A Qualitative Study Investigating Experiences, Perceptions, and Healthcare System Performance in Relation to the Surveillance of Typhoid Fever in Madagascar.

BACKGROUND: The burden of typhoid fever (TF) in sub-Saharan Africa is largely unknown but is increasingly thought to be high, given that water and sanitary conditions remain unimproved in many countries. To address this gap in information, the Typhoid Fever Surveillance in Africa Program (TSAP) founded a surveillance system for TF in 10 African countries. This study was a component of the TSAP surveillance project in Madagascar. METHODS: The study entailed a qualitative assessment of patients' experiences and perceptions of services for febrile symptoms at the studies' rural and urban sentinel public health clinics. The study examined influences on the use of these facilities, alternative sources of care, and providers' descriptions of medical consultations and challenges in providing services. Data were collected through semistructured and open-ended individual interviews and a focus group with patients, caregivers, and medical personnel. RESULTS: Thirty-three patients and 12 healthcare providers participated in the data collection across the 2 healthcare facilities. The quality of services, cost, and travel distance were key factors that enabled access to and use of these clinics. Divergent healthcare-seeking patterns were related to variability in the care utilized, socioeconomic status, and potential distance from the facilities : These factors influenced delivery of care, patient access, and the health facilities' capacity to identify cases of febrile illness such as TF. CONCLUSIONS: This approach provided an in-depth investigation and understanding of healthcare-seeking behavior at the study facilities, and factors that facilitated or acted as barriers to their use. Our findings demonstrate the relevance of these public health clinics as sites for the surveillance of TF in their role as central healthcare sources for families and communities within these rural and urban areas of Madagascar.

Diagnosing Salmonella enterica Serovar Typhi Infections by Polymerase Chain Reaction Using EDTA Blood Samples of Febrile Patients From Burkina Faso.

BACKGROUND: Globally, there are an estimated 22 million cases of Salmonella enterica serovar Typhi infection each year. However, this figure is likely to be an underestimate due to the low sensitivity of blood culture in S. Typhi diagnosis. The aim of this study was to diagnose S. Typhi by conventional polymerase chain reaction (PCR) using patient's blood preserved with ethylenediamine tetraacetic acid (EDTA). METHODS: From April 2012 to September 2013, typhoid fever surveillance was conducted in Polesgo and Nioko, 2 dry slum areas in Ouagadougou, Burkina Faso. Blood culture was performed for febrile patients using an automated blood culture system. Additional blood was collected in EDTA tubes from those patients and preserved at -80°C. DNA was extracted from EDTA blood and PCR was performed to identify presence of S. Typhi. Randomly selected PCR products were further sequenced to identify S. Typhi-specific amplicons. RESULTS: Of 1674 patients, S. Typhi was isolated from 18 (1.1%) individuals by blood culture. EDTA blood was collected from 1578 patients, of which 298 EDTA samples were tested by PCR. Salmonella Typhi-specific DNA was identified in 44 (14.8%) samples. The sensitivity of S. Typhi-specific PCR from EDTA blood was 89% (74%-100%) among the blood culture-positive cases. Sixteen S. Typhi-positive PCR products were sequenced, and 13 retrieved the sequence of a S. Typhi-specific amplicon. CONCLUSIONS: These findings suggest that blood culture-based diagnoses of S. Typhi underestimate the burden of typhoid fever in Burkina Faso. PCR could be considered as an alternative method for the identification and diagnosis of S. Typhi in blood samples.

A Multicountry Molecular Analysis of Salmonella enterica Serovar Typhi With Reduced Susceptibility to Ciprofloxacin in Sub-Saharan Africa.

