Odds of Hospitalization for COVID-19 After 3 vs 2 Doses of mRNA COVID-19 Vaccine by Time Since Booster Dose.

This study assesses the association between COVID-19 mRNA booster immunization compared with vaccination with the primary mRNA vaccination series alone and odds of hospitalization for COVID-19.

Comparative vaccine effectiveness against severe COVID-19 over time in US hospital administrative data: a case-control study.

BACKGROUND: Research suggests the protection offered by COVID-19 vaccines might wane over time, prompting consideration of booster vaccinations. Data on which vaccines offer the most robust protection over time, and which patients are most vulnerable to attenuating protection, could help inform potential booster programmes. In this study, we used comprehensive hospitalisation data to estimate vaccine effectiveness over time. METHODS: In this case-control study, we used data from a large US health-care system to estimate vaccine effectiveness against severe SARS-CoV-2 infection and examined variation based on time since vaccination, vaccine type, and patients' demographic and clinical characteristics. We compared trends in attenuation of protection across vaccines and used a multivariable model to identify key factors associated with risk for severe breakthrough infection. Patients were considered to have severe COVID-19 if they were admitted to the hospital, had a final coded diagnosis of COVID-19 (according to International Classification of Diseases Tenth Revision code U07.1) or a positive nucleic acid amplification test for symptomatic SARS-CoV-2 during their hospitalisation, and were treated with remdesivir or dexamethasone during hospitalisation. FINDINGS: Between April 1, 2021, and Oct 26, 2021, we observed 9667 admissions for severe COVID-19 (ie, cases). Overall, 1293 (13·4%) of 9667 cases were fully vaccinated at the time of admission, compared with 22 308 (57·7%) of 38 668 controls, who were admitted to hospital for other reasons. The median time between vaccination and hospital admission among cases was 162 days (IQR 118-198). Overall vaccine effectiveness declined mostly over the course of the summer, from 94·5% (95% CI 91·4-96·5) in April, 2021 (pre-delta), to 84·0% (81·6-86·1) by October, 2021. Notably, vaccine effectiveness declined over time, from 94·0% (95% CI 92·8-95·0) at days 50-100 after vaccination to 80·4% (77·8-82·7) by days 200-250 after vaccination. After 250 days, vaccine effectiveness declines were even more notable. Among those who received the BNT162b2 (Pfizer-BioNTech) vaccine, vaccine effectiveness fell from an initial peak of 94·9% (93·2-96·2) to 74·1% (69·6-77·9) by days 200-250 after vaccination. Protection from the mRNA-1273 (Moderna) and Ad26.COV2 (Janssen) vaccines declined less over time, although the latter offered lower overall protection. Holding other factors constant, the risk of severe breakthrough infection was most strongly associated with age older than 80 years (adjusted odds ratio 1·76, 95% CI 1·43-2·15), vaccine type (Pfizer 1·39, 0·98-1·97; Janssen 14·53, 8·43-25·03; both relative to Moderna), time since vaccination (1·05, 1·03-1·07; per week after week 8 when protection peaks, technically), and comorbidities including organ transplantation (3·44, 95% CI 2·12-5·57), cancer (1·93, 1·60-2·33), and immunodeficiency (1·49, 1·13-1·96). INTERPRETATION: Vaccination remains highly effective against hospitalisation, but vaccine effectiveness declined after 200 days, particularly for older patients or those with specific comorbidities. Additional protection (eg, a booster vaccination) might be warranted for everyone, but especially for these populations. In addition to promoting general vaccine uptake, clinicians and policy makers should consider prioritising booster vaccinations in those most at risk of severe COVID-19. FUNDING: None.

Iterative Assembly of Macrocyclic Lactones using Successive Ring Expansion Reactions.

