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Abstract Background This trial is a parallel, two-arm, non-blinded cluster randomised controlled trial that is under way in Singapore, with the aim of measuring the efficacy of male Wolbachia-infected Aedes aegypti deployments in reducing dengue incidence in an endemic setting with all four dengue serotypes in circulation. The trial commenced in July 2022 and is expected to conclude in September 2024. The original study protocol was published in December 2022. Here, we describe amendments that have been made to the study protocol since commencement of the trial. Methods The key protocol amendments are (1) addition of an explicit definition of Wolbachia exposure for residents residing in intervention sites based on the duration of Wolbachia exposure at point of testing, (2) incorporation of a high-dimensional set of anthropogenic and environmental characteristics in the analysis plan to adjust for baseline risk factors of dengue transmission, and (3) addition of alternative statistical analyses for endpoints to control for post hoc imbalance in cluster-based environmental and anthropogenic characteristics. Discussion The findings from this study will provide the first experimental evidence for the efficacy of releasing male-Wolbachia infected mosquitoes to reduce dengue incidence in a cluster-randomised controlled trial. The trial will conclude in 2024 and results will be reported shortly thereafter. Trial registration ClinicalTrials.gov, identifier: NCT05505682. Registered on 16 August 2022. Retrospectively registered. Last updated 11 November 2023.

Background: This trial is a parallel, two-arm, non-blinded cluster randomised controlled trial that is under way in Singapore, with the aim of measuring the efficacy of male Wolbachia-infected Aedes aegypti deployments in reducing dengue incidence in an endemic setting with all four dengue serotypes in circulation. The trial commenced in July 2022 and is expected to conclude in September 2024. The original study protocol was published in December 2022. Here, we describe amendments that have been made to the study protocol since commencement of the trial. Methods: The key protocol amendments are (1) addition of an explicit definition of Wolbachia exposure for residents residing in intervention sites based on the duration of Wolbachia exposure at point of testing, (2) incorporation of a high-dimensional set of anthropogenic and environmental characteristics in the analysis plan to adjust for baseline risk factors of dengue transmission, and (3) addition of alternative statistical analyses for endpoints to control for post hoc imbalance in cluster-based environmental and anthropogenic characteristics. Discussion: The findings from this study will provide the first experimental evidence for the efficacy of releasing male-Wolbachia infected mosquitoes to reduce dengue incidence in a cluster-randomised controlled trial. The trial will conclude in 2024 and results will be reported shortly thereafter. Trial registration: ClinicalTrials.gov, identifier: NCT05505682. Registered on 16 August 2022. Retrospectively registered. Last updated 11 November 2023. [ABSTRACT FROM AUTHOR]

Abstract Background The malaria incidence data from a malaria prevention study from the Rift Valley, Central Ethiopia, were reanalysed. The objective was to investigate whether including an administrative structure within the society, which may have required consideration in the protocol or previous analysis, would provide divergent outcomes on the effect measures of the interventions. Methods A cluster-randomized controlled trial lasting 121 weeks with 176 clusters in four groups with 6071 households with 34,548 persons was done: interventions combining indoor residual spraying (IRS) and insecticide-treated nets (ITNs), IRS alone, ITNs alone and routine use. The primary outcome was malaria incidence. A multilevel negative binomial regression model was employed to examine the impact of the kebele (smallest administrative unit) and the proximity of homes to the primary mosquito breeding sites as potential residual confounders (levels). The study also assessed whether these factors influenced the effect measures of the interventions. Results The study's initial findings revealed 1183 malaria episodes among 1059 persons, with comparable effects observed across the four intervention groups. In the reanalysis, the results showed that both ITN + IRS (incidence rate ratio [IRR] 0.63, P

