Cost-effectiveness of 4CMenB vaccination against gonorrhea: importance of dosing schedule, vaccine sentiment, targeting strategy, and duration of protection.

BACKGROUND: Observational evidence suggests the 4CMenB meningococcal vaccine may partially protect against gonorrhea, with one dose being two-thirds as protective as two. We examined the cost-effectiveness of vaccinating men-who-have-sex-with-men (MSM) in England, with one- or two-dose primary vaccination. METHODS: Integrated transmission-dynamic health-economic modeling explored the effects of targeting strategy, first- and second-dose uptake levels, and duration of vaccine protection, using observational estimates of vaccine protection. RESULTS: Vaccination with one or two primary doses is always cost-saving, irrespective of uptake, although vaccine sentiment is an important determinant of impact and cost-effectiveness. The most impactful and cost-effective targeting is offering "Vaccination-according-to-Risk" (VaR), to all patients with gonorrhea plus those reporting high numbers of sexual partners. If VaR is not feasible to implement then the more-restrictive strategy of "Vaccination-on-Diagnosis" (VoD) with gonorrhea is cost-effective, but much less impactful. Under conservative assumptions, VaR(2-dose) saves £7.62M(95%CrI:1.15-17.52) and gains 81.41(28.67-164.23) QALYs over 10 years; VoD(2-dose) saves £3.40M(0.48-7.71) and gains 41.26(17.52-78.25) QALYs versus no vaccination. Optimistic versus pessimistic vaccine-sentiment assumptions increase net benefits by ∼30%(VoD) or ∼60%(VaR). CONCLUSIONS: At UK costs, targeted 4CMenB vaccination of MSM gains QALYs and is cost-saving at any uptake level. Promoting uptake maximizes benefits and is an important role for behavioral science.

Does Rectoanal Intussusception Limit Improvements in Clinical Outcome and Quality of Life After Sacral Nerve Stimulation for Fecal Incontinence?