Macrocyclic lactones can be prepared from lactams and hydroxyacid derivatives via an efficient 3- or 4-atom iterative ring expansion protocol. The products can also be expanded using amino acid-based linear fragments, meaning that macrocycles with precise sequences of hydroxy- and amino acids can be assembled in high yields by "growing" them from smaller rings, using a simple procedure in which high dilution is not required. The method should significantly expedite the practical synthesis of diverse nitrogen containing macrolide frameworks.

Hyperglycemia predicts mortality after CABG: postoperative hyperglycemia predicts dramatic increases in mortality after coronary artery bypass graft surgery.

OBJECTIVE: Risk of morbidity and mortality after coronary artery bypass graft surgery (CABG) is higher in patients with clinical diabetes mellitus (DM). We evaluated whether outcomes are affected by postoperative hyperglycemia in CABG patients independent of preoperative DM diagnosis. RESEARCH DESIGN AND METHODS: A total of 2297 consecutive CABG patients were studied. The first glucose value after surgery completion (mean 15 min) was tested as a predictor of outcome. Primary outcome variables were prolonged ventilation (>24 h), deep sternal wound infection, renal failure, permanent stroke, any reoperation, length of stay (>14 days) and mortality. All outcomes except for prolonged ventilation and length of stay were tracked out to 30 days postoperatively. Patients were stratified by glycemic control: Low (glucose <80), normal (referent, glucose 80-110), high (glucose 111-200) and very high (glucose >200 mg/dl). Multivariable logistic regression was used to determine the independent predictive value of glycemic groups, adjusted for outcome specific risk scores from the Society of Thoracic Surgeons model. RESULTS: Patient distribution among groups low through very high were 44 (1.9%), 476 (20.7%), 1425 (62.0%) and 352 (15.3%). Greater complication rates were noted in the very high group when compared with the referent group: prolonged ventilation (adjusted odds ratio (OR)=2.66, P<.001), length of stay >14 days (adjusted OR=2.06, P=.004) and mortality (adjusted OR=7.71, P<.001). CONCLUSION: Patients with blood glucose values >200 mg/dl immediately after CABG had an increased risk of complications, including mortality, independent of a clinical diagnosis of DM. This study documents the high risk associated with early postoperative hyperglycemia in this group, suggesting the need for prospective trials of glycemic control.

Incremental survival benefit with adherence to standardized heart failure core measures: a performance evaluation study of 2958 patients.

BACKGROUND: In 2002, the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) established four heart failure (HF) core measures to standardize and improve health care quality in the United States. Although adherence to these HF care processes may be improving, their collective impact on survival is not yet settled. METHODS: JCAHO HF measures were implemented within a 20-hospital health care system. Eligible patients had a principal discharge diagnosis of HF. Metrics representing compliance with these measures were derived and their relationship with 1-year survival was examined using an adjusted Cox proportional hazards regression. RESULTS: A total of 2958 patients met study criteria. The average age was 73 years, 50% were male, and 9.9% were smokers. One-year survival benefits were seen in an item-by-item evaluation of HF measures for angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy (hazard ratio [HR] = 0.69), left ventricular function assessment (HR = 0.83), and patient education (HR = 0.79). When assessed collectively, improved survival was seen among patients eligible for two (HR = 0.53), three (HR = 0.36), or four HF measures (HR = 0.65). Further, we found a positive and incremental relationship between the degree of adherence and survival (P = .008). CONCLUSION: Adherence to JCAHO HF core measures is associated with improved 1-year survival after HF hospitalization. This validates these simple and effective performance measures and justifies efforts to implement them in all eligible patients with HF.

The paradox of obesity in patients with heart failure.

PURPOSE: Heart failure (HF) patients often have comorbid conditions that confound management and adversely affect prognosis. The purpose of this study was to determine whether the obesity paradox is also present in hospitalized HF patients in an integrated healthcare system. DATA SOURCES: A cohort of 2707 patients with a primary diagnosis of HF was identified within an integrated, 20-hospital healthcare system. Patients were identified by ICD-9 codes or a left ventricular ejection fraction < or =40% dating back to 1995. Body mass index (BMI) was calculated using the first measured height and weight when hospitalized with HF. Survival rates were calculated using Kaplan Meier estimation. Hazard ratios for 3-year mortality with 95% confidence intervals were assessed using Cox regression, controlling for age, gender, and severity of illness at time of diagnosis. CONCLUSIONS: Three-year survival rates paradoxically improved for patients with increasing BMI. Survival rates for the larger three BMI quartiles were significantly better than for the lowest quartile after adjusting for severity of illness, age, and gender. IMPLICATIONS FOR PRACTICE: While obesity increases the risk of developing HF approximately twofold, reports involving stable outpatients suggest that obesity is associated with improved survival after the development of HF. This finding is paradoxical because obesity increases the risk and worsens the prognosis of other cardiovascular diseases.

Spondylitic changes in long-finned pilot whales (Globicephala melas) stranded on Cape Cod, Massachusetts, USA, between 1982 and 2000.

The primary bone pathology diagnoses recognized in cetacea are osteomyelitis and spondylosis deformans. In this study, we determined the prevalence, type, and severity of vertebral pathology in 52 pilot whales, a mass stranding species that stranded on Cape Cod, Massachusetts, between 1982 and 2000. Eleven whales (21%) had hyperostosis and ossification of tendon insertion points on and between vertebrae, chevron bones, and costovertebral joints, with multiple fused blocks of vertebrae. These lesions are typical of a group of interrelated diseases described in humans as spondyloarthropathies, specifically ankylosing spondylitis, which has not been fully described in cetacea. In severe cases, ankylosing spondylitis in humans can inhibit mobility. If the lesions described here negatively affect the overall health of the whale, these lesions may be a contributing factor in stranding of this highly sociable species.

Improvements in 1-year cardiovascular clinical outcomes associated with a hospital-based discharge medication program.

BACKGROUND: Despite recent advances in the treatment and prevention of cardiovascular disease, a treatment gap for secondary prevention medications still exists. OBJECTIVE: To develop and implement a program ensuring appropriate prescription of aspirin, statins, beta-blockers, angiotensin-converting enzyme inhibitors, and warfarin at hospital discharge. DESIGN: A nonrandomized before-after study comparing patients hospitalized before (1996-1998) and after (1999-2002) implementation of a discharge medication program (DMP). Patients were followed for up to 1 year. SETTING: The 10 largest hospitals in the Utah-based Intermountain Health Care system. PATIENTS: In the pre-DMP and DMP time periods, 26,000 and 31,465 patients, respectively, were admitted to cardiovascular services (n = 57,465). MEASUREMENTS: Prescription of indicated medications at hospital discharge; postdischarge death or readmission. RESULTS: By 1 year, the rate of prescription of each medication increased significantly to more than 90% (P < 0.001); this rate was sustained. At 1 year, unadjusted absolute event rates for readmission and death, respectively, were 210 per 1000 person-years and 96 per 1000 person-years before DMP implementation and 191 per 1000 person-years and 70 per 1000 person-years afterward. Relative risk for death and readmission at 30 days decreased after DMP implementation; hazard ratios (HRs) for death and readmission were 0.81 (95% CI, 0.73 to 0.89) and 0.92 (CI, 0.87 to 0.99) (P < 0.001 and P = 0.017, respectively). At 1 year, risk for death continued to decrease (hazard ratio, 0.79 [CI, 0.75 to 0.84]; P < 0.001) while risk for readmission stabilized (hazard ratio, 0.94 [CI, 0.90 to 0.98]; P = 0.002), probably because survivors had more opportunities to be readmitted. LIMITATIONS: The study design was observational and nonrandomized, and the authors could not control for potential confounders or determine the extent to which secular trends accounted for the observed improvements. CONCLUSIONS: A relatively simple quality improvement program aimed at enhancing the prescription of appropriate discharge medications among cardiovascular patients is feasible and can be sustained within an integrated multihospital system. Such a program may be associated with improvements in cardiovascular readmission rates and mortality.