The impact of acute pneumococcal disease on health state utility values: a systematic review.

PURPOSE: Streptococcus pneumoniae infections remain a significant source of morbidity and mortality worldwide. The purpose of this review was to summarize the impact of pneumococcal disease on health state utilities (HSU) in the acute phase of illness. METHODS: We searched MEDLINE, EMBASE, EconLit, the Health Technology Assessment Database, the National Health Economic Evaluation Database, and Tufts Cost-Effectiveness Registry (up to January 2020) for primary studies. Eligible studies elicited HSU estimates using preference-based instruments for the acute phase of infection of pneumococcal syndromes including acute otitis media, pneumonia/lower respiratory tract infections, bacteremia/sepsis, and meningitis. Two reviewers independently conducted screening, data extraction and quality appraisal. RESULTS: We screened 10,178 studies, of which 26 met our inclusion criteria. Cohort sizes ranged from 8 to 2060 respondents. The most frequently studied syndrome was pneumonia (n = 17), followed by acute otitis media (n = 9), meningitis (n = 7) and bacteremia/sepsis (n = 4). Overall, each syndrome was associated with a substantial impact on HSU. Bacteremia/sepsis (range: - 0.331 to 0.992) and meningitis (range: - 0.330 to 0.977) were generally associated with the lowest HSU, followed by pneumonia (range: - 0.054 to 0.998) and acute otitis media (range: 0.064 to 0.970). HSU estimates varied considerably by treatment setting, elicitation method and type of respondent. The only study to compare pneumococcal infections to non-pneumococcal infections in the same population revealed significantly lower HSU estimates among pneumococcal infections. CONCLUSIONS: Pneumococcal syndromes are associated with decreased HSU estimates. Given the considerable heterogeneity in methods and source populations as well as study quality, care should be taken to select the most appropriate estimates.

Impact of Pneumococcal Vaccination on Pneumonia Hospitalizations and Related Costs in Ontario: A Population-Based Ecological Study.

Background: In Ontario, Canada, pneumococcal conjugate vaccine (PCV) was approved for infants in 2001 and became part of the publicly funded routine immunization schedule in 2005. We assessed the population-level impact of PCV on pneumonia hospitalizations and related costs. Methods: We used the difference-in-differences approach to evaluate the impact of pneumococcal vaccination on pneumonia hospitalizations and related costs, using nonpneumonia hospitalization as the control condition. We extracted monthly hospitalization costs, stratified by age group, from population-based health administrative data between April 1992 and March 2014. The study period was divided into 5 intervals: prevaccine period, availability of 7-valent PCV (PCV7) for private purchase, public funding for PCV7, replacement of PCV7 with 10-valent PCV (PCV10), and replacement of PCV10 with 13-valent PCV (PCV13). Results: A total of 1063700 pneumonia hospitalizations were recorded during the study period. In the vaccine-eligible age group, pneumonia hospitalizations declined by 34% (95% confidence interval, 32%-37%), 38% (32%-43%), and 45% (40%-51%) and hospitalization-related costs declined by 38% (25%-51%), 39% (33%-45%), and 46% (41%-52%) after public funding for PCV7, PCV10, and PCV13, respectively. Pneumonia hospitalizations and related costs also declined substantially for PCV-ineligible older children and elderly persons (aged >65 years). Conclusions: Our results suggest that the publicly funded PCV immunization program is responsible for substantial reductions in pneumonia hospitalizations and related healthcare costs, among both young children eligible for publicly funded vaccination and other age groups not included in the publicly funded program.

BioAdvance Patient Support Program Survey: Positive Perception of Intravenous Infusions of Infliximab.

