Effectiveness of a comprehensive package based on electronic medication monitors at improving treatment outcomes among tuberculosis patients in Tibet: a multicentre randomised controlled trial.

BACKGROUND: WHO recommends that electronic medication monitors, a form of digital adherence technology, be used as a complement to directly observed treatment (DOT) for tuberculosis, as DOT is inconvenient and costly. However, existing evidence about the effectiveness of these monitors is inconclusive. Therefore, we evaluated the effectiveness of a comprehensive package based on electronic medication monitors among patients with tuberculosis in Tibet Autonomous Region (hereafter Tibet), China. METHODS: This multicentre, randomised controlled trial recruited patients from six counties in Shigatse, Tibet. Eligible participants had drug-susceptible tuberculosis and were aged 15 years or older when starting standard tuberculosis treatment. Tuberculosis doctors recruited patients from the public tuberculosis dispensary in each county and the study statistician randomly assigned them to the intervention or control group based on the predetermined randomised allocation sequence. Intervention patients received an electronic medication monitor box. The box included audio medication-adherence reminders and recorded box-opening data, which were transmitted to a cloud-based server and were accessible to health-care providers to allow remote adherence monitoring. A linked smartphone app enabled text, audio, and video communication between patients and health-care providers. Patients were also provided with a free data plan. Patients selected a treatment supporter (often a family member) who was trained to support patients with using the electronic medication monitor and app. Patients in the control group received usual care plus a deactivated electronic medication monitor, which only recorded and transmitted box-opening data that was not made available to health-care providers. The control group also had no access to the app or trained treatment supporters. The primary outcome was a binary indicator of poor monthly adherence, defined as missing 20% or more of planned doses in the treatment month, measured using electronic medication monitor opening data, and verified by counting used medication blister packages during consultations. We recorded other secondary treatment outcomes based on national tuberculosis reporting data. We analysed the primary outcome based on the intention-to-treat population. This trial is registered at ISRCTN, 52132803. FINDINGS: Between Nov 17, 2018, and April 5, 2021, 278 patients were enrolled into the study. 143 patients were randomly assigned to the intervention group and 135 patients to the control group. Follow-up ended when the final patient completed treatment on Oct 4, 2021. In the intervention group, 87 (10%) of the 854 treatment months showed poor adherence compared with 290 (37%) of the 795 months in the control group. The corresponding adjusted risk difference for the intervention versus control was -29·2 percentage points (95% CI -35·3 to -22·2; p<0·0001). Five of the six secondary treatment outcomes also showed clear improvements, including treatment success, which was found for 133 (94%) of the 142 individuals in the intervention arm and 98 (73%) of the 134 individuals in the control arm, with an adjusted risk difference of 21 percentage points (95% CI 12·4-29·4); p<0·0001. INTERPRETATION: The interventions were effective at improving tuberculosis treatment adherence and outcomes, and the trial suggests that a comprehensive package involving electronic medication monitors might positively affect tuberculosis programmes in high-burden and low-resource settings. FUNDING: TB REACH.

Host diversity and behavior determine patterns of interspecies transmission and geographic diffusion of avian influenza A subtypes among North American wild reservoir species.

Wild birds can carry avian influenza viruses (AIV), including those with pandemic or panzootic potential, long distances. Even though AIV has a broad host range, few studies account for host diversity when estimating AIV spread. We analyzed AIV genomic sequences from North American wild birds, including 303 newly sequenced isolates, to estimate interspecies and geographic viral transition patterns among multiple co-circulating subtypes. Our results show high transition rates within Anseriformes and Charadriiformes, but limited transitions between these orders. Patterns of transition between species were positively associated with breeding habitat range overlap, and negatively associated with host genetic distance. Distance between regions (negative correlation) and summer temperature at origin (positive correlation) were strong predictors of transition between locations. Taken together, this study demonstrates that host diversity and ecology can determine evolutionary processes that underlie AIV natural history and spread. Understanding these processes can provide important insights for effective control of AIV.

Using antenatal care as a platform for malaria surveillance data collection: study protocol.

