Attributable Cost of Adult Respiratory Syncytial Virus Illness Beyond the Acute Phase.

Background: Estimates of the cost of medically attended lower respiratory tract illness (LRTI) due to respiratory syncytial virus (RSV) in adults, especially beyond the acute phase, is limited. This study was undertaken to estimate the attributable costs of RSV-LRTI among US adults during, and up to 1 year after, the acute phase of illness. Methods: A retrospective observational matched-cohort design and a US healthcare claims repository (2016-2019) were employed. The study population comprised adults aged ≥18 years with RSV-LRTI requiring hospitalization (RSV-H), an emergency department visit (RSV-ED), or physician office/hospital outpatient visit (RSV-PO/HO), as well as matched comparison patients. All-cause healthcare expenditures were tallied during the acute phase of illness (RSV-H: from admission through 30 days postdischarge; ambulatory RSV: during the episode) and long-term phase (end of acute phase to end of following 1-year period). Results: The study population included 4526 matched pairs of RSV-LRTI and comparison patients (RSV-H: n = 970; RSV-ED: n = 590; RSV-PO/HO: n = 2966). Mean acute-phase expenditures were $42 179 for RSV-H (vs $5154 for comparison patients), $4409 for RSV-ED (vs $377), and $922 for RSV-PO/HO (vs $201). By the end of the 1-year follow-up period, mean expenditures-including acute and long-term phases-were $101 532 for RSV-H (vs $36 302), $48 701 for RSV-ED (vs $27 131), and $28 851 for RSV-PO/HO (vs $20 523); overall RSV-LRTI attributable expenditures thus totaled $65 230, $21 570, and $8327, respectively. Conclusions: The cost of RSV-LRTI requiring hospitalization or ambulatory care among US adults is substantial, and the economic impact of RSV-LTRI may extend well beyond the acute phase of illness.

Rates of Lower Respiratory Tract Illness in US Adults by Age and Comorbidity Profile.

INTRODUCTION: While it is widely recognized that older adults, adults with chronic medical conditions (CMC), and adults with immunocompromising conditions (IC) are at increased risk of lower respiratory tract illness (LRTI), evidence of the magnitude of increased risk is limited. This study was thus undertaken to characterize rates of hospitalized and ambulatory LRTI among United States (US) adults by age and comorbidity profile. METHODS: A retrospective cohort design and US healthcare claims database (2016-2019) were employed. Study population included adults aged ≥ 18 years and was stratified by age and comorbidity profile (CMC-, CMC+ , IC). LRTI was ascertained overall and by pathogen pathogen (e.g., respiratory syncytial virus [RSV]), and was classified by care setting (hospital, emergency department [ED], physician office/hospital outpatient [PO/HO]). RESULTS: Relative rates (RR) of LRTI generally increased with older age across care settings (vs. 18-49 years), with the most marked increase for hospitalizations: for LRTI-hospitalized, RRs ranged from 3.3 for 50-64 years to 46.6 for ≥ 85 years; for LRTI-ED and LRTI-PO/HO, RRs ranged from 1.0 to 2.7 and from 1.3 to 1.5, respectively. Within age groups, LRTI rates were also consistently higher among CMC+ and IC adults (vs. CMC- adults). Age-specific RRs of LRTI patients hospitalized due to RSV were largely comparable to overall LRTI; age-specific RRs for other care settings, and RRs for CMC+ and IC adults (vs. CMC- adults), were generally higher for LRTI due to RSV. CONCLUSIONS: Incidence of LRTI, including that due to RSV, especially for events requiring acute inpatient care, is markedly higher among older adults and adults of all ages with CMC or IC.

Identifying Conditions for Protein Synthesis Inside Giant Vesicles Using Microfluidics toward Standardized Artificial Cell Production.

