Effectiveness and Safety of COPD Maintenance Therapy with Tiotropium/Olodaterol versus LABA/ICS in a US Claims Database

Malaltia pulmonar obstructiva crònica; Corticosteroides; OlodaterolEnfermedad pulmonar obstructiva crónica; Corticosteroides; OlodaterolChronic obstructive pulmonary disease; Corticosteroids; OlodaterolIntroduction In patients with chronic obstructive pulmonary disease (COPD), treatment with long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) combination therapy significantly improves lung function versus LABA/inhaled corticosteroid (ICS). To investigate whether LAMA/LABA could provide better clinical outcomes than LABA/ICS, this non-interventional database study assessed the risk of COPD exacerbations, pneumonia, and escalation to triple therapy in patients with COPD initiating maintenance therapy with tiotropium/olodaterol versus any LABA/ICS combination. Methods Administrative healthcare claims and laboratory results data from the US HealthCore Integrated Research DatabaseSM were evaluated for patients with COPD initiating tiotropium/olodaterol versus LABA/ICS treatment (January 2013–March 2019). Patients were aged at least 40 years with a diagnosis of COPD (but not asthma) at cohort entry. A Cox proportional hazard regression model was used (as-treated analysis) to assess risk of COPD exacerbation, community-acquired pneumonia, and escalation to triple therapy, both individually and as a combined risk of any one of these events. Potential imbalance of confounding factors between cohorts was handled using fine stratification, reweighting, and trimming by exposure propensity score (high-dimensional); subgroup analyses were conducted on the basis of blood eosinophil levels and exacerbation history. Results The total population consisted of 61,985 patients (tiotropium/olodaterol n = 2684; LABA/ICS n = 59,301); after reweighting, the total was 42,953 patients (tiotropium/olodaterol n = 2600; LABA/ICS n = 40,353; mean age 65 years; female 54.5%). Patients treated with tiotropium/olodaterol versus LABA/ICS experienced a reduction in the risk of COPD exacerbations (adjusted hazard ratio 0.76 [95% confidence interval 0.68, 0.85]), pneumonia (0.74 [0.57, 0.97]), escalation to triple therapy (0.22 [0.19, 0.26]), and any one of these events (0.45 [0.41, 0.49]); the combined risk was similar irrespective of baseline eosinophils and exacerbation history. Conclusions In patients with COPD, tiotropium/olodaterol was associated with a lower risk of COPD exacerbations, pneumonia, and escalation to triple therapy versus LABA/ICS, both individually and in combination; the combined risk was reduced irrespective of baseline eosinophils or exacerbation history.Support for this project and the journal’s Open Access Fee were funded by Boehringer Ingelheim International GmbH. No Rapid Service Fee was received by the journal for the publication of this article

Seroepidemiology of Human Bocavirus Infection in Jamaica

Human bocavirus (HBoV) is a newly identified human parvovirus. HBoV is associated with upper and lower respiratory tract infections and gastroenteritis in children. Little is known about the seroepidemiology of HBoV in populations in the Caribbean.In a cross-sectional study conducted at the University Hospital of the West Indies in Kingston, Jamaica, 287 blood samples were collected from pediatric patients and tested for the presence of HBoV-specific antibody using a virus-like-particle based enzyme-linked immunosorbent assay (ELISA).HBoV-specific antibodies were found to be present in 220/287 (76.7%) of samples collected from the pediatric population. Seroprevalence of HBoV was highest in those ≥2 years old. The seroepidemiological profile suggests that most children are exposed to HBoV during the first two years of life in Jamaica.HBoV infection is common in children in Jamaica. HBoV seroprevalence rates in the Caribbean are similar to those previously reported in other areas of the world

Stillbirth, ischemic placental disease, and neonatal opioid withdrawal syndrome following exposure to opioid analgesic medication during pregnancy