BACKGROUND: Sacral nerve stimulation is a treatment option for severe, medically refractory fecal incontinence, although its use in patients with anatomic abnormalities remains controversial. OBJECTIVE: This study aimed to determine whether patients with rectoanal intussusception achieve similar benefits from device implantation to patients without rectoanal intussusception. DESIGN: Retrospective review of a prospectively maintained database. Demographics and clinical data were collected for each patient, including preoperative pelvic floor testing. Defecographies were reanalyzed in a blinded manner. Preoperative rectoanal intussusception was determined on the basis of the Oxford system (grade III-IV vs not; grade V excluded). SETTINGS: Academic-affiliated pelvic health center. PATIENTS: All patients undergoing sacral nerve stimulation for fecal incontinence between July 2011 and July 2019. MAIN OUTCOME MEASURES: Cleveland Clinic Florida Incontinence/Wexner Scores, Fecal Incontinence Severity Indices, and Fecal Incontinence Quality of Life Indices at 1 year. RESULTS: One hundred sixty-nine patients underwent sacral nerve stimulation for fecal incontinence during the study period. The average age was 60.3 years and 91% were female. Forty-six patients (27.2%) had concomitant rectoanal intussusception (38 patients [22.5%] grade III and 8 patients [4.7%] grade IV). Before surgery, patients reported an average of 10.8 accidents per week and a Wexner score of 15.7, with no difference between patients with and without rectoanal intussusception ( p = 0.22 and 0.95). At 1 year after surgery, the average Wexner score was 9.5. There was no difference in postoperative Wexner scores (10.4 vs 9.2, p = 0.23) or improvement over time between patients with and without rectoanal intussusception (-6.7 vs -5.7, p = 0.40). Similarly, there was no difference in quality of life or frequency of incontinence to liquid or solid stool. LIMITATIONS: Single-institution, moderate sample size, incomplete survey response. CONCLUSIONS: Concomitant rectoanal intussusception does not appear to affect clinical outcomes or quality of life after sacral nerve stimulation for fecal incontinence. Appropriate patients with fecal incontinence and rectoanal intussusception can be considered for sacral nerve stimulation placement. See Video Abstract at http://links.lww.com/DCR/C192 . LA INTUSUSCEPCIN RECTOANAL LIMITA LAS MEJORAS EN EL RESULTADO CLNICO Y LA CALIDAD DE VIDA DESPUS DE LA NEUROESTIMULACION SACRA PARA LA INCONTINENCIA FECAL: ANTECEDENTES:La neuroestimulación sacra es una opción de tratamiento para la incontinencia fecal grave refractaria al tratamiento médico, aunque su uso en pacientes con anomalías anatómicas sigue siendo controvertido.OBJETIVO:Determinar si los pacientes con intususcepción rectoanal logran beneficios similares de la implantación del dispositivo a los pacientes sin intususcepción rectoanal.DISEÑO:Revisión retrospectiva de una base de datos mantenida prospectivamente. Se recopilaron datos demográficos y clínicos de cada paciente, incluidas las pruebas preoperatorias del piso pélvico. Las defecografías se volvieron a analizar de forma ciega. La intususcepción rectoanal preoperatoria se determinó según el sistema de Oxford (grado III-IV vs. no; grado V excluido).ESCENARIO:Centro académico de salud pélvica.PACIENTES:Todos los pacientes sometidos a neuroestimulación sacra por incontinencia fecal entre julio de 2011 y julio de 2019.PRINCIPALES MEDIDAS DE RESULTADO:Cleveland Clinic Florida Incontinence/Wexner Scores, Índices de gravedad de la incontinencia fecal, Índices de calidad de vida de la incontinencia fecal al año.RESULTADOS:169 pacientes se sometieron a neuroestimulación sacra por incontinencia fecal durante el período de estudio. La edad promedio fue de 60.3 años y el 91% eran mujeres. Cuarenta y seis pacientes (27.2%) tenían intususcepción rectoanal concomitante (38 [22.5%] grado III y 8 [4.7%] grado IV). Antes de la cirugía, los pacientes informaron un promedio de 10.8 accidentes por semana y una puntuación de Wexner de 15.7 sin diferencia entre pacientes con y sin intususcepción rectoanal (p = 0.22 y 0.95). Un año después de la cirugía, la puntuación promedio de Wexner fue de 9.5. No hubo diferencia en las puntuaciones de Wexner posoperatorias (10.4 frente a 9.2, p = 0.23) o mejoría con el tiempo entre los pacientes con y sin intususcepción rectoanal (-6.7 frente a -5.7, p = 0.40). De manera similar, no hubo diferencia en la calidad de vida o la frecuencia de incontinencia de heces líquidas o sólidas.LIMITACIONES:Institución única, tamaño de muestra moderado, respuesta de encuesta incompleta.CONCLUSIÓN:La intususcepción rectoanal concomitante no parece afectar los resultados clínicos o la calidad de vida después de la neuroestimulación sacra para la incontinencia fecal. Los pacientes apropiados con incontinencia fecal e intususcepción rectoanal pueden ser considerados para la neuroestimulación sacra. Consulte Video Resumen en http://links.lww.com/DCR/C192(Traducción-Dr. Jorge Silva Velazco ).

Public health impact and cost-effectiveness of gonorrhoea vaccination: an integrated transmission-dynamic health-economic modelling analysis.

BACKGROUND: Gonorrhoea is a rapidly growing public health threat, with rising incidence and increasing drug resistance. Evidence that the MeNZB and four-component serogroup B meningococcal (4CMenB) vaccines, designed against Neisseria meningitidis, can also offer protection against gonorrhoea has created interest in using 4CMenB for this purpose and for developing gonorrhoea-specific vaccines. However, cost-effectiveness, and how the efficacy and duration of protection affect a gonorrhoea vaccine's value, have not been assessed. METHODS: We developed an integrated transmission-dynamic health-economic model, calibrated using Bayesian methods to surveillance data (from the Genitourinary Medicine Clinic Activity Dataset and the Gonococcal Resistance to Antimicrobials Surveillance Programme) on men who have sex with men (MSM) in England. We considered vaccination of MSM from the perspective of sexual health clinics, with and without vaccination offered to all adolescents in schools (vaccination before entry [VbE]), comparing three realistic approaches to targeting: vaccination on attendance (VoA) for testing; vaccination on diagnosis (VoD) with gonorrhoea; or vaccination according to risk (VaR), offered to patients diagnosed with gonorrhoea plus individuals who test negative but report having more than five sexual partners per year. For the primary analysis, vaccine impact was assessed relative to no vaccination in a conservative baseline scenario wherein time-varying behavioural parameters (sexual risk behaviour and screening rates) stabilise. To calculate the value of vaccination per dose administered, the value of vaccination was calculated by summing the averted costs of testing and treatment, and the monetary value of quality-adjusted life-year (QALY) gains with a QALY valued at £20 000. Costs were in 2018-19 GB£, and both costs and QALYs were discounted at 3·5% per year. We analysed the effects of varying vaccine uptake (0·5, 1, or 2 times HPV vaccine uptake by MSM in sexual health clinics in England), vaccine efficacy (1-100%) and duration of protection (1-20 years), and the time-horizon considered (10 years and 20 years). In addition, we calculated incremental cost-effectiveness ratios for the use of 4CMenB using assumed vaccine prices. FINDINGS: VbE has little impact on gonorrhoea diagnoses, with only 1·7% of MSM vaccinated per year. VoA has the largest impact but requires more vaccine doses than any other strategy, whereas VoD has a moderate impact but requires many fewer doses than VoA. VaR has almost the same impact as VoA but with fewer doses administered than VoA. VaR is the most cost-effective strategy for vaccines of moderate efficacy or duration of protection (or both), although VoD is more cost-effective for very protective and long-lasting vaccines. Even under conservative assumptions (efficacy equivalent to that of MeNZB and protection lasting for 18 months after two-dose primary vaccination and 36 months after single-dose booster vaccination), 4CMenB administered under VaR would likely be cost-saving at its current National Health Service price, averting an estimated mean 110 200 cases (95% credible interval 36 500-223 600), gaining a mean 100·3 QALYs (31·0-215·8), and saving a mean £7·9 million (0·0-20·5) over 10 years. A hypothetical gonorrhoea vaccine's value is increased more by improving its efficacy than its duration of protection-eg, 30% protection lasting 2 years has a median value of £48 (22-85) per dose over 10 years; doubling efficacy increases the value to £102 (53-144) whereas doubling the duration of protection increases it to £72 (34-120). INTERPRETATION: We recommend that vaccination of MSM against gonorrhoea according to risk in sexual health clinics in England with the 4CMenB vaccine be considered. Development of gonorrhoea-specific vaccines should prioritise maximising efficacy over duration of protection. FUNDING: Medical Research Council (UK), National Institute for Health Research (UK).

The J-IDEA Pandemic Planner: A Framework for Implementing Hospital Provision Interventions During the COVID-19 Pandemic.

BACKGROUND: Planning for extreme surges in demand for hospital care of patients requiring urgent life-saving treatment for coronavirus disease 2019 (COVID-19), while retaining capacity for other emergency conditions, is one of the most challenging tasks faced by health care providers and policymakers during the pandemic. Health systems must be well-prepared to cope with large and sudden changes in demand by implementing interventions to ensure adequate access to care. We developed the first planning tool for the COVID-19 pandemic to account for how hospital provision interventions (such as cancelling elective surgery, setting up field hospitals, or hiring retired staff) will affect the capacity of hospitals to provide life-saving care. METHODS: We conducted a review of interventions implemented or considered in 12 European countries in March to April 2020, an evaluation of their impact on capacity, and a review of key parameters in the care of COVID-19 patients. This information was used to develop a planner capable of estimating the impact of specific interventions on doctors, nurses, beds, and respiratory support equipment. We applied this to a scenario-based case study of 1 intervention, the set-up of field hospitals in England, under varying levels of COVID-19 patients. RESULTS: The Abdul Latif Jameel Institute for Disease and Emergency Analytics pandemic planner is a hospital planning tool that allows hospital administrators, policymakers, and other decision-makers to calculate the amount of capacity in terms of beds, staff, and crucial medical equipment obtained by implementing the interventions. Flexible assumptions on baseline capacity, the number of hospitalizations, staff-to-beds ratios, and staff absences due to COVID-19 make the planner adaptable to multiple settings. The results of the case study show that while field hospitals alleviate the burden on the number of beds available, this intervention is futile unless the deficit of critical care nurses is addressed first. DISCUSSION: The tool supports decision-makers in delivering a fast and effective response to the pandemic. The unique contribution of the planner is that it allows users to compare the impact of interventions that change some or all inputs.

