Comparison of illumigene Group A Streptococcus Assay with Culture of Throat Swabs from Children with Sore Throats in the New Zealand School-Based Rheumatic Fever Prevention Program.

Group A streptococcal (GAS) pharyngitis is a particularly important condition in areas of New Zealand where the incidence of acute rheumatic fever remains unacceptably high. Prompt diagnosis and treatment of GAS pharyngitis are cornerstones of the Rheumatic Fever Prevention Programme, but these are hindered by the turnaround time of culture. Tests with excellent performance and rapid turnaround times are needed. For this study, throat swabs (Copan ESwabs) were collected from schoolchildren self-identifying with a sore throat. Samples were tested by routine culture and the illumigene GAS assay using loop-mediated isothermal amplification. Discrepant results were resolved by retesting of the same specimen by an alternative molecular assay. Seven hundred fifty-seven throat swab specimens were tested by both methods. The performance characteristics of the illumigene assay using culture on blood agar as the "gold standard" and following discrepancy analysis were as follows: sensitivity, 82% and 87%, respectively; specificity, 93% and 98%, respectively; positive predictive value, 61% and 88%, respectively; and negative predictive value, 97% and 97%, respectively. In our unique setting of a school-based throat swabbing program, the illumigene assay did not perform quite as well as described in previous reports. Despite this, its improved sensitivity and rapid turnaround time compared with those of culture are appealing.

Intragenomic Conflict over Dispersal.

Intragenomic conflict may arise when social partners are more related through one parent than the other-for example, owing to individuals or gametes of one sex dispersing further prior to fertilization. In particular, genes originating from the former parent are favored to promote selflessness, and those originating from the latter parent are favored to promote selfishness. While the impact of patterns of dispersal on the evolution of intragenomic conflict has received recent attention, the consequences of intragenomic conflict for the evolution of dispersal remain to be explored. We suggest that if the evolution of dispersal is driven at least in part by kin selection, differential relatedness of social partners via their mothers versus their fathers may lead to an intragenomic conflict, with maternal-origin genes and paternal-origin genes favoring different rates of dispersal. As an illustration, we extend a classic model of the evolution of dispersal to explore how intragenomic conflict may arise between an individual's maternal-origin and paternal-origin genes over whether that individual should disperse in order to ease kin competition. Our analysis reveals extensive potential for intragenomic conflict over dispersal and predicts that genes underpinning dispersal phenotypes may exhibit parent-of-origin-specific expression, which may facilitate their discovery.

National Survey of US HIV Clinicians: Knowledge and Attitudes About the Affordable Care Act and Opinions of its Impact on Quality of Care and Barriers to Care.

BACKGROUND: The Affordable Care Act's (ACA's) major reforms started in 2014. In addition to assessing HIV clinicians' ACA knowledge and attitudes, this study aims to evaluate HIV clinicians' perspectives on whether the ACA has impacted the quality of HIV care and whether it addresses the main barriers to HIV care. METHODS: HIV clinicians were emailed a survey weblink in 2018. Descriptive statistics, Mann-Whitney U tests, and binary logistic regression were performed. RESULTS: Of the 211 survey participants, the majority (70%) answered all 4 knowledge questions correctly. About 80% knew correctly whether their state had expanded Medicaid. Participants from Medicaid expansion states were more likely to report an improved ability to provide high-quality care compared with participants from Medicaid nonexpansion states (50% vs 34%; P = .01). The average response to whether the ACA addresses the main barriers to HIV care was neutral and did not differ based on Medicaid status. The top 3 main barriers to HIV care cited were mental health, substance use, and transportation. CONCLUSIONS: HIV clinicians in Medicaid expansion states were more likely to report an improved ability to provide high-quality care since ACA implementation compared with those in Medicaid nonexpansion states. However, HIV clinicians across the United States are concerned that the ACA does not address the main barriers to HIV care. To be successful, the "Ending the HIV Epidemic" initiative should address these identified barriers.

The association between medical spending and health status: A study of selected African countries.

