Adult immunization against hepatitis B: Does the number of jabs matter?

BACKGROUND: At least one-half of adults beginning an immunization series with a three-dose hepatitis B virus (HBV) vaccine (ENGERIX-B, RECOMBIVAX-B) have been reported not to receive the third dose. Use of a two-dose vaccine may improve adherence and lead to greater overall levels of seroprotection. OBJECTIVE: To examine expected levels of adherence and overall seroprotection at one year among adults in routine clinical settings beginning an immunization series with either ENGERIX-B or the two-dose HBV vaccine, HEPLISAV-B. METHODS: Decision-analytic model comparing expected levels of adherence and overall seroprotection at one year among a hypothetical cohort of one million previously unvaccinated adults aged ≥ 30 years receiving first doses of either ENGERIX-B or HEPLISAV-B in a routine clinical setting. We stratified the population by age (30-49 years vs ≥ 50 years) to allow for possible differences in adherence and seroprotection. We estimated our model using published adherence rates for HBV vaccines, and reported seroprotection rates by number of doses administered. We also compared total expected costs of HBV immunization with each vaccine. RESULTS: Use of a two-dose rather than three-dose HBV vaccine would increase the expected number of adults seroprotected at one year by 275,000 per one million persons beginning immunization series, largely reflecting a gain of 290,000 in the expected number of persons fully vaccinated. Results were similar for the two age groups. While the cost per dose of HEPLISAV-B exceeds that of ENGERIX-B, its estimated mean cost per person seroprotected at one year is $50-$70 (∼15%) lower. CONCLUSIONS: Use of a two-dose HBV vaccine would increase the number of adults fully seroprotected at one year compared with the number expected with a three-dose vaccine. Notwithstanding its higher unit cost, mean expected cost per person seroprotected is substantially lower for HEPLISAV-B than ENGERIX-B as a result of much higher levels of seroprotection.

Clinical staging in amyotrophic lateral sclerosis: analysis of Edaravone Study 19.

OBJECTIVE: This was a post hoc analysis of the Edaravone Phase III Study MCI186-19 ('Study 19') to examine the utility of clinical staging systems as end points in clinical trials in amyotrophic lateral sclerosis (ALS). METHODS: Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised item scores from Study 19 were retrospectively mapped to King's stage and Milano-Torino staging (MiToS) stage. We assessed the percentage of patients who experienced progression in King's and MiToS stages during Study 19. We also assessed disease progression in subgroups of patients according to baseline King's stage. RESULTS: During double-blind treatment, the percentage of patients who experienced a progression in King's stage was lower for edaravone (42.0%, 95% CI 30.4% to 53.6%) than placebo (55.9%, 95% CI 44.1% to 67.6%). The most pronounced effect was noted among patients who were in stage 1 and was maintained throughout open-label treatment. An analysis of a ≥2-stage progression in MiToS stage showed no difference between treatment arms during double-blind treatment, but during the open-label period, more rapid progression was noted among patients in the placebo-edaravone arm than among those in the edaravone-edaravone arm (log-rank test, p<0.001). CONCLUSIONS: The King's and MiToS staging systems provided utility in assessing clinical progression in Edaravone Study 19. These findings may support the use of staging systems as end points in ALS clinical trials and to understand the timing of benefit as measured by these scales.

Pharmacotherapy patterns in patients with chronic idiopathic constipation beginning treatment with linaclotide or lubiprostone in the United States.