BACKGROUND: Salmonella enterica serovar Typhi is a predominant cause of bloodstream infections in sub-Saharan Africa (SSA). Increasing numbers of S. Typhi with resistance to ciprofloxacin have been reported from different parts of the world. However, data from SSA are limited. In this study, we aimed to measure the ciprofloxacin susceptibility of S. Typhi isolated from patients with febrile illness in SSA. METHODS: Febrile patients from 9 sites within 6 countries in SSA with a body temperature of ≥38.0°C were enrolled in this study. Blood samples were obtained for bacterial culture, and Salmonella isolates were identified biochemically and confirmed by multiplex polymerase chain reaction (PCR). Antimicrobial susceptibility of all Salmonella isolates was performed by disk diffusion test, and minimum inhibitory concentrations (MICs) against ciprofloxacin were measured by Etest. All Salmonella isolates with reduced susceptibility to ciprofloxacin (MIC > 0.06 µg/mL) were screened for mutations in quinolone resistance-determining regions in target genes, and the presence of plasmid-mediated quinolone resistance (PMQR) genes was assessed by PCR. RESULTS: A total of 8161 blood cultures were performed, and 100 (1.2%) S. Typhi, 2 (<0.1%) Salmonella enterica serovar Paratyphi A, and 27 (0.3%) nontyphoid Salmonella (NTS) were isolated. Multidrug-resistant S. Typhi were isolated in Kenya (79% [n = 38]) and Tanzania (89% [n = 8]) only. Reduced ciprofloxacin-susceptible (22% [n = 11]) S. Typhi were isolated only in Kenya. Among those 11 isolates, all had a Glu133Gly mutation in the gyrA gene combined with either a gyrA (Ser83Phe) or gyrB mutation (Ser464Phe). One Salmonella Paratyphi A isolate with reduced susceptibility to ciprofloxacin was found in Senegal, with 1 mutation in gyrA (Ser83Phe) and a second mutation in parC (Ser57Phe). Mutations in the parE gene and PMQR genes were not detected in any isolate. CONCLUSIONS: Salmonella Typhi with reduced susceptibility to ciprofloxacin was not distributed homogenously throughout SSA. Its prevalence was very high in Kenya, and was not observed in other study countries. Continuous monitoring of antimicrobial susceptibility is required to follow the potential spread of antimicrobial-resistant isolates throughout SSA.

The Typhoid Fever Surveillance in Africa Program (TSAP): Clinical, Diagnostic, and Epidemiological Methodologies.

BACKGROUND: New immunization programs are dependent on data from surveillance networks and disease burden estimates to prioritize target areas and risk groups. Data regarding invasive Salmonella disease in sub-Saharan Africa are currently limited, thus hindering the implementation of preventive measures. The Typhoid Fever Surveillance in Africa Program (TSAP) was established by the International Vaccine Institute to obtain comparable incidence data on typhoid fever and invasive nontyphoidal Salmonella (iNTS) disease in sub-Saharan Africa through standardized surveillance in multiple countries. METHODS: Standardized procedures were developed and deployed across sites for study site selection, patient enrolment, laboratory procedures, quality control and quality assurance, assessment of healthcare utilization and incidence calculations. RESULTS: Passive surveillance for bloodstream infections among febrile patients was initiated at thirteen sentinel sites in ten countries (Burkina Faso, Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar, Senegal, South Africa, Sudan, and Tanzania). Each TSAP site conducted case detection using these standardized methods to isolate and identify aerobic bacteria from the bloodstream of febrile patients. Healthcare utilization surveys were conducted to adjust population denominators in incidence calculations for differing healthcare utilization patterns and improve comparability of incidence rates across sites. CONCLUSIONS: By providing standardized data on the incidence of typhoid fever and iNTS disease in sub-Saharan Africa, TSAP will provide vital input for targeted typhoid fever prevention programs.

Lifetime Prevalence of Attention-Deficit Hyperactivity Disorder in Young Adults: Examining Variations in the Socioeconomic Gradient.

OBJECTIVE: It has only recently been accepted that attention-deficit hyperactivity disorder (ADHD) persists into adulthood. Accordingly, less is known about adult diagnostic and treatment prevalence. We aimed to determine the lifetime prevalence of ADHD diagnosis and psychostimulant prescriptions for young adults in the province of Manitoba and to explore how diagnosis differs according to sociodemographic characteristics and age at diagnosis; and to investigate whether a socioeconomic gradient exists within young adults with a lifetime ADHD diagnosis, as well as the variables that moderate the gradient. METHODS: Using the Manitoba Population Health Research Data Repository, our cross-sectional analysis used 24 fiscal years of data (1984/85 to 2008/09) and included all adults aged 18 to 29 during 2007/08 to 2008/09 in Manitoba (n = 207 544) who had a lifetime diagnosis of ADHD (n = 14 762). Regression analyses tested for differences in rates by sex, region, age, age at diagnosis, and socioeconomic status. RESULTS: Lifetime prevalence for ADHD diagnosis (7.11%) and psychostimulant prescriptions (3.09%) differed according to sex, region, and age. In contrast to previous Manitoban research on childhood ADHD, the socioeconomic gradient for ADHD diagnosis was not found in young adulthood. When region was accounted for, a small negative gradient in the urban population and a positive gradient in the rural population were evident. People from the highest income quintile were significantly less likely to be diagnosed before age 18, compared with other income quintiles. CONCLUSIONS: Given the high lifetime prevalence of ADHD in Manitoban young adults and significant socioeconomic correlates for diagnosis, further investigation into the trajectory of this relatively unexplored population is recommended.