Background: The report from the World Health Organization (WHO) reveals that health spending worldwide remains highly unequal as more than 80% of the world's population live in low and middle-income countries but only account for about 20% of global health expenditure. Another report by the WHO on the state of health financing in Africa published in 2013 intimates that countries that are part of their member states are still on the average level in meeting set goals in financing key health projects. Objective: The study set out to investigate the association between public and private spending and health status for eight selected African countries, namely Burundi, Eritrea, Ethiopia, Kenya, Rwanda, Sudan, Tanzania and Uganda. Health status indicators include the incidence of tuberculosis, mortality rates, maternal deaths and prevalence of HIV. Methods: Descriptive statistics and pairwise correlation are used to assess the relationship between healthcare spending and health status. Random and fixed effect models are further employed to provide insights into the association between descriptive statistics and pairwise correlation. We used annual data from the year 2000 to 2014 obtained from world development indicators. Results: The relationship between healthcare spending (public and private) and health status is statistically significant. Public healthcare expenditure has a higher association than private expenditure in reducing the mortality rate, tuberculosis and HIV for the average country in our sample. For example, an increase in public healthcare spending is negatively associated and statistically significant at 5% or better in reducing female mortality, male mortality, tuberculosis and HIV. Private healthcare spending is more impactful in the area of maternal deaths, where it is associated negatively and statistically significant at 1%. An increase in private healthcare spending is linked to a reduction in maternal deaths. We also compared the association between an increase in healthcare spending on males versus females and observed that public health expenditure impacts the health status of both sexes equally, however, private health expenditure provides a greater positive benefit to males. It is worth remembering that two goals of the United Nations agenda on sustainable development are gender equality and ensuring healthcare for all. Conclusion: The findings of this research call for the selected African countries to pay more attention to public healthcare expenditure in order to improve health status, especially since private healthcare which provides access to healthcare facilities for some poor people leads to costs that are a burden. So, future research should focus on analyzing components of private healthcare spending such as direct household out-of-pocket spending, private insurance and direct service payments by private corporations as dependent variables to understand what form of private investment should be encouraged.

The ideal technique for processing SpyBite tissue specimens: a prospective, single-blinded, pilot-study of histology and cytology techniques.

Background and study aims Diagnostic sensitivity for indeterminate biliary lesions remains suboptimal. Cytology techniques may mitigate the impediment of small cholangioscopic specimens. Our primary aim was to compare cell block cytology (CB) with standard histology for foregut SpyBite (SB) specimens. Our secondary aim was to assess CB in biliary SB biopsies. Patients and methods This was a two-phase prospective pilot study. In phase one, a prospective pilot study, foregut SB specimens from three sites (4 per site per patient per processing technique) were allocated to CB or histology, and assessed by a single, blinded pathologist. The gold standard comprised two standard forceps (CFB) histological specimens per site per patient. Specimen ease of processing, size and number, adequacy for diagnosis and artefact were evaluated. In phase two, CB was used for consecutive patients with indeterminate biliary lesions, and compared with phase one CB results. Results In phase one, 240 SB foregut biopsies were performed in 10 patients, 227 specimens recorded by pathologist. Specimen origin was identified in 100 % and 97 % of histology and CB batches respectively. Specimens were significantly larger in the histology group (2.02 mm vs 1.49 mm, P  < 0.05). There was a trend to less crush artifact with CB, and no difference in processing difficulty. In phase two, 11 patients (63.0 ±12.7 years, 91 % female) underwent SpyGlass (SG) assessment of suspected indeterminate stricture (n = 8) or mass (n = 3), and six underwent SB. All CB specimens were adequate for diagnosis. Specimen parameters were not significantly different from luminal CB outcomes. Conclusions In this pilot study, cell block cytology showed similar results as histological analysis of SpyBite specimens in the analysis of biliary stricture.

Modified UCN2 Peptide Acts as an Insulin Sensitizer in Skeletal Muscle of Obese Mice.