Abstract Background Long-term reinforcement in the role of primary care and improvement the healthcare system as a whole requires the involvement of GPs in clinical research processes. However, many clinical studies fail due to failure to achieve sample population targets amongst GPs and their patients. This issue has been identified and discussed, but effective strategies to overcome it are still lacking. One of the reasons is that the positions, requirements, and experiences of GPs on participating in clinical research have hardly been examined up to now. Methods The years 2021 and 2022 saw three quantitative and qualitative surveys amongst GPs in Germany with the aim of shedding light on the attitudes, experiences, and potential issues regarding the involvement of primary care in clinical research projects and participation in cluster-randomised controlled trials (cRCTs) in a general sense. This overview summarises and abstracts conclusions gained from the exploratory series of studies and compares the results with the current research situation. From here, this contribution will then develop an approach towards optimising the integration of GPs into clinical research. Results Most of the GPs asked associated clinical research with opportunities and potential such as closing gaps in healthcare, using evidence-based instruments, optimising diagnostic and therapeutic management, and reinforcement of multiprofessional healthcare. Even so, many GPs unsure as to how far primary care in particular would stand to benefit from studies of this type in the long term. Respondents were also divided on willingness to participate in clinical research. GPs having already participated in Innovation Fund projects generally saw a benefit regarding intervention and cost–benefit relationship. However, some also reported major hurdles and stress factors such as excessive documentation and enrolment requirements, greater interference in practice routines, and sometimes poor integration into project processes such as in communication and opportunities to play an active role in the project. Conclusions Results from the studies presented provide indications as to how GPs perceive clinical research projects and cRCTs as a whole and from their existing project experience, and on the requirements that studies would have to meet for GPs to be willing to participate. In particular, making sure that clinical studies fully conform with GPs would play a major role; this especially applies to freedom to make medical decisions, limitation of documentation obligations, interference in regular practice routine, greater involvement in research planning, and long-term reinforcement in the role of primary care. Clinical research projects and cRCTs should be planned, designed, and communicated for clear and visible relevance to everyday primary care.

Abstract Rationale The effectiveness of immunisation with pneumococcal conjugate vaccine (PCV) has been demonstrated in many countries. However, the global impact of PCV is limited by its cost, which has prevented its introduction in some countries. Reducing the cost of PCV programmes will facilitate further vaccine introductions and improve the sustainability of PCV in low-income countries when they transition from subsidised vaccine supply. We are conducting a large, population-level, cluster-randomised field trial (PVS) of an alternative reduced-dose schedule of PCV compared to the standard schedule. We are also conducting a nested sub-study at the individual level to investigate the immunogenicity of the two schedules and their effects on pneumococcal carriage acquisition (PVS-AcqImm). Methods and design PVS-AcqImm is a prospective, cluster-randomised trial of an alternative schedule of one dose of PCV scheduled at age 6 weeks with a booster dose at age 9 months compared to the standard of three primary doses scheduled at 6, 10, and 14 weeks of age. Sub-groups within the alternative schedule group receive yellow fever vaccine separately or co-administered with PCV at 9 months of age. The primary endpoints are (a) concentrations of vaccine-type anti-pneumococcal IgG at 18 months of age, (b) proportions with yellow fever neutralising antibody titre ≥ 1:8 4 weeks after separate or co-administration of PCV and yellow fever vaccines, and (c) rate of nasopharyngeal vaccine-type pneumococcal acquisition from 10–14 months of age. Participants and field staff are not masked to group allocation while measurement of the laboratory endpoints is masked. Approximately equal numbers of participants are resident in each of 28 randomly allocated geographic clusters (14 clusters in each group); 784 enrolled for acquisition measurements and 336 for immunogenicity measurements. Purpose This statistical analysis plan (SAP) describes the PVS-AcqImm cohort and follow-up criteria to be used in different analyses. The SAP defines the endpoints and describes how adherence to the interventions will be presented. We describe the approach to analyses and how we will account for the effect of clustering. Defining the SAP prior to the conduct of analysis will avoid bias in analyses that may arise from prior knowledge of trial findings. Trial registration ISRCTN, ISRCTN7282161328. Registered on 28 November 2019. https://www.isrctn.com/ISRCTN72821613 . Protocol: MRCG SCC number 1670, LSHTM Ref 17683. Current protocol version: 6.0, 24 May 2021. Version: 1.0 (5 April 2023); SAP revisions—none.

Rationale: The effectiveness of immunisation with pneumococcal conjugate vaccine (PCV) has been demonstrated in many countries. However, the global impact of PCV is limited by its cost, which has prevented its introduction in some countries. Reducing the cost of PCV programmes will facilitate further vaccine introductions and improve the sustainability of PCV in low-income countries when they transition from subsidised vaccine supply. We are conducting a large, population-level, cluster-randomised field trial (PVS) of an alternative reduced-dose schedule of PCV compared to the standard schedule. We are also conducting a nested sub-study at the individual level to investigate the immunogenicity of the two schedules and their effects on pneumococcal carriage acquisition (PVS-AcqImm). Methods and design: PVS-AcqImm is a prospective, cluster-randomised trial of an alternative schedule of one dose of PCV scheduled at age 6 weeks with a booster dose at age 9 months compared to the standard of three primary doses scheduled at 6, 10, and 14 weeks of age. Sub-groups within the alternative schedule group receive yellow fever vaccine separately or co-administered with PCV at 9 months of age. The primary endpoints are (a) concentrations of vaccine-type anti-pneumococcal IgG at 18 months of age, (b) proportions with yellow fever neutralising antibody titre ≥ 1:8 4 weeks after separate or co-administration of PCV and yellow fever vaccines, and (c) rate of nasopharyngeal vