Spatial clusters of gonorrhoea in England with particular reference to the outcome of partner notification: 2012 and 2013

Background: This study explored spatial-temporal variation in diagnoses of gonorrhoea to identify and quantify endemic areas and clusters in relation to patient characteristics and outcomes of partner notification (PN) across England, UK. Methods: Endemic areas and clusters were identified using a two-stage analysis with Kulldorff’s scan statistics (SaTScan). Results Of 2,571,838 tests, 53,547 diagnoses were gonorrhoea positive (positivity = 2.08%). The proportion of diagnoses in heterosexual males was 1.5 times that in heterosexual females. Among index cases, men who have sex with men (MSM) were 8 times more likely to be diagnosed with gonorrhoea than heterosexual males (p<0.0001). After controlling for age, gender, ethnicity and deprivation rank, 4 endemic areas were identified including 11,047 diagnoses, 86% of which occurred in London. 33 clusters included 17,629 diagnoses (34% of total diagnoses in 2012 and 2013) and spanned 21 locations, some of which were dominated by heterosexually acquired infection, whilst others were MSM focused. Of the 53,547 diagnoses, 14.5% (7,775) were the result of PN. The proportion of patients who attended services as a result of PN varied from 0% to 61% within different age, gender and sexual orientation cohorts. A third of tests resulting from PN were positive for gonorrhoea. 25% of Local Authorities (n = 81, 95% CI: 20.2, 29.5) had a higher than expected proportion for female PN diagnoses as compared to 16% for males (n = 52, 95% CI: 12.0, 19.9). Conclusions: The English gonorrhoea epidemic is characterised by spatial-temporal variation. PN success varied between endemic areas and clusters. Greater emphasis should be placed on the role of PN in the control of gonorrhoea to reduce the risk of onward transmission, re-infection, and complications of infection

Epidemiology of Sexually Transmitted Infections in Visitors for the London 2012 Olympic Games: A Review of Attendees at Sexual Health Services

BACKGROUND: Mass gatherings and large sporting events, such as the Olympics, may potentially pose a risk of increased sexually transmitted infection (STI) transmission and increase burden on local STI services. The objectives of this analysis were to assess whether the STI profile of Olympic visitors differed from that of the local STI clinic population and to investigate what impact these visitors had on local STI services. METHODS: Self-administered questionnaires (completed by 29,292 patients) were used to determine the visitor status of patients attending 20 STI clinics, between July 20, 2012, and September 16, 2012, in the host cities, London and Weymouth. Using routine surveillance data from the Genitourinary Medicine Clinic Activity Dataset version 2, Olympic visitors were compared with usual attendees (local residents and non-Olympic visitors) in terms of their demographic characteristics, services utilized, and STIs diagnosed using univariate and multivariate methods. RESULTS: Compared with usual attendees, Olympic visitors were more likely to be heterosexual males (56.0% vs. 34.9%, P = 0.001), aged between 15 and 24 years of age (47.1% vs. 34.0%, P = 0.001), of white ethnicity (81.9% vs. 66.4%, P = 0.001), and born in Australasia, Asia, North America, or South America (18.8% vs. 12.0%, P = 0.006). Olympic visitors constituted 1% of new clinic attendances and were less likely to be diagnosed as having a new STI (adjusted odds ratio, 0.69; 95% confidence interval, 0.48–0.98; P = 0.040). CONCLUSIONS: In this first multisite study to examine the effect of Olympic visitors on local sexual health services, the 2012 Olympic Games was found to have minimal impact. This suggests that a “business as usual” approach would have been sufficient

Practical observations - the COVID-19 influence on Latvian early intervention work with first episode psychosis (FEP) patients

publishersversionPeer reviewe

Infant hospitalisations and fatalities averted by the maternal pertussis vaccination programme in England, 2012-2017: Post-implementation economic evaluation

In October 2012, a maternal pertussis vaccination programme was implemented in England following an increased incidence and mortality in infants. We evaluated the cost-effectiveness of the programme by comparing pertussis-related infant hospitalisations and deaths in 2012-2017 with non-vaccination scenarios. Despite considerable uncertainties, findings support the cost-effectiveness of the programme

Preferences for First-Line Chronic Lymphocytic Leukemia Treatments: Results From a Multinational Study on the Perspectives of Patients and Physicians

Bersabeh Sile,1 Dipen Patel,2 Dahbia Horchi,3 Bleuenn Rault,3 Emily Mulvihill,4 Kathleen Beusterien,4 Katherine Stewart,2 Paulo Miranda,2 Xavier Guillaume3 1AstraZeneca, Cambridge, UK; 2AstraZeneca, Gaithersburg, MD, USA; 3Oracle Life Sciences, Paris, France; 4Oracle Life Sciences, North Kansas City, MO, USACorrespondence: Xavier Guillaume, Oracle Life Sciences, 198 Avenue de France, Paris, 75013, France, Tel + 33 6 14 57 45 95, Email [email protected]: Few studies have explored physician and patient preferences for the treatment of chronic lymphocytic leukemia (CLL) related to treatment efficacy, adverse events (AEs), and treatment duration. Thus, this observational, mixed-methods study investigated patients’ and physicians’ preferences for CLL first-line treatments.Materials and Methods: An online discrete choice experiment in five countries among 192 patients and 259 physicians in the US, the UK, Germany, France, and Australia examined the importance of outcomes and treatment attributes.Results: Increasing 5-year progression-free survival (5-year PFS) was most important to patients and physicians, with a relative importance (RI) of 30.3% among patients and 37.8% among physicians, followed by reducing the risks of common side effects (RI 21.6% among patients, 22.9% among physicians) and adverse events (AEs) leading to treatment discontinuation (RI 22.1% among patients, 20.6% among physicians). Patients strongly preferred time limited treatment regimen over treatment to progression (TTP). Specifically, patients and physicians would require a 6.4% vs 2.3% increase in 5-year PFS, a 19.4% vs 8.9% decrease in the risk of common all grades side effects, and a 7.5% vs 3.7% decrease in the risk of treatment discontinuation due to AEs, respectively, to compensate for a daily oral medication taken indefinitely vs daily oral medication taken for 24 months.Conclusion: Overall, patients and physicians favor time-limited treatment regimens over TTP and value treatments with greater PFS benefits followed by lower side effects. Patients and physicians were both willing to trade-off switching from time-limited treatment to TTP for a better 5-year PFS, decrease side effects, and risk of treatment discontinuation due to AEs.Keywords: chronic lymphocytic leukemia, first-line treatment, discrete choice experiment, fixed-duration treatment, patient and physician preference

Personalised risk-prediction tools for cryptococcal meningitis mortality to guide treatment stratification in sub-Saharan Africa: a prognostic modelling study based on pooled analysis of two randomised controlled trials

Background: Cryptococcal meningitis is a major driver of global HIV-related mortality, and validated approaches to stratify mortality risk could help to target effective treatment strategies. We aimed to develop and validate models to predict risk of all-cause mortality in people with HIV-associated cryptococcal meningitis in sub-Saharan African countries. Methods: For this prediction modelling study, we pooled individual-level data from the ACTA (ISRCTN45035509) and AMBITION-cm (ISRCTN72509687) randomised controlled trials. Data in ACTA were collected between Feb 12, 2013, and Jan 10, 2017, and data in AMBITION-cm were collected between Jan 31, 2018, and June 11, 2021. Adults aged 18 years or older with a first episode of HIV-associated cryptococcal meningitis were recruited to both trials. Exclusion criteria included pregnancy or lactation; receipt of high-dose anti-fungal treatment doses before screening; and contraindications to trial medication. Participants were recruited from nine hospitals across Cameroon, Malawi, Tanzania, and Zambia in ACTA and eight hospitals across Botswana, Malawi, South Africa, Uganda, and Zimbabwe in AMBITION-cm. We developed two primary multivariable logistic-regression models for the primary outcome of 2-week mortality: a basic model for use in a resource-limited setting that contained only candidate predictors that are routinely, programmatically obtained at hospital admission and a research model for which all predefined candidate predictors were considered for inclusion. We used internal–external cross-validation to evaluate model performance across countries within the development cohort (ie, data from all countries except Malawi participants in AMBITION-cm), before validation of discrimination, calibration, and net benefit in held-out data from Malawi. Findings: We included 674 eligible participants from ACTA and 814 from AMBITION-cm in the pooled analysis (total sample size 1488). 1263 participants were included in model development, with 225 from the Malawi site in AMBITION-cm held out for validation. 222 (17·6%) of 1263 participants in the development set and 21 (9·3%) of 225 participants in the validation set met the primary model outcome of 2-week mortality. We retained five predictors in the basic model and seven in the research model. Predictors in both models were Glasgow Coma Scale score, Eastern Cooperative Oncology Group performance status, haemoglobin, blood neutrophil count, and treatment. Additional predictors in the research model were cerebrospinal fluid opening pressure and log10 cerebrospinal fluid quantitative cryptococcal culture. Discrimination was relatively consistent between study sites for both models (pooled C statistic 0·75 [95% CI 0·68–0·82] for the basic model and 0·78 [0·75–0·82] for the research model), but calibration was more heterogeneous (pooled calibration slope 0·87 [95% CI 0·57 to 1·17] and 0·83 [0·69 to 0·97], pooled calibration in the large 0·00 [–0·54 to 0·55] and –0·02 [–0·46 to 0·42], for the basic and research models, respectively). In held-out validation, discrimination of both models was slightly higher than estimates from internal–external cross-validation (C statistic 0·78 [95% CI 0·70–0·87] in the basic model and 0·85 [0·79–0·92] in the research model). Calibration assessment suggested overestimation of risk, particularly in the high-risk range: calibration slope 1·04 (95% CI 0·54 to 1·55), calibration in the large –0·55 (–1·02 to –0·07). When comparing single, high-dose liposomal amphotericin B plus 14 days of flucytosine plus fluconazole with 1 week of amphotericin B plus flucytosine in AMBITION-cm, hazard ratios were 0·50 (95% CI 0·26–0·97) in the low-risk stratum and 0·96 (0·67–1·37) in the high-risk stratum for the basic model, and 0·61 (0·31–1·18) in the low-risk stratum and 1·03 (0·72–1·47) in the high-risk stratum for the research model. Interpretation: Both models accurately predicted 2-week mortality in people with HIV and have the potential to be incorporated into future treatment-stratification approaches in low-income and middle-income countries. Funding: National Institute for Health Research