To expand the range of practical applications of artificial cells, it is important to standardize the production process of giant (cell-sized) vesicles that encapsulate reconstituted biochemical reaction systems. For this purpose, a rapidly developing microfluidics-based giant vesicle generation system is a promising approach, similar to the droplet assay systems that are already widespread in the market. In this study, we examined the composition of the solutions used to generate vesicles encapsulating the in vitro transcription-translation (IVTT) system. We show that tuning of the lipid composition and adding poly(vinyl alcohol) to the outer solution improved the stability of the transition process into the lipid membrane so that protein synthesis proceeded in vesicles. The direct integration of α-hemolysin nanopores synthesized in situ was also demonstrated. These protein-synthesizing monodisperse giant vesicles can be prepared by using a simple microfluidic fabrication/operation with a commercial IVTT system.

Pericapsular nerve group block for osteoarthritis-related chronic hip joint pain: a case report.

BACKGROUND: Pericapsular nerve group (PENG) block has shown effectiveness for acute hip pain associated with fractures and surgery. Herein, PENG block was performed for osteoarthritis (OA)-related chronic hip joint pain. CASE PRESENTATION: A 65-year-old woman presented left hip pain. She had bilateral hip osteoarthritis that improved with medications; however, a fall resulted in left hip pain. She experienced severe pain on movements, which required walking aids. To alleviate the hip pain, a PENG block was performed under ultrasound guidance. Transient muscle weakness occurred in 2 of 5 times. After 5 blocks, she regained the ability to walk without assistive devices. Pain did not recur even after 6 months. CONCLUSIONS: Repeated PENG blocks of short-acting local anesthetics alone could be an effective pain management technique for chronic hip pain. For safety, the appropriate injection site and local anesthetic dosage must be carefully considered.

Pneumococcal vaccine uptake among Medicare Beneficiaries aged ≥65 years following the shared clinical decision-making recommendation for 13-valent pneumococcal conjugate vaccine in 2019.

BACKGROUND: In November 2019, the US Advisory Committee on Immunization Practices recommended shared clinical decision-making (SCDM) for use of 13-valent pneumococcal conjugate vaccine (PCV13) among immunocompetent elderly adults. The impact of SCDM on PCV13 use in this population, immunocompromised persons, and vulnerable subgroups has not been well documented. METHODS: Using Medicare Research Identifiable Files (01/2018 - 09/2020), monthly uptake of pneumococcal vaccine (PCV13, 23-valent pneumococcal polysaccharide vaccine [PPSV23]) was identified among fee-for-service beneficiaries aged ≥ 65 years with Part B coverage and no evidence of prior PCV13. Uptake was stratified by vaccine, risk profile, and demographics. RESULTS: Among the > 12 M beneficiaries included each month, PCV13 uptake declined from > 70% of pneumococcal vaccinations before SCDM to < 60% after SCDM (02/2020). Reductions in PCV13 uptake were consistent across vulnerable subgroups as well as immunocompromised persons. CONCLUSIONS: PCV13 use decreased among immunocompetent and immunocompromised persons alike, despite continued routine PCV13 recommendation for the latter group.

Cost-effectiveness of using a 20-valent pneumococcal conjugate vaccine to directly protect adults in England at elevated risk of pneumococcal disease.

OBJECTIVES: Despite the current pneumococcal vaccination program in England for older adults and adults with underlying conditions, disease burden remains high. We evaluated cost-effectiveness of 20-valent pneumococcal conjugate vaccine (PCV20) compared to current pneumococcal recommendations for adults in England. METHODS: Lifetime outcomes/costs of invasive pneumococcal disease (IPD) and community-acquired pneumonia (CAP) among adults aged 65-99 years and adults aged 18-64 years with underlying conditions in England were projected using a deterministic cohort model. Vaccination with PCV20 was compared with 23-valent pneumococcal polysaccharide vaccine (PPV23) from the National Health Service perspective. RESULTS: PCV20 was cost saving compared with PPV23 in base case and most sensitivity analyses. In the base case, replacing PPV23 with PCV20 prevented 7,789 and 140,046 cases of IPD and hospitalized CAP, respectively, and 22,199 associated deaths, resulting in incremental gain of 91,375 quality-adjusted life-years (QALYs) and incremental savings of £160M. In probabilistic sensitivity analyses, PCV20 (vs. PPV23) was cost saving in 85% of simulations; incremental cost per QALY was below £30,000 in 99% of simulations. CONCLUSIONS: PCV20 vaccination in adults aged 65-99 years and those aged 18-64 years with underlying comorbidities in England is expected to prevent more hospitalizations, save more lives, and yield lower overall costs than current recommendations for PPV23.

