Researching COVID to Enhance Recovery (RECOVER) adult study protocol: Rationale, objectives, and design.

IMPORTANCE: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. METHODS: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms. DISCUSSION: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options. REGISTRATION: NCT05172024.

Rilpivirine versus efavirenz in HIV-1-infected subjects receiving emtricitabine/tenofovir DF: pooled 96-week data from ECHO and THRIVE Studies.

OBJECTIVES: Week 96 efficacy and safety of the non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (RPV) was compared to efavirenz (EFV) in subset of 1,096 subjects who received emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in pooled data from 2 phase 3 studies. METHODS: ECHO and THRIVE are double-blind, double-dummy, randomized, active-controlled, non-inferiority phase 3 studies of RPV versus EFV plus 2 NRTIs in antiretroviral-naïve adult subjects. The primary and secondary endpoints were the proportion of subjects with HIV-1 RNA <50 copies/ mL using an intent-to-treat, time to loss of virologic response (ITT-TLOVR) analysis at weeks 48 and 96, respectively. Safety, tolerability, immunologic response, adherence level, and other measures were also evaluated. RESULTS: At week 48, noninferior efficacy of RPV+FTC/TDF over EFV+FTC/TDF was established, and at week 96 RPV+FTC/TDF remained noninferior (77% overall response rate in both groups). Through week 96, rates of virologic failure were higher in the RPV+FTC/ TDF group, with low and similar rates of virologic failure and resistance mutations occurring during the second year of follow-up. Treatment with RPV+FTC/TDF was associated with a lower rate of discontinuation due to adverse events and grade 2-4 adverse events including dizziness, abnormal dreams/nightmares, rash, and lipid abnormalities. CONCLUSIONS: The pooled ECHO and THRIVE studies demonstrated noninferiority of RPV+FTC/TDF in achieving virologic response with safety and tolerability advantages over EFV+FTC/TDF through 96 weeks. Higher rates of virologic failure in the RPV+FTC/TDF group were balanced with higher rates of discontinuations due to adverse events in the EFV+FTC/TDF group.

Antibody responses to Bordetella pertussis antigens and clinical correlations in elderly community residents.

A serological study to determine the frequency of Bordetella pertussis infection in 100 adults aged >/=65 years was carried out over a 3-year period. Ten serum samples (collected every 4 months) from each subject were examined for IgA and IgG antibodies to the following B. pertussis antigens: pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin, and fimbriae-2. A >/=2-fold titer increase in ELISA units from one time period to the next was considered serological evidence of infection. The rate of serologically defined infection (i.e., in which there was an increase in titer against any antigen) was 19.7 per 100 person-years. With the use of more specific criteria that indicate definite B. pertussis infection (>/=2-fold increase in titer to PT) and probable B. pertussis infection (>/=2-fold increase in titer to PT or >/=2-fold increase to fimbriae-2), the rates were 3.3 and 8.0 per 100 person-years, respectively. Fifty percent of individuals with definite B. pertussis infections had time-associated symptomatology. Antibody patterns over time suggest that antibody to FHA and perhaps to pertactin is stimulated by infections with other organisms, as well as B. pertussis infections. Our data suggest that symptomatic pertussis occurs in elderly individuals. Consideration should be given to immunization of the elderly with acellular pertussis vaccines.

Predisposition to urinary tract epithelial metaplasia in Schistosoma haematobium infection.

Although there is strong epidemiologic evidence linking Schistosoma haematobium infection with carcinoma of the bladder, the utility of cytologic screening for urinary tract cancer has not been critically evaluated in S. haematobium-endemic populations. The present cross-sectional study examined urine cytology findings among 1,014 residents (ages 1 to 91) of the S. haematobium-endemic Msambweni area of Coast Province, Kenya. Among 705 evaluable cytology specimens, prevalence of inflammation (39%), hyperkeratosis (30%), metaplasia (33%), and frank atypia (0.4%) was notably higher than in previously studied, non-endemic populations. Overall, S. haematobium infection was strongly associated with increased risk for cytologic abnormality (> 2.8-fold relative risk of metaplasia or hyperkeratosis; P < 0.001). Age-group analysis confirmed parallel increases in metaplasia and S. haematobium infection prevalence early in life (from age I to 15 for both boys and girls). However, above age 20, metaplasia prevalence persisted at 33-45% prevalence despite a decline in infection prevalence and intensity. Prevalence of advanced (moderate or severe) metaplasia showed two age-related peaks: the first at 10-14 years of age (at the time of peak infection), and the second among subjects > or = 60 years old. No cancers were detected in the study population either on cytology or on follow-up ultrasound examination. These data suggest an age-dependent progression of cellular abnormalities in the urinary epithelium that is associated with chronic S. haematobium infection, which becomes independent of concurrent infection intensity as subjects grow older. Implications for cancer screening are discussed.

Performance of third-year primary-care-track students in an integrated curriculum at Case Western Reserve University.