Roadmap for Optical Tweezers 2023

Optical tweezers are tools made of light that enable contactless pushing, trapping, and manipulation of objects ranging from atoms to space light sails. Since the pioneering work by Arthur Ashkin in the 1970s, optical tweezers have evolved into sophisticated instruments and have been employed in a broad range of applications in life sciences, physics, and engineering. These include accurate force and torque measurement at the femtonewton level, microrheology of complex fluids, single micro- and nanoparticle spectroscopy, single-cell analysis, and statistical-physics experiments. This roadmap provides insights into current investigations involving optical forces and optical tweezers from their theoretical foundations to designs and setups. It also offers perspectives for applications to a wide range of research fields, from biophysics to space exploration

Personalised risk-prediction tools for cryptococcal meningitis mortality to guide treatment stratification in sub-Saharan Africa: a prognostic modelling study based on pooled analysis of two randomised controlled trials

Background: Cryptococcal meningitis is a major driver of global HIV-related mortality, and validated approaches to stratify mortality risk could help to target effective treatment strategies. We aimed to develop and validate models to predict risk of all-cause mortality in people with HIV-associated cryptococcal meningitis in sub-Saharan African countries. Methods: For this prediction modelling study, we pooled individual-level data from the ACTA (ISRCTN45035509) and AMBITION-cm (ISRCTN72509687) randomised controlled trials. Data in ACTA were collected between Feb 12, 2013, and Jan 10, 2017, and data in AMBITION-cm were collected between Jan 31, 2018, and June 11, 2021. Adults aged 18 years or older with a first episode of HIV-associated cryptococcal meningitis were recruited to both trials. Exclusion criteria included pregnancy or lactation; receipt of high-dose anti-fungal treatment doses before screening; and contraindications to trial medication. Participants were recruited from nine hospitals across Cameroon, Malawi, Tanzania, and Zambia in ACTA and eight hospitals across Botswana, Malawi, South Africa, Uganda, and Zimbabwe in AMBITION-cm. We developed two primary multivariable logistic-regression models for the primary outcome of 2-week mortality: a basic model for use in a resource-limited setting that contained only candidate predictors that are routinely, programmatically obtained at hospital admission and a research model for which all predefined candidate predictors were considered for inclusion. We used internal–external cross-validation to evaluate model performance across countries within the development cohort (ie, data from all countries except Malawi participants in AMBITION-cm), before validation of discrimination, calibration, and net benefit in held-out data from Malawi. Findings: We included 674 eligible participants from ACTA and 814 from AMBITION-cm in the pooled analysis (total sample size 1488). 1263 participants were included in model development, with 225 from the Malawi site in AMBITION-cm held out for validation. 222 (17·6%) of 1263 participants in the development set and 21 (9·3%) of 225 participants in the validation set met the primary model outcome of 2-week mortality. We retained five predictors in the basic model and seven in the research model. Predictors in both models were Glasgow Coma Scale score, Eastern Cooperative Oncology Group performance status, haemoglobin, blood neutrophil count, and treatment. Additional predictors in the research model were cerebrospinal fluid opening pressure and log10 cerebrospinal fluid quantitative cryptococcal culture. Discrimination was relatively consistent between study sites for both models (pooled C statistic 0·75 [95% CI 0·68–0·82] for the basic model and 0·78 [0·75–0·82] for the research model), but calibration was more heterogeneous (pooled calibration slope 0·87 [95% CI 0·57 to 1·17] and 0·83 [0·69 to 0·97], pooled calibration in the large 0·00 [–0·54 to 0·55] and –0·02 [–0·46 to 0·42], for the basic and research models, respectively). In held-out validation, discrimination of both models was slightly higher than estimates from internal–external cross-validation (C statistic 0·78 [95% CI 0·70–0·87] in the basic model and 0·85 [0·79–0·92] in the research model). Calibration assessment suggested overestimation of risk, particularly in the high-risk range: calibration slope 1·04 (95% CI 0·54 to 1·55), calibration in the large –0·55 (–1·02 to –0·07). When comparing single, high-dose liposomal amphotericin B plus 14 days of flucytosine plus fluconazole with 1 week of amphotericin B plus flucytosine in AMBITION-cm, hazard ratios were 0·50 (95% CI 0·26–0·97) in the low-risk stratum and 0·96 (0·67–1·37) in the high-risk stratum for the basic model, and 0·61 (0·31–1·18) in the low-risk stratum and 1·03 (0·72–1·47) in the high-risk stratum for the research model. Interpretation: Both models accurately predicted 2-week mortality in people with HIV and have the potential to be incorporated into future treatment-stratification approaches in low-income and middle-income countries. Funding: National Institute for Health Research