The control of lipid metabolism by mRNA splicing in Drosophila.

The storage of lipids is an evolutionarily conserved process that is important for the survival of organisms during shifts in nutrient availability. Triglycerides are stored in lipid droplets, but the mechanisms of how lipids are stored in these structures are poorly understood. Previous in vitro RNAi screens have implicated several components of the spliceosome in controlling lipid droplet formation and storage, but the in vivo relevance of these phenotypes is unclear. In this study, we identify specific members of the splicing machinery that are necessary for normal triglyceride storage in the Drosophila fat body. Decreasing the expression of the splicing factors U1-70K, U2AF38, U2AF50 in the fat body resulted in decreased triglyceride levels. Interestingly, while decreasing the SR protein 9G8 in the larval fat body yielded a similar triglyceride phenotype, its knockdown in the adult fat body resulted in a substantial increase in lipid stores. This increase in fat storage is due in part to altered splicing of the gene for the ß-oxidation enzyme CPT1, producing an isoform with less enzymatic activity. Together, these data indicate a role for mRNA splicing in regulating lipid storage in Drosophila and provide a link between the regulation of gene expression and lipid homeostasis.

Biochemical markers for assessment of calcium economy and bone metabolism: application in clinical trials from pharmaceutical agents to nutritional products.

Nutrition plays an important role in osteoporosis prevention and treatment. Substantial progress in both laboratory analyses and clinical use of biochemical markers has modified the strategy of anti-osteoporotic drug development. The present review examines the use of biochemical markers in clinical research aimed at characterising the influence of foods or nutrients on bone metabolism. The two types of markers are: (i) specific hormonal factors related to bone; and (ii) bone turnover markers (BTM) that reflect bone cell metabolism. Of the former, vitamin D metabolites, parathyroid hormone, and insulin-like growth factor-I indicate responses to variations in the supply of bone-related nutrients, such as vitamin D, Ca, inorganic phosphate and protein. Thus modification in bone remodelling, the key process upon which both pharmaceutical agents and nutrients exert their anti-catabolic or anabolic actions, is revealed. Circulating BTM reflect either osteoclastic resorption or osteoblastic formation. Intervention with pharmacological agents showed that early changes in BTM predicted bone loss and subsequent osteoporotic fracture risk. New trials have documented the influence of nutrition on bone-tropic hormonal factors and BTM in adults, including situations of body-weight change, such as anorexia nervosa, and weight loss by obese subjects. In osteoporosis-prevention studies involving dietary manipulation, randomised cross-over trials are best suited to evaluate influences on bone metabolism, and insight into effects on bone metabolism may be gained within a relatively short time when biochemical markers are monitored.

Patient educational needs of patients undergoing surgery for lung cancer.

There often exists a discrepancy between the information health care professionals (HCPs) provide to patients in preoperative teaching sessions and the information patients perceive as important. This study's purpose was to determine what information patients undergoing a lung cancer surgical resection wanted to learn before and after their surgery and also to uncover the information HCPs currently provide to these patients. Ten patients were interviewed preoperatively and postoperatively, and eleven HCPs involved in both their preoperative and postoperative care were interviewed. Emerging themes were noted. Patients reported that the most helpful aspects of the preoperative education included surgical details and the importance of physiotherapy, including exercises. Postoperatively, patients wished they had known more about postoperative pain. HCPs provided information that they felt prepared, informed and empowered their patients. Overall, patients expressed satisfaction with the information they received; they felt prepared for their surgery but not for postoperative pain control.

Dairy in adulthood: from foods to nutrient interactions on bone and skeletal muscle health.

The risk of fragility fractures exponentially increases with aging. Reduced mass and strength of both bone in osteoporosis and skeletal muscle in sarcopenia play a key role in the age-related incidence of fragility fractures. Undernutrition is often observed in the elderly, particularly in those subjects experiencing osteoporotic fractures, more likely as a cause than a consequence. Calcium (Ca), inorganic phosphate (Pi), vitamin D, and protein are nutrients that impact bone and skeletal muscle integrity. Deficiency in the supply of these nutrients increases with aging. Dairy foods are rich in Ca, Pi, and proteins and in many countries are fortified with vitamin D. Dairy foods are important souces of these nutrients and go a long way to meeting the recommendations, which increase with aging. This review emphaszes the interactions between these 4 nutrients, which, along with physical activity, act through cellular and physiological pathways favoring the maintenance of both bone and skeletal muscle structure and function.

Meta-analysis of single-session behavioral interventions to prevent sexually transmitted infections: implications for bundling prevention packages.