BACKGROUND: While many malaria-endemic countries have health management information systems that can measure and report malaria trends in a timely manner, these routine systems have limitations. Periodic community cross-sectional household surveys are used to estimate malaria prevalence and intervention coverage but lack geographic granularity and are resource intensive. Incorporating malaria testing for all women at their first antenatal care (ANC) visit (i.e., ANC1) could provide a more timely and granular source of data for monitoring trends in malaria burden and intervention coverage. This article describes a protocol designed to assess if ANC-based surveillance could be a pragmatic tool to monitor malaria. METHODS: This is an observational, cross-sectional study conducted in Benin, Burkina Faso, Mozambique, Nigeria, Tanzania, and Zambia. Pregnant women attending ANC1 in selected health facilities will be tested for malaria infection by rapid diagnostic test and administered a brief questionnaire to capture key indicators of malaria control intervention coverage and care-seeking behaviour. In each location, contemporaneous cross-sectional household surveys will be leveraged to assess correlations between estimates obtained using each method, and the use of ANC data as a tool to track trends in malaria burden and intervention coverage will be validated. RESULTS: This study will assess malaria prevalence at ANC1 aggregated at health facility and district levels, and by gravidity relative to current pregnancy (i.e., gravida 1, gravida 2, and gravida 3 +). ANC1 malaria prevalence will be presented as monthly trends. Additionally, correlation between ANC1 and household survey-derived estimates of malaria prevalence, bed net ownership and use, and care-seeking will be assessed. CONCLUSION: ANC1-based surveillance has the potential to provide a cost-effective, localized measure of malaria prevalence that is representative of the general population and useful for tracking monthly changes in parasite prevalence, as well as providing population-representative estimates of intervention coverage and care-seeking behavior. This study will evaluate the representativeness of these measures and collect information on operational feasibility, usefulness for programmatic decision-making, and potential for scale-up of malaria ANC1 surveillance.

Agricultural and geographic factors shaped the North American 2015 highly pathogenic avian influenza H5N2 outbreak.

The 2014-2015 highly pathogenic avian influenza (HPAI) H5NX outbreak represents the largest and most expensive HPAI outbreak in the United States to date. Despite extensive traditional and molecular epidemiological studies, factors associated with the spread of HPAI among midwestern poultry premises remain unclear. To better understand the dynamics of this outbreak, 182 full genome HPAI H5N2 sequences isolated from commercial layer chicken and turkey production premises were analyzed using evolutionary models able to accommodate epidemiological and geographic information. Epidemiological compartmental models embedded in a phylogenetic framework provided evidence that poultry type acted as a barrier to the transmission of virus among midwestern poultry farms. Furthermore, after initial introduction, the propagation of HPAI cases was self-sustainable within the commercial poultry industries. Discrete trait diffusion models indicated that within state viral transitions occurred more frequently than inter-state transitions. Distance and sample size were very strongly supported as associated with viral transition between county groups (Bayes Factor > 30.0). Together these findings indicate that the different types of midwestern poultry industries were not a single homogenous population, but rather, the outbreak was shaped by poultry industries and geographic factors.

Characteristics of Persons With Secondary Detection of Severe Acute Respiratory Syndrome Coronavirus 2 ≥90 days After First Detection, New Mexico 2020.

The New Mexico Department of Health (NMDOH) conducted a matched case-control study to compare 315 persons (cases) with and 945 persons (controls) without severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) secondary detection (ie, positive SARS-CoV-2 test ≥90 days after first detection as of December 10, 2020). Compared with controls, cases had greater odds of higher SARS-CoV-2 testing frequency (adjusted odds ratio [aOR] = 1.2), being female (aOR = 1.6), being non-Hispanic American Indian/Alaska Native (aOR = 2.3), having diabetes mellitus (aOR = 1.8), and residing and/or working in detention and/or correctional facilities (aOR = 4.7). Diagnostic tools evaluating infectiousness at secondary detection are urgently needed to inform infection control practices.

Evaluation of a package of risk-based pharmaceutical and lifestyle interventions in patients with hypertension and/or diabetes in rural China: A pragmatic cluster randomised controlled trial.

BACKGROUND: Primary prevention of cardiovascular disease (CVD) requires adequate control of hypertension and diabetes. We designed and implemented pharmaceutical and healthy lifestyle interventions for patients with diabetes and/or hypertension in rural primary care, and assessed their effectiveness at reducing severe CVD events. METHODS AND FINDINGS: We used a pragmatic, parallel group, 2-arm, controlled, superiority, cluster trial design. We randomised 67 township hospitals in Zhejiang Province, China, to intervention (34) or control (33). A total of 31,326 participants were recruited, with 15,380 in the intervention arm and 15,946 in the control arm. Participants had no known CVD and were either patients with hypertension and a 10-year CVD risk of 20% or higher, or patients with type 2 diabetes regardless of their CVD risk. The intervention included prescription of a standardised package of medicines, individual advice on lifestyle change, and adherence support. Control was usual hypertension and diabetes care. In both arms, as usual in China, most outpatient drug costs were out of pocket. The primary outcome was severe CVD events, including coronary heart disease and stroke, during 36 months of follow-up, as recorded by the CVD surveillance system. The study was implemented between December 2013 and May 2017. A total of 13,385 (87%) and 14,745 (92%) participated in the intervention and control arms, respectively. Their mean age was 64 years, 51% were women, and 90% were farmers. Of all participants, 64% were diagnosed with hypertension with or without diabetes, and 36% were diagnosed with diabetes only. All township hospitals and participants completed the 36-month follow-up. At 36 months, there were 762 and 874 severe CVD events in the intervention and control arms, respectively, yielding a non-significant effect on CVD incidence rate (1.92 and 2.01 per 100 person-years, respectively; crude incidence rate ratio = 0.90 [95% CI: 0.74, 1.08; P = 0.259]). We observed significant, but small, differences in the change from baseline to follow-up for systolic blood pressure (-1.44 mm Hg [95% CI: -2.26, -0.62; P < 0.001]) and diastolic blood pressure (-1.29 mm Hg [95% CI: -1.77, -0.80; P < 0.001]) in the intervention arm compared to the control arm. Self-reported adherence to recommended medicines was significantly higher in the intervention arm compared with the control arm at 36 months. No safety concerns were identified. Main study limitations include all participants being informed about their high CVD risk at baseline, non-blinding of participants, and the relatively short follow-up period available for judging potential changes in rates of CVD events. CONCLUSIONS: The comprehensive package of pharmaceutical and healthy lifestyle interventions did not reduce severe CVD events over 36 months. Improving health system factors such as universal coverage for the cost of essential medicines is required for successful risk-based CVD prevention programmes. TRIAL REGISTRATION: ISRCTN registry ISRCTN58988083.

Addressing Unintentional Exclusion of Vulnerable and Mobile Households in Traditional Surveys in Kathmandu, Dhaka, and Hanoi: a Mixed-Methods Feasibility Study.

The methods used in low- and middle-income countries' (LMICs) household surveys have not changed in four decades; however, LMIC societies have changed substantially and now face unprecedented rates of urbanization and urbanization of poverty. This mismatch may result in unintentional exclusion of vulnerable and mobile urban populations. We compare three survey method innovations with standard survey methods in Kathmandu, Dhaka, and Hanoi and summarize feasibility of our innovative methods in terms of time, cost, skill requirements, and experiences. We used descriptive statistics and regression techniques to compare respondent characteristics in samples drawn with innovative versus standard survey designs and household definitions, adjusting for sample probability weights and clustering. Feasibility of innovative methods was evaluated using a thematic framework analysis of focus group discussions with survey field staff, and via survey planner budgets. We found that a common household definition excluded single adults (46.9%) and migrant-headed households (6.7%), as well as non-married (8.5%), unemployed (10.5%), disabled (9.3%), and studying adults (14.3%). Further, standard two-stage sampling resulted in fewer single adult and non-family households than an innovative area-microcensus design; however, two-stage sampling resulted in more tent and shack dwellers. Our survey innovations provided good value for money, and field staff experiences were neutral or positive. Staff recommended streamlining field tools and pairing technical and survey content experts during fieldwork. This evidence of exclusion of vulnerable and mobile urban populations in LMIC household surveys is deeply concerning and underscores the need to modernize survey methods and practices.

Antibiotic practices among household members and their domestic animals within rural communities in Cumilla district, Bangladesh: a cross-sectional survey.

BACKGROUND: Antibiotic resistance is a global threat to human health, and inappropriate use of antibiotics in humans and animals is widely considered to be a key driver of antibiotic resistant infections. Antibiotic use in humans and animals is growing rapidly in low- and, particularly, middle-income countries. However, there is little detailed understanding about practices related to the use of antibiotics in humans and animals within community settings in such countries. Here we aimed to understand the antibiotic practices of rural households across Cumilla district, Bangladesh, in relation to household members and their domestic animals. METHODS: In 2018 we conducted a cross-sectional survey using representative cluster sampling methods. We collected self-reported information from 682 female and 620 male household heads, with women also asked about their children's antibiotic practices. RESULTS: Only 48% (95% CI: 40, 56%) of women and men had heard of antibiotics, and among those women and men who were aware of antibiotics and the children of those women 70% (95% CI: 64, 76%) reported having previously taken antibiotics, while among these individuals who reported previously taking antibiotics 21% (95% CI: 18, 25%) said they had done so most recently within the last month. Risky/inappropriate antibiotic practices in humans and animals were often reported. For example, among women and men who were aware of antibiotics and the children of those women 52% (95% CI: 40, 63%) reported previously taking antibiotics for a "cough/cold", despite antibiotics being typically inappropriate for use against viral upper respiratory tract infections. Among poultry-owning respondents who were aware of antibiotics 11% (95% CI: 8, 15%) reported previously giving healthy poultry antibiotics, mainly for growth/prophylaxis, while among cattle-owning respondents who were aware of antibiotics and reported previously giving their cattle feed 20% (95% CI: 9, 37%) said the feed had contained antibiotics at least sometimes. CONCLUSIONS: Our results highlight the need for context-adapted interventions at both the community level and the health systems level to reduce inappropriate antibiotic use among humans and domestic animals in rural Bangladesh. Successfully reducing inappropriate use of antibiotics among humans and animals is a required and critical step in tackling antimicrobial resistance.

A process for developing a sustainable and scalable approach to community engagement: community dialogue approach for addressing the drivers of antibiotic resistance in Bangladesh.

BACKGROUND: Community engagement approaches that have impacted on health outcomes are often time intensive, small-scale and require high levels of financial and human resources. They can be difficult to sustain and scale-up in low resource settings. Given the reach of health services into communities in low income countries, the health system provides a valuable and potentially sustainable entry point that would allow for scale-up of community engagement interventions. This study explores the process of developing an embedded approach to community engagement taking the global challenge of antibiotic resistance as an example. METHODS: The intervention was developed using a sequential mixed methods study design. This consisted of: exploring the evidence base through an umbrella review, and identifying key international standards on the appropriate use of antibiotics; undertaking detailed formative research through a) a qualitative study to explore the most appropriate mechanisms through which to embed the intervention within the existing health system and community infrastructure, and to understand patterns of knowledge, attitudes and practice regarding antibiotics and antibiotic resistance; and b) a household survey - which drew on the qualitative findings - to quantify knowledge, and reported attitudes and practice regarding antibiotics and antibiotic resistance within the target population; and c) drawing on appropriate theories regarding change mechanisms and experience of implementing community engagement interventions to co-produce the intervention processes and materials with key stakeholders at policy, health system and community level. RESULTS: A community engagement intervention was co-produced and was explicitly designed to link into existing health system and community structures and be appropriate for the cultural context, and therefore have the potential to be implemented at scale. We anticipate that taking this approach increases local ownership, as well as the likelihood that the intervention will be sustainable and scalable. CONCLUSIONS: This study demonstrates the value of ensuring that a range of stakeholders co-produce the intervention, and ensuring that the intervention is designed to be appropriate for the health system, community and cultural context.

Global phylodynamic analysis of avian paramyxovirus-1 provides evidence of inter-host transmission and intercontinental spatial diffusion.

BACKGROUND: Avian avulavirus (commonly known as avian paramyxovirus-1 or APMV-1) can cause disease of varying severity in both domestic and wild birds. Understanding how viruses move among hosts and geography would be useful for informing prevention and control efforts. A Bayesian statistical framework was employed to estimate the evolutionary history of 1602 complete fusion gene APMV-1 sequences collected from 1970 to 2016 in order to infer viral transmission between avian host orders and diffusion among geographic regions. Ancestral states were estimated with a non-reversible continuous-time Markov chain model, allowing transition rates between discrete states to be calculated. The evolutionary analyses were stratified by APMV-1 classes I (n = 198) and II (n = 1404), and only those sequences collected between 2006 and 2016 were allowed to contribute host and location information to the viral migration networks. RESULTS: While the current data was unable to assess impact of host domestication status on APMV-1 diffusion, these analyses supported the sharing of APMV-1 among divergent host taxa. The highest supported transition rate for both classes existed from domestic chickens to Anseriformes (class I:6.18 transitions/year, 95% highest posterior density (HPD) 0.31-20.02, Bayes factor (BF) = 367.2; class II:2.88 transitions/year, 95%HPD 1.9-4.06, BF = 34,582.9). Further, among class II viruses, domestic chickens also acted as a source for Columbiformes (BF = 34,582.9), other Galliformes (BF = 34,582.9), and Psittaciformes (BF = 34,582.9). Columbiformes was also a highly supported source to Anseriformes (BF = 322.0) and domestic chickens (BF = 402.6). Additionally, our results provide support for the diffusion of viruses among continents and regions, but no interhemispheric viral exchange between 2006 and 2016. Among class II viruses, the highest transition rates were estimated from South Asia to the Middle East (1.21 transitions/year; 95%HPD 0.36-2.45; BF = 67,107.8), from Europe to East Asia (1.17 transitions/year; 95%HPD 0.12-2.61; BF = 436.2) and from Europe to Africa (1.06 transitions/year, 95%HPD 0.07-2.51; BF = 169.3). CONCLUSIONS: While migration appears to occur infrequently, geographic movement may be important in determining viral diversification and population structure. In contrast, inter-order transmission of APMV-1 may occur readily, but most events are transient with few lineages persisting in novel hosts.

Long-term outcomes of an educational intervention to reduce antibiotic prescribing for childhood upper respiratory tract infections in rural China: Follow-up of a cluster-randomised controlled trial.

BACKGROUND: Inappropriate antibiotic prescribing causes widespread serious health problems. To reduce prescribing of antibiotics in Chinese primary care to children with upper respiratory tract infections (URTIs), we developed an intervention comprising clinical guidelines, monthly prescribing review meetings, doctor-patient communication skills training, and education materials for caregivers. We previously evaluated our intervention using an unblinded cluster-randomised controlled trial (cRCT) in 25 primary care facilities across two rural counties. When our trial ended at the 6-month follow-up period, we found that the intervention had reduced antibiotic prescribing for childhood URTIs by 29 percentage points (pp) (95% CI -42 to -16). METHODS AND FINDINGS: In this long-term follow-up study, we collected our trial outcomes from the one county (14 facilities and 1:1 cluster randomisation ratio) that had electronic records available 12 months after the trial ended, at the 18-month follow-up period. Our primary outcome was the antibiotic prescription rate (APR)-the percentage of outpatient prescriptions containing any antibiotic(s) for children aged 2 to 14 years who had a primary diagnosis of a URTI and had no other illness requiring antibiotics. We also conducted 15 in-depth interviews to understand how interventions were sustained. In intervention facilities, the APR was 84% (1,171 out of 1,400) at baseline, 37% (515 out of 1,380) at 6 months, and 54% (2,748 out of 5,084) at 18 months, and in control facilities, it was 76% (1,063 out of 1,400), 77% (1,084 out of 1,400), and 75% (2,772 out of 3,685), respectively. After adjusting for patient and prescribing doctor covariates, compared to the baseline intervention-control difference, the difference at 6 months represented a 6-month intervention-arm reduction in the APR of -49 pp (95% CI -63 to -35; P < 0.0001), and compared to the baseline difference, the difference at 18 months represented an 18-month intervention-arm reduction in the APR of -36 pp (95% CI -55 to -17; P < 0.0001). Compared to the 6-month intervention-control difference, the difference at 18 months represented no change in the APR: 13 pp (95% CI -7 to 33; P = 0.21). Factors reported to sustain reductions in antibiotic prescribing included doctors' improved knowledge and communication skills and focused prescription review meetings, whereas lack of supervision and monitoring may be associated with relapse. Key limitations were not including all clusters from the trial and not collecting returned visits or sepsis cases. CONCLUSIONS: Our intervention was associated with sustained and substantial reductions in antibiotic prescribing at the end of the intervention period and 12 months later. Our intervention may be adapted to similar resource-poor settings. TRIAL REGISTRATION: ISRCTN registry ISRCTN14340536.

Analysis of loss to follow-up in 4099 multidrug-resistant pulmonary tuberculosis patients.

Loss to follow-up (LFU) of ≥2 consecutive months contributes to the poor levels of treatment success in multidrug-resistant tuberculosis (MDR-TB) reported by TB programmes. We explored the timing of when LFU occurs by month of MDR-TB treatment and identified patient-level risk factors associated with LFU.We analysed a dataset of individual MDR-TB patient data (4099 patients from 22 countries). We used Kaplan-Meier survival curves to plot time to LFU and a Cox proportional hazards model to explore the association of potential risk factors with LFU.Around one-sixth (n=702) of patients were recorded as LFU. Median (interquartile range) time to LFU was 7 (3-11) months. The majority of LFU occurred in the initial phase of treatment (75% in the first 11 months). Major risk factors associated with LFU were: age 36-50 years (HR 1.3, 95% CI 1.0-1.6; p=0.04) compared with age 0-25 years, being HIV positive (HR 1.8, 95% CI 1.2-2.7; p<0.01) compared with HIV negative, on an individualised treatment regimen (HR 0.7, 95% CI 0.6-1.0; p=0.03) compared with a standardised regimen and a recorded serious adverse event (HR 0.5, 95% CI 0.4-0.6; p<0.01) compared with no serious adverse event.Both patient- and regimen-related factors were associated with LFU, which may guide interventions to improve treatment adherence, particularly in the first 11 months.

Factors associated with self-reported anal cancer screening history in men who have sex with men.

Background Men who have sex with men (MSM) are at greater risk of developing anal cancer caused by human papillomavirus (HPV) than the rest of the general population. Currently, there are no formal national guidelines in the US advising men how and when to get anal cancer screening. We sought to assess differences in demographics, familiarity and anxiety about anal cancer among men who report having had anal cancer screening (i.e. anal cytology and/or a digital anorectal examination (DARE)). METHODS: MSM were recruited to participate in a study to assess the feasibility of teaching self and partner anal examinations as a means of screening for anal cancer. Data for this secondary analysis were obtained using a written pre-test and a computer-assisted self-interview. Factors associated with screening were assessed with multivariable logistic regression to allow calculation of adjusted odds ratios (aORs). RESULTS: Of the 197 participants with data, 145 (73.6%) reported having had anal cancer screening (either anal cytology, DARE or both) during their lifetime. Men who were younger, Black and HIV-negative were associated with decreased odds of reporting any type of anal cancer screening. For example, compared with White men, Black men were 80% less likely to report screening (aOR 0.2; 95% confidence interval (CI) 0.1-0.5). Self-perception of anal cancer knowledge was not associated with screening in multivariable analysis (aOR 1.6; 95% CI 0.6-3.9). CONCLUSIONS: Age, race and HIV status were independently associated with a history of anal cancer screening.

Transmission Dynamics of Highly Pathogenic Avian Influenza Virus A(H5Nx) Clade 2.3.4.4, North America, 2014-2015.

Eurasia highly pathogenic avian influenza virus (HPAIV) H5 clade 2.3.4.4 emerged in North America at the end of 2014 and caused outbreaks affecting >50 million poultry in the United States before eradication in June 2015. We investigated the underlying ecologic and epidemiologic processes associated with this viral spread by performing a comparative genomic study using 268 full-length genome sequences and data from outbreak investigations. Reassortant HPAIV H5N2 circulated in wild birds along the Pacific flyway before several spillover events transmitting the virus to poultry farms. Our analysis suggests that >3 separate introductions of HPAIV H5N2 into Midwest states occurred during March-June 2015; transmission to Midwest poultry farms from Pacific wild birds occurred ≈1.7-2.4 months before detection. Once established in poultry, the virus rapidly spread between turkey and chicken farms in neighboring states. Enhanced biosecurity is required to prevent the introduction and dissemination of HPAIV across the poultry industry.

A phase II clinical study to assess the feasibility of self and partner anal examinations to detect anal canal abnormalities including anal cancer.

OBJECTIVE: Anal cancer is a common cancer among men who have sex with men (MSM); however, there is no standard screening protocol for anal cancer. We conducted a phase II clinical trial to assess the feasibility of teaching MSM to recognise palpable masses in the anal canal which is a common sign of anal cancer in men. METHODS: A clinician skilled in performing digital anorectal examinations (DARE) used a pelvic manikin to train 200 MSM, aged 27-78 years, how to do a self-anal examination (SAE) for singles or a partner anal examination (PAE) for couples. The clinician then performed a DARE without immediately disclosing results, after which the man or couple performed an SAE or PAE, respectively. Percentage agreement with the clinician DARE in addition to sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for the SAE, PAE and overall. RESULTS: Men had a median age of 52 years, 42.5% were African American and 60.5% were HIV positive. DARE detected abnormalities in 12 men while the men's SAE/PAEs detected 9 of these. A total of 93.0% of men classified the health of their anal canal correctly (95% CI 89.5 to 96.5). Overall percentage agreement, sensitivity and specificity were 93.0%, 75.0% and 94.2%, respectively, while PPV and NPV were 45.0% and 98.3%, respectively. The six men who detected the abnormality had nodules/masses ≥3 mm in size. More than half of men (60.5%) reported never checking their anus for an abnormality; however, after performing an SAE/PAE, 93.0% said they would repeat it in the future. CONCLUSION: These results suggest that tumours of ≥3 mm may be detectable by self or partner palpation among MSM and encourage further investigation given literature suggesting a high cure rate for anal cancer tumours ≤10 mm.

Cost-effectiveness analysis of a multi-dimensional intervention to reduce inappropriate antibiotic prescribing for children with upper respiratory tract infections in China.

BACKGROUND: We developed a multifaceted intervention to reduce antibiotic prescription rate for children with upper respiratory tract infections (URTIs) among primary care doctors in township hospitals in China. The intervention achieved a 29% (95% CI 16-42) absolute risk reduction in antibiotic prescribing. This study was to assess the cost-effectiveness of our intervention at reducing antibiotic prescribing in rural primary care facilities as measured by the intervention's effect on the antibiotic prescription rates for childhood URTIs. METHODS: We took a healthcare provider perspective, measuring costs of consultation (time cost of doctor), prescription monitoring process and peer-review meetings (time cost of participants) and medication costs. Costs on provider side were collected through a bespoke questionnaire from all 25 township hospitals in December 2016, while medication costs were collected prospectively in the trial. Incremental cost-effectiveness ratios were calculated by dividing the mean difference in cost of the two trial arms by the mean difference in antibiotic prescribing rate. RESULTS: This showed an incremental cost of $0.03 per percentage point reduction in antibiotic prescribing. In addition to this incremental cost, the cost of implementing the intervention, including training and materials delivered by township hospitals, was $390.65 (SD $145.68) per healthcare facility. CONCLUSIONS: This study shows that a multifaceted intervention programme, when embedded into routine practice, is very cost-effective at reducing antibiotic prescribing in primary care facilities and has the potential of scale up in similar resource limited settings.

A qualitative investigation among men who have sex with men on the acceptability of performing a self- or partner anal exam to screen for anal cancer.

PURPOSE: Persistent infection with oncogenic human papillomavirus (HPV) is the primary cause of anal cancer, a disease that disproportionately affects men who have sex with men (MSM); however, there is no uniform screening protocol to detect anal cancer. This qualitative study explores whether a self-anal exam (SAE) or partner anal exam (PAE), that includes self-palpation or palpation of a partner's anal canal, is an acceptable and self-efficacious screening test, which will cue appropriate follow-up care in MSM. METHODS: Twenty-four MSM living in Houston took part in four focus group sessions eliciting their responses to a study teaching them to perform an SAE or PAE (SAE/PAE). Participants were asked about the acceptability and feasibility of executing an SAE/PAE routinely. Thematic analysis of session transcripts was used to identify common patterns in participant responses. RESULTS: Overall, participants expressed self-efficacy for performing an SAE/PAE and voiced a preference for being taught the procedure by a clinician. Participants agreed that they would consult with a clinician if they ever discovered an abnormality while performing an SAE/PAE. A lack of knowledge about anal cancer among MSM may present a barrier to adopting SAE/PAE. In discussing their experience of the exams, some participants suggested that it could become a routine practice for them. CONCLUSIONS: Our findings suggest that SAE and PAE, as a screen for anal cancer, are acceptable and feasible to MSM. Future research should explore attitudes and beliefs of MSM, with the aim of improving anal cancer education and understanding of pathologic findings.

Impact of China's essential medicines scheme and zero-mark-up policy on antibiotic prescriptions in county hospitals: a mixed methods study.