Adapting hospital capacity to meet changing demands during the COVID-19 pandemic.

BACKGROUND: To calculate hospital surge capacity, achieved via hospital provision interventions implemented for the emergency treatment of coronavirus disease 2019 (COVID-19) and other patients through March to May 2020; to evaluate the conditions for admitting patients for elective surgery under varying admission levels of COVID-19 patients. METHODS: We analysed National Health Service (NHS) datasets and literature reviews to estimate hospital care capacity before the pandemic (pre-pandemic baseline) and to quantify the impact of interventions (cancellation of elective surgery, field hospitals, use of private hospitals, deployment of former medical staff and deployment of newly qualified medical staff) for treatment of adult COVID-19 patients, focusing on general and acute (G&A) and critical care (CC) beds, staff and ventilators. RESULTS: NHS England would not have had sufficient capacity to treat all COVID-19 and other patients in March and April 2020 without the hospital provision interventions, which alleviated significant shortfalls in CC nurses, CC and G&A beds and CC junior doctors. All elective surgery can be conducted at normal pre-pandemic levels provided the other interventions are sustained, but only if the daily number of COVID-19 patients occupying CC beds is not greater than 1550 in the whole of England. If the other interventions are not maintained, then elective surgery can only be conducted if the number of COVID-19 patients occupying CC beds is not greater than 320. However, there is greater national capacity to treat G&A patients: without interventions, it takes almost 10,000 G&A COVID-19 patients before any G&A elective patients would be unable to be accommodated. CONCLUSIONS: Unless COVID-19 hospitalisations drop to low levels, there is a continued need to enhance critical care capacity in England with field hospitals, use of private hospitals or deployment of former and newly qualified medical staff to allow some or all elective surgery to take place.

Comparison of molecular testing strategies for COVID-19 control: a mathematical modelling study.

BACKGROUND: WHO has called for increased testing in response to the COVID-19 pandemic, but countries have taken different approaches and the effectiveness of alternative strategies is unknown. We aimed to investigate the potential impact of different testing and isolation strategies on transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We developed a mathematical model of SARS-CoV-2 transmission based on infectiousness and PCR test sensitivity over time since infection. We estimated the reduction in the effective reproduction number (R) achieved by testing and isolating symptomatic individuals, regular screening of high-risk groups irrespective of symptoms, and quarantine of contacts of laboratory-confirmed cases identified through test-and-trace protocols. The expected effectiveness of different testing strategies was defined as the percentage reduction in R. We reviewed data on the performance of antibody tests reported by the Foundation for Innovative New Diagnostics and examined their implications for the use of so-called immunity passports. FINDINGS: If all individuals with symptoms compatible with COVID-19 self-isolated and self-isolation was 100% effective in reducing onwards transmission, self-isolation of symptomatic individuals would result in a reduction in R of 47% (95% uncertainty interval [UI] 32-55). PCR testing to identify SARS-CoV-2 infection soon after symptom onset could reduce the number of individuals needing to self-isolate, but would also reduce the effectiveness of self-isolation (around 10% would be false negatives). Weekly screening of health-care workers and other high-risk groups irrespective of symptoms by use of PCR testing is estimated to reduce their contribution to SARS-CoV-2 transmission by 23% (95% UI 16-40), on top of reductions achieved by self-isolation following symptoms, assuming results are available at 24 h. The effectiveness of test and trace depends strongly on coverage and the timeliness of contact tracing, potentially reducing R by 26% (95% UI 14-35) on top of reductions achieved by self-isolation following symptoms, if 80% of cases and contacts are identified and there is immediate testing following symptom onset and quarantine of contacts within 24 h. Among currently available antibody tests, performance has been highly variable, with specificity around 90% or lower for rapid diagnostic tests and 95-99% for laboratory-based ELISA and chemiluminescent assays. INTERPRETATION: Molecular testing can play an important role in prevention of SARS-CoV-2 transmission, especially among health-care workers and other high-risk groups, but no single strategy will reduce R below 1 at current levels of population immunity. Immunity passports based on antibody tests or tests for infection face substantial technical, legal, and ethical challenges. FUNDING: UK Medical Research Council.