Evidence-based, single-session behavioral interventions are urgently needed for preventing the spread of HIV and other sexually transmitted infections (STIs). To estimate the efficacy of single-session, behavioral interventions for STI prevention, we collected data from 29 single-session interventions (20 studies; n = 52 465) with an STI outcome. Infection with an STI was 35% less likely (odds ratio = 0.65; 95% confidence interval = 0.55-0.77) among intervention group participants than among control group participants. Single-session interventions offer considerable benefits in terms of disease prevention and create minimal burden for both the patient and the provider. Brief and effective STI prevention interventions are a valuable tool and can be readily adapted to bolster the benefits of biomedical technologies focusing on the prevention of HIV and other STIs.

Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the Birt-Hogg-Dubé syndrome.

Birt-Hogg-Dubé (BHD) syndrome is a rare inherited genodermatosis characterized by hair follicle hamartomas, kidney tumors, and spontaneous pneumothorax. Recombination mapping in BHD families delineated the susceptibility locus to 700 kb on chromosome 17p11.2. Protein-truncating mutations were identified in a novel candidate gene in a panel of BHD families, with a 44% frequency of insertion/deletion mutations within a hypermutable C(8) tract. Tissue expression of the 3.8 kb transcript was widespread, including kidney, lung, and skin. The full-length BHD sequence predicted a novel protein, folliculin, that was highly conserved across species. Discovery of disease-causing mutations in BHD, a novel kidney cancer gene associated with renal oncocytoma or chromophobe renal cancer, will contribute to understanding the role of folliculin in pathways common to skin, lung, and kidney development.

Adherence to highly active antiretroviral therapy (HAART): a meta-analysis.

This meta-analysis synthesizes eighty-four observational studies, conducted across twenty countries, to determine the mean proportion of people who reported ≥90% adherence to prescribed highly active antiretroviral therapy (HAART) and to identify the factors associated with high levels of adherence. Eight electronic databases were searched to locate all relevant studies available by January 2010, which were then coded for sample characteristics and adherence levels. The average rate of reporting ≥90% adherent HAART adherence is 62%. However, this proportion varies greatly across studies. In particular, a greater proportion of individuals maintaining ≥90% adherence to HAART is more likely in studies with higher proportions of men who have sex with men (MSM) and lower proportions of injection drug users (IDU), with participants in an earlier stage of infection, and in studies conducted in countries characterized by lower Human Development Index (HDI) scores.

School nurses and children with diabetes: a descriptive study.

BACKGROUND: Managing diabetes in children is complex. The aims of this descriptive study were to describe the care provided to children with diabetes by school nurses using case management, to identify differences in care on the basis of the workload of the nurse and the age of the child, to explore the role of the nurse in responding to emergencies, and to describe the relationship between case management and quality of life. METHODS: School nurses completed an expanded health assessment. Individualized goals were established and interventions were provided on the basis of a protocol. Quantitative and qualitative data for children enrolled during the 2009-2010 academic year were analyzed. RESULTS: Eighty-six children were enrolled. The most common goals were related to establishing a safe school environment. Interventions varied depending on the workload of the nurse and the age of the child. Nurses assigned to 1-2 schools provided more intervention days (mean, 40.3 days) than did nurses assigned to 3-4 schools (mean, 24.4 days) (P < .05), particularly in the area of direct care. A total of 25 students experienced an emergency at school that initiated a cascade of events involving the parent (in 100% of cases), the teacher (in 96%), management of hyperglycemia (in 100%), and/or management of hypoglycemia (in 96%). For teens, case management improved quality of life, particularly the ability to communicate with health professionals. LIMITATIONS: The sample was small, and there was no comparison group. CONCLUSIONS: School nurses are effective in using case management to enhance the health and well-being of children with diabetes. This study should be replicated with a larger sample, a comparison group, and the inclusion of clinical outcomes.

Unconventional Care at a Convention Center: An Overview of Patient Focused Care at a COVID-19 Alternative Care Site in New Orleans.

In March 2020, the State of Louisiana opened an alternative care site at the New Orleans Convention Center, known as the Medical Monitoring Station (MMS). The facility was designed, constructed, and staffed to serve a population with basic medical needs as they recovered from COVID-19. As the MMS prepared to open, local hospitals indicated a greater need for assistance with patients requiring a higher acuity of care and populations unable to be discharged due to infection risks. In response to this, the capabilities of the facility were altered to accommodate primarily elderly patients, with significant comorbidities, requiring extensive care. This manuscript presents the demographics of the first 250 patients seen at the MMS, and describes the most critical policies/protocols, interventions, and resources that proved successful in adjusting to effectively serve its population.

