistence, and bleeding and cardiovascular (CV) outcomes in post-MI patients who initiate ticagrelor 60 mg in routine clinical practice (NCT04568083). The study will include electronic health data in the United States (US; Medicare, commercial claims) and Europe (Sweden, Italy, United Kingdom, Germany). Characteristics will be described among patients with and without ticagrelor 60 mg ≥1 year post-MI. Assuming an a priori threshold of 5000 person-years on-treatment is met, to ensure sufficient precision, clinical outcomes (bleeding and CV events) among patients treated with ticagrelor 60 mg will be assessed. Risk factors for clinical outcomes and treatment discontinuation will be assessed in patients with ticagrelor 60 mg and meta-analysis used to combine estimates across databases. Cohort selection will initiate from the ticagrelor 60 mg US and European approval dates and end February 2020. An estimated total of 7250 patients prescribed ticagrelor 60 mg are expected to be included. DISCUSSION: An increased understanding of patterns of ticagrelor 60 mg use and associated clinical outcomes among high-risk patients with a prior MI is needed. The a priori specified stepwise approach adapted in this observational study is expected to generate useful evidence for clinical decision-making and treatment optimization.

Oral Anticoagulation Therapy for Venous Thromboembolism in Norway: Time Trends and Treatment Patterns.

PURPOSE: Data describing treatment patterns of patients with venous thromboembolism (VTE) patients in Scandinavia are scarce. This study sought to address this scarcity by describing demographic and clinical characteristics, trends in the use of oral anticoagulants (OACs), and treatment patterns in patients treated for VTE in Norway between 2013 and 2017. METHODS: Using data from Norway's nationwide registries, a cohort study included patients newly (after 2008) treated OACs who were diagnosed with VTE between January 2013 and December 2017 and were dispensed an OAC (warfarin, apixaban, rivaroxaban, dabigatran, or edoxaban) within 30 days. Patient characteristics and the percentage of patients with VTE who initiated treatment with each OAC for each calendar year were reported. Initial therapy persistence was assessed using Kaplan-Meier curves and compared between the OAC groups using the log-rank test. FINDINGS: The comorbidity burden was similar between patients taking warfarin and those taking apixaban but lower among patients taking rivaroxaban. Direct oral anticoagulant (DOAC) use increased from 33.2% to 93.6% during the study period, whereas warfarin use decreased. Persistence was higher in the apixaban cohort compared with the warfarin cohort, with the difference mostly apparent after 6 months, whereas persistence was similar between the patients taking rivaroxaban and those taking warfarin. IMPLICATIONS: Between 2013 and 2017, DOAC use among patients with VTEs increased markedly in Norway, whereas the use of warfarin decreased. Patients taking apixaban had higher persistence compared with those taking warfarin, whereas patients taking warfarin and those taking rivaroxaban had similar persistence. Further studies with longer follow-up are required to examine the use of extended OAC treatment for VTE.

Burden of Pertussis in COPD: A Retrospective Database Study in England.

Chronic obstructive pulmonary disease (COPD) may increase the risk and severity of pertussis infection. Health care resource utilization (HCRU) and direct medical costs (DMC) of treating pertussis among patients with COPD are unknown. Reported incidence of pertussis among individuals aged ≥ 50 years with COPD was assessed in Clinical Practice Research Datalink and Hospital Episode Statistics databases during 2009-2018 using a retrospective cohort design. HCRU and DMC from the National Health Service perspective were compared between patients with COPD and pertussis and propensity score-matched patients with COPD without pertussis. Seventy-eight new pertussis events were identified among 387 086 patients with COPD aged ≥ 50 years (incidence rate: 4.73; 95% confidence interval 3.74-5.91 per 100 000 person-years). HCRU and DMC were assessed among 67 patients with COPD and pertussis and 267 matched controls. During the month before the pertussis diagnosis, the rates of general practitioner (GP)/nurse visits (4289 vs. 1774 per 100 patient-years) and accident and emergency visits (182 vs. 18 per 100 patient-years) were higher in the pertussis cohort; GP/nurse visits (2935 vs. 1705 per 100 patient-years) were also higher during the following 2 months (all p < 0.001). During the month before the pertussis diagnosis, annualized per-patient total DMC were £2012 higher in the pertussis cohort (£3729 vs. £1717; p < 0.001); during the following 2 months, they were £2407 higher (£5498 vs. £3091; p < 0.001). In conclusion, a pertussis episode among individuals with COPD resulted in significant increases in HCRU and DMC around the pertussis event.

Clinical characteristics and factors associated with triple therapy use in newly diagnosed patients with COPD.

There is limited information about the initiation of triple therapy (TT) in patients with chronic obstructive pulmonary disease (COPD) in primary care. This was an observational, population-based study in patients identified from a primary care electronic medical records database in Catalonia from 2011 to 2015 aimed to identify the use of TT in patients with newly diagnosed COPD. A total of 69,668 newly diagnosed patients were identified of whom 11,524 (16.5%) initiated TT, of whom 8626 initiated TT at or immediately after COPD diagnosis. Among them, 72.3% were GOLD A/B, 14.6% were frequent exacerbators, and 7.1% had asthma-COPD overlap (ACO). Variables associated with TT initiation were: male sex, older age, previous exacerbations, ACO, a previous treatment regimen containing an inhaled corticosteroid, previous pneumonia, and history of lung cancer. A significant number of COPD patients in Primary Care initiated TT shortly after or even before an established COPD diagnosis.

Treatment Pathways Before and After Triple Therapy in COPD: A Population-based Study in Primary Care in Spain / Vías de tratamiento antes y después de la triple terapia en EPOC: estudio poblacional en atención primaria en España

Background: Recent data from real world clinical practices on the use of Triple Therapy (TT) in patients with COPD are scarce.Methods: Observational population-based study with longitudinal follow-up in patients with COPD identified in a primary care electronic medical records database in Catalonia, covering 80% of the general population. The aims were to characterize COPD patients who initiated TT and to describe treatment pathways before and after TT initiation. Time to and probability of step down or complete discontinuation of TT was described using restricted mean survival time and Kaplan•Meier analysis.Results: A total of 34,018 COPD patients initiated TT during the study period. Of them, 23,867 (70.1%) were GOLD A/B. 18,453 (54.2%) were non-exacerbators, 9931 (29.2%) infrequent exacerbators, 5634 (16.5%) frequent exacerbators and 1923 (5.6%) had asthma-COPD overlap. Drugs most frequently used prior to initiation of TT were long-acting antimuscarinics (22.5%) and combination of long-acting beta2 agonists/inhaled corticosteroids (15.2%). A total of 11,666 (34.3%) stepped down and 1091 (3.2%) discontinued TT during follow-up. Step down following TT was more likely in patients with severe COPD, especially during the first year; however, discontinuation was more common among patients with mild COPD. (AU)

Antecedentes: Se dispone de pocos datos recientes de práctica clínica en el mundo real sobre el uso de la triple terapia (TT) en pacientes con EPOC.Métodos: Estudio observacional de base poblacional con seguimiento longitudinal en pacientes con EPOC identificados en una base de datos de historiales médicos electrónicos de atención primaria en Cataluña, que abarca el 80% de la población general. Los objetivos fueron caracterizar a los pacientes con EPOC que iniciaron la TT, y describir las vías de tratamiento antes y después del inicio de la TT. Se describió el tiempo y la probabilidad de desescalada o la suspensión completa de la TT utilizando el tiempo de supervivencia medio restringido y el análisis de Kaplan-Meier.Resultados: Un total de 34.018 pacientes con EPOC iniciaron TT durante el período de estudio. De ellos, 23.867 (70,1%) eran GOLD A/B, 18.453 (54,2%) eran no exacerbadores, 9.931 (29,2%) exacerbadores infrecuentes, 5.634 (16,5%) exacerbadores frecuentes y 1.923 (5,6%) presentaban superposición asma-EPOC. Los fármacos que se usaron con mayor frecuencia antes del inicio de la TT fueron los antimuscarínicos de acción prolongada (22,5%), y la combinación de agonistas beta2 de acción prolongada/corticosteroides inhalados (15,2%). Un total de 11.666 pacientes (34,3%) desescalaron la TT y 1.091 (3,2%) suspendieron el tratamiento durante el seguimiento. La desescalada después de la TT fue más probable en pacientes con EPOC grave, especialmente durante el primer año; sin embargo, la suspensión fue más común en pacientes con EPOC leve. (AU)

