Public Health Expenditures and Clinical and Social Complexity of Tuberculosis Cases-Alameda County, California, July-December 2017.

CONTEXT: Alameda County, California, is a high tuberculosis (TB) burden county that reported a TB incidence rate of 8.1 per 100 000 during 2017. It is the only high TB burden California county that does not have a public health-funded TB clinic. OBJECTIVE: To describe TB public health expenditures and clinical and social complexities of TB case-patients. DESIGN, SETTING, AND PARTICIPANTS: Public health surveillance of confirmed and possible TB case-patients reported to Alameda County Public Health Department during July 1, 2017, to December 31, 2017. Social complexity status was categorized for all case-patients using surveillance data; clinical complexity status, either by surveillance definition or by the Charlson Comorbidity Index (CCI), was categorized only for confirmed TB case-patients. MAIN OUTCOME MEASURES: Total public health and per patient expenditures were stratified by insurance status. Cohen's kappa assessed concordance between clinical complexity definitions. All comparisons were conducted using Fisher's exact or Kruskal-Wallis tests. RESULTS: Of 81 case-patients reported, 68 (84%) had confirmed TB, 29 (36%) were socially complex, and 15 (19%) were uninsured. Total public health expenditures were $487 194, and 18% of expenditures were in nonlabor domains, 57% of which were for TB treatment, diagnostics, and insurance, with insured patients also incurring such expenditures. Median per patient expenditures were significantly higher for uninsured and government-insured patients than for privately insured patients ($7007 and $5045 vs $3704; P = .03). Among confirmed TB case-patients, 72% were clinically complex by surveillance definition and 53% by the CCI; concordance between definitions was poor (κ = 0.25; 95% confidence interval, 0.03-0.46). CONCLUSIONS: Total public health expenditures approached $500 000. Most case-patients were clinically complex, and about 20% were uninsured. While expenditures were higher for uninsured case-patients, insured case-patients still incurred TB treatment, diagnostic, and insurance-related expenditures. State and local health departments may be able to use our expenditure estimates by insurance status and description of clinically complex TB case-patients to inform efforts to allocate and secure adequate funding.

Multidrug-Resistant Infections in the Developing World.

Antimicrobials are essential in reducing morbidity and mortality from infectious diseases globally. However, due to the lack of effective surveillance measures and widespread overuse, there is an increasing threat to the effectiveness of antimicrobials. Although there is a global increase in antimicrobial resistance, low- and middle-income countries share a much higher burden. Antimicrobial stewardship efforts such as effective surveillance and reduction in overuse can help combat the increase in antimicrobial resistance.

Relationship between neighborhood census-tract level socioeconomic status and respiratory syncytial virus-associated hospitalizations in U.S. adults, 2015-2017.

BACKGROUND: Respiratory syncytial virus (RSV) infection causes substantial morbidity and mortality in children and adults. Socioeconomic status (SES) is known to influence many health outcomes, but there have been few studies of the relationship between RSV-associated illness and SES, particularly in adults. Understanding this association is important in order to identify and address disparities and to prioritize resources for prevention. METHODS: Adults hospitalized with a laboratory-confirmed RSV infection were identified through population-based surveillance at multiple sites in the U.S. The incidence of RSV-associated hospitalizations was calculated by census-tract (CT) poverty and crowding, adjusted for age. Log binomial regression was used to evaluate the association between Intensive Care Unit (ICU) admission or death and CT poverty and crowding. RESULTS: Among the 1713 cases, RSV-associated hospitalization correlated with increased CT level poverty and crowding. The incidence rate of RSV-associated hospitalization was 2.58 (CI 2.23, 2.98) times higher in CTs with the highest as compared to the lowest percentages of individuals living below the poverty level (≥ 20 and < 5%, respectively). The incidence rate of RSV-associated hospitalization was 1.52 (CI 1.33, 1.73) times higher in CTs with the highest as compared to the lowest levels of crowding (≥5 and < 1% of households with > 1 occupant/room, respectively). Neither CT level poverty nor crowding had a correlation with ICU admission or death. CONCLUSIONS: Poverty and crowding at CT level were associated with increased incidence of RSV-associated hospitalization, but not with more severe RSV disease. Efforts to reduce the incidence of RSV disease should consider SES.

Pyogenic Arthritis.

The incidence of septic arthritis among children in developed countries is estimated to be 4 to 10 cases per 100,000 children per year, peaking at about age 3 years. The most common causative organism is Staphylococcus aureus, although the microbiology varies by age. Prompt diagnosis and treatment is critical to prevent long-term sequelae. Empiric therapy should target the most likely causative organism(s) and total duration generally falls between 10 days and 4 weeks depending on clinical course, patient age, and organism. A short intravenous course is sufficient in most cases. Unusual and alternate causes of arthritis should be considered in special cases. [Pediatr Ann. 2019;48(9):e354-e359.].

A complex regulatory network coordinating cell cycles during C. elegans development is revealed by a genome-wide RNAi screen.

The development and homeostasis of multicellular animals requires precise coordination of cell division and differentiation. We performed a genome-wide RNA interference screen in Caenorhabditis elegans to reveal the components of a regulatory network that promotes developmentally programmed cell-cycle quiescence. The 107 identified genes are predicted to constitute regulatory networks that are conserved among higher animals because almost half of the genes are represented by clear human orthologs. Using a series of mutant backgrounds to assess their genetic activities, the RNA interference clones displaying similar properties were clustered to establish potential regulatory relationships within the network. This approach uncovered four distinct genetic pathways controlling cell-cycle entry during intestinal organogenesis. The enhanced phenotypes observed for animals carrying compound mutations attest to the collaboration between distinct mechanisms to ensure strict developmental regulation of cell cycles. Moreover, we characterized ubc-25, a gene encoding an E2 ubiquitin-conjugating enzyme whose human ortholog, UBE2Q2, is deregulated in several cancers. Our genetic analyses suggested that ubc-25 acts in a linear pathway with cul-1/Cul1, in parallel to pathways employing cki-1/p27 and lin-35/pRb to promote cell-cycle quiescence. Further investigation of the potential regulatory mechanism demonstrated that ubc-25 activity negatively regulates CYE-1/cyclin E protein abundance in vivo. Together, our results show that the ubc-25-mediated pathway acts within a complex network that integrates the actions of multiple molecular mechanisms to control cell cycles during development.

Control of Cdc14 activity coordinates cell cycle and development in Caenorhabditis elegans.

Much of our understanding of the function and regulation of the Cdc14 family of dual-specificity phosphatases originates from studies in yeasts. In these unicellular organisms Cdc14 is an important regulator of M-phase events. In contrast, the Caenorhabditis elegans homolog, cdc-14, is not necessary for mitosis, rather it is crucial for G(1)/S regulation to establish developmental cell-cycle quiescence. Despite the importance of integrating cdc-14 regulation with development, the mechanisms by which this coordination occurs are largely unknown. Here, we demonstrate that several processes conspire to focus the activity of cdc-14. First, the cdc-14 locus can produce at least six protein variants through alternative splicing. We find that a single form, CDC-14C, is the key variant acting during vulva development. Second, CDC-14C expression is limited to a subset of cells, including vulva precursors, through post-transcriptional regulation. Lastly, the CDC-14C subcellular location, and thus its potential interactions with other regulatory proteins, is regulated by nucleocytoplasmic shuttling. We find that the active export of CDC-14C from the nucleus during interphase is dependent on members of the Cyclin D and Crm1 families. We propose that these mechanisms collaborate to restrict the activity of cdc-14 as central components of an evolutionarily conserved regulatory network to coordinate cell-cycle progression with development.