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Background Speech impairments are common with Parkinson’s disease (reported prevalence 68%), increasing conversational demands, reliance on family and social withdrawal. Objective(s) The PD COMM trial compared the clinical and cost-effectiveness of two speech and language therapy approaches: Lee Silverman Voice Treatment LOUD and National Health Service speech and language therapy for the treatment of speech or voice problems in people with Parkinson’s disease to no speech and language therapy (control) and against each other. Design PD COMM is a phase III, multicentre, three-arm, unblinded, randomised controlled trial. Participants were randomised in a 1 : 1 : 1 ratio to control, National Health Service speech and language therapy or Lee Silverman Voice Treatment LOUD via a central computer-generated programme, using a minimisation procedure with a random element, to ensure allocation concealment. Mixed-methods process and health economic evaluations were conducted. Setting United Kingdom outpatient and home settings. Participants People with idiopathic Parkinson’s disease, with self-reported or carer-reported speech or voice problems. We excluded people with dementia, laryngeal pathology and those within 24 months of previous speech and language therapy. Interventions The Lee Silverman Voice Treatment LOUD intervention included maximum effort drills and high-effort speech production tasks delivered over four 50-minute therapist-led personalised sessions per week, for 4 weeks with prescribed daily home practice. National Health Service speech and language therapy content and dosage reflected local non-Lee Silverman Voice Treatment speech and language therapy practices, usually 1 hour, once weekly, for 6 weeks. Trained, experienced speech and language therapists or assistants provided interventions. The control was no speech and language therapy until the trial was completed. Main outcome measures Primary outcome: Voice Handicap Index total score at 3 months. Secondary outcomes: Voice Handicap Index subscales, Parkinson’s Disease Questionnaire-39; Questionnaire on Acquired Speech Disorders; EuroQol-5D-5L; ICEpop Capabilities Measure for Older Adults; Parkinson’s Disease Questionnaire – Carers; resource utilisation; and adverse events. Assessments were completed pre-randomisation and at 3, 6 and 12 months post randomisation. Results Three hundred and eighty-eight participants were randomised to Lee Silverman Voice Treatment LOUD (n = 130), National Health Service speech and language therapy (n = 129) and control (n = 129). The impact of voice problems at 3 months after randomisation was lower for Lee Silverman Voice Treatment LOUD participants than control [−8.0 (99% confidence interval: −13.3, −2.6); p = 0.001]. There was no evidence of improvement for those with access to National Health Service speech and language therapy when compared to control [1.7 (99% confidence interval: −3.8, 7.1); p = 0.4]. Participants randomised to Lee Silverman Voice Treatment LOUD reported a lower impact of their voice problems than participants randomised to National Health Service speech and language therapy [99% confidence interval: −9.6 (−14.9, −4.4); p 70 years); disease severity measured using the Hoehn and Yahr staging (1.0–2.5, 3.0–5.0) and severity of speech measured using the Voice Handicap Index (VHI) total score (≤ 33, mild 34–44, moderate 45–61, severe > 61). To avoid any possibility of the treatment allocation becoming predictable, a random element was included within the randomisation process. Once the participant was randomised into the trial, they were given a unique trial identifier and the treatment allocation was confirmed by e-mail to the site. The primary outcome measure for the trial was patient-reported VHI total score at 3 months. The VHI measures the psychosocial consequences of voice disorders and provides an overall perception of effectiveness of voice-related communication. The VHI comprises of 30 questions (0–120 negatively scored) divided into emotional, functional and physical subscales (0–40 subscale score). Secondary outcomes were: the VHI subscales; the Parkinson’s Disease Questionnaire-39, a validated, health-related quality-of-life measure specific to PD; the Questionnaire on Acquired Speech Disorders, self-reported participation restriction related to speech and communication; the participant-rated EuroQol5D (5-level version) which provides a simple descriptive profile and a single index value for health status; the ICEpop Capabilities Measure for Older Adults (ICECAP-O), a measure of capability in older people for use in economic evaluations; a disease-specific participant resource usage questionnaire; carer quality of life, measured using the PD Questionnaire – carer; and adverse events. For participants in either SLT arm, any vocal strain or abuse believed to be associated with treatment was identified by the therapists at the participants’ SLT session and was reported in the adverse event log. All participant-reported resource usage forms completed for the trial were checked to ensure that no vocal strain or abuse had occurred in outpatient appointments with ENT specialists. At the 12-month clinical visit, the medical professional also checked whether any adverse events had occurred since entering the trial. There were two nested studies within this trial: a process evaluation and an economic evaluation. A process evaluation of the content of the interventions examined participants’ and therapists’ reported content of a subset of the two SLT interventions. Individual participant therapy data recorded by participants and therapists during the PD COMM trial were extracted from treatment record forms and therapy notes. Extraction category headings were piloted and reflected the Template for Intervention Description and Replication intervention reporting guidelines, with ongoing refinement as extraction progressed and components of the interventions were identified which were inadequately accounted for in the initial framework. The process evaluation of the implementation of the interventions used normalisation process theory which is highly attuned to the challenges of complex interventions as it encourages looking at systems as a whole. We considered that its conceptual framework would assist the interpretation and synthesis of data and analysis to explain what implementation processes took place and the interactions and gaps between the PD COMM interventions, the changing context, speech and language therapists and their practice. A within-trial economic evaluation in the form of cost–utility analysis was conducted from the perspective of the NHS. The primary results were expressed in terms of cost per quality-adjusted life-year (QALY) gained at 12 months for the three trial comparisons. Additional secondary analyses were performed from the NHS, personal social services perspective, broader societal perspective and using the capability approach, which uses broader measures of capability well-being. Results The mean age of participants in PD COMM was approximately 70 years old, and 74% were male (286/388). The mean duration of PD was between 5 and 6 years, with a broad range from newly diagnosed to over 30 years, and the majority (61%) were in Hoehn and Yahr stage of 2 or less (