OBJECTIVE: To evaluate the impact of the national essential medicines scheme and zero-mark-up policy on antibiotic prescribing behaviour. METHODS: In rural Guangxi, a natural experiment compared one county hospital which implemented the policy with a comparison hospital which did not. All outpatient and inpatient records in 2011 and 2014 were extracted from the two hospitals. Primary outcome indicator was antibiotic prescribing rate (APR) among children aged 2-14 presenting in outpatients with a primary diagnosis of upper respiratory tract infection (URTI). We organised independent physician reviews to determine inappropriate prescribing for inpatients. Difference-in-difference analyses based on multivariate regressions were used to compare APR over time after adjusting potential confounders. We conducted 12 in-depth interviews with paediatricians, hospital directors and health officials. RESULTS: A total of 8219 and 4142 outpatient prescriptions of childhood URTIs were included in the intervention and comparison hospitals, respectively. In 2011, APR was 30% in the intervention and 88% in the comparison hospital. In 2014, the intervention hospital significantly reduced outpatient APR by 21% (95% CI:-23%, -18%), intravenous infusion by 58% (95% CI: -64%, -52%) and prescription cost by 31 USD (95% CI: -35, -28), compared with the controls. We collected 251 inpatient records, but did not find reductions in inappropriate antibiotic use. Interviews revealed that the intervention hospital implemented a thorough antibiotics stewardship programme containing training, peer review of prescriptions and restrictions for overprescribing. CONCLUSION: The national essential medicines scheme and zero-mark-up policy, when implemented with an antimicrobial stewardship programme, may be associated with reductions in outpatient antibiotic prescribing and intravenous infusions.

Assessment of contemporary genetic diversity and inter-taxa/inter-region exchange of avian paramyxovirus serotype 1 in wild birds sampled in North America.

BACKGROUND: Avian paramyxovirus serotype 1 (APMV-1) viruses are globally distributed, infect wild, peridomestic, and domestic birds, and sometimes lead to outbreaks of disease. Thus, the maintenance, evolution, and spread of APMV-1 viruses are relevant to avian health. METHODS: In this study we sequenced the fusion gene from 58 APMV-1 isolates recovered from thirteen species of wild birds sampled throughout the USA during 2007-2014. We analyzed sequence information with previously reported data in order to assess contemporary genetic diversity and inter-taxa/inter-region exchange of APMV-1 in wild birds sampled in North America. RESULTS: Our results suggest that wild birds maintain previously undescribed genetic diversity of APMV-1; however, such diversity is unlikely to be pathogenic to domestic poultry. Phylogenetic analyses revealed that APMV-1 diversity detected in wild birds of North America has been found in birds belonging to numerous taxonomic host orders and within hosts inhabiting multiple geographic regions suggesting some level of viral exchange. However, our results also provide statistical support for associations between phylogenetic tree topology and host taxonomic order/region of sample origin which supports restricted exchange among taxa and geographical regions of North America for some APMV-1 sub-genotypes. CONCLUSIONS: We identify previously unrecognized genetic diversity of APMV-1 in wild birds in North America which is likely a function of continued viral evolution in reservoir hosts. We did not, however, find support for the emergence or maintenance of APMV-1 strains predicted to be pathogenic to poultry in wild birds of North America outside of the order Suliformes (i.e., cormorants). Furthermore, genetic evidence suggests that ecological drivers or other mechanisms may restrict viral exchange among taxa and regions of North America. Additional and more systematic sampling for APMV-1 in North America would likely provide further inference on viral dynamics for this infectious agent in wild bird populations.

Hospitalizations for COVID-19 Among American Indian and Alaska Native Adults (≥ 18 Years Old) - New Mexico, March-September 2020.

To assess the presence of racial disparity during the COVID-19 pandemic, the New Mexico Department of Health (NMDOH) sought to compare the case rate and risk of hospitalization between persons of American Indian and Alaska Native (AI/AN) race and persons of other races in New Mexico from March 1 through September 30, 2020. Using NMDOH COVID-19 surveillance data, age-standardized COVID-19 case and hospitalization risks were compared between adults (≥ 18 years old) of AI/AN and other races. We compared age, sex, and comorbidities between hospitalized adults of AI/AN and other races. Among AI/AN persons, age-standardized COVID-19 case and hospitalization risks were 3.7 (95% CI 3.6-3.8) and 10.5 (95% CI 9.8-11.2) times as high as persons of other races. Hospitalized AI/AN patients had higher proportions of diabetes mellitus (48% vs. 33%, P < 0.0001) and chronic liver disease (8% vs. 5%, P = 0.0004) compared to hospitalized patients of other races. AI/AN populations have disproportionately higher risk of COVID-19 hospitalization compared to other races in New Mexico. By identifying etiologic factors that contribute to inequity, public health partners can implement culturally appropriate health interventions to mitigate disease severity within AI/AN communities.