In 1994, Case Western Reserve University School of Medicine established a Primary Care Track (PCT) with an integrated curriculum as part of The Robert Wood Johnson Foundation's Generalist Physician Initiative. This study compared the performance of the first cohort of students to participate in the PCT third year with that of their classmates and determined student attitudes toward their experiences. The performances of 24 PCT and 81 traditional students on the Medical School Admissions Test (MCAT) and the United States Medical Licensure Examination (USMLE) Step 1 and 2 were compared using analysis of variance. Grades on the six core clerkships were compared using chi-square analysis. Performances of the PCT students and a subset of traditional students on the generalist school's objective structured clinical exam (OSCE) were compared using multivariate analysis. The students reported their perceptions on a questionnaire. The traditional students had significantly higher scores on the physical science section of the MCAT and on the USMLE Step 1, but at the end of year three, their USMLE Step 2 scores did not differ. Grade distributions in the core clerkships did not differ, except in psychiatry, where the PCT students received honors significantly more often. The PCT students had a lower mean score on the internal medicine National Board of Medicine Examiners shelf exam but performed better on the generalist OSCE exam. A majority of PCT students reported that they would choose the integrated third year again and recommend it to others.

Presenting two incongruent color words on a single trial does not alter Stroop interference.

Two experiments showed that having two incongruent words present on a single Stroop trial (e.g., both red and green in blue, say "blue") did not alter interference relative to having only one incongruent word. This was true whether the two incongruent words were presented successively at several stimulus onset asynchronies (Experiment 1) or simultaneously in adjacent positions (Experiment 2). We argue that the first word captures attention and "locks out" others, preventing additional interference.

Thought suppression: an experimental investigation of spider phobics.

Researchers have observed that attempts to suppress a thought cause either an immediate increase in the occurrence of the thought (i.e. immediate enhancement effect) or a delayed increase in the occurrence of the thought (i.e. rebound effect). In this study, we examined whether suppression of a personally-relevant, emotional thought item (i.e. a spider to spider phobics) results in an immediate enhancement or a rebound effect. Forty-eight spider phobics were randomly assigned to either a suppression group or a control group. Subjects spent three 5-min periods alone monitoring their thoughts. During the first period, subjects in both groups were instructed to 'think about anything'. During the second period, subjects in the suppression group were instructed 'not to think of a spider', whereas subjects in the control group were instructed to 'think about anything'. During the third period, subjects in both groups were instructed to 'think about anything'. The number of spider-related thoughts was recorded for each period. Results from the second period failed to support an immediate enhancement effect. Evidence for a rebound effect, however, was obtained in the third period. The theoretical and clinical implications of these findings are discussed.

Acute respiratory illness in older community residents.

OBJECTIVE: To describe the 3-year incidence of acute respiratory illness in a population of noninstitutionalized elderly persons. DESIGN: Cohort analytic study with an observation period of 3 years. SETTING: Large midwestern urban community. SUBJECTS: 574 noninstitutionalized persons aged 65 years and older, of whom 349 were living independently, 110 were in congregate settings, and 115 were living independently and regularly caring for small children. METHODS: Subjects were interviewed and examined by nurse practitioners at intake and every 4 months. Acute illness and convalescent visits were made when illnesses were reported by participants. MAIN OUTCOME MEASURES: The incidence of acute respiratory illness was used to test the hypothesis that elderly persons taking care of children have the highest incidence, congregate-dwellers intermediate incidence, and those living independently the lowest incidence. RESULTS: The average incidence of acute respiratory illness was 2.5 per 100 person months, comparable to rates reported in the National Health Survey. The incidence of respiratory illness was significantly greater in subjects living in congregate settings or regularly caring for young children. Similarly, greater proportions of persons in the congregate and child-care groups reported at least one episode of illness (P < .05). A more detailed analysis of exposure shows that acute respiratory illness was significantly more common in subjects who had contact with children (P < .05). This risk was definitely present during the months November through February, and probably also during July through October, but was not observed for March through June. CONCLUSIONS: Elderly persons living in the community experience low rates of acute upper respiratory illness. Contact with children increases their risk of developing such illnesses during certain seasons of the year.

Epidemiology of pertussis and reactions to pertussis vaccine.

It remains clear that pertussis is a dangerous infectious disease that is well-controlled in industrialized countries by widespread immunization. In the developing world, it remains a source of high morbidity and mortality because of previously inadequate immunization programs. However, because of the intense efforts of the World Health Organization's Expanded Programme on Immunization, the effects of pertussis have already been ameliorated and show promise of being within a decade of approximating the situation in the developed world. Pertussis can be controlled only by immunization; other measures such as antimicrobial therapy offer negligible benefit. A problem that has been addressed in recent years is the excessive reactivity of whole-cell pertussis vaccine, which undoubtedly includes components of the organism that are irrelevant to the induction of immunity and are excessively reactive. Although epidemiologic studies appear to have largely, if not completely, absolved pertussis vaccine of responsibility for inducing death or permanent neurologic disability, a less reactive vaccine is highly desirable, not only to promote acceptance of a full course of immunization for the world's children but also for simple humanitarian reasons. Additionally, it has become evident that, because of waning immunity, pertussis increasingly occurs in adults. A less reactive vaccine would offer opportunity for reinforcement of immunity beyond childhood. The development of better, though as yet incomplete, understanding of the biology of Bordetella pertussis and its relation to humanity offers the opportunity for the production of less reactive vaccines free of irrelevant components. Acellular pertussis vaccines have been used exclusively in Japan for more than 10 years, and one such preparation, combined with diphtheria and tetanus toxoids, was licensed in the United States in late 1991 for use as the fourth and fifth doses of DTP, given at 15 months and prior to school entry. Field trials of this and other acellular DTP preparations are currently under way to determine their clinical efficacy in infants. It is probable that, within a very few years, whole-cell pertussis vaccine will be replaced by these newer preparations and that, in addition, the acellular product will be combined with other antigens, such as Haemophilus influenzae type b vaccine.