Background Chronic limb-threatening ischaemia with ischaemic pain and/or tissue loss. Objective To examine the clinical and cost-effectiveness of a vein bypass-first compared to a best endovascular treatment-first revascularisation strategy in preventing major amputation or death. Design Superiority, open, pragmatic, multicentre, phase III randomised trial. Setting Thirty-nine vascular surgery units in the United Kingdom, and one each in Sweden and Denmark. Participants Patients with chronic limb-threatening ischaemia due to atherosclerotic peripheral arterial disease who required an infra-popliteal revascularisation, with or without an additional more proximal infra-inguinal revascularisation procedure, to restore limb perfusion. Interventions A vein bypass-first or a best endovascular treatment-first infra-popliteal, with or without an additional more proximal infra-inguinal revascularisation strategy. Main outcome measures The primary outcome was amputation-free survival. Secondary outcomes included overall survival, major amputation, further revascularisation interventions, major adverse limb event, health-related quality of life and serious adverse events. Methods Participants were randomised to a vein bypass-first or a best endovascular treatment-first revascularisation strategy. The original sample size of 600 participants (247 events) was based on a hazard ratio of 0.66 with amputation-free survival rates of 0.72, 0.62, 0.53, 0.47 and 0.35 in years 1–5 in the best endovascular treatment-first group with 90% power and alpha at p = 0.05. The sample size was revised to an event-based approach as a result of increased follow-up time due to slower than anticipated recruitment rates. Participants were followed up for a minimum of 2 years. A cost-effectiveness analysis was employed to estimate differences in total hospital costs and amputation-free survival between the groups. Additionally, a cost–utility analysis was carried out and the total cost and quality-adjusted life-years, 2 and 3 years after randomisation were used. Results Between 22 July 2014 and 30 November 2020, 345 participants were randomised, 172 to vein bypass-first and 173 to best endovascular treatment-first. Non-amputation-free survival occurred in 108 (63%) of 172 patients in the vein bypass-first group and 92 (53%) of 173 patients in the best endovascular treatment-first group [adjusted hazard ratio 1.35 (95% confidence interval 1.02 to 1.80); p = 0.037]. Ninety-one (53%) of 172 patients in the vein bypass-first group and 77 (45%) of 173 patients in the best endovascular treatment-first group died [adjusted hazard ratio 1.37 (95% confidence interval 1.00 to 1.87)]. Over follow-up, the economic evaluation discounted results showed that best endovascular treatment-first was associated with £1690 less hospital costs compared to vein bypass-first. The cost utility analysis showed that compared to vein bypass-first, best endovascular treatment-first was associated with £224 and £2233 less discounted hospital costs and 0.016 and 0.085 discounted quality-adjusted life-year gain after 2 and 3 years from randomisation. Limitations Recruiting patients to the Bypass versus Angioplasty in Severe Ischaemia of the Leg Trial-2 trial was difficult and the target number of events was not achieved. Conclusions A best endovascular treatment-first revascularisation strategy was associated with better amputation-free survival, which was largely driven by fewer deaths. Overall, the economic evaluation results suggest that best endovascular treatment-first dominates vein bypass-first in the cost-effectiveness analysis and cost–utility analysis as it was less costly and more effective than a vein bypass-first strategy. Future work The Bypass versus Angioplasty in Severe Ischaemia of the Leg Trial-2 investigators have a data sharing agreement with the BEst Surgical Therapy in patients with Chronic Limb threatening Ischaemia investigators. One output of this collaboration will be an individual patient data meta-analysis. Study registration Current Controlled Trials ISRCTN27728689. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/35/45) and is published in full in Health Technology Assessment; Vol. 28, No. 65. See the NIHR Funding and Awards website for further award information. Plain language summary Atherosclerosis, or narrowing of the arteries, can occur as a result of smoking, high blood pressure, diabetes, or high cholesterol in the blood. Atherosclerosis can affect any artery, including those supplying the legs, where the condition is called peripheral arterial disease. The most severe form of peripheral arterial disease is chronic limb-threatening ischaemia which can cause severe pain in the foot as well as ulcers and gangrene. Unless the blood supply to the leg and foot is improved, by a process called revascularisation, people with chronic limb-threatening ischaemia are at high risk of amputation and death. The blood supply can be improved by using a vein from the leg to bypass around the blockages (vein bypass) or by using a balloon (angioplasty) or small metal tubes (stents) to reopen the blocked arteries (best endovascular treatment). There is debate about which type of revascularisation is best in terms of preventing amputation and death, especially in people who need revascularisation of the arteries below the knee. Bypass versus Angioplasty in Severe Ischaemia of the Leg Trial-2 is the first randomised controlled trial to compare vein bypass-first and best endovascular treatment-first in this group of patients. Bypass versus Angioplasty in Severe Ischaemia of the Leg Trial-2 found that people randomised to a vein bypass-first revascularisation strategy were 35% more likely to require a major amputation or die than those randomised to a best endovascular treatment-first strategy. Most of this difference in favour of best endovascular treatment-first was due to a higher number of patients dying in the vein bypass-first group. Best endovascular treatment-first was also cheaper for the National Health Service. The results of this study suggest that in patients with chronic limb-threatening ischaemia due to peripheral arterial disease in the arteries below the knee, who are suitable for both vein bypass and best endovascular treatment and where there is uncertainty as to which is best, best endovascular treatment should be offered first rather than vein bypass. Scientific summary Background Chronic limb-threatening ischaemia (CLTI) is the severest manifestation of peripheral arterial disease (PAD) and presents with ischaemic pain at rest or tissue loss (ulceration, gangrene or both) or both. The researchers compared the effectiveness of a vein bypass (VB)-first with a best endovascular treatment (BET)-first revascularisation strategy in terms of preventing major amputation and death in patients with CLTI who required an infra-popliteal (IP) revascularisation, with or without an additional more proximal infra-inguinal revascularisation procedure, to restore limb perfusion. Objectives The primary objective of the study was to examine the effectiveness and cost-effectiveness of using a VB-first compared to a BET-first revascularisation strategy in terms of preventing major (above the ankle) amputation or death from any cause [amputation-free survival (AFS)] in patients with CLTI who required an IP, with or without an additional more proximal infra-inguinal revascularisation procedure, to restore limb perfusion. Design Superiority, open-label, pragmatic, multicentre, phase III randomised trial. Setting Thirty-nine vascular surgery units in the United Kingdom, and one each in