The neuropeptide urocortin 2 (UCN2) and its receptor corticotropin-releasing hormone receptor 2 (CRHR2) are highly expressed in skeletal muscle and play a role in regulating energy balance and glucose metabolism. We investigated a modified UCN2 peptide as a potential therapeutic agent for the treatment of obesity and insulin resistance, with a specific focus on skeletal muscle. High-fat-fed mice (C57BL/6J) were injected daily with a PEGylated UCN2 peptide (compound A) at 0.3 mg/kg subcutaneously for 14 days. Compound A reduced body weight, food intake, whole-body fat mass, and intramuscular triglycerides compared with vehicle-treated controls. Furthermore, whole-body glucose tolerance was improved by compound A treatment, with increased insulin-stimulated Akt phosphorylation at Ser473 and Thr308 in skeletal muscle, concomitant with increased glucose transport into extensor digitorum longus and gastrocnemius muscle. Mechanistically, this is linked to a direct effect on skeletal muscle because ex vivo exposure of soleus muscle from chow-fed lean mice to compound A increased glucose transport and insulin signaling. Moreover, exposure of GLUT4-Myc-labeled L6 myoblasts to compound A increased GLUT4 trafficking. Our results demonstrate that modified UCN2 peptides may be efficacious in the treatment of type 2 diabetes by acting as an insulin sensitizer in skeletal muscle.

Negative feedback regulation of FGF signaling levels by Pyst1/MKP3 in chick embryos.

BACKGROUND: The importance of endogenous antagonists in intracellular signal transduction pathways is becoming increasingly recognized. There is evidence in cultured mammalian cells that Pyst1/MKP3, a dual specificity protein phosphatase, specifically binds to and inactivates ERK1/2 mitogen-activated protein kinases (MAPKs). High-level Pyst1/Mkp3 expression has recently been found at many sites of known FGF signaling in mouse embryos, but the significance of this association and its function are not known. RESULTS: We have cloned chicken Pyst1/Mkp3 and show that high-level expression in neural plate correlates with active MAPK. We show that FGF signaling regulates Pyst1 expression in developing neural plate and limb bud by ablating and/or transplanting tissue sources of FGFs and by applying FGF protein or a specific FGFR inhibitor (SU5402). We further show by applying a specific MAP kinase kinase inhibitor (PD184352) that Pyst1 expression is regulated via the MAPK cascade. Overexpression of Pyst1 in chick embryos reduces levels of activated MAPK in neural plate and alters its morphology and retards limb bud outgrowth. CONCLUSIONS: Pyst1 is an inducible antagonist of FGF signaling in embryos and acts in a negative feedback loop to regulate the activity of MAPK. Our results demonstrate both the importance of MAPK signaling in neural induction and limb bud outgrowth and the critical role played by dual specificity MAP kinase phosphatases in regulating developmental outcomes in vertebrates.

First Presentation Acute Rheumatic Fever is Preventable in a Community Setting: A School-based Intervention.

BACKGROUND: Robust evidence is lacking for community initiatives to prevent first presentation acute rheumatic fever (ARF) by group A streptococcal (GAS) pharyngitis treatment. METHODS: We measured the effect of introducing a sore throat clinic program on first presentation ARF into 61-year 1-8 schools with students 5-13 years of age (population ≈25,000) in Auckland, New Zealand. The study period was 2010-2016. A generalized linear mixed model investigated ARF rate changes before and after the staggered introduction of school clinics. Nurses and lay workers treated culture-proven GAS sore throats (including siblings) with 10 days of amoxicillin. ARF cases were identified from a population-based secondary prophylaxis register. Annual pharyngeal GAS prevalence was assessed in a subset. RESULTS: ARF rates in 5-13 year olds dropped from 88 [95% confidence interval (CI): 79-111] per 100,000 preclinics to 37 (95% CI: 15-83) per 100,000 after 2 years of clinic availability, a 58% reduction. No change in rate was demonstrated before the introduction of clinics [P = 0.88; incidence risk ratio for a 1-year change: 0.98 (95% CI: 0.63-1.52)], but there was a significant decrease of first presentation ARF rates with time after the introduction of the sore throat program [P = 0.008; incidence risk ratio: 0.61 (95% CI: 0.43-0.88)]. Pharyngeal GAS cross-sectional prevalence fell from 22.4% (16.5-30.5) preintervention to 11.9% (8.6-16.5) and 11.4% (8.2-15.7) 1 or 2 years later (P = 0.005). CONCLUSIONS: ARF declined significantly after school-based GAS pharyngitis management using oral amoxicillin paralleled by a decline in pharyngeal GAS prevalence.

Negative feedback predominates over cross-regulation to control ERK MAPK activity in response to FGF signalling in embryos.

Expression of the gene encoding the MKP-3/Pyst1 protein phosphatase, which inactivates ERK MAPK, is induced by FGF. However, which intracellular signalling pathway mediates this expression is unclear, with essential roles proposed for both ERK and PI(3)K in chick embryonic limb. Here, we report that MKP-3/Pyst1 expression is sensitive to inhibition of ERK or MAPKK, that endogenous MKP-3/Pyst1 co-localizes with activated ERK, and expression of MKP-3/Pyst1 in mice lacking PDK1, an essential mediator of PI(3)K signalling. We conclude that MKP-3/Pyst1 expression is mediated by ERK activation and that negative feedback control predominates in limiting the extent of FGF-induced ERK activity.

Expression of csal1 in pre limb-bud chick embryos.

The spalt family of transcriptional repressors has been implicated in limb, heart, ear and kidney development and truncating mutations in a human gene, SALL1, result in the autosomal dominant disorder Townes-Brocks syndrome. Here we show the expression pattern of the chick orthologue of the SALL1 gene, csal1, during early development. We found csal1 expression in the heart and in the pharynx, a source of inductive signals during heart development. Expression was also seen in involuting mesoderm and later in presegmented paraxial mesoderm. We also describe expression in the ectoderm and neural plate of the early embryo and subsequent expression in the neural tube.

Nurse-led school-based clinics for rheumatic fever prevention and skin infection management: evaluation of Mana Kidz programme in Counties Manukau.

AIM: To evaluate registered nurse-led school clinics in 61 primary and intermediate schools in Counties Manukau. METHODS: The evaluation (conducted August­December, 2014) collated evidence concerning service delivery, outcomes, value for money and effectiveness. RESULTS: 97% (23,756/24,497) of eligible children were consented, 11% (20,696/191,423) of throat swabs taken (February 2013­September 2014) were culture positive for Group A Streptococcus (GAS); 20,176 were treated. Mana Kidz teams treated (includes cleaning and covering alone) 17,593 skin infections and actioned 4,178 school health referrals. A pre-programme cross sectional GAS pharyngeal prevalence demonstrated a relative risk 1.8 (1.3­2.3) (95%CI) of being pharyngeal GAS positive in 2013 compared to 2014. Hospitalisations for acute rheumatic fever (ARF) and skin infections for children aged 5­12 years living in Counties Manukau are declining and this appears to be temporally related to the introduction of the Mana Kidz programme. Effective engagement with children, parents/ whanau and improved health literacy was demonstrated, especially knowledge about sore throats, ARF, medication adherence and skin infection. The programme was delivered at $280 per participating child in the 2013/14 financial year. CONCLUSION: Mana Kidz is an effective programme with a substantial contribution to health care for children, aged 5­12 years, identified at increased risk of poor health outcomes.

Medical choices available for management of menopause.

The indications for hormone therapy (HT) have changed markedly since the 1980s; they now include the treatment of menopausal symptoms and the prevention and treatment of osteoporosis in the short term. Long-term therapy is discouraged because of the small increase in risk of breast cancer after 5 years of therapy. Careful assessment of the midlife woman allows for individualized risk-benefit analysis with the formulation of a specific health management plan. Lifestyle advice and modification form the cornerstone of management-followed by therapeutic options if appropriate indications exist. In some industrialized countries alternative therapies are preferred despite little scientific evidence of their efficacy. The choices of hormonal products have increased, with the introduction of new formulations and routes of administration allowing for more optimal treatment of the menopause, especially in the presence of concurrent medical conditions, for example, diabetes, breast cancer or fibroids.