BACKGROUND: Chronic idiopathic constipation (CIC) is a common gastrointestinal disorder in community settings. Limited information exists on its treatment with the prosecretory agents linaclotide and lubiprostone. This retrospective cohort study investigated real-world pharmacotherapy patterns of linaclotide and lubiprostone. METHODS: Patients (≥18 years) with CIC who received linaclotide or lubiprostone between January 2013 and December 2015 were identified in a United States health insurance claims database. Follow-up was from the date of the earliest claim for either drug to the end of continuous enrolment or switch to the alternative agent. Patterns of pharmacotherapy, evidence of irritable bowel syndrome (IBS), and concomitant use of selective serotonin reuptake inhibitors were examined using the International Classification of Diseases, Ninth or Tenth Revision, Clinical Modification codes and National Drug Codes. RESULTS: In total, 43,164 and 17,743 patients with CIC received linaclotide and lubiprostone, respectively (~80% women, mean age ~47 years). Approximately 40% of subjects (linaclotide: 40.1%; lubiprostone: 37.6%) had evidence of IBS. Over a mean follow-up of 17 months, mean (standard deviation) treatment duration in patients without IBS was 6.6 (7.9) months for linaclotide and 4.5 (6.5) months for lubiprostone. Treatment episodes >180 days were more common with linaclotide (36.1%) than with lubiprostone (23.2%). At 12 months, Kaplan-Meier estimates of switching from lubiprostone to linaclotide and from linaclotide to lubiprostone were 13.4 and 5.6%, respectively. The number of patients receiving serotonin reuptake inhibitors was unchanged with treatment (~22%). CONCLUSIONS: Most patients with CIC receive linaclotide or lubiprostone for <6 months; few remain on therapy for >1 year. Additional research is warranted to understand the potential reason(s) for early discontinuation.

Predictors of Imminent Risk of Nonvertebral Fracture in Older, High-Risk Women: The Framingham Osteoporosis Study.

Osteoporosis treatment decisions are often based solely on BMD or on 10-year fracture risk; little is known about factors increasing imminent fracture risk. Understanding factors contributing to imminent risk of fracture is potentially useful for personalizing therapy, especially among those at high risk. Our aim was to identify predictors of nonvertebral fracture for 1- and 2-year periods in women at high risk for fracture. The Framingham Osteoporosis Study cohort included 1470 women (contributing 2778 observations), aged ≥65 years with BMD hip T-score ≤ -1.0, or history of fragility fracture (irrespective of T-score). Nonvertebral fractures were ascertained prospectively over 1 year and 2 years following a baseline BMD scan. Potential risk factors included age, anthropometric variables, comorbidities/medical history, cognitive function, medications, history of fracture, self-rated health, falls in the past year, smoking, physical performance, hip BMD T-score, Activities of Daily Living (ADL) score, and caffeine and alcohol intakes. Predictive factors with p value ≤ 0.10 in bivariate Cox proportional hazards regression models were subsequently considered in multivariable models. Mean baseline age was 75 years (SD 6.0). During 1-year follow-up, 89 nonvertebral fractures occurred; during 2-year follow-up, 176 fractures occurred. Of the variables considered in the bivariate models, significant predictors of nonvertebral fractures included age, history of fracture, self-rated health, falls in the prior year, BMD T-score, ADL, renal disease, dementia, and current use of nitrates, beta-blockers, calcium channel blockers, or antidepressants. In multivariable models, significant independent risk factors were history of fracture, self-rated health, hip BMD T-score, and use of nitrates. Significant 1-year results were attenuated at the 2-year follow-up. In addition to the traditional factors of BMD and fracture history, self-rated health and use of nitrates were independently associated with imminent risk of fracture in older, high-risk women. These specific risk factors thus may be useful in identifying which women to target for therapy.

Pneumonia in young adults with asthma: impact on subsequent asthma exacerbations.