Understanding Relationships Between Chlamydial Infection, Symptoms, and Testing Behavior: An Analysis of Data from Natsal-3.

BACKGROUND: Genital chlamydia is the most commonly diagnosed sexually transmitted infection worldwide and can have serious long-term sequelae. Numerous countries invest substantially in testing but evidence for programs' effectiveness is inconclusive. It is important to understand the effects of testing programs in different groups of people. METHODS: We analyzed data on sexual behavior and chlamydia tests from 16-to 24-year olds in Britain's third National Survey of Sexual Attitudes and Lifestyles, considering test setting, reason, and result. We conducted descriptive analysis accounting for survey design and nonresponse, and Bayesian analysis using a mathematical model. RESULTS: Most men testing due to symptoms tested in sexual health settings (63%; 95% confidence interval 43%-84%) but most women testing due to symptoms were tested by general practitioners (59%; 43%-76%). Within behavioral groups, positivity of chlamydia screens (tests not prompted by symptoms or partner notification) was similar to population prevalence. Screening rates were higher in women and in those reporting more partners: median (95% credible interval) rates per year in men were 0.30 (0.25-0.36) (0 new partners), 0.45 (0.37-0.54) (1 new partner), and 0.60 (0.50-0.73) (≥2 new partners). In women, they were 0.61 (0.53-0.69) (0 new partners), 0.89 (0.75-1.04) (1 new partner), and 1.2 (1.0-1.4) (≥2 new partners). CONCLUSIONS: Proportion of testing occurring in sexual health is not a proxy for proportion prompted by symptoms. Test positivity depends on a combination of force of infection and screening rate and does not simply reflect prevalence or behavioral risk. The analysis highlights the value of recording testing reason and behavioral characteristics to inform cost-effective control.

Assessing local chlamydia screening performance by combining survey and administrative data to account for differences in local population characteristics.

Reducing health inequalities requires improved understanding of the causes of variation. Local-level variation reflects differences in local population characteristics and health system performance. Identifying low- and high-performing localities allows investigation into these differences. We used Multilevel Regression with Post-stratification (MRP) to synthesise data from multiple sources, using chlamydia testing as our example. We used national probability survey data to identify individual-level characteristics associated with chlamydia testing and combined this with local-level census data to calculate expected levels of testing in each local authority (LA) in England, allowing us to identify LAs where observed chlamydia testing rates were lower or higher than expected, given population characteristics. Taking account of multiple covariates, including age, sex, ethnicity, student and cohabiting status, 5.4% and 3.5% of LAs had testing rates higher than expected for 95% and 99% posterior credible intervals, respectively; 60.9% and 50.8% had rates lower than expected. Residual differences between observed and MRP expected values were smallest for LAs with large proportions of non-white ethnic populations. London boroughs that were markedly different from expected MRP values (≥90% posterior exceedance probability) had actively targeted risk groups. This type of synthesis allows more refined inferences to be made at small-area levels than previously feasible.

Changes in chlamydia prevalence and duration of infection estimated from testing and diagnosis rates in England: a model-based analysis using surveillance data, 2000-15.

BACKGROUND: Chlamydia screening programmes have been implemented in several countries, but the effects of screening on incidence, prevalence, and reproductive sequelae remain unclear. In England, despite increases in testing with the rollout of the National Chlamydia Screening Programme (NCSP; 2003-08), prevalence estimated in 10-yearly population-based surveys was similar before (1999-2001) and after (2010-12) the programme. However, the precision of these previous estimates was limited by the low numbers of infections. We aimed to establish annual, rather than 10-yearly, estimates of chlamydia prevalence and infection duration. METHODS: In this model-based analysis, we used previously published minimum and maximum estimates and Public Health England data for chlamydia test coverage and diagnoses in men and women aged 15-24 years in England, before, during, and after the scale-up of national chlamydia screening. We used a mechanistic model, which accounted for symptomatic chlamydia testing and asymptomatic screening, to estimate changes in prevalence and average duration of infections for each year. We describe estimates derived from the maximum and minimum numbers of tests and diagnoses as maximum and minimum estimates, regardless of their relative magnitude. FINDINGS: The data included numbers of tests and diagnoses in men and women aged 15-19 years and 20-24 years in England each year from 2000 to 2015. We estimated reductions in prevalence and average infection duration in both sexes once screening was fully implemented. From 2008 to 2010, estimated posterior median prevalence reductions in people aged 15-24 years were 0·68 percentage points (95% credible interval 0·26-1·40; minimum) and 0·66 percentage points (0·25-1·37; maximum) for men and 0·77 percentage points (0·45-1·27) for women (minimum and maximum estimates were the same for women). Over the same time period, mean duration of infection reduced by 75 days (95% credible interval 17-255; minimum) and 74 days (95% credible interval 17-247; maximum) in men and 30 days (22-40) in women. Since 2010, some of the progress made by the NCSP has been reversed, alongside a reduction in testing. INTERPRETATION: Our analysis provides the first evidence for a reduction in chlamydia prevalence in England concurrent with large-scale population testing. It also shows a consistent decline in the average duration of infections, which is a measure of screening effectiveness that is unaffected by behavioural changes. FUNDING: National Institute for Health Research, Medical Research Council.

