Considering equity in priority setting using transmission models: Recommendations and data needs.

OBJECTIVES: Disease transmission models are used in impact assessment and economic evaluations of infectious disease prevention and treatment strategies, prominently so in the COVID-19 response. These models rarely consider dimensions of equity relating to the differential health burden between individuals and groups. We describe concepts and approaches which are useful when considering equity in the priority setting process, and outline the technical choices concerning model structure, outputs, and data requirements needed to use transmission models in analyses of health equity. METHODS: We reviewed the literature on equity concepts and approaches to their application in economic evaluation and undertook a technical consultation on how equity can be incorporated in priority setting for infectious disease control. The technical consultation brought together health economists with an interest in equity-informative economic evaluation, ethicists specialising in public health, mathematical modellers from various disease backgrounds, and representatives of global health funding and technical assistance organisations, to formulate key areas of consensus and recommendations. RESULTS: We provide a series of recommendations for applying the Reference Case for Economic Evaluation in Global Health to infectious disease interventions, comprising guidance on 1) the specification of equity concepts; 2) choice of evaluation framework; 3) model structure; and 4) data needs. We present available conceptual and analytical choices, for example how correlation between different equity- and disease-relevant strata should be considered dependent on available data, and outline how assumptions and data limitations can be reported transparently by noting key factors for consideration. CONCLUSIONS: Current developments in economic evaluations in global health provide a wide range of methodologies to incorporate equity into economic evaluations. Those employing infectious disease models need to use these frameworks more in priority setting to accurately represent health inequities. We provide guidance on the technical approaches to support this goal and ultimately, to achieve more equitable health policies.

Treatment success after rhinosurgery: an evaluation of subjective and objective parameters.

PURPOSE: Septal deviation and nose deformities are widely prevalent. As a consequence, patients may complain about difficulties in nasal breathing leading to a perception of diminished disease-specific quality of life. In a prospective randomized trial, we aimed to analyse the outcome of septoplasty (SPL) and septorhinoplasty (SRP) on patient satisfaction. METHODS: Patients with functional indication for SPL (n = 19) or SRP (n = 54) were included and randomized for additional turbinoplasty. Preoperative clinical symptoms were collected with SNOT-20 GAV (Sinu-nasal outcome test-20-German adapted version) and NOSE© (nasal obstruction symptom evaluation) questionnaires. The final evaluation of treatment success was performed 9 months after surgery with SNOT-20 GAV, NOSE© and a self-established feedback questionnaire. Nasal breathing and obstruction were objectively measured with rhinomanometry and acoustic rhinometry [minimum cross-sectional area 2 (MCA2)]. RESULTS: Minimum cross-sectional area 2 was statistically improved compared to the pre-treatment value in SPL (p = 0.0004) and SRP (p = 0.0001). Regarding MCA2 values of matched patient groups, similar findings were detected (SPL: p = 0.0013, SRP: p < 0.0001). Sinu-nasal outcome test-20 GAV and NOSE© scores were significantly reduced after both surgical procedures (NOSE©: SPL: p < 0.0001, SRP: p < 0.0001; SNOT-20 GAV: SPL: p = 0.0068, SRP: p < 0.0001). Evaluation of patient satisfaction in a self-established feedback questionnaire revealed a motivation of 81% of patients to redo the surgery (SPL 13/16, SRP 34/42) and a notably general satisfaction of 86% for SPL and 80% for SRP. CONCLUSION: Rhinosurgery leads to quantitative better nasal breathing and increased disease-specific satisfaction. However, this study implies the importance of the right selection of patients and the correct indication of the surgical technique.

Community-based health workers implementing universal access to HIV testing and treatment: lessons from South Africa and Zambia-HPTN 071 (PopART).