Treatment Pathways Before and After Triple Therapy in COPD: A Population-based Study in Primary Care in Spain.

BACKGROUND: Recent data from real world clinical practices on the use of Triple Therapy (TT) in patients with COPD are scarce. METHODS: Observational population-based study with longitudinal follow-up in patients with COPD identified in a primary care electronic medical records database in Catalonia, covering 80% of the general population. The aims were to characterize COPD patients who initiated TT and to describe treatment pathways before and after TT initiation. Time to and probability of step down or complete discontinuation of TT was described using restricted mean survival time and Kaplan-Meier analysis. RESULTS: A total of 34,018 COPD patients initiated TT during the study period. Of them, 23,867 (70.1%) were GOLD A/B. 18,453 (54.2%) were non-exacerbators, 9931 (29.2%) infrequent exacerbators, 5634 (16.5%) frequent exacerbators and 1923 (5.6%) had asthma-COPD overlap. Drugs most frequently used prior to initiation of TT were long-acting antimuscarinics (22.5%) and combination of long-acting beta2 agonists/inhaled corticosteroids (15.2%). A total of 11,666 (34.3%) stepped down and 1091 (3.2%) discontinued TT during follow-up. Step down following TT was more likely in patients with severe COPD, especially during the first year; however, discontinuation was more common among patients with mild COPD. CONCLUSION: Most patients initiating treatment with TT were non exacerbators and continued on the same treatment over time regardless severity of disease. Stepping down was more frequent in severe patients, while discontinuation was more common among mild patients. Overall, it appears that TT is extensively used in primary care for treatment of patients with COPD.

Using Social Media to Uncover Treatment Experiences and Decisions in Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome Who Are Ineligible for Intensive Chemotherapy: Patient-Centric Qualitative Data Analysis.

BACKGROUND: Until recently, treatment options were limited for patients with acute myeloid leukemia and myelodysplastic syndrome (AML and MDS) who are ineligible for intensive chemotherapy. Owing to the condition's rapid progression, it is difficult to identify what is most important to patients when making treatment decisions. Patients' needs can be better addressed by gaining a deeper understanding of their perspectives, which is valuable in the decision-making process. The Food and Drug Administration recently encouraged the use of social media as a tool to gain insight on patients' perspectives regarding symptoms experienced and the impacts of their disease. OBJECTIVE: This study aimed to use disease-specific social media posts by patients with AML or MDS who are ineligible for intensive chemotherapy and their caregivers to capture factors they feel are most important, and to provide current evidence to inform and characterize these perspectives. METHODS: Posts by patients with AML or MDS and their caregivers were extracted from publicly available discussions on 3 large AML- or MDS-specific sites. These posts were manually reviewed to only include patients who are ineligible for intensive chemotherapy. A total of 1443 posts from 220 AML patients/caregivers and 2733 posts from 127 MDS patients/caregivers met the study inclusion criteria. A qualitative data analysis (QDA) of a sample of 85 patients'/caregivers' posts was conducted to identify themes, and a targeted QDA of posts from 79 users focused on treatment decision discussions. Posts were manually reviewed, and relevant text segments were coded and grouped into categories and overall themes. RESULTS: Eighty-six percent (73/85) of users in the overall QDA had relevant information about the key objectives. The most commonly discussed treatment experience theme was the humanistic burden of AML or MDS in terms of emotional/physical impact and impact on family (86%, 63/73 of users), followed by treatment decisions (56%, 41/73) and unmet needs (50%, 37/73). In the QDA of treatment decisions, 60 posts from 45 users contained relevant information. Patients commonly reported the desire to reach specific milestones, including birthdays and weddings. They wished for a better quality of life over quantity of life, did not want the risk of suffering from side effects, and expressed a clear preference to be at home rather than in a hospital or care home. CONCLUSIONS: This study was a novel application of disease-specific social media. It highlighted experiences in the current treatment of AML and MDS, including information gaps, patient/caregiver uncertainty, and the importance of understanding patients'/caregivers' goals and opinions. A clear finding from this research was the importance of reaching certain personal life goals and being at home with family and friends. The analysis showed that patients/caregivers face additional challenges, including humanistic impacts and a lack of information regarding treatment options.