BACKGROUND: Opioid use has been associated with adverse pregnancy outcomes including neonatal opioid withdrawal syndrome (NOWS) and certain congenital malformations. Less intensively studied in relationship to prescription opioid exposure are stillbirth and ischemic placental disease (IPD), including preeclampsia, placental abruption, and intrauterine growth restriction (IUGR)/being born small for gestational age (SGA), which often result in preterm birth. Little is also known about how NOWS risk varies by the specific prescription opioid used. Given the highly prevalent and growing use of prescription opioid analgesics during pregnancy, a better understanding of their impact on these less studied outcomes as well as the association between NOWS and specific opioid medications is needed. METHODS: Three studies were performed using a cohort derived from the Medicaid Analytic eXtract (MAX), which contains administrative billing data for Medicaid enrollees in 46 states and Washington DC. These studies assessed (1) the association between prescription opioid use leading up to delivery and the risk of stillbirth, (2) the association between prescription opioid use and the risk of ischemic placental disease including pre-eclampsia, placental abruption, intrauterine growth restriction (IUGR) and preterm delivery, and (3) the association between properties of prescription opioid use and risk of NOWS. For Study 1, a case-control approach was utilized, with controls sampled from the cohort at risk to mirror the gestational age at stillbirth observed in the US population. Cases and controls were compared with respect to demographic and clinical characteristics, and odds ratios were calculated based on opioid exposure occurring within 4, 8, and 20 weeks prior to the stillbirth event of control sampling date. Study 2 used a cohort design in which risks of each component of ischemic placental disease were compared between opioid exposed and unexposed women according to timing of exposure during pregnancy (early, late and both early and late). Study 3 compared pregnancies exposed to opioids in the last 90 days before delivery based on characteristics of the opioid used. Relative risks were calculated for NOWS unadjusted, adjusted for characteristics of the medications used (including MMEs), and adjusted for confounding by demographic characteristics and medical history using fine stratification and reweighting of an exposure propensity score. Odds ratios of stillbirth, hazard ratios of ischemic placental disease, and relative risks of NOWS, with their 95% confidence intervals (CI) were estimated overall and within subgroups of interest. Because the analyses relied on administrative claims that require assumptions about timing of pregnancy and may not adequately capture illicit opioid use, other illicit drug use, smoking and obesity, probabilistic bias analyses were employed to estimate the impact of exposure misclassification and unmeasured confounding. RESULTS: Study 1: Among eligible pregnancies in the MAX database, we identified 25,565 stillbirths and 255,650 controls. A small increased risk was observed for exposure in the four weeks prior to delivery (adjusted odds ratio 1.24, 95% CI 1.16 – 1.32), with attenuation of the effect when considering alternate exposure windows of 8 or 20 weeks prior to the stillbirth event or control sampling date. Some differences were observed by specific medication used, with no meaningful increase observed for codeine (aOR 1.09, 95% CI 0.98 – 1.22) and a modest increase for oxycodone (aOR 1.39, 95% CI 1.16 – 1.67). Exploration of the 1.24-fold increase for exposure to any opioid in the four weeks prior to delivery suggests potential for reverse causation whereby medication could have been dispensed after recognition of fetal death, with opioid dispensings in the week of pregnancy loss associated with an aOR of 1.48 (1.34 – 1.63) and dispensings in the 2nd – 4th weeks prior to pregnancy loss associated with an aOR of 1.09 (95% CI 0.97 – 1.23). This could also be compatible with a triggering effect with a specific etiologically relevant window. Study 2: Of 1,833,871 eligible pregnancies, ≥2 opioid dispensings were filled by 6.5%. We observed an early exposure aHR of 1.34 (95% CI 1.26–1.43) for placental abruption, 1.21 (1.18–1.23) for preterm delivery, 1.13 (1.09–1.17) for SGA, and 0.95 (0.91–0.98) for preeclampsia. Estimates for late exposure were attenuated for each ischemic placental disease outcome. Exposure both early and late was associated with higher aHRs for placental abruption (1.62, 1.47–1.78), preterm delivery (1.37, 1.33–1.42) and SGA (1.26, 1.19–1.33), but not preeclampsia (0.99, 0.93–1.05). Study 3: We compared 16,202 codeine, 1,244 tramadol, 4,540 oxycodone, 260 methadone, 90 hydromorphone, and 63 morphine users vs. 25,710 hydrocodone users. When compared to hydrocodone users, adjusted relative risk of NOWS was lower for use of weak agonists [codeine (RR 0.57, 95% CI 0.46–0.70) and tramadol (1.06, 0.73–1.56)] and higher for use of strong agonists [oxycodone (1.87, 1.66–2.11), hydromorphone (2.03, 1.09–3.78), morphine (2.84, 1.30–6.22), and methadone (3.02, 2.45–3.73)]. Long half-life opioids had a slightly increased risk compared to short half-life products (1.33, 1.12–1.56). DISCUSSION: Opioid use proximate to delivery does not appear to be a major trigger of stillbirth, although a weak effect cannot be excluded. Prescription opioids may modestly increase risk of placental abruption, preterm birth, and SGA, but they do not appear to be associated with preeclampsia. The risk of NOWS in infants with exposed to opioids during the 90 days before delivery, however, was different based on the type of opioid used. This information may help prescribers with opioid analgesic selection for pain management in late pregnancy.2024-05-18T00:00:00