The global expansion of HIV testing, prevention and treatment services is necessary to achieve HIV epidemic control and promote individual and population health benefits for people living with HIV (PLHIV) in sub-Saharan Africa. Community-based health workers (CHWs) could play a key role in supporting implementation at scale. In the HPTN 071 (PopART) trial in Zambia and South Africa, a cadre of 737 study-specific CHWs, working closely with government-employed CHW, were deployed to deliver a 'universal' door-to-door HIV prevention package, including an annual offer of HIV testing and referral services for all households in 14 study communities. We conducted a process evaluation using qualitative and quantitative data collected during the trial (2013-2018) to document the implementation of the CHW intervention in practice. We focused on the recruitment, retention, training and support of CHWs, as they delivered study-specific services. We then used these descriptions to: (i) analyse the fidelity to design of the delivery of the intervention package, and (ii) suggest key insights for the transferability of the intervention to other settings. The data included baseline quantitative data collected with the study-specific CHWs (2014-2018); and qualitative data from key informant interviews with study management (n = 91), observations of CHW training events (n = 12) and annual observations of and group discussions (GD) with intervention staff (n = 68). We show that it was feasible for newly recruited CHWs to implement the PopART intervention with good fidelity, supporting the interpretation of the trial outcome findings. This was despite some challenges in managing service quality and CHW retention in the early years of the programme. We suggest that by prioritizing the adoption of key elements of the in-home HIV services delivery intervention model-including training, emotional support to workers, monitoring and appropriate remuneration for CHWs-these services could be successfully transferred to new settings.

Value of turbinoplasty in rhinosurgery - a controlled randomized study.

BACKGROUND: Turbinoplasty is a common procedure in patients with nasal obstruction and hypertrophy of the nasal turbinates. A general recommendation regarding the necessity of turbinoplasty in functional rhinosurgery is still missing. For the first time, the value of turbinoplasty in septo- and septorhinoplasty regarding patient satisfaction as well as objective data in rhinomanometry and acoustic rhinometry was analyzed in a prospective randomized controlled trial. METHODOLOGY: 73 patients with nasal obstruction due to septal deviation and / or a deviated nose were included in the study. After randomization, anterior turbinoplasty was or was not performed during septo- or septorhinoplasty. Pre- and postoperative rhinomanometry and acoustic rhinometry were accomplished. NOSE© and SNOT 20 questionnaires were completed by the patients before and 9 months after surgery. Additionally, the patients were asked about their subjective satisfaction. RESULTS: 81% of the patients were subjectively satisfied with the postoperative improvement of nasal breathing. There was a significant improvement in the values of NOSE© and SNOT 20 questionnaires with no relevant difference between the two study groups. Acoustic rhinometry and rhinomanometry showed values in MCA1 and 2, Vol 1 and Vol 2 as well as higher nasal flows with no statistically significant difference between the two study groups. CONCLUSIONS: Patient satisfaction after functional septo- and septorhinoplasty is high and does not seem to be affected by turbinate surgery. There was no statistically significant difference in the postoperative results regarding objective rhinological measurements with or without turbinoplasty. As extensive resections of the turbinates can have a negative impact on nasal physiology, the indication for turbinoplasty must be considered carefully.

How can we evaluate the cost-effectiveness of health system strengthening? A typology and illustrations.

Health interventions often depend on a complex system of human and capital infrastructure that is shared with other interventions, in the form of service delivery platforms, such as healthcare facilities, hospitals, or community services. Most forms of health system strengthening seek to improve the efficiency or effectiveness of such delivery platforms. This paper presents a typology of ways in which health system strengthening can improve the economic efficiency of health services. Three types of health system strengthening are identified and modelled: (1) investment in the efficiency of an existing shared platform that generates positive benefits across a range of existing interventions; (2) relaxing a capacity constraint of an existing shared platform that inhibits the optimization of existing interventions; (3) providing an entirely new shared platform that supports a number of existing or new interventions. Theoretical models are illustrated with examples, and illustrate the importance of considering the portfolio of interventions using a platform, and not just piecemeal individual analysis of those interventions. They show how it is possible to extend principles of conventional cost-effectiveness analysis to identify an optimal balance between investing in health system strengthening and expenditure on specific interventions. The models developed in this paper provide a conceptual framework for evaluating the cost-effectiveness of investments in strengthening healthcare systems and, more broadly, shed light on the role that platforms play in promoting the cost-effectiveness of different interventions.

Priorities for action on the social determinants of health: Empirical evidence on the strongest associations with life expectancy in 54 low-income countries, 1990-2012.