Efficacy of HIV prevention interventions in Latin American and Caribbean nations, 1995-2008: a meta-analysis.

This meta-analysis synthesized 37 HIV prevention interventions (from 28 studies) that were evaluated in Latin American and Caribbean nations. These studies were obtained through systematic searches of English, Spanish, and Portuguese-language databases available as of January 2009. Overall, interventions significantly increased knowledge (d = 0.40) and condom use (d = 0.25) but the effects varied widely. Interventions produced more condom use when they focused on high-risk individuals, distributed condoms, and explicitly addressed social-cultural components. The best-fitting models utilized factors related to geography, especially indices of a nations' human development index (HDI) and income inequality (i.e., Gini index). Interventions that provided at least 3 h of content succeeded better when HDI and income inequality were lower, suggesting that intensive HIV prevention activities succeed best where the need is greatest. Implications for HIV intervention development in Latin America and the Caribbean are discussed.

A network-individual-resource model for HIV prevention.

HIV is transmitted through dyadic exchanges of individuals linked in transitory or permanent networks of varying sizes. A theoretical perspective that bridges key individual level elements with important network elements can be a complementary foundation for developing and implementing HIV interventions with outcomes that are more sustainable over time and have greater dissemination potential. Toward that end, we introduce a Network-Individual-Resource (NIR) model for HIV prevention that recognizes how exchanges of resources between individuals and their networks underlies and sustains HIV-risk behaviors. Individual behavior change for HIV prevention, then, may be dependent on increasing the supportiveness of that individual's relevant networks for such change. Among other implications, an NIR model predicts that the success of prevention efforts depends on whether the prevention efforts (1) prompt behavior changes that can be sustained by the resources the individual or their networks possess; (2) meet individual and network needs and are consistent with the individual's current situation/developmental stage; (3) are trusted and valued; and (4) target high HIV-prevalence networks.

PKA phosphorylation activates the calcium release channel (ryanodine receptor) in skeletal muscle: defective regulation in heart failure.

The type 1 ryanodine receptor (RyR1) on the sarcoplasmic reticulum (SR) is the major calcium (Ca2+) release channel required for skeletal muscle excitation-contraction (EC) coupling. RyR1 function is modulated by proteins that bind to its large cytoplasmic scaffold domain, including the FK506 binding protein (FKBP12) and PKA. PKA is activated during sympathetic nervous system (SNS) stimulation. We show that PKA phosphorylation of RyR1 at Ser2843 activates the channel by releasing FKBP12. When FKB12 is bound to RyR1, it inhibits the channel by stabilizing its closed state. RyR1 in skeletal muscle from animals with heart failure (HF), a chronic hyperadrenergic state, were PKA hyperphosphorylated, depleted of FKBP12, and exhibited increased activity, suggesting that the channels are "leaky." RyR1 PKA hyperphosphorylation correlated with impaired SR Ca2+ release and early fatigue in HF skeletal muscle. These findings identify a novel mechanism that regulates RyR1 function via PKA phosphorylation in response to SNS stimulation. PKA hyperphosphorylation of RyR1 may contribute to impaired skeletal muscle function in HF, suggesting that a generalized EC coupling myopathy may play a role in HF.

Reversible alopecia associated with high blood mercury levels and early menopause: a report of two cases.

OBJECTIVE: The aim of this study was to report on two women in early menopause with alopecia and high mercury (Hg) levels which reversed with a decrease in toxic levels. METHODS: Retrospective chart review and case studies in a reproductive endocrinology practice. RESULTS: A 43-year-old woman initially evaluated for early menopause later experienced sudden circumscribed hair loss on the scalp. Blood tests indicated elevated Hg levels and further investigation revealed a diet high in tuna. Levels fell with elimination of dietary tuna. Another woman, 39 years old was complaining of severe hot flashes, night sweats, and menstrual irregularity also developed alopecia. Treated unsuccessfully for low testosterone, blood tests indicated high Hg levels and simultaneous hair loss was observed; recommendation to alter diet, including fish intake, was followed by a reversal of alopecia, along with a decrease in blood Hg levels. Literature searches were conducted with a focus on Hg toxicity or poisoning with symptom of alopecia. CONCLUSIONS: Women of reproductive age frequently seek treatment for what is thought to be hormone-related hair loss especially at menopause. Two women demonstrated a strong temporal correlation to high Hg levels associated with early menopause, which was reversible. The development of alopecia in the setting of mild Hg intoxication has not been reported in the medical literature despite its appearance in the popular press. Measurement of Hg levels should be considered in women with alopecia and its relationship to early menopause is unclear but bears further research.