Sweden and Denmark. Participants Those with CLTI due to atherosclerotic PAD and who required an IP revascularisation, with or without an additional more proximal infra-inguinal revascularisation procedure, to restore limb perfusion. Interventions A VB-first or a BET-first IP, with or without an additional more proximal infra-inguinal revascularisation strategy, to restore limb perfusion. Most VBs were constructed with great saphenous vein and originated from the common or superficial femoral arteries. Most endovascular interventions comprised plain balloon angioplasty with selective use of plain or drug-eluting stents. Outcome measures The primary outcome was AFS defined as time to first major (above the ankle) amputation or death from any cause. Secondary outcomes included: time to death from any cause (overall survival); time to major amputation of the trial leg; major adverse limb event (defined as major amputation of the trial leg, or any further major revascularisation intervention to the trial leg, following the first revascularisation intervention); major adverse cardiac event (defined as chronic limb-threatening ischaemia and/or major amputation affecting the non-trial leg, myocardial infarction, transient ischaemic attack or stroke); 30-day morbidity and mortality; relief of ischaemic pain as determined by visual analogue scale and opiate usage; health- related quality of life using generic [EuroQol-5 Dimensions, five-level version (EQ-5D-5L), Short Form questionnaire-12 items, ICEpop CAPability measure for Older people] and disease-specific (the Vascular Quality of Life Questionnaire) tools; further major revascularisation intervention to the trial leg (following the first revascularisation intervention); re-intervention and crossover intervention (where re-intervention is defined as the same, and a crossover procedure is defined as an alternative, revascularisation procedure to the first revascularisation procedure post-randomisation); healing of tissue loss (ulcers, gangrene) at or below the ankle presumed to be caused by PAD as assessed by the perfusion, extent, depth, infection and sensation score, the Wound Ischaemia and foot Infection tool; and haemodynamic measurements (ankle–brachial pressure index, and toe brachial pressure index). Serious adverse events were collected up to 30 days post first revascularisation. Economic evaluation analyses in the form of cost-effectiveness and cost–utility analysis (CUA) were conducted from the perspective of the UK NHS alongside the trial. The base case analyses considered only hospital costs and an additional scenario and subgroup analyses were carried out. Sample size The original sample size was based on a time-to-event analysis to be undertaken 2 years after completion of recruitment. It was anticipated that recruitment would take place over 3 years: 20% of patients recruited in year 1, 40% in year 2 and 40% in year 3. Based on the Bypass versus Angioplasty in Severe Ischaemia of the Leg Trial (BASIL-1) trial. AFS rates were assumed to be 0.72 in year 1, 0.62 in year 2, 0.53 in year 3, 0.47 in year 4 and 0.35 in year 5. Allowing for a 10% attrition rate and based on the survival estimates calculated using the BASIL-1 data, a population of 600 participants (247 primary outcome events) would have 90% power to detect a reduction in AFS of one-third [hazard ratio (HR) 0.66] at the 5% significance level. The initial assumptions made in this trial concerning recruitment rates were not achieved; therefore, recruitment continued beyond year 3. As a result, the median length of follow-up was longer than originally planned. Therefore, the number of randomised participants required to observe 247 events (as per the original sample size target) was reduced due to the increased exposure time. With support of the funder and independent oversight from the Data Monitoring Committee, recruitment rates, length of follow-up, and pooled event rates over time were modelled to predict the number of participants needed to reach 247 events, with 24 months minimum follow-up in each participant. The modelling was updated approximately every 6 months based on emerging data. Results Between 22 July 2014 and 30 November 2020, 345 participants were randomised, 172 to the VB-first group and 173 to the BET-first group. The baseline characteristics of the two groups were similar. Major amputation or death occurred in 108 (63%) of 172 patients in the VB-first group and 92 (53%) of 173 patients in the BET-first group {adjusted HR 1.35 [95% confidence interval (CI) 1.02 to 1.80]; p = 0.037}. Ninety-one (53%) of 172 patients in the VB-first group and 77 (45%) of 173 patients in the BET-first group died [adjusted HR 1.37 (95% CI 1.00 to 1.87)]. In both groups the commonest causes of morbidity and mortality, including those occurring within 30 days of their first revascularisation, were cardiovascular and respiratory events. Over follow-up, the economic evaluation results showed that BET-first was associated with £1690 less hospital costs compared to VB-first with additional survival without amputation. The cost utility analysis showed that compared to VB-first, BET-first was associated with £2524 and £2233 less hospital costs and 0.016 and 0.085 QALY gain after 2 and 3 years from randomisation. Conclusions In the BASIL-2 trial, a BET-first revascularisation strategy was associated with a better AFS, which was largely driven by fewer deaths in the BET-first group. In both the CUA and cost-effectiveness analysis (CEA) analyses and from a NHS and societal perspective BET-first dominated VB-first and is therefore a highly cost-effective intervention for the NHS. These data suggest a greater role for BET in the management of patients with CLTI who require an IP revascularisation to restore limb perfusion. In patients with CLTI who required an IP, with or without an additional more proximal infra-inguinal revascularisation procedure, to restore limb perfusion, a BET-first revascularisation strategy was associated with reduced hospital costs (£1690) and improved AFS (0.429 years), out to 7 years following randomisation. BET-first therefore dominated VB-first in the CEA. Similarly, in the health-related quality of life the CUA, BET-first was cost-saving with improved QALYs (£2524 and £2233 less hospital costs and 0.016 and 0.085 more QALYs at 2 and 3 years, respectively) and so dominated VB-first. This economic analysis therefore shows that BET-first is a cost-effective option from an NHS and societal perspective. The sensitivity analysis supported the base-case analysis and BET-first was found to be cost-effective at different willingness-to-pay thresholds. Similar findings were found in all other scenario analyses when considering costs of primary and other hospital healthcare services, taking a broader societal perspective, which includes out-of-pocket expenditure and the costs associated with productivity loss, patient’s adherence to study protocol, the impact of imputation by focusing on participants with complete hospital cost and EQ-5D-5L data only. However, these findings should be interpreted cautiously given the large number of imputed cost values and the substantial probability of a very small QALY difference. Study registration Current Controlled Trials ISRCTN27728689. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/35/45) and is published in full in Health Technology Assessment; Vol. 28, No. 65. See the NIHR Funding and Awards website for further award information.

In this work we performed a review regarding the improvement of microscopical optical imaging assisted by using microspheres, focusing on the most recent technologies. We have been reviewed the utilizing of the superlens and nanojet concepts in order to understand the working principles of microspheres in terms of magnification and resolution improvement. Some researches about the parameters effecting on microsphere imaging technique have been presented including the effect of microsphere’s material and size, the effect of immersion medium, and the plasmonic layer effect. Additionally, some applications that serve from this technique have been illustrated.

Background. Amoebiasis is one of the major public health problems, it is caused by the genus Entamoeba which includes several species, such as E. histolytica, E. dispar and E. moshkovskii. Purposes. The present study aimed to differentiate among Entamoeba spp. by using molecular method (PCR) and to identify characteristic serum markers (IgG and IL-6) according to species. Methods. About 697 stool samples were collected from children under five years old, and blood samples (3 ml) of venous blood were collected from patients with positive microscopic examination to evaluate some immune parameters (IL-6, IgG) for children infected with the parasite using the ELISA test. DNA extraction was carried out from fecal samples using a special stool DNA extraction kit and Multiplex PCR primers were designed to detect E. histolytica, E. dispar and E. moshkovskii. Results. About 100(14.34%) were infected with Entamoeba spp. by microscopic examination and 68 samples DNA-samples were positive. Fifty samples 50% were infected with E. histolytica, and 12% with a mixed infection. A significant increase (p≤0.05) in the concentration of IgG immunoglobulin in the sera of children infected with the E. histolytica parasite. A significant increase (p≤0.05) in the concentration of interleukin-6 in the sera of patients groups infected with Entamoeba spp., the highest significant increase (p≤0.05) was recorded in patients group infected with the E. moshkovskii. Conclusion. Molecular tests have the ability to detect and distinguish between the Entamoeba species infecting humans. Amoebiasis caused an increase in the concentration of IgG and interleukin-6.

Background Sexually transmitted infections disproportionately affect young people and men who have sex with men. Chlamydia is Britain’s most common sexually transmitted infection. Partner notification is a key intervention to reduce transmission of sexually transmitted infections and human immunodeficiency virus but is hard to implement. Accelerated partner therapy is a promising new approach. Objectives determine the effectiveness, costs and acceptability of accelerated partner therapy for chlamydia in heterosexual people model the cost effectiveness of accelerated partner therapy and impact on chlamydia transmission develop and cost partner notification interventions for men who have sex with men. Design Mixed-methods study to develop a new sex partner classification and optimise accelerated partner therapy; cluster crossover randomised controlled trial of accelerated partner therapy, with process and cost-consequence evaluation; dynamic modelling and health economic evaluation; systematic review of economic studies of partner notification for sexually transmitted infections in men who have sex with men; qualitative research to co-design a novel partner notification intervention for men who have sex with men with bacterial sexually transmitted infections. Settings Sexual health clinics and community services in England and Scotland. Participants Women and men, including men who have sex with men and people with mild learning disabilities. Interventions Accelerated partner therapy offered as an additional partner notification method. Main outcome measures Proportion of index patients with positive repeat chlamydia test (primary outcome); proportion of sex partners treated; costs per major outcome averted and quality-adjusted life-year; predicted chlamydia prevalence; experiences of accelerated partner therapy. Data sources Randomised controlled trial: partnership type, resource use, outcomes, qualitative data: economic analysis, modelling and systematic review: resource use and unit costs from the randomised controlled trial, secondary sources. Results The sex partner classification defined five types. Accelerated partner therapy modifications included simplified self-sampling packs and creation of training films. We created a clinical management and partner notification data collection system. In the randomised controlled trial, all 17 enrolled clinics completed both periods; 1536 patients were enrolled in the intervention phase and 1724 were enrolled in the control phase. Six hundred and sixty-six (43%) of 1536 index patients in the intervention phase and 800 (46%) of 1724 in the control phase were tested for Chlamydia trachomatis at 12–24 weeks after contact tracing consultation; 31 (4.7%) in the intervention phase and 53 (6.6%) in the control phase had a positive Chlamydia trachomatis test result [adjusted odds ratio 0.66 (95% confidence interval 0.41 to 1.04); p = 0.071]. The proportion of index patients with ≥ 1 sex partner treated was 88.0% (775/881) in intervention and 84.6% (760/898) in control phase, adjusted odds ratio 1.27 (95% confidence interval 0.96 to 1.68; p = 0.10). Overall, 293/1536 (19.1%) index patients chose accelerated partner therapy for 305 partners, of which partner types were: committed/established, 166/305 (54.4%); new, 85/305 (27.9%); occasional, 45/305 (14.8%); and one-off, 9/305 (3.0%). Two hundred and forty-eight accepted accelerated partner therapy and 241 partners were sent accelerated partner therapy packs, 120/241 (49.8%) returned chlamydia/gonorrhoea samples (78/119, 65.5%, positive for chlamydia, no result in one), but only 60/241 (24.9%) human immunodeficiency virus and syphilis samples (all negative). The primary outcomes of the randomised trial were not statistically significantly different at the 5% level. However, the economic evaluation found that accelerated partner therapy could be less costly compared with routine care, and mathematical modelling of effects and costs extrapolated beyond the trial end points suggested that accelerated partner therapy could be more effective and less costly than routine care in terms of major outcome averted and quality-adjusted life-years’. Healthcare professionals did not always offer accelerated partner therapy but felt that a clinical management and partner notification data collection system enhanced data recording. Key elements of a multilevel intervention supporting men who have sex with men in partner notification included: modifying the cultural and social context of men who have sex with men communities; improving skills and changing services to facilitate partner notification for one-off partners; and working with dating app providers to explore digital partner notification options. The systematic review found no evaluations of partner notification for men who have sex with men. Modelling of gonorrhoea and human immunodeficiency virus co-infection in men who have sex with men was technically challenging. Limitations In the randomised controlled trial, enrolment, follow-up and repeat infections were lower than expected, so statistical power was lower than anticipated. We were unable to determine whether