Background: Recent studies of community-acquired pneumonia (CAP) have recognized acute cardiac complications-such as myocardial infarction, arrhythmia, or congestive heart failure (CHF)-as frequent complications during the acute process. As well, a prolonged vulnerability to exacerbations of underlying comorbidities-such as CHF and COPD-has been observed following CAP. We hypothesized that young adults with underlying asthma could also be adversely impacted over a prolonged time period following CAP.Methods: Using a retrospective matched-cohort design and data from a US private healthcare claims repository (>15 M persons annually), we selected all adults 18-49 years of age with evidence of asthma as their only comorbidity for inclusion in the source population. Then, from the source population, we matched one comparison patient to each CAP patient based on index date, age, sex, and selected markers for health status (eg, history of asthma-related healthcare encounters), and evaluated subsequent outpatient and inpatient encounters for asthma exacerbations.Results: Asthma exacerbations were identified twice as often in the 12 months subsequent to acute CAP. Cumulative incidence proportions for asthma exacerbations requiring hospitalization or emergency department care after 12 months of follow-up were 19.9% for those previously hospitalized with CAP versus 9.0% for matched comparison patients (difference, 10.9%; p<0.001), and were 12.4% for non-hospitalized CAP patients versus 7.7% for matched counterparts (difference, 4.7%; p<0.001).Conclusion: Our analysis provides further evidence that acute CAP has a prolonged impact on respiratory health.

Decline in Pneumococcal Disease Attenuated in Older Adults and Those With Comorbidities Following Universal Childhood PCV13 Immunization.

BACKGROUND: Following introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in the United States, epidemiology of pneumococcal disease shifted such that disease incidence in the elderly exceeded that in children. We evaluated the impact of replacing PCV7 with PCV13 on disease burden in adults and identified age/risk-specific subgroups with the highest remaining disease burden. METHODS: A retrospective design and data from two US healthcare claims repositories were used. Study population included adults aged ≥18 years and was stratified by age (18-49, 50-64, 65-74, ≥75) and risk profile (healthy, at-risk, high-risk). Rate ratios comparing invasive pneumococcal disease (IPD), all-cause hospitalized pneumonia (ACHP), and pneumococcal pneumonia requiring hospitalization among at-risk and high-risk adults vs healthy counterparts were estimated for 2007-2010 (pre-PCV13), 2011-2012 (peri-PCV13), and 2013-2015 (post-PCV13). RESULTS: Across study periods, IPD and ACHP rates increased with age (2-27 times higher in persons ≥75 vs 18-49) and comorbidity (4-20 times higher in high-risk vs healthy). From pre- to post-PCV13 period, IPD rates declined 5%-48% and ACHP rates declined 4%-19% across age and risk groups (ACHP did not decline in persons ≥75). Decline in IPD and ACHP was attenuated among older adults and those with comorbidities. Accordingly, rate ratios among at-risk and high-risk persons (vs healthy counterparts) increased during the peri- and post-PCV13 periods compared with the pre-PCV13 period. CONCLUSIONS: The switch to PCV13 was associated with large declines in pneumococcal disease among US adults. However, the decline was attenuated with increasing age (and, for ACHP, was absent in persons ≥75) and in those with comorbidities.

Relationship of American Spinal Injury Association Impairment Scale Grade to Post-injury Hospitalization and Costs in Thoracic Spinal Cord Injury.

BACKGROUND: The lifetime economic burden of thoracic spinal cord injury (SCI) is known to be high, but evidence of variability of costs in relation to the American Spinal Injury Association Impairment Scale (AIS) grade is limited. OBJECTIVE: To estimate lifetime economic costs of hospitalization by AIS grade in thoracic SCI. METHODS: Using SCI Model Systems data from January 2000 to March 2016 from the National Spinal Cord Injury Statistical Center, we estimated mean total annual days of all-cause hospitalization by AIS grade among persons with thoracic SCI, based on assessments 1, 5, and 10 yr post-injury. We combined this information with secondary cost data and projections of life expectancy to estimate lifetime economic costs of hospitalization by AIS grade in persons aged 35 yr at time of thoracic SCI. Future costs were discounted to present value at 3% annually. RESULTS: One year post-injury, mean total annual days of hospitalization ranged from 2.1 for persons with AIS-D injuries to 5.9 for those who were AIS-A. Similar differences were noted 5 and 10 yr post-SCI. The estimated net present value of expected lifetime costs of hospitalization following thoracic SCI at age 35 yr was $321 534, $249 514, $188 989, and $68 120 (2015 US$) for AIS-A, AIS-B, AIS-C, and AIS-D injuries, respectively. CONCLUSION: Persons with less severe thoracic SCI, as reflected in AIS grade, spend fewer days in hospital over their lifetimes, leading to lower costs of inpatient care. Therapies improving AIS grade following thoracic SCI may provide cost savings in addition to addressing substantial unmet need.