Comparing different technologies for active TB case-finding among the homeless: a transmission-dynamic modelling study.

Homeless persons have elevated risk of tuberculosis (TB) and are under-served by conventional health services. Approaches to active case-finding (ACF) and treatment tailored to their needs are required. A transmission-dynamic model was developed to assess the effectiveness and efficiency of screening with mobile Chest X-ray, GeneXpert, or both. Effectiveness of ACF depends upon the prevalence of infection in the population (which determines screening 'yield'), patient willingness to wait for GeneXpert results, and treatment adherence. ACF is efficient when TB prevalence exceeds 78/100,000 and 46% of drug sensitive TB cases and 33% of multi-drug resistant TB cases complete treatment. This threshold increases to 92/100,000 if additional post-ACF enhanced case management (ECM) increases treatment completion to 85%. Generally, the most efficient option is one-step screening of all patients with GeneXpert, but if too many patients (>27% without ECM, >19% with ECM) are unwilling to wait the 90 minutes required then two-step screening using chest X-ray (which is rapid) followed by GeneXpert for confirmation of TB is the most efficient option. Targeted ACF and support services benefit health through early successful treatment and averting TB transmission and disease. The optimal strategy is setting-specific, requiring careful consideration of patients' needs regarding testing and treatment.

Prevalence of and risk factors for active tuberculosis in migrants screened before entry to the UK: a population-based cross-sectional study.

BACKGROUND: An increasing number of countries with low incidence of tuberculosis have pre-entry screening programmes for migrants. We present the first estimates of the prevalence of and risk factors for tuberculosis in migrants from 15 high-incidence countries screened before entry to the UK. METHODS: We did a population-based cross-sectional study of applicants for long-term visas who were screened for tuberculosis before entry to the UK in a pilot programme between Oct 1, 2005, and Dec 31, 2013. The primary outcome was prevalence of bacteriologically confirmed tuberculosis. We used Poisson regression to estimate crude prevalence and created a multivariable logistic regression model to identify risk factors for the primary outcome. FINDINGS: 476 455 visa applicants were screened, and the crude prevalence of bacteriologically confirmed tuberculosis was 92 (95% CI 84-101) per 100 000 individuals. After adjustment for age and sex, factors that were strongly associated with an increased risk of bacteriologically confirmed disease at pre-entry screening were self-report of close or household contact with an individual with tuberculosis (odds ratio 11·6, 95% CI 7·0-19·3; p<0·0001) and being an applicant for settlement and dependant visas (1·3, 1·0-1·6; p=0·0203). INTERPRETATION: Migrants reporting contact with an individual with tuberculosis had the highest risk of tuberculosis at pre-entry screening. To tackle this disease burden in migrants, a comprehensive and collaborative approach is needed between countries with pre-entry screening programmes, health services in the countries of origin and migration, national tuberculosis control programmes, and international public health bodies. FUNDING: Wellcome Trust, Medical Research Council, and UK National Institute for Health Research.

Pre-entry screening programmes for tuberculosis in migrants to low-incidence countries: a systematic review and meta-analysis.