accelerated partner therapy sped up partner treatment. Mathematical modelling of gonorrhoea/human immunodeficiency virus co-infection in men who have sex with men remained at an experimental stage. It was not feasible to include healthcare professionals in the men who have sex with men intervention development due to the COVID-19 pandemic. Conclusions Although the evidence that the intervention reduces repeat infection was not conclusive, the trial results suggest that accelerated partner therapy can be safely offered as a contact tracing option and is also likely to be cost saving, but is best suited to sex partners with emotional connection to the index patient. The Programme’s findings about classification of sexual partner types can be implemented in sexual health care with auditable outcomes. Future work Further research is needed on how to increase uptake of accelerated partner therapy and increase sexually transmitted infections self-sampling by partners; understand how services can use partnership-type information to improve partner notification, especially for those currently underserved; overcome challenges in modelling sexually transmitted infections and human immunodeficiency virus co-infection in men who have sex with men; develop and evaluate an intervention to optimise partner notification among men who have sex with men, focusing on one-off partnerships. Trial registration This trial is registered as ISRCTN15996256. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research Programme (NIHR award ref: RP-PG-0614-20009) and is published in full in Programme Grants for Applied Research; Vol. 12, No. 2. See the NIHR Funding and Awards website for further award information. Plain language summary We aimed to improve the sexual health of people most impacted by sexually transmitted infections and human immunodeficiency virus (young people and men who have sex with men), by preventing transmission and reducing undiagnosed infection. We focused on partner notification (contact tracing and management), particularly accelerated partner therapy. Our research included: a clinical trial interview/focus group studies literature reviews mathematical modelling and health economic evaluations. Firstly, we improved accelerated partner therapy by finding out what people did/didn’t like about it and which types of sex partners might use it. We included some people with mild learning difficulties to see if they could help us improve accelerated partner therapy for people who might find self-managed care tricky. Then, we measured accelerated partner therapy’s value for money in a large clinical trial in people with chlamydia, Britain’s commonest sexually transmitted infection. Finally, we worked with men who have sex with men, sexual healthcare professionals, public health and health planners to make recommendations for new partner notification methods to suit their needs. We found accelerated partner therapy could be less costly than current practices and likely reduce transmission of chlamydia in the population. Our new classification of partnership types showed that accelerated partner therapy suited ‘emotionally connected’, rather than one-off, partners. These partners are important for controlling onward transmission but are traditionally harder to reach. Findings from our stakeholder event suggest that partner notification approaches for men who have sex with men are likely to work best by involving communities as well as clinics, but we were only able to focus on sexually transmitted infections other than human immunodeficiency virus due to COVID-19 impacts. Future research should aim to improve partner notification for one-off partners, simplify the sexually transmitted infection and human immunodeficiency virus self-testing kits used in accelerated partner therapy, explore the pros and cons of immediate antibiotics, and develop and evaluate a system-wide partner notification approach for men who have sex with men, guided by health economics evaluation. Scientific summary Background Sexually transmitted infection (STI) diagnoses have increased since 2010. Young people and men who have sex with men (MSM) are disproportionately affected. Chlamydia is the most commonly reported STI in Britain. Two-thirds of chlamydia infections are diagnosed in heterosexual people under 25 years, while gonorrhoea, syphilis and human immunodeficiency virus (HIV) infections are more common in MSM. Preventing onward transmission is essential to STI and HIV control. Partner notification (PN), also known as contact tracing and management, is a key intervention in which sex partners (SPs) of people with diagnosed infections are identified, tested and treated. PN also provides opportunities to engage people at high risk of infection who might not present for care. Better PN for MSM with infections such as gonorrhoea could enable earlier HIV diagnosis in partners because co-infection is common in this group. However, PN is challenging, and monitoring of performance is limited by the lack of standardised outcome measures and blunt classifications of sex partnership types. Accelerated partner therapy (APT) is a promising new PN method, but its role in preventing transmission is unknown. Aims and objectives The Limiting Undetected Sexually Transmitted infections to RedUce Morbidity (LUSTRUM) Programme aimed to improve the sexual health of people at high risk of STIs and HIV by improving PN outcomes. The Programme had three interconnecting streams: STREAM A: Accelerated partner therapy trial preparation and implementation Specific objectives: Develop a clinically useful SP classification. Optimise the acceptability of the APT intervention. Determine the effectiveness and costs of APT and understand how APT worked in practice. STREAM B: Mathematical modelling and health economic analysis Specific objectives: Quantify the effects of APT on chlamydia transmission and re-infection. Estimate the cost effectiveness of APT, compared with standard PN. STREAM C: Development of partner notification interventions for men who have sex with men Specific objectives: Explore costs and outcomes of PN and testing for HIV. Investigate PN for gonorrhoea in MSM to identify undiagnosed HIV infection using mathematical modelling. Explore barriers and facilitators to PN for bacterial STIs and develop a PN intervention. Methods A1. Development of a clinically usable sex partner classification We synthesised evidence about partnership types from: the third British National Survey of Sexual Attitudes and Lifestyles, 259 dating applications and published literature. Then, we conducted qualitative interviews with members of the public and patients (n = 57), and health professionals (n = 27). We developed definitions for partnership types through external multidisciplinary expert consultation. A2. Optimisation of the accelerated partner therapy intervention We analysed videos of APT role-play consultations and synthesised published evidence about relevant behaviours; explored barriers and facilitators to receiving or delivering APT, including focused work with 25 people with mild learning disabilities, 56 members of the public and patients and 30 healthcare professionals (HCPs); modified and specified key components of APT, wrote a manual and training package, and created online videos. A3. Randomised controlled trial of accelerated partner therapy We conducted a cluster crossover randomised controlled trial with a process and