Characteristics of prescription opioid analgesics in pregnancy and risk of neonatal opioid withdrawal syndrome in newborns.

Importance: Prescription opioids are often used during pregnancy even though they are associated with neonatal opioid withdrawal syndrome (NOWS). Most studies of adverse outcomes of opioid use for pain have assessed only the class-wide outcome despite the pharmacodynamic and pharmacokinetic heterogeneity across opioid medications. Question: Does risk of neonatal opioid withdrawal syndrome (NOWS) after in utero exposure to prescription opioids vary across commonly prescribed types of opioids? Findings: In this cohort study of 48 202 opioid-exposed pregnancies with live-born neonates, strong agonists were associated with a higher risk of NOWS compared with weak agonists, and long half-life opioids were associated with an increased risk compared with short half-life products. These associations were independent of morphine milligram equivalents. Meaning: The study suggests that knowing the varying opioid-specific risk of NOWS associated with in utero exposure may help prescribers select opioids for pain management in late stages of pregnancy

Seroepidemiology of HBoV shown by age group.

<p>The no. of serum samples screened and the percentage of seropositive individuals are shown for each age group; bars indicate standard errors.</p

Comparative Effectiveness of Bivalent (Original/Omicron BA.4/BA.5) COVID-19 Vaccines in Adults

The emergence of Omicron variants coincided with declining vaccine-induced protection against SARS-CoV-2. Two bivalent mRNA vaccines, mRNA-1273.222 (Moderna) and BNT162b2 Bivalent (Pfizer-BioNTech), were developed to provide greater protection against the predominate circulating variants by including mRNA that encodes both the ancestral (original) strain and BA.4/BA.5. We estimated their relative vaccine effectiveness (rVE) in preventing COVID-19-related outcomes in the US using a nationwide dataset linking primary care electronic health records and pharmacy/medical claims data. The study population (aged ≥18 years) received either vaccine between 31 August 2022 and 28 February 2023. We used propensity score weighting to adjust for baseline differences between groups. We estimated the rVE against COVID-19-related hospitalizations (primary outcome) and outpatient visits (secondary) for 1,034,538 mRNA-1273.222 and 1,670,666 BNT162b2 Bivalent vaccine recipients, with an adjusted rVE of 9.8% (95% confidence interval: 2.6–16.4%) and 5.1% (95% CI: 3.2–6.9%), respectively, for mRNA-1273.222 versus BNT162b2 Bivalent. The incremental relative effectiveness was greater among adults ≥ 65; the rVE against COVID-19-related hospitalizations and outpatient visits in these patients was 13.5% (95% CI: 5.5–20.8%) and 10.7% (8.2–13.1%), respectively. Overall, we found greater effectiveness of mRNA-1273.222 compared with the BNT162b2 Bivalent vaccine in preventing COVID-19-related hospitalizations and outpatient visits, with increased benefits in older adults