Public health and budgetary impact of 20-valent pneumococcal conjugate vaccine for adults in England.

BACKGROUND: Despite use of 23-valent pneumococcal polysaccharide vaccine (PPV23) in England, disease burden among at-risk adults remains high. We evaluated the public health and budgetary impact of 20-valent pneumococcal conjugate vaccine (PCV20) compared to the current adult pneumococcal vaccination program. METHODS: Five-year outcomes and costs of invasive pneumococcal disease (IPD) and community-acquired pneumonia (CAP) among adults aged 65-99 years and adults aged 18-64 years with underlying conditions in England were projected using a deterministic cohort model. Hypothetical vaccination with PCV20 versus PPV23 was compared from the National Health Service (NHS) perspective. RESULTS: Replacing PPV23 with PCV20 would prevent 785 IPD hospitalizations, 11,751 CAP hospitalizations, and 1,414 deaths over 5 years, and would reduce medical care costs by £48.5 M. With vaccination costs higher by £107.2 M, projected net budgetary impact is £58.7 M. The budgetary impact would be greatest in year 1 (£26.3 M), and would decrease over time (to £1.6 M by year 5). The average budget increase (£11.7 M/year) represents <0.01% of the Department of Health and Social Care total budget and <3% of the vaccine budget. CONCLUSIONS: Use of PCV20 among adults currently eligible for PPV23 in England would substantially reduce the burden of pneumococcal disease, with modest budgetary impact.

Burden of pneumococcal disease due to serotypes covered by the 13-valent and new higher-valent pneumococcal conjugate vaccines in the United States.

The addition of pneumococcal conjugate vaccines (PCVs) to the United States (US) national immunization program led to significant reductions in incidence, mortality, and associated sequelae caused by pneumococcal disease (PD) in children and adults through direct and indirect protection. However, there remains clinical and economic burden due to PD caused by serotypes not included in the current 13-valent PCV (PCV13) formulation. To address this unmet need, 15-valent PCV (PCV15) and 20-valent PCV (PCV20), containing additional serotypes to PCV13, were recently approved in the US for adults and are anticipated for pediatrics in the near future. The study objective was to estimate the annual number of cases, deaths, and economic burden of PD due to serotypes included in PCV13, PCV15, and PCV20 for both US pediatric and adult populations. An Excel-based model was developed to calculate clinical and economic outcomes using published age-group specific serotype coverage; incidence of invasive PD, community-acquired pneumonia, and acute otitis media; case fatality rates; and disease-related costs. The results showed that across all age groups, the estimated annual PD cases and associated deaths covered by PCV13 serotypes were 914,199 and 4320, respectively. Compared with PCV13 serotypes, the additional 2 and 7 serotypes covered by PCV15 and PCV20 were attributed with 550,475 and 991,220 annual PD cases, as well as 1425 and 3226 annual deaths, respectively. This clinical burden translates into considerable economic costs ranging from $903 to $1,928 million USD that could be potentially addressed by PCV15 and PCV20. The additional serotypes included in PCV20 contribute substantially to the clinical and economic PD burden in the US pediatric and adult populations. Despite the success of the PCV13 pediatric national immunization program and increased adult uptake of PCV13 and 23-valent polysaccharide vaccine, broader PCV serotype coverage is needed across all ages to further reduce pneumococcal disease burden.

Classification of drugs for evaluating drug interaction in drug development and clinical management.