Personalized benefit-risk assessments combining clinical trial and real-world data provide further insights into which patients may benefit most from therapy: Demonstration for a new oral antiplatelet therapy.

PURPOSE: Quantitative benefit-risk (B-R) assessments are used to characterize treatment by combining key benefits and risks into a single metric but have historically been done for the "average" patient. Our aim was to conduct an individualized assessment for the oral antiplatelet vorapaxar by combining trial and real-world data to further personalize the treatment profiles. METHODS: Using linked UK health care databases, we developed risk prediction equations for key ischemic and bleeding events using Cox proportional hazards models. Trial hazard ratios, relative to placebo, were applied to baseline risk estimates to compute expected attributable risks, summed to derive a per-patient net clinical benefit (NCB). High risk subgroups were defined a priori, and Gaussian mixture models (GMM) were fit to characterize the NCB distribution and identify subgroups with similar NCBs. RESULTS: NCB was consistently positive for all subgroups, likely due to the outcome correlation, and would remain positive with a 12-fold increase in bleeding risk. GMMs identified three distinct NCB subgroups. Compared with the middle/lower NCB subgroups, those with a higher NCB tended to be older, female, and have higher CV disease burden. CONCLUSIONS: Personalized B-R assessments are feasible and clinically valuable and can be used to better predict who would benefit most from therapy.

The cost of preterm labor and preterm birth for mothers with uncomplicated pregnancies and their infants in Italy: a retrospective cohort study.

BACKGROUND: Preterm labor (PTL)/preterm birth (PTB) impose significant burden on health-care systems. Women with uncomplicated pregnancies at risk of PTL/PTB have not been widely investigated, and published evidence on the costs of these women and their infants in Italy is absent. We aimed to describe women with uncomplicated pregnancies and associated costs for these women and their infants. METHODS: Data on women aged 12-44 years with uncomplicated pregnancies who delivered between 1 September 2009 and 31 December 2014 with PTL diagnosis alone or PTL and PTB were included from four Italian databases. Costs were examined during pregnancy, delivery, and 3 years after delivery for mothers and infants, overall and by gestational age (GA). RESULTS: A total of 3058 mothers linked to 3333 infants were included. Costs during pregnancy were €1777. Costs during delivery for PTL/PTB mothers and their infants ranged from €3174 (GA ≥37) to €21007 (GA <28). Combined maternal and infant costs appeared higher for births with lower GAs (<37) in the three-year follow-up. CONCLUSIONS: In Italy, PTL/PTB mothers with uncomplicated pregnancies with infants at lower GAs appeared to incur higher medical costs compared to mothers with infants at higher GAs in all three time periods, with particularly marked differences found when considering mother and infant combined costs.

Short and long-term costs among women experiencing preterm labour or preterm birth: the German experience.

BACKGROUND: Preterm labour and birth (PTL/PTB) is characterised by major health and developmental risks for children, life-changing consequences for their families, and substantial healthcare and economic challenges for wider society. While it is known that PTL/PTB impacts infant healthcare costs in the short and long term in Germany, maternal costs have not been described in detail. The aim of this study was to comprehensively describe costs and resource use among PTL/PTB mothers during pregnancy, at hospitalisation for delivery, and up to three years after delivery-overall and according to gestational age (GA) at delivery. METHODS: This study used data from the Statutory Health Insurance (SHI) sample of the AOK Hessen database in Germany. Mothers aged 12-44 years with deliveries between 2009 and 2013 and > 9 months of medical history prior to delivery were included. PTL/PTB mothers were defined by an International Classification of Diseases, 10th Revision (ICD-10) code for PTL during pregnancy, a diagnosis-related group (DRG) code indicating birthweight < 2500 g, or delivery of an infant < 37 weeks GA. Inpatient and outpatient resource use and total direct medical costs were examined during pregnancy, at delivery hospitalisation, and up to three years post-delivery. RESULTS: Of all mothers, 2147 (20%) experienced PTL/PTB. During pregnancy, median costs for PTL/PTB mothers were €2130. During delivery hospitalisation, the mean length of stay for all PTL/PTB mothers was 6.0 days, and median costs were €2037. Length of stay and costs declined with increasing GA. Long term, PTL/PTB mothers' total median costs were €607 in Year 1, €332 in Year 2, and €388 in Year 3 post-delivery. In each year after delivery, median costs appeared to be greater for mothers who delivered at lower GAs. CONCLUSION: In this description of costs and resource use among PTL/PTB mothers in Germany throughout the pregnancy and up to three years after delivery, the greatest costs were noted prior to delivery. Costs appeared to decrease with increasing GA, particularly during the delivery hospitalisation and the first year after delivery.

An analysis of characteristics of post-authorisation studies registered on the ENCePP EU PAS Register.

BACKGROUND: The objective of this study was to investigate the study design characteristics of Post-Authorisation Studies (PAS) requested by the European Medicines Agency which were recorded on the European Union (EU) PAS Register held by the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP). METHODS: We undertook a cross-sectional descriptive analysis of all studies registered on the EU PAS Register as of 18 th October 2016. RESULTS: We identified a total of 314 studies on the EU PAS Register, including 81 (26%) finalised, 160 (51%) ongoing and 73 (23%) planned. Of those studies identified, 205 (65%) included risk assessment in their scope, 133 (42%) included drug utilisation and 94 (30%) included effectiveness evaluation. Just over half of the studies (175; 56%) used primary data capture, 135 (43%) used secondary data and 4 (1%) used a hybrid design combining both approaches. Risk assessment and effectiveness studies were more likely to use primary data capture (60% and 85% respectively as compared to 39% and 14% respectively for secondary). The converse was true for drug utilisation studies where 59% were secondary vs. 39% for primary. For type 2 diabetes mellitus, database studies were more commonly used (80% vs 3% chart review, 3% hybrid and 13% primary data capture study designs) whereas for studies in oncology, primary data capture were more likely to be used (85% vs 4% chart review, and 11% database study designs). CONCLUSIONS: Results of this analysis show that study objectives and therapeutic area influence PAS design in terms of type of data capture used.

Decrease in rate of multiple sclerosis-related hospitalizations in Portugal.

We sought to investigate the rate of multiple sclerosis (MS)-related hospitalizations in Portugal and assess whether there have been temporal changes as described in other countries. Using data from the Portuguese National Discharge Registry, we observed that between 2008 and 2013 the rate of MS-related hospitalizations decreased by 44%, from 15.9/100 person-years (95% confidence interval (CI: 14.9-16.9) in 2008 to 8.9/100 person-years (95% CI: 8.2-9.6) in 2013. The change in hospitalization rates is in accordance with what has been observed in other countries, and coincides with the release of new therapies for MS in Portugal.