The WHO Commission on the Social Determinants of Health set out an impressive collection of policy proposals on the social determinants of health. However, a serious weakness for securing implementation is the difficulty for policymakers in identifying priorities for action. The objective of this study is to determine a small set of the most influential determinants using existing data and an empirical approach. 45 Indicators from the World Bank's World Development Indicators are selected to measure attainment for the determinants proposed by the Commission. Panel data models of life expectancy at birth for 54 low-income countries over the years 1990-2012 (1188 country-years) are estimated. Each determinant is subjected to a robustness test using Extreme Bound Analysis, to determine the stability of its estimated impact on life expectancy. For 20 robust and significant determinants the magnitude of association with life expectancy is determined. The largest average increases in life expectancy at 14.5 months per capita is associated with a one standard deviation reduction in HIV prevalence among children, followed by advances in gender equality at 9.4 months. Improvements in life expectancy between 6 and 9 months are associated with agricultural production, political stability, access to clean water and sanitation, good governance, and primary school enrolment. Improvements below 6 months are associated with increases in private health expenditure and overseas development assistance, and control of armed conflict and HIV prevalence among men. There is no evidence that national income, public spending on healthcare and education, secondary schooling, terms of international trade, employment, debt service and relief, out-of-pocket expenditures, agricultural ex- or imports, lifestock production, foreign investment, urbanization or environmental degradation are robustly associated with population health. Results provide support for the relevance of some proposed policies. The findings can inform priorities for future research and policy action on the social determinants of health.

Full genome ultra-deep pyrosequencing associates G-to-A hypermutation of the hepatitis B virus genome with the natural progression of hepatitis B.

Human APOBEC3 (A3) cytosine deaminases are antiviral restriction factors capable of editing the genome the hepatitis B virus (HBV). Despite the importance of the human A3 protein family for the innate immune response little is known about the clinical relevance for hepatitis B. The aim of this study was to utilize ultra-deep pyrosequencing (UDPS) data to analyse the phenomenon of G-to-A hypermutation of the complete HBV genome and to relate it to fundamental characteristics of patients with chronic hepatitis B. By analysing the viral population of 80 treatment naïve patients (47 HBeAg-positive and 33 HBeAg-negative), we identified an unequal distribution of G-to-A hypermutations across the genome. Our data indicate that G-to-A hypermutation occurs predominantly in a region between nucleotide positions 600 and 1800 a region which is usually single stranded in matured HBV particles. This implies that A3 likely edits HBV in the virion. Hypermutation rates for HBeAg-negative patients were more than 10-fold higher than those of HBeAg-positive patients. For HBeAg-negative patients higher hypermutation rates were significantly associated with the degree of fibrosis. Additionally, we found that for HBeAg-positive chronic hepatitis G-to-A hypermutation rates were significantly associated with the relative prevalence of the G1764A mutation, which is related to HBeAg seroconversion. In total, our data imply an important association of hypermutation mediated by A3 deaminases with the natural progression of chronic hepatitis B infections both in terms of HBeAg seroconversion and disease progression towards cirrhosis.

Employment, work hours and weight gain among middle-aged women.

OBJECTIVE: To investigate the influence of employment and work hours on weight gain and weight loss among middle-aged women. DESIGN: Quantile regression techniques were used to estimate the influence of employment and hours worked on percentage weight change over 2 years across the entire distribution of weight change in a cohort of middle-aged women. A range of controls was included in the models to isolate the effect of work status. SUBJECTS: A total of 9276 women aged 45-50 years at baseline who were present in both the 1996 and 1998 surveys of the Australian Longitudinal Study of Women's Health. The women were a representative sample of the Australian population. RESULTS: Being out of the labour force or unemployed was associated with lower weight gain and higher weight loss than being employed. The association was stronger at low to moderate levels of weight gain. Among employed women, working regular (35-40), long (41-48) or very long (49+) hours was associated with increasingly higher levels of weight gain compared with working part-time hours. The association was stronger for women with greater weight gain overall. The association between unemployment and weight change became insignificant when health status was controlled for. CONCLUSIONS: Employment was associated with more weight gain and less weight loss. Among the employed, working longer hours was associated with more weight gain, especially at the higher levels of weight gain where the health consequences are more serious. These findings suggest that as women work longer hours they are more likely to make lifestyle choices that are associated with weight gain.

Response to interferon alfa is hepatitis B virus genotype dependent: genotype A is more sensitive to interferon than genotype D.

BACKGROUND AND AIMS: Current interferon alfa (IFN) treatment of chronic hepatitis B has limited efficacy. The role of hepatitis B virus (HBV) genotypes for response to IFN was investigated. PATIENTS AND METHODS: HBV genotype was determined by direct sequencing of the HBV X gene in 165 consecutive patients with chronic replicative hepatitis B treated with standard IFN. HBV genotype A or D was found in 144 cases. RESULTS: Sustained response (six months after treatment) to standard IFN therapy was higher in HBV genotype A compared with HBV genotype D infected patients (49% v 26%; p<0.005). Sustained response to IFN was 46% versus 24% (p<0.03) in hepatitis B e antigen (HBeAg) positive hepatitis (n = 99) and 59% versus 29% (p<0.05) in HBeAg negative hepatitis (n = 45) for HBV genotype A compared with HBV genotype D. HBeAg status had no negative impact on IFN response. Multivariate logistic regression identified HBV genotype A and high pretreatment alanine aminotransferase levels (>2 x upper limit of normal) as independent positive predictive parameters of IFN response. CONCLUSIONS: The present study indicates that HBV genotypes A and D are important and independent predictors of IFN responsiveness in chronic hepatitis B. HBV genotype adapted treatment regimens may further improve treatment efficacy in chronic hepatitis B.

Diagnostic impact of cerebral transit time in the identification of microangiopathy in dementia: A transcranial ultrasound study.

BACKGROUND AND PURPOSE: The diagnosis and quantification of microangiopathy in dementia is difficult. The assessment of small-vessel disease requires expensive and sophisticated nuclear medicine techniques. This study was performed to identify microangiopathy related to the integrity of cerebral microcirculation by sonographic measurements (arteriovenous cerebral transit time [cTT]). METHODS: We performed transcranial color-coded duplex sonography in 40 patients with vascular dementia, 20 patients with Alzheimer's disease or Lewy body disease, and 25 age-matched controls. The clinical diagnosis was established by history of dementia and neuroimaging findings. Cognitive impairment was assessed by the Mini-Mental State Examination and Alzheimer's Disease Assessment Scale. cTT is defined as the time required by an ultrasound contrast agent to pass from a cerebral artery to a vein. This was measured by recording the power-Doppler intensity curves in the P2 segment of the posterior cerebral artery and the vein of Galen. Previous studies have shown a prolongation of cTT in patients with cerebral microangiopathy. RESULTS: cTT was substantially prolonged in patients with vascular dementia (5.8 seconds; 25th percentile 4.5; 75th percentile 7.5; U test, P<0.001) compared with controls (3.1 seconds; 2.3; 3.4) but not in patients with degenerative dementia (3.7 seconds; 3.7; 4.2). In patients with vascular dementia, cTT was significantly correlated with cognitive impairment. CONCLUSIONS: cTT may be useful tool to disclose small-vessel disease in demented patients. Examination is noninvasive and quickly performed. It may be also useful in follow-up examinations in patients undergoing therapy.

Experience with two types of electromyography monitoring electrodes during thyroid surgery.

PURPOSE: To prevent damage to the recurrent laryngeal nerve during thyroid or parathyroid surgery, spontaneous and evoked electromyography (EMG) can be used to locate the recurrent laryngeal nerve or determine when the nerve is being disturbed. Two commercial electrodes have been introduced to receive laryngeal EMG. This study compares the clinical performance of the two electrodes. PATIENTS AND METHODS: The Xomed-Treace endotracheal tube electrode (Xomed-Treace, Jacksonville, FL) and the RLN postcricoid laryngeal electrode (RLN Systems, Jefferson City, MO) were placed concomitantly in 11 patients during 14 surgical procedures. RESULTS: The RLN electrode provided feedback as to placement by providing a heart-beat artifact. The RLN electrode was found to be both more sensitive and more electrically noisy. On stimulation, the Xomed tube electrode produced generally higher EMG amplitudes, perhaps because of the different muscles they monitor. In one case, the Xomed tube failed to provide-EMG responses. Only at low electrical stimulation intensities could left and right vocalis muscles be identified with the Xomed tube. A laryngologist was needed to place the RLN electrode, whereas the attending anesthesiologist was able to place the Xomed tube. CONCLUSION: Both electrodes provided useful EMG information and helped confirm the location of the recurrent laryngeal nerve. Who will place the electrode, tumors extrinsic or intrinsic to the larynx, cost, and size requirements should be considered when choosing an electrode.

[Fluoride excretion in schoolchildren with differing systemic fluoride care]. / Fluoridausscheidung bei Schülern mit unterschiedlicher systemischer Fluoridversorgung.

The aim of the present study was to collect data on urinary fluoride output in 8-16-year old students exposed to either drinking water fluoridation (DWF), or domestic salt fluoridation (DSF). Spot urine samples were collected in the canton of Basel-Stadt (DWF, n = 123), in the canton of Berne (DSF, n = 264), in the county of Davos (DSF, n = 241), and in the city of Winterthur (DSF, n = 40). Furthermore, fluoride concentrations were determined in plasma samples drawn from 33 students from Winterthur. The urinary fluoride concentrations were higher in Basel and Davos (0.62 +/- 0.35 mg/l; 0.61 +/- 0.42 mg/l) than in Berne and Winterthur (0.46 +/- 0.42 mg/l; 0.50 +/- 0.31 mg/l). A relatively high natural fluoride content (0.3 mg/l) in the drinking water explained the difference in urine fluoride concentration between students from Davos and the two other regions with domestic salt fluoridation (Berne, Winterthur). The average fluoride concentration in plasma was 12.7 +/- 3.8 ng/ml. We concluded that, in general, the supply with fluoride consumed with fluoridated domestic salt is close to the level obtained with drinking water fluoridation. However, in areas with very low systemic fluoride supplementation through the drinking water this level might not be reached with salt as the only source of systemic fluoride. Also, the data confirmed the safety of domestic salt fluoridation.

Multimodality therapy for unresectable squamous cell carcinoma of the head and neck.

Eighteen patients with unresectable Stage III or IV squamous cell carcinoma of the head and neck were treated with induction therapy consisting of sequential methotrexate and 5-fluorouracil. This was followed by full course radiation therapy and radical neck dissection for those with residual neck disease. Those with local control were then treated with vinblastine, bleomycin, and cisplatin (VBP). Although 79% of patients achieved a partial or complete response to chemotherapy, only 50% of patients achieved local control. Marked mucositis limited the dose and schedule of radiation therapy. The methotrexate and 5-fluorouracil combination appears to be too toxic for multimodality therapy of advanced head and neck cancer.

Low-grade adenocarcinoma of the nasal cavity and paranasal sinuses.

The pathologic features and the behavior of 50 cases of adenocarcinoma (excluding adenoid cystic carcinoma and mucoepidermoid carcinoma) of the sinonasal tract are presented. The cases were divided on histologic grounds into 23 low-grade and 27 high-grade neoplasms. The low grade lesions had a well developed glandular pattern throughout, very uniform nuclei, and minimal mitotic activity. The high grade tumors had a less uniform glandular pattern, commonly with solid or sheet-like areas, manifested nuclear pleomorphism, and generally had a higher mitotic rate. The low-grade group had a prognosis markedly better than the high-grade group. Since the literature tends to consider all sinonasal adenocarcinomas as relentlessly progressive neoplasms with poor prognosis, it is important to recognize this category of low grade neoplasm in order that treatment and prognostication can be better related to their behavior.

Mucoepidermoid-adenosquamous carcinoma of the larynx and hypopharynx: a report of 21 cases and a review of the literature.

Twenty-one cases of mucoepidermoid-adenosquamous carcinoma (MEC/ASC) of the larynx and hypopharynx were collected and reviewed from the Armed Forces Institute of Pathology tumor registry from 1945 to 1979. This is the largest series of such lesions in this location reported to date. In addition, the literature was reviewed and 32 previous cases noted. The overall five-year survival was 77%, although low-grade mucoepidermoid carcinoma had a better survival than did adenosquamous-high-grade mucoepidermoid carcinoma.