BACKGROUND: Several high-income countries have pre-entry screening programmes for tuberculosis. We aimed to establish the yield of pre-entry screening programmes to inform evidence-based policy for migrant health screening. METHODS: We searched six bibliographic databases for experimental or observational studies and systematic reviews, which reported data on migrant screening for active or latent tuberculosis by any method before migration to a low-incidence country. Primary outcomes were principal reported screening yield of active tuberculosis, yield of culture-confirmed cases, and yield of sputum smear for acid-fast bacilli cases. Where appropriate, fixed-effects models were used to summarise the yield of pre-entry screening across included studies. FINDINGS: We identified 15 unique studies with data for 3 739 266 migrants screened pre-entry for tuberculosis between 1982 and 2010. Heterogeneity was high for all primary outcomes. After stratification by prevalence in country of origin, heterogeneity was reduced for culture-confirmed and smear-confirmed cases. Yield of culture-confirmed cases increased with prevalence in the country of origin, and summary estimates ranged from 19·7 (95% CI 10·3-31·5) cases identified per 100 000 individuals screened in countries with a prevalence of 50-149 cases per 100 000 population to 335·9 (283·0-393·2) per 100 000 in countries with a prevalence of greater than 350 per 100 000 population. INTERPRETATION: Targeting high-prevalence countries could result in the highest yield for active disease. Pre-entry screening should be considered as part of a broad package of measures to ensure early diagnosis and effective management of migrants with active tuberculosis, and be integrated with initiatives that address the health needs of migrants. FUNDING: Wellcome Trust, UK National Institute for Health Research, Medical Research Council, Public Health England.

Congenital chondrodystrophy of unknown origin in beef herds.

Congenital chondrodystrophy of unknown origin (CCUO), often referred to as 'acorn calf disease' or congenital joint laxity and dwarfism (CJLD), has been reported in beef cattle in Canada, the United States, Europe, South Africa, New Zealand and Australia. An association of CCUO with grazing drought-affected pastures, feeding hay-only or silage-only diets or supplementation with apple pulp suggests a nutritional cause such as a mineral deficiency. This review compares published reports on CCUO in order to identify common features among outbreaks and to provide a basis for future research into the condition. A protocol for investigation of outbreaks is provided to improve the outcome of future comparisons.

Dedicated outreach service for hard to reach patients with tuberculosis in London: observational study and economic evaluation.

OBJECTIVE: To assess the cost effectiveness of the Find and Treat service for diagnosing and managing hard to reach individuals with active tuberculosis. DESIGN: Economic evaluation using a discrete, multiple age cohort, compartmental model of treated and untreated cases of active tuberculosis. SETTING: London, United Kingdom. Population Hard to reach individuals with active pulmonary tuberculosis screened or managed by the Find and Treat service (48 mobile screening unit cases, 188 cases referred for case management support, and 180 cases referred for loss to follow-up), and 252 passively presenting controls from London's enhanced tuberculosis surveillance system. MAIN OUTCOME MEASURES: Incremental costs, quality adjusted life years (QALYs), and cost effectiveness ratios for the Find and Treat service. RESULTS: The model estimated that, on average, the Find and Treat service identifies 16 and manages 123 active cases of tuberculosis each year in hard to reach groups in London. The service has a net cost of £1.4 million/year and, under conservative assumptions, gains 220 QALYs. The incremental cost effectiveness ratio was £6400-£10,000/QALY gained (about €7300-€11,000 or $10,000-$16 000 in September 2011). The two Find and Treat components were also cost effective, even in unfavourable scenarios (mobile screening unit (for undiagnosed cases), £18,000-£26,000/QALY gained; case management support team, £4100-£6800/QALY gained). CONCLUSIONS: Both the screening and case management components of the Find and Treat service are likely to be cost effective in London. The cost effectiveness of the mobile screening unit in particular could be even greater than estimated, in view of the secondary effects of infection transmission and development of antibiotic resistance.

Screening of immigrants in the UK for imported latent tuberculosis: a multicentre cohort study and cost-effectiveness analysis.