Dysfunctional uterine bleeding.

BACKGROUND: Dysfunctional uterine bleeding (DUB) is the major cause of heavy menstrual bleeding and impacts on women's health both medically and socially. OBJECTIVE: This article reviews the management of DUB. DISCUSSION: Dysfunctional uterine bleeding is defined as heavy menstrual uterine bleeding not due to any recognisable cause and is therefore a diagnosis of exclusion. Other conditions such as uterine fibroids, endometrial polyps and systemic diseases should be excluded by appropriate investigations. In the adolescent, investigations for a coagulopathy should be performed. The pathophysiology of DUB is largely unknown but occurs in both ovulatory and anovulatory menstrual cycles. Medical treatments include nonsteroidal anti-inflammatory drugs or antiprostaglandins, tranexamic acid, the progestogen releasing intrauterine device, combined oral contraceptive pills, and other hormonal therapies. As no medical treatment is superior to another, each woman should be individually assessed as to appropriate management. Surgical treatments include endometrial ablation and hysterectomy.

Premature menopause. 'I feel like an alien'.

BACKGROUND: Those women who experience premature menopause require special needs as the consequences to their health, physically and emotionally, both in the immediate and the long term are more significant. OBJECTIVE: To present a management and treatment profile. DISCUSSION: The incidence of spontaneous premature menopause is approximately 1% of women under 40 years with an increase up to 8-10% when menopause is the consequence of gynaecological surgery, chemotherapy and radiotherapy. Diagnosis is often delayed. Careful investigation should occur over a number of months to confirm the diagnosis. Sensitive discussion of the diagnosis and management in a supportive manner will help the young woman to adjust to the menopause and accept appropriate hormonal therapy. Many other issues, including emotional, sexual, reproductive, societal and relationships may also need help.

Menopause forum--a case discussion on midlife issues.

The authors of our theme articles this month discuss their approach to the assessment and management of a woman presenting with issues relating to menopause and midlife.

Nurse-led school-based clinics for skin infections and rheumatic fever prevention: results from a pilot study in South Auckland.

AIM: To assess the acceptability and feasibility of delivering targeted primary health care in a decile one primary school setting. METHOD: A pilot public health nurse (PHN)-led clinic was set up in a South Auckland primary school (roll approximately 400). The clinic was based on a previous sore throat clinic model with modifications aimed at improving programme feasibility and effectiveness. The timely identification and treatment of Group A Streptococcal (GAS) throat infections to prevent rheumatic fever (RF), and the prevention and treatment of four skin infections (cellulitis, impetigo, infected eczema and scabies) were the focus. The pilot ran for 15 weeks from April to July 2011. Evaluation included documentation review, key school and healthcare stakeholder interviews and parent questionnaires. RESULTS: The consent rate was 92.2%. Of a total 722 throat swabs taken from 337 students, 94 were GAS positive. Ninety-eight assessments of skin conditions were completed at which 76 had a skin infection diagnosed, the most common infection being impetigo (n=46). Thirty-one skin infections were diagnosed in the first week of the pilot. PHN workload was high with a total of 539 phone calls, 137 home visits and 51 school-based parent consultations. The approach was highly acceptable to the majority of key stakeholders. Extrapolating pilot costs results in an estimated annual cost of $510 per student for the programme. CONCLUSION: It is likely to be both acceptable and feasible to take this model of delivering targeted primary health care to school aged children and use it on a larger scale. The complexity of providing this type of service should not be underestimated and it is essential that robust processes are in place to ensure smooth, safe running of such a programme. Long-term outcome evaluation will be vital to assess programme effectiveness.

Registered nurse assessment and treatment of skin sepsis in New Zealand schools: the development of protocols.