PURPOSE: To understand the perception of intravenous infusions in patients receiving infliximab (Remicade) within the BioAdvance patient support program (PSP). DESIGN: Intravenous infusion of infliximab occurs at approximately 200 clinics across Canada and is managed via the BioAdvance PSP. Patients were invited to complete a 28-question survey on demographics, disease/treatment characteristics, health rating, lifestyle, employment, and perception of intravenous infusions and the BioAdvance program. METHODOLOGY: Analyses were exploratory and descriptive; collected data were self-reported ordinal (Likert scale, unfavorable-to-favorable, 1-10). The Wilcoxon signed-rank test was used to assess statistical significance, and multinomial logistic regression identified predictors of a positive perception of intravenous infusions. RESULTS: 1,712 patients completed the survey. Most respondents had been treated with infliximab for >2 years (58%), had not been previously treated with a biologic (74%), and were receiving treatment for inflammatory bowel disease (76%). Sixty-two percent of patients were employed and most traveled for personal/work reasons (57%) and had a busy/active lifestyle (76%) while attending the BioAdvance clinics. Before treatment, participants rated their perceived favorability of intravenous infusions at 5/10 (median; interquartile range, 5-7); after multiple infusions, their rating increased significantly to 8 (7-9) (P<.001). Regression analysis identified four predictors of a positive infusion experience: French language, favorable ratings of health, accuracy of physician's description, and satisfaction with their BioAdvance coordinator. The vast majority of participants were likely to recommend the BioAdvance PSP. CONCLUSION: The survey results indicate that the majority of patients receiving infliximab have a positive infusion experience within the BioAdvance PSP.

The epidemiology and healthcare costs of community-acquired pneumonia in Ontario, Canada: a population-based cohort study.

OBJECTIVES: The aim of the present study was to determine incidence-based short- and long-term healthcare costs attributable to community-acquired pneumonia (CAP) from the healthcare payer perspective in Ontario, Canada. METHODS: We conducted a retrospective population-based matched cohort study of residents in Ontario, Canada using health administrative data. We identified subjects with an incident episode of CAP (exposed subjects) between 1 January 2012 and 31 December 2014. The index date of each episode was based on the first inpatient or outpatient claim for pneumonia. Exposed subjects were matched without replacement to unexposed subjects from the general population using hard and propensity score matching on age, sex, income quintile, rural residence, comorbidities, and healthcare costs prior to index date. Attributable costs represented the mean difference in costs between the exposed subjects and their matched pairs. RESULTS: We identified 692,090 subjects with at least one episode of CAP between 1 January 2012 and 31 December 2014. Adults aged 65 years and older had the highest annual incidence rate of 50.1 episodes per 1,000 person-years, while adults aged 18-64 years and children (aged 0-17) had incidence rates of 12.9 and 24.7 episodes per 1,000 person-years, respectively. The majority of episodes involved care exclusively in the outpatient setting (92.6%), with most of these episodes involving a single physician visit. The mean attributable costs were $1,595 (95% CI: $1,572-$1,616) per outpatient CAP episode and $12,576 (95% CI: $12.392-$12,761) per inpatient CAP episode. Attributable costs were significantly higher for adult subjects and those with time spent in the intensive care unit. Alternative case definitions yielded different results, although demonstrated the same overall trends across groups. CONCLUSION: CAP is associated with substantially increased acute and long-term healthcare costs compared to unexposed subjects. This study highlights the burden of CAP in both the inpatient and outpatient setting, and will serve to inform strategic healthcare planning for future interventions and healthcare programs.

Clinical manifestations and health outcomes associated with Zika virus infections in adults: A systematic review.

BACKGROUND: Zika virus (ZIKV) has generated global interest in the last five years mostly due to its resurgence in the Americas between 2015 and 2016. It was previously thought to be a self-limiting infection causing febrile illness in less than one quarter of those infected. However, a rise in birth defects amongst children born to infected pregnant women, as well as increases in neurological manifestations in adults has been demonstrated. We systemically reviewed the literature to understand clinical manifestations and health outcomes in adults globally. METHODS: This review was registered prospectively with PROPSERO (CRD 42018096558). We systematically searched for studies in six databases from inception to the end of September 2020. There were no language restrictions. Critical appraisal was completed using the Joanna Briggs Institute Critical Appraisal Tools. FINDINGS: We identified 73 studies globally that reported clinical outcomes in ZIKV-infected adults, of which 55 studies were from the Americas. For further analysis, we considered studies that met 70% of critical appraisal criteria and described subjects with confirmed ZIKV. The most common symptoms included: exanthema (5,456/6,129; 89%), arthralgia (3,809/6,093; 63%), fever (3,787/6,124; 62%), conjunctivitis (2,738/3,283; 45%), myalgia (2,498/5,192; 48%), headache (2,165/4,722; 46%), and diarrhea (337/2,622; 13%). 36/14,335 (0.3%) of infected cases developed neurologic sequelae, of which 75% were Guillain-Barré Syndrome (GBS). Several subjects reported recovery from peak of neurological complications, though some endured chronic disability. Mortality was rare (0.1%) and hospitalization (11%) was often associated with co-morbidities or GBS. CONCLUSIONS: The ZIKV literature in adults was predominantly from the Americas. The most common systemic symptoms were exanthema, fever, arthralgia, and conjunctivitis; GBS was the most prevalent neurological complication. Future ZIKV studies are warranted with standardization of testing and case definitions, consistent co-infection testing, reporting of laboratory abnormalities, separation of adult and pediatric outcomes, and assessing for causation between ZIKV and neurological sequelae.