cost-consequence evaluation. Dynamic modelling is described in Stream B. Clusters were 17 sexual health clinics in diverse areas of England and Scotland. Participants [index patients (IPs)] were heterosexual women and men, aged ≥ 16 years with a positive test for Chlamydia trachomatis and/or a clinical diagnosis of pelvic inflammatory disease or cervicitis (women) or non-gonococcal urethritis or epididymo-orchitis (men) and reporting at least one contactable sexual partner in the past 6 months. Intervention: APT was offered as an additional partner notification method for IPs. A HCP assessed their SP(s) by telephone, then sent or gave the IP antibiotics and STI and HIV self-sampling kits for their partner(s). The control arm received standard PN alone. The intervention was implemented at the level of the sexual health clinic, with clinics randomised to intervention or control arm in the first phase by random permutation. The primary outcome was the proportion of IPs testing positive for C. trachomatis 12–24 weeks after the PN consultation. Secondary outcomes included: the proportion of SPs treated; the proportion of partners notified; costs; cost effectiveness; model-predicted chlamydia prevalence. The primary outcome analysis was by intention to treat, fitting random-effects logistic regression models that account for clustering of IPs within clinics and trial periods. Process evaluation: We collected qualitative data through six focus groups and individual interviews (n = 10) with purposively sampled HCPs (n = 34 from 14 sites), IPs (n = 15) and SPs who received APT (n = 17). Quantitative data were collected within a clinical management and PN data collection system (RELAY). Cost-consequence analysis (CCA): We collected data on costs and resource use during the trial and used unit costs from the trial and the Personal Social Services Research Unit. B1 and B2. Modelling the effects of accelerated partner therapy on Chlamydia trachomatis transmission We developed a new deterministic transmission model with a dedicated PN module, which allowed us to identify the effects of different index-partner combinations on chlamydia prevalence. We considered a population aged 16–34 years and calibrated the model to data from the third British National Survey of Sexual Attitudes and Lifestyles. We then extended a previous modelling framework, informed by data from the C. trachomatis transmission model and the trial, to quantify expected rates of chlamydia reinfection (Estcourt CS, Stirrup O, Copas A, Low N, Mapp F, Saunders J, et al. Accelerated partner therapy contact tracing for people with chlamydia (LUSTRUM): a crossover cluster-randomised controlled trial. Lancet Public Health 2022;7(10):e853–65. https://doi.org/10.1016/S2468-2667(22)00204-3). B3. Cost-effectiveness analysis of accelerated partner therapy compared with standard partner notification We developed a spreadsheet-based model using output from the C. trachomatis transmission model to estimate the impact of APT on healthcare costs, major outcomes averted (MOA) and quality-adjusted life-years (QALYs) in a simulated population of 100,000 adults aged 16–34 years. We calculated incremental cost-effectiveness ratios (ICERs) for APT, compared with standard PN and undertook sensitivity and scenario analyses. C1. Systematic review of economic studies of interventions related to partner notification for sexually transmitted infections in men who have sex with men We searched six electronic databases up to June 2020. We included economic evaluation and cost analysis studies if participants were MSM with any STI and/or HIV and the intervention was related to PN, testing or treatment and summarised evidence using a narrative synthesis. C2. Partner notification for bacterial sexually transmitted infections in men who have sex with men as a way to detect undiagnosed human immunodeficiency virus infection in partners We reviewed modelling studies of PN and pre-exposure prophylaxis interventions in MSM and attempted to model PN with co-infections with gonorrhoea HIV. C3. Barriers and facilitators of accelerated partner therapy and development of a novel partner notification intervention for men who have sex with men First, we conducted a stakeholder event with 45 participants from across Britain [MSM, public health experts, service commissioners, multidisciplinary sexual HCPs, non-governmental organisations (NGOs), academics and dating app providers]. We explored the diverse and multilevelled social, cultural and healthcare system-level context shaping poor PN outcomes for one-off partners. We conducted qualitative in-depth interview studies with men who had experienced PN (n = 14, Stream A) and focus groups with MSM (n = 28), clinical and other stakeholders (n = 11) to explore barriers and facilitators to PN. We used the behaviour change wheel within co-design of a potential new PN intervention. Results A1. We created usable definitions for five SP types (committed/established, new, occasional, one-off, sex work), broadly predicated on duration of the relationship, likelihood of future sex and degree of emotional connection. A2. Modifications to the APT intervention included simplification of the patient packs, creation of ‘how to’ training films for participants and HCPs. People with mild learning disabilities found APT acceptable but described feeling overwhelmed by the packs. They recommended using photographs instead of diagrams of anatomical sites for self-sampling, and an ‘easy read’ format. The new partner types and APT processes were built into a new clinical management and PN data collection system called RELAY. A3. In the trial, all 17 clinics completed both periods. One thousand five hundred and thirty-six and 1724 IPs provided data in intervention and control phases. In intervention and control phases, 666 (43.4%) and 800 (46.4%) IPs were tested for C. trachomatis; 31 (4.7%) and 53 (6.6%) were positive, adjusted odds ratio (aOR) 0.66 [95% confidence interval (CI) 0.41 to 1.04; p = 0.07]. The proportion with ≥ 1 SP treated was 775/881 (88.0%) in intervention and 760/898 (84.6%) in the control phase, aOR 1.27 (95% CI 0.96 to 1.68; p = 0.10) (Estcourt C, Mapp F, Stirrup O, Copas A, Howarth A, Owusu M, et al. O18.2 Does Accelerated partner therapy improve partner notification outcomes for people with chlamydia? The LUSTRUM cluster cross-over randomised control trial. Sex Transm Infect 2021;97:A57–8. http://doi.org/10.1136/sextrans-2021-sti.153). In total, 4807 SPs were reported, of whom 1636 (34%) were committed/established partners. Overall, 293/1536 (19.1%) of IPs in intervention phase chose APT for a total of 305 partners, of whom 248 accepted. Partner types were committed/established, 166/305 (54.4%); new, 85/305 (27.9%); occasional, 45/305 (14.8%); and one-off, 9/305 (3.0%). Common reasons for IPs to decline APT included: preferred face-to-face conversation 400/1832 (21.8%), partner already in clinic 388/1832 (21.2%), unwilling to engage with partner 206/1832 (11.2%), preferred partner to attend clinic 202/1832 (11.0%) and partner overseas 150/1832 (8.2%). Of 241 partners sent APT packs, 120/241 (49.8%) returned chlamydia and gonorrhoea testing samples, of which 78/119 (65.5%) were positive for chlamydia (no result in one), but only 60/241 (24.9%) HIV and syphilis samples (all negative). In an unplanned analysis, 2/106 (2.0%) IPs, who were offered APT and accepted it for one or more partners, tested positive for chlamydia at 12–24 weeks. Of IPs not selecting APT or whose partners refused, 29/560 (5.2%) had a positive result on repeat testing. The process evaluation showed that overall intervention fidelity was good and APT was well liked by those who delivered and received it. Overall, we found a mixed picture of an intuitive, coherent intervention struggling to gain purchase within already pressured services. HCPs preferred RELAY to their clinic systems because it helped them standardise PN. However, many sites struggled to scale up the trial processes owing to continual external pressures to adapt services to achieve efficiencies. In some services, APT was perceived as time-consuming and without palpable impact. This observation was related to the absence of a reduction in patient numbers in clinic waiting rooms. In this way, the ‘invisibility’ of the effectiveness of APT curtailed the establishment of positive feedback loops driving normalisation within services. In the CCA, APT cost more than standard PN (£91.23 vs. £75.21). Where accepted, it was more effective than standard PN with an absolute effect difference of 5.26%. B1 and B2. In the model, chlamydia positivity was highest for symptomatic index cases of low sexual activity, with infected partners who were typically asymptomatic and highly sexually active. Partner notification for this index–partner combination would prevent the most transmission. Increasing the number of treated partners from current levels in Britain (0.51, 95% credible interval, CI 0.21 to 0.80) by 25% would reduce chlamydia prevalence by 18% (95% CI 5% to 44%) in both women and men within 5 years. Reducing the time to partner treatment alone had a minor effect on reducing prevalence. Together, these results suggest that PN typically identifies sexual partners who are likely to further transmit chlamydia and that APT could further reduce prevalence if PN uptake increases. B3. In the cost-effectiveness analysis, the base-case results showed APT cost less and was more effective than standard PN in terms of MOA and QALYs, and therefore cost-saving. The results were supported by deterministic sensitivity analysis and scenario analysis for most scenarios, with ICERs very low and well within accepted thresholds. C1. There was very little published evidence on health economic aspects of PN in MSM. This supports the need for new interventions with parallel economic evaluation. C2. Published models have not examined the impact on HIV diagnosis of PN for bacterial STIs, and interventions cannot be extrapolated between countries. There were challenges in fitting the model of gonorrhoea/HIV co-infection to data, including issues with parameter identifiability. C3. We considered APT for MSM (and their more emotionally connected partners) and developed recommendations for a multilevel, multistakeholder intervention targeting MSM with other types of partners for whom PN is known to be more challenging. Key intervention elements included: a co-ordinated and coproduced mass and social media intervention to change norms and beliefs to challenge stigma and other barriers to PN; NGO peer-led work reducing STI-related stigma and persuading MSM to participate actively in PN to protect others and their communities; working with MSM to enable them to prepare for PN interactions and encourage HCP action, monitoring systems to directly address one-off PN outcomes; dating app providers promoting appropriate PN messaging. Conclusions The Programme provides findings about APT, which show promise for future PN. RELAY could be added to clinic systems for recording PN outcomes and processes. The Programme identified gaps in research about PN for one-off, and other partnerships with poor outcomes and high potential for onward sexual transmission. Data from the trial also suggested that APT uptake might be lower for people belonging to ethnic minority groups, although it was not powered to formally evaluate any such differences. The process evaluation and the work in Stream C identify a need for interventions that reach beyond sexual health services. Future work Future work should identify PN approaches for one-off partners; determine how to provide real-time or fast feedback for practitioners on the impact of interventions whose value is not obvious; further research is needed on how to increase uptake of APT, explore the pros and cons of immediate antibiotics, and optimise the uptake of self-sampling in partners, particularly people with mild learning disabilities; understand how services can use sex partnership-type information to improve PN methods, especially for hard-to-reach groups; develop and evaluate a system intervention to increase readiness in MSM for and engagement with PN for bacterial STIs, focusing on one-off partnerships and addressing economic factors and partnership type. Trial registration This trial is registered as ISRCTN15996256. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research Programme (NIHR award ref: RP-PG-0614-20009) and is published in full in Programme Grants for Applied Research; Vol. 12, No. 2. See the NIHR Funding and Awards website for further award information.

Abstract Background Bacterial vaginosis is a common and distressing condition for women. Short-term antibiotic treatment is usually clinically effective, but recurrence is common. We assessed the effectiveness of intravaginal lactic acid gel versus oral metronidazole for treating recurrent bacterial vaginosis. Methods We undertook an open-label, multicentre, parallel group, randomised controlled trial in nineteen UK sexual health clinics and a university health centre. Women aged ≥ 16 years, with current bacterial vaginosis symptoms and a preceding history of bacterial vaginosis, were randomised in a 1:1 ratio using a web-based minimisation algorithm, to 400 mg twice daily oral metronidazole tablets or 5 ml once daily intravaginal lactic acid gel, for 7 days. Masking of participants was not possible. The primary outcome was participant-reported resolution of symptoms within 2 weeks. Secondary outcomes included time to first recurrence of symptoms, number of recurrences and repeat treatments over 6 months and side effects. Results Five hundred and eighteen participants were randomised before the trial was advised to stop recruiting by the Data Monitoring Committee. Primary outcome data were available for 79% (204/259) allocated to metronidazole and 79% (205/259) allocated to lactic acid gel. Resolution of bacterial vaginosis symptoms within 2 weeks was reported in 70% (143/204) receiving metronidazole versus 47% (97/205) receiving lactic acid gel (adjusted risk difference -23·2%; 95% confidence interval -32.3 to -14·0%). In those participants who had initial resolution and for whom 6 month data were available, 51 of 72 (71%) women in the metronidazole group and 32 of 46 women (70%) in the lactic acid gel group had recurrence of symptoms, with median times to first recurrence of 92 and 126 days, respectively. Reported side effects were more common following metronidazole than lactic acid gel (nausea 32% vs. 8%; taste changes 18% vs. 1%; diarrhoea 20% vs. 6%, respectively). Conclusions Metronidazole was more effective than lactic acid gel for short-term resolution of bacterial vaginosis symptoms, but recurrence is common following both treatments. Lactic acid gel was associated with fewer reported side effects. Trial registration ISRCTN14161293 , prospectively registered on 18th September 2017.

Background: Bacterial vaginosis is a common and distressing condition associated with serious comorbidities. Antibiotic treatment is usually clinically effective in the short term, but recurrence is common and side effects can occur. Objectives: The objective is to assess whether or not intravaginal lactic acid gel is clinically effective and cost-effective for treating recurrent bacterial vaginosis compared with oral metronidazole (Flagyl, Sanofi). Design: This was an open-label, multicentre, parallel-arm, randomised (1 : 1) controlled trial. Setting: This took place in one general practice and 19 sexual health centres in the UK. Participants: Women aged ≥ 16 years with bacterial vaginosis symptoms and one or more episode(s) within the past 2 years took part. Interventions: The interventions were 5 ml of intravaginal lactic acid gel taken once daily for 7 days (intervention) or 400-mg oral metronidazole tablets taken twice daily for 7 days (control). Main outcome measures: The primary outcome was the resolution of bacterial vaginosis symptoms 14 days after randomisation. The secondary outcomes were time to first recurrence of symptoms; number of recurrences and treatment courses over 6 months; microbiological resolution on microscopy of vaginal smears at week 2; time to resolution of symptoms; tolerability, adherence and acceptability of the treatment; prevalence of concurrent sexually transmitted infections; quality of life; and cost-effectiveness. Results: Recruitment stopped prior to reaching the target of 1900 participants on recommendation from the Data Monitoring Committee and Trial Steering Committee after a planned review of the results indicated that the research question had been answered. Overall, 518 participants were randomised and primary outcome data were available for 409 participants (79%; 204 in the metronidazole arm, 205 in the lactic acid gel arm). Participant-reported symptom resolution at week 2 was higher with metronidazole (143/204; 70%) than with lactic acid gel (97/205; 47%) (adjusted risk difference –23.2%, 95% confidence interval –32.3% to –14.0%). Recurrence in 6 months in a subset of participants who had initial resolution and were available for follow-up was similar across arms (metronidazole arm: 51/72, 71%; lactic acid gel arm: 32/46, 70%). A higher incidence of some side effects was reported with metronidazole than with lactic acid gel (nausea 32% vs. 8%; taste changes 18% vs. 1%; diarrhoea 20% vs. 6%, respectively). At week 2, the average cost per participant with resolved symptoms was £86.94 (metronidazole), compared with £147.00 (lactic acid gel). Some participants preferred using lactic acid gel even if they perceived it to be less effective than metronidazole. Limitations: Loss to follow-up for collection of the primary outcome data was 21% and was similar in both arms. There is a risk of bias owing to missing outcome data at 3 and 6 months post treatment. Conclusions: A higher initial response was seen with metronidazole than with lactic acid gel, but subsequent treatment failure was common with both. Lactic acid gel was less cost-effective than metronidazole. In general, women disliked taking repeated courses of metronidazole and preferred lactic acid gel, even when they were aware that it was less likely to provide symptom resolution. In the absence of effective curative therapy, further evaluation of non-antibiotic treatments to control the symptoms of recurrent bacterial vaginosis is required to improve quality of life for these patients. Further microbiological analysis of vaginal samples would be useful to identify additional factors affecting response to treatment. Trial registration: Current Controlled Trials ISRCTN14161293. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 2. See the NIHR Journals Library website for further project information.

BACKGROUND:Surgical site infection (SSI) is a worldwide problem which has morbidity, mortality and financial consequences. The incidence rate of SSI is high in Low- and Middle-Income countries (LMICs) compared to high income countries, and the costly surgical complication can raise the potential risk of financial catastrophe. OBJECTIVE:The aim of the study is to critically appraise studies on the cost of SSI in a range of LMIC studies and compare these estimates with a reference standard of high income European studies who have explored similar SSI costs. METHODS:A systematic review was undertaken using searches of two electronic databases, EMBASE and MEDLINE In-Process & Other Non-Indexed Citations, up to February 2019. Study characteristics, comparator group, methods and results were extracted by using a standard template. RESULTS:Studies from 15 LMIC and 16 European countries were identified and reviewed in full. The additional cost of SSI range (presented in 2017 international dollars) was similar in the LMIC ($174-$29,610) and European countries ($21-$34,000). Huge study design heterogeneity was encountered across the two settings. DISCUSSION:SSIs were revealed to have a significant cost burden in both LMICs and High Income Countries in Europe. The magnitude of the costs depends on the SSI definition used, severity of SSI, patient population, choice of comparator, hospital setting, and cost items included. Differences in study design affected the comparability across studies. There is need for multicentre studies with standardized data collection methods to capture relevant costs and consequences of the infection across income settings.

determine the prevalence of the Amoebic dysentery among children under the The present study aims to age of five years in Thi-Qar province during the period from October 2022 to August 2023 and to study the effects of some factors such as sex, age, location, source of drinking water and others on the prevalence of the disease. Study was carried out at the Bint Al-Huda Educational Hospital for Women and Children and Mohammed al-Musawi Hospital in Thi-Qar Province, 697 samples of feces were collected from children with diarrhea and examined by direct microscopic examination. The results showed that 100 out of 697 and %14.34 % of children were infected with Entamoeba spp. No significant differences (p>0.05) were recorded in prevalence of Entamoeba spp. according to sex and the infected males %7.46% more than infected females 6.88%. A significant differences (p≤0.05) were observed in the prevalence of Entamoeba spp. according to age groups, the highest infection percent on the age group (48-60 months) 5% and the lowest infection percent on the age group (<12 months) 1.43 %. No significant differences (p>0.05) were recorded in prevalence of Entamoeba spp. according to months of the year, the high percent 23.33% in June and the lowest percent 10.67% in November. The study recorded significant differences (p≤0.05) in infection percent according to the location, the percent of infected children living in rural 9.75% more than infected children living in the urban 4.59%. The study recorded significant differences in prevalence of Entamoeba spp. according parent educational level. The high percent of infection was recorded in children belonging to parents without educational attainment 6.89%. The results showed that there were no differences (p>0.05) in prevalence of Entamoeba spp. according to source of drinking water. [ABSTRACT FROM AUTHOR]