During new drug development, clinical drug interaction studies are carried out in accordance with the mechanism of potential drug interactions evaluated by in vitro studies. The obtained information should be provided efficiently to medical experts through package inserts and various information materials after the drug's launch. A recently updated Japanese guideline presents general procedures that are considered scientifically valid at the present moment. In this review, we aim to highlight the viewpoints of the Japanese guideline and enumerate drugs that were involved or are anticipated to be involved in evident pharmacokinetic drug interactions and classify them by their clearance pathway and potential intensity based on systematic reviews of the literature. The classification would be informative for designing clinical studies during the development stage, and the appropriate management of drug interactions in clinical practice.

Association between Pneumonia, Fracture, Stroke, Heart Attack and Other Hospitalizations with Changes in Mobility Disability and Gait Speed in Older Adults.

Pathophysiological changes after acute hospitalizations may influence physical functioning in older adults, which can lead to disability and loss of independence. This study evaluated the association between pneumonia, fracture, heart attack, stroke, and other hospitalizations with major mobility disability (MMD) and gait speed. This was a secondary analysis of the Lifestyle Interventions and Independence for Elders (LIFE) Study, which was conducted across eight sites during 2010-2013 with longitudinal follow-up for 1635 individuals over an average of 2.6 years. Participants included adults ≥70 years old with pre-existing mobility limitations randomized to a physical activity intervention or a health education control arm. Hospitalizations were recorded via self-report and adjudicated by medical reviewers. MMD was measured by the inability to complete a 400 m walk test, or other proxies, as a binary outcome. Gait speed was recorded during the walk test in meters per second (m/s) and measured on a linear scale. Mixed-effects repeated measures regression adjusted for baseline demographics, comorbid conditions, and frailty. Among the 1635 participants, there were 1458 hospitalizations, which included 80 (5.5% of all hospitalizations) cases of pneumonia, 92 (6.3%) hospitalized fractures, 87 (6.0%) heart attacks, and 61 (4.2%) strokes. In the short-term measurement period immediately following hospitalization (1 day to 6 months), stroke (OR = 3.98 (3.41-4.54)) had the strongest association with MMD followed by fracture (OR = 3.03 (2.54-3.52)), pneumonia (OR = 2.76 (2.23-3.30)), and heart attack (OR = 2.03 (1.52-2.53)). Associations with long-term (6-12 months after) MMD were decreased or not significant for all causes. Pneumonia, fracture, stroke, and other hospitalizations were associated with short-term relative gait speed changes between -4.8% up to -19.5%, and only fracture was associated with long-term changes. Hospitalizations for pneumonia, heart attack, stroke, and fractures were associated with short-term decreases in mobility in older adults. Older adults may be at risk for decreased mobility and disability following acute hospitalizations, with the magnitude determined by the cause of the precipitating event.

Single-cell analysis of human skin identifies CD14+ type 3 dendritic cells co-producing IL1B and IL23A in psoriasis.

Inflammatory skin diseases including atopic dermatitis (AD) and psoriasis (PSO) are underpinned by dendritic cell (DC)-mediated T cell responses. Currently, the heterogeneous human cutaneous DC population is incompletely characterized, and its contribution to these diseases remains unclear. Here, we performed index-sorted single-cell flow cytometry and RNA sequencing of lesional and nonlesional AD and PSO skin to identify macrophages and all DC subsets, including the newly described mature LAMP3+BIRC3+ DCs enriched in immunoregulatory molecules (mregDC) and CD14+ DC3. By integrating our indexed data with published skin datasets, we generated a myeloid cell universe of DC and macrophage subsets in healthy and diseased skin. Importantly, we found that CD14+ DC3s increased in PSO lesional skin and co-produced IL1B and IL23A, which are pathological in PSO. Our study comprehensively describes the molecular characteristics of macrophages and DC subsets in AD and PSO at single-cell resolution, and identifies CD14+ DC3s as potential promoters of inflammation in PSO.

Mortality and readmission in the year following hospitalization for pneumonia among US adults.

BACKGROUND: Increasing evidence suggests the impact of pneumonia persists beyond hospital discharge and the acute phase of respiratory symptoms. We characterized short-term and long-term risks of mortality and hospital readmission across the adult age span and spectrum of comorbidities. METHODS: Retrospective cohort design and Optum's de-identified Integrated Claims-Clinical dataset (2012-2018) were employed. Study population comprised adults who had ≥1 pneumonia hospitalization; each hospitalization ≥365 days apart was considered. Cumulative risks of all-cause mortality (from pneumonia hospitalization through 360-day post-discharge period) and all-cause hospital readmission (during 360-day post-discharge period) were summarized on an overall basis as well as by age and comorbidity profile (i.e., healthy, at-risk, high-risk). RESULTS: Study population totaled 37,006 patients who contributed 38,809 pneumonia hospitalizations; mean age was 71 years, 51% were female, and 88% had at-risk (33%) or high-risk (55%) conditions. Mortality was 3.5% in hospital, 8.2% from admission to 30 days post-discharge, and 17.7% from admission to 360 days post-discharge. Hospital readmission was 12.5% during the 30-day post-discharge period, and 42.3% during the 360-day post-discharge period. Mortality risk increased with age and severity of comorbidity profile; readmission risk was highest for persons aged 65-74 years and persons with high-risk conditions. CONCLUSIONS: All-cause mortality up to 1 year following pneumonia hospitalization was substantial, and was associated with increasing age and worsening comorbidity profile. Both readmission and mortality were greater at all ages in at-risk and high-risk subgroups (vs. healthy counterparts). Strategies that prevent pneumonia and/or associated pathophysiologic changes, especially among individuals with comorbidities, have the potential to reduce morbidity and mortality.

Effect of Inpatient and Outpatient Pneumonia on Mobility Disability, Gait Speed, and Physical Activity in Older Adults.

Pathophysiological changes caused by pneumonia may influence physical functioning in older adults. This study was a secondary analysis of the Lifestyle Interventions and Independence for Elders (LIFE) Study. The LIFE Study included 1635 individuals over an average follow-up of 2.6 years at eight clinical sites during 2010-2013. Adults ≥70 years-old with mobility limitations (Short Physical Performance Battery score ≤9) were randomized to a physical activity (exercise) intervention or health education control arm. This analysis evaluated the association between pneumonia events and major mobility disability (MMD), gait speed, and physical activity levels. Pneumonia events, classified as inpatient or outpatient, were assessed by self-report during longitudinal follow-up. MMD was measured by the inability to complete a 400-m walk test, or other proxies, as a binary outcome and separately analyzed as "short-term" and "long-term" MMD. Short-term MMD was defined as MMD occurring in the assessment period immediately following (between 1-day to 6-months after) a pneumonia event and long-term was in the following assessment period (6 to 12 months after the event). Short- and long-term gait speed was similarly recorded during the walk test in meters per second (m/s) and measured on a linear scale. Physical activity levels were captured via accelerometry and shown visually. Mixed-effects repeated measures regression adjusted for intervention assignment, baseline demographics, comorbid conditions, and frailty. Among the 1635 participants, n = 174 (10.7%) had a pneumonia event of which 80 (46% of events) were hospitalized. Those with pneumonia during follow-up had higher baseline medication use, prior hospitalizations, and higher prevalence of lung disorders but similar baseline functioning. Pneumonia hospitalization was associated with a 4-fold increase [OR = 4.1 (3.2-5.0)] and outpatient events were associated with a 2-fold increase [OR = 2.6 (2.1-3.1)] in the odds of short-term MMD. Pneumonia hospitalizations, but not outpatient events, were associated with a nearly 10% decrement in short-term gait speed. Pneumonia events were not associated with either long-term MMD or gait speed outcomes. Physical activity levels decreased from baseline immediately following the pneumonia episode (10-30% reductions) and returned to baseline after 6 months. These results emphasize the importance of managing pneumonia risk factors to prevent disease in order to maintain physical independence and activity in older adults.

High-fat diet induces a predisposition to follicular hyperkeratosis and neutrophilic folliculitis in mice.

BACKGROUND: Neutrophilic folliculitis is an inflammatory condition of hair follicles. In some neutrophilic folliculitis, such as in patients with acne and hidradenitis suppurativa, follicular hyperkeratosis is also observed. Neutrophilic folliculitis is often induced and/or exacerbated by a high-fat diet (HFD). However, the molecular mechanisms by which an HFD affects neutrophilic folliculitis are not fully understood. OBJECTIVE: Our aim was to elucidate how an HFD promotes the development of neutrophilic folliculitis. METHODS: Mice were fed an HFD, and their skin was subjected to histologic, RNA sequencing, and imaging mass spectrometry analyses. To examine the effect of an HFD on neutrophil accumulation around the hair follicles, phorbol 12-myristate 13-acetate (PMA) was used as an irritant to the skin. RESULTS: Histologic analysis revealed follicular hyperkeratosis in the skin of HFD-fed mice. RNA sequencing analysis showed that genes related to keratinization, especially in upper hair follicular keratinocytes, were significantly upregulated in HFD-fed mice. Application of PMA to the skin induced neutrophilic folliculitis in HFD-fed mice but not in mice fed a normal diet. Accumulation of neutrophils in the skin and around hair follicles was dependent on CXCR2 signaling, and CXCL1 (a CXCR2 ligand) was produced mainly by hair follicular keratinocytes. Imaging mass spectrometry analysis revealed an increase in fatty acids in the skin of HFD-fed mice. Application of these fatty acids to the skin induced follicular hyperkeratosis and caused PMA-induced neutrophilic folliculitis even in mice fed a normal diet. CONCLUSION: An HFD can facilitate the development of neutrophilic folliculitis with the induction of hyperkeratosis of hair follicles and increased neutrophil infiltration around the hair follicles via CXCR2 signaling.

Attributable Cost of Adult Hospitalized Pneumonia Beyond the Acute Phase.

BACKGROUND: While much is known about the cost of community-acquired pneumonia (CAP) during the acute phase of illness, little is known about the potential attributable cost of CAP thereafter. OBJECTIVE: The aim of this study was to assess long-term attributable costs associated with CAP among adults in US clinical practice. METHODS: A retrospective matched cohort design and data from a US private healthcare claims repository were employed. In each month during the study period (2011-2016), adults who were hospitalized for CAP in that month ('CAP patients') were matched (1:1, without replacement) on demographic, clinical, and healthcare profiles to adults who did not develop CAP in that month ('comparison patients'). All-cause healthcare expenditures were tallied for the qualifying CAP hospitalization and during the 30-day period post-discharge (collectively, 'acute phase'), as well as from the end of the acute phase to the end of the 3-year follow-up period ('long-term phase'). RESULTS: The study population included 43,975 matched pairs of CAP patients and comparison patients. Expenditures averaged $33,380 (95% confidence interval [CI] $32,665-$34,161) for the CAP hospitalization and $4568 (95% CI $4385-$4749) during the 30-day period thereafter (vs. $2075 [95% CI $1989-$2167] in total for the comparison patients). During the long-term phase, all-cause expenditures averaged $83,463 (95% CI $81,318-$85,784) for CAP patients versus $51,017 (95% CI $49,553-$52,491) for comparison patients, and thus attributable expenditures during this phase totaled $32,446 (95% CI $29,847-$35,075). The majority of attributable CAP expenditures (53% of $68,319) occurred during the acute phase, while 21%, 14%, and 12% occurred during the first, second, and third years, respectively, after the acute phase. CONCLUSIONS: Our findings provide additional evidence that the cost of CAP requiring hospitalization is high, and that the impact of CAP extends well beyond the expected time for resolution of acute inflammatory signs.

Adverse Drug Reaction Relief System in Japan: From Clinical Perspective.