Point-of-care diagnostic tests for influenza in the emergency department: A cost-effectiveness analysis in a high-risk population from a Canadian perspective.

BACKGROUND: Our objective was to assess the cost-effectiveness of novel rapid diagnostic tests: rapid influenza diagnostic tests (RIDT), digital immunoassays (DIA), rapid nucleic acid amplification tests (NAAT), and other treatment algorithms for influenza in high-risk patients presenting to hospital with influenza-like illness (ILI). METHODS: We developed a decision-analytic model to assess the cost-effectiveness of diagnostic test strategies (RIDT, DIA, NAAT, clinical judgement, batch polymerase chain reaction) preceding treatment; no diagnostic testing and treating everyone; and not treating anyone. We modeled high-risk 65-year old patients from a health payer perspective and accrued outcomes over a patient's lifetime. We reported health outcomes, quality-adjusted life years (QALYs), healthcare costs, and net health benefit (NHB) to measure cost-effectiveness per cohort of 100,000 patients. RESULTS: Treating everyone with no prior testing was the most cost-effective strategy, at a cost-effectiveness threshold of $50,000/QALY, in over 85% of simulations. This strategy yielded the highest NHB of 15.0344 QALYs, but inappropriately treats all patients without influenza. Of the novel rapid diagnostics, NAAT resulted in the highest NHB (15.0277 QALYs), and the least number of deaths (1,571 per 100,000). Sensitivity analyses determined that results were most impacted by the pretest probability of ILI being influenza, diagnostic test sensitivity, and treatment effectiveness. CONCLUSIONS: Based on our model, treating high-risk patients presenting to hospital with influenza-like illness, without performing a novel rapid diagnostic test, resulted in the highest NHB and was most cost-effective. However, consideration of whether treatment is appropriate in the absence of diagnostic confirmation should be taken into account for decision-making by clinicians and policymakers.

Chrna5 genotype determines the long-lasting effects of developmental in vivo nicotine exposure on prefrontal attention circuitry.

Maternal smoking during pregnancy repeatedly exposes the developing fetus to nicotine and is linked with attention deficits in offspring. Corticothalamic neurons within layer VI of the medial prefrontal cortex are potential targets in the disruption of attention circuitry by nicotine, a process termed teratogenesis. These prefrontal layer VI neurons would be likely targets because they are developmentally excited and morphologically sculpted by a population of nicotinic acetylcholine receptors (nAChRs) that are sensitive to activation and/or desensitization by nicotine. The maturational effects of these α4ß2* nAChRs and their susceptibility to desensitization are both profoundly altered by the incorporation of an α5 subunit, encoded by the chrna5 gene. Here, we investigate nicotine teratogenesis in layer VI neurons of wildtype and α5(-/-) mice. In vivo chronic nicotine exposure during development significantly modified apical dendrite morphology and nAChR currents, compared with vehicle control. The direction of the changes was dependent on chrna5 genotype. Surprisingly, neurons from wildtype mice treated with in vivo nicotine resembled those from α5(-/-) mice treated with vehicle, maintaining into adulthood a morphological phenotype characteristic of immature mice together with reduced nAChR currents. In α5(-/-) mice, however, developmental in vivo nicotine tended to normalize both adult morphology and nAChR currents. These findings suggest that chrna5 genotype can determine the effect of developmental in vivo nicotine on the prefrontal cortex. In wildtype mice, the lasting alterations to the morphology and nAChR activation of prefrontal layer VI neurons are teratogenic changes consistent with the attention deficits observed following developmental nicotine exposure.