Risk of exacerbation following pneumonia in adults with heart failure or chronic obstructive pulmonary disease.

BACKGROUND: Recent evidence demonstrates increased short-term risk of cardiac complications and respiratory failure among patients with heart failure (HF) and chronic obstructive pulmonary disease (COPD), respectively, concurrent with an episode of community-acquired pneumonia (CAP). We evaluated patients with pre-existing HF or COPD, beginning 30 days after CAP diagnosis, to determine if CAP had a prolonged impact on their underlying comorbidity. METHODS: A retrospective matched-cohort design using US healthcare claims was employed. In each month of accrual, patients with HF or COPD who developed CAP ("CAP patients") were matched (1:1, without replacement, on demographic and clinical profiles) to patients with HF or COPD who did not develop CAP ("comparison patients"). All patients were aged ≥40 years, and were pneumonia free during prior 1-year period. Exacerbation beginning 30 days after the CAP diagnosis and for the subsequent 1-year period were compared between CAP and comparison patients. FINDINGS: 38,010 (4·6%) HF patients and 48,703 (5·9%) COPD patients experienced a new CAP episode requiring hospitalization or outpatient care only, and were matched to comparison patients. In the HF subset, CAP patients were 47·2% more likely to experience an exacerbation vs patients without CAP (17·8% vs. 12·1%; p<0·001); in the COPD subset, CAP patients were 42·3% more likely to experience an exacerbation (16·2% vs. 11·4%; p<0·001). CONCLUSIONS: Our data provide evidence that CAP foreshadows a prolonged increase in risk of exacerbation of underlying HF or COPD in adults, and suggests a potential benefit to CAP prevention strategies.

Hospitalizations for osteoporosis-related fractures: Economic costs and clinical outcomes.

BACKGROUND: Osteoporotic fractures frequently require inpatient care, and are associated with elevated risks of morbidity, mortality, and re-hospitalization. A comprehensive evaluation of healthcare costs, resource utilization, and outcomes associated with osteoporosis (OP)-related fractures treated in US hospitals was undertaken. METHODS: A retrospective analysis using the Premier Perspective Database (2010 - 2013) was conducted. Study population comprised patients aged ≥ 50 years hospitalized with a principal diagnosis of a closed or pathologic fracture commonly associated with OP; the first qualifying hospitalization was designated the "index admission". Patients with evidence of major trauma, malignancy, or other non-OP conditions that may lead to pathologic fracture during the index admission were excluded. Study measures included healthcare costs (in 2013 USD), length of stay (LOS), intensive care unit (ICU) use, and mortality during the index admission, as well as 60-day fracture-related readmission. RESULTS: A total of 268,477 patients were admitted to hospital (n = 548 hospitals) with a principal diagnosis of an OP-related fracture; mean (SD) age was 78 (11) years, 75% were female, 69% had ≥ 2 comorbidities, and 82% of patients had a diagnostic code for accidental fall. Among all OP-related fracture admissions, mean (95% CI) hospital cost was $12,839 (12,784-12,893) and LOS was 5.1 (5.1-5.1) days; during the admission, ICU use was 7.4% (7.3-7.5) and mortality was 1.5% (1.5-1.6), and during the 60-day post-discharge period, fracture-related readmission was 2.3% (2.2-2.4). CONCLUSIONS: Hospital costs associated with the acute treatment of OP-related fractures are substantial, especially among patients with fractures of the hip, femur, and spine. Among patients with vertebral fractures-the second most common reason for admission-mortality and ICU use were notably high, and costs and LOS were higher than among those with non-vertebral fractures (excluding hip). Interventions that are effective in reducing fracture risk have the potential to yield substantial cost savings.