Adverse drug reaction (ADR) relief system in Japan is comprehensively described in this article. Particularly, review process during ADR relief evaluation is focused from clinical perspective. The significance of clinical review process and roles of a physician medical reviewer in the ADR relief system in Japan are also discussed. The current ADR Relief Service in Japan requires criteria for compensation eligibility including the "proper" use of the medication associated with the adverse event, and reasonably plausible association between the drug and the adverse event. The criteria are primarily reviewed at the ADR relief department of Pharmaceuticals and Medical Devices Agency (PMDA). In this article, after introducing framework of the ADR relief system in Japan including review processes at PMDA, actual process of the ADR relief assessment is described. In more details, we explain appropriate indication and appropriate usage in the ADR relief evaluation and unexpected/unwritten ADR in the Japanese package insert. Also described are time period for the payment, causality assessment between ADRs and the death, and pitfalls during the evaluation of the ADR relief system in Japan. In the last part, current issues and future directions are referred.

Social communication impairments and restricted, repetitive patterns (Kodawari) considered from the Comprehension section of the WISC-IV in autism spectrum disorder

Abstract Background Many studies have used the Wechsler Intelligence Scale (WISC) to examine the characteristics of autism spectrum disorder (ASD). However, most studies have been based on profile analysis, not on content analysis. Objective The objective of the present study was to apply the WISC-IV to clinical assessment of ASD and clarify how the characteristics of the disorder were reflected in specific items. Methods The study participants were 20 patients aged 5-16 years diagnosed with ASD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). We recruited 20 patients with attention-deficit/hyperactivity disorder (ADHD) and 20 patients with other disorders (neurotic disorders) as controls. We then compared the scores of the ninth item of the WISC-IV ("Comprehension") among the three groups. Results The differences observed between the ASD vs. the other disorders group were not significant by the standard scoring method. Thus, a two-level scoring method of 0 and ≥1 point was adopted. As a result, significantly more participants in the ASD group scored 0 points compared with the ADHD and other disorders groups. Discussion The results of the present study revealed that a characteristic of ASD appeared in the ninth item of "Comprehension" on the WISC-IV.

Evaluating the cost-effectiveness of a sequential pneumococcal vaccination compared to single-dose vaccination strategy for adults in Hong Kong.

Two vaccines, 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13), are widely available for the prevention of pneumococcal disease in adults. However, it is unclear how cost-effective these pneumococcal vaccine choices are in the Hong Kong healthcare environment. We aimed to assess the cost-effectiveness of a sequential administration of PCV13 followed by PPSV23 compared to a single dose of PPSV23 vaccination for pneumococcal disease control in Hong Kong adults aged ≥65 years and individuals aged 20-64 years with immunocompromising and chronic conditions. A previously developed deterministic cohort sequential model was applied to compare the outcomes of two vaccination strategies from a societal perspective. Population-specific model input, including incidence, mortality, case-fatality, risk group distribution, vaccination costs, disease management, and productivity loss, was estimated from a Hong Kong-wide electronic medical database. Costs were valued in US$ in 2017. Vaccination strategies with an incremental cost-effectiveness ratio (ICER, defined as incremental cost per QALY saved) less than one local GDP per capita ($46,193 in 2017) were defined as highly cost-effective. Deterministic sensitivity analyses (SA) were conducted. Compared with single-dose PPSV23, sequential vaccination of PCV13 followed by PPSV23 was cost-saving for adults aged ≥20 years. In the deterministic SA, the base-case results were robust for tested parameter uncertainties. Future vaccination policies should consider the cost-effectiveness of a sequential vaccination strategy as a measure to reduce the vaccine-preventable pneumococcal disease burden in Hong Kong.

Development of a new Japanese guideline on drug interaction for drug development and appropriate provision of information.

Drug interactions, in particular with concomitant drugs having a narrow therapeutic range, sometimes cause serious adverse drug reactions or attenuation of the therapeutic effect. Therefore, evaluation of the characteristics and severities of possible drug interactions in drug development is essential to understand such interactions to help prevent any potential risk for patients. In Japan, a regulatory document which was notified in 2001 to outline the basic principles of drug interaction studies during drug development was revised as a new guideline after 17 years to present general procedures that are currently considered scientifically valid. This article aims to present an overview of development process of the new Japanese guideline for investigating drug interactions and show the impact of implementating this guideline on drug interaction evaluations, thereby providing future perspectives of regulatory activities on drug interactions.