BACKGROUND: Skin infection is the commonest medical cause of hospitalisation in school children. Disadvantaged children, usually Maori or Pacific, have high rates of preventable diseases. AIM: To improve access to early treatment for skin infections using nurse-led school clinics in South Auckland, including provision of antibiotics under delegated standing orders. METHOD: Evidence-based protocols for the recognition and treatment of skin sepsis were developed following a literature search. A training package was developed for health professionals involved and outcome data were collected from a pilot study in which the protocols were trialled. RESULTS: An algorithm for diagnosis of skin infections was adapted from Steer et al (Bull World Health Organ. 2009;87:173-9). Fusidic acid ointment was recommended as first-line treatment for localised impetigo. Twice daily oral cephalexin was recommended for extensive impetigo and cellulitis, for palatability and simplicity of dosing. Fifty-six episodes of skin infection received treatment under standing orders in the first 15 weeks of the pilot study. CONCLUSION: Robust evidence to determine optimal choice, dosage and duration of antibiotic therapy for skin sepsis in children is lacking. The algorithms described are consistent with available evidence and provide a pragmatic approach for use in registered nurse (RN)-led school clinics.

Measuring faculty retention and success in academic medicine.

PURPOSE: To develop and demonstrate the usefulness of quantitative methods for assessing retention and academic success of junior faculty in academic medicine. METHOD: The authors created matched sets of participants and nonparticipants in a junior faculty development program based on hire date and academic series for newly hired assistant professors at the University of California, San Diego (UCSD), School of Medicine between 1988 and 2005. They used Kaplan-Meier and Cox proportional hazards survival analyses to characterize the influence of covariates, including gender, ethnicity, and program participation, on retention. They also developed a new method for quantifying academic success based on several measures including (1) leadership and professional activities, (2) honors and awards, (3) research grants, (4) teaching and mentoring/advising activities, and (5) publications. The authors then used these measures to compare matched pairs of participating and nonparticipating faculty who were subsequently promoted and remained at UCSD. RESULTS: Compared with matched nonparticipants, the retention of junior faculty who participated in the faculty development program was significantly higher. Among those who were promoted and remained at UCSD, the academic success of faculty development participants was consistently greater than that of matched nonparticipants. This difference reached statistical significance for leadership and professional activities. CONCLUSIONS: Using better quantitative methods for evaluating retention and academic success will improve understanding and research in these areas. In this study, use of such methods indicated that organized junior faculty development programs have positive effects on faculty retention and may facilitate success in academic medicine.

Improving the discharge process by embedding a discharge facilitator in a resident team.

BACKGROUND: Hospital discharges are vulnerable periods for patient safety, especially in teaching hospitals where discharges are done by residents with competing demands. We sought to assess whether embedding a nurse practitioner on a medical team to help physicians with the discharge process would improve communication, patient follow-up, and hospital reutilization. METHODS: A 5-month randomized controlled trial was conducted on the medical service at an academic tertiary-care hospital. A nurse practitioner was randomly assigned to 1 resident team to complete discharge paperwork, arrange follow-up appointments and prescriptions, communicate discharge plans with nursing and primary care physicians, and answer questions from discharged patients. RESULTS: Intervention patients had more discharge summaries completed within 24 hours (67% vs. 47%, P < 0.001). Similarly, they had more follow-up appointments scheduled by the time of discharge (62% vs. 36%, P < 0.0001) and attended those appointments more often within 2 weeks (36% vs. 23%, P < 0.0002). Intervention patients knew whom to call with questions (95% vs. 85%, P = 0.003) and were more satisfied with the discharge process (97% vs. 76%, P < 0.0001). Attending rounds on the intervention team finished on time (45% vs. 31%, P = 0.058), and residents signed out on average 46 minutes earlier each day. There was no significant difference between the groups in 30-day emergency department visits or readmissions. CONCLUSIONS: Helping resident physicians with the discharge process improves many aspects of discharge communication and patient follow-up, and saves residents' time, but had no effect on hospital reutilization for a general medicine population.