BACKGROUND: Continuing rises in tuberculosis notifications in the UK are attributable to cases in foreign-born immigrants. National guidance for immigrant screening is hampered by a lack of data about the prevalence of, and risk factors for, latent tuberculosis infection in immigrants. We aimed to determine the prevalence of latent infection in immigrants to the UK to define which groups should be screened and to quantify cost-effectiveness. METHODS: In our multicentre cohort study and cost-effectiveness analysis we analysed demographic and test results from three centres in the UK (from 2008 to 2010) that used interferon-γ release-assay (IGRA) to screen immigrants aged 35 years or younger for latent tuberculosis infection. We assessed factors associated with latent infection by use of logistic regression and calculated the yields and cost-effectiveness of screening at different levels of tuberculosis incidence in immigrants' countries of origin with a decision analysis model. FINDINGS: Results for IGRA-based screening were positive in 245 of 1229 immigrants (20%), negative in 982 (80%), and indeterminate in two (0·2%). Positive results were independently associated with increases in tuberculosis incidence in immigrants' countries of origin (p=0·0006), male sex (p = 0·046), and age (p < 0·0001). National policy thus far would fail to detect 71% of individuals with latent infection. The two most cost-effective strategies were to screen individuals from countries with a tuberculosis incidence of more than 250 cases per 100,000 (incremental cost-effectiveness ratio [ICER] was £17,956 [£1=US$1·60] per prevented case of tuberculosis) and at more than 150 cases per 100,000 (including immigrants from the Indian subcontinent), which identified 92% of infected immigrants and prevented an additional 29 cases at an ICER of £20,819 per additional case averted. INTERPRETATION: Screening for latent infection can be implemented cost-effectively at a level of incidence that identifies most immigrants with latent tuberculosis, thereby preventing substantial numbers of future cases of active tuberculosis. FUNDING: Medical Research Council and Wellcome Trust.

Risk factors for congenital chondrodystrophy of unknown origin in beef cattle herds in south-eastern Australia.

A case-control study was conducted on 46 farms in south-eastern Australia with a recent history of congenital chondrodystrophy of unknown origin (CCUO) between 2002 and 2007. For each farm data was collected using face-to-face interviews concerning the management of case and control mobs during the gestation period in which affected calves were born. Data concerning the paddocks in which gestating cattle were maintained was also collected for analysis. Three separate multivariable models were constructed using generalised linear mixed models (GLMMs). The first model was based on the dichotomous outcome of mob status (affected/not affected) and included explanatory variables for management and environment factors. The second model used a novel approach, taking into account the number of cases in affected mobs in order to utilise available data. The outcome events/trials was used where the numerator was equal to the number of affected calves in a mob, and the denominator was equal to the total number of calves in the mob. The third model used the dichotomous outcome paddock status and included environmental and soil variables for paddocks involved with case and control mobs. Confounding for dam age and year affected was included in the mob outcome models, and random effects for paddock and farm were incorporated into the models. The birth of CCUO calves was associated with dams grazing native pastures on hilly terrain during gestation. Low levels of pasture were also associated with the outcome. The two models used for the mob outcome were similar in many respects. The events/trial model included the use of supplemental feed and an interaction term. This study demonstrates an association between a maternal nutritional disturbance and the occurrence of CCUO.

The association between congenital chondrodystrophy of unknown origin (CCUO) in beef cattle and drought in south-eastern Australia.

Reports of congenital chondrodystrophy of unknown origin (CCUO) have been anecdotally associated with periods of drought during the gestation period of affected beef calves. Reported sporadically in the past, the incidence of CCUO has increased in south-eastern Australia and has been reported every year between 2002 and 2007. A maternal nutritional deficiency arising from poor quality pastures and supplements has been suggested as contributing to the disorder. With an increase in drought occurrence predicted by climate change models, it is possible that the incidence will increase into the future. Retrospective data collected during a case control study was used to determine if the occurrence of cases of CCUO was associated with rainfall deficiency during gestation. A total of 799 cases occurring on 46 farms in south-eastern Australia were identified and a time series of cases was created. The association of both average monthly and three-month average rainfall with cases of CCUO revealed a significant negative correlation (r=-0.29 and r=-0.37 respectively, P<0.05) five months prior to the birth of CCUO calves on the farms studied. Logistic regression analysis showed a 3.3 (CI 1.8; 5.8, P<0.001) times increased risk of CCUO calves when the three-month average rainfall was in the lowest decile five months prior to the birth of calves. This information may be used to alert farmers as to when high quality supplemental feed may be provided to improve maternal nutrition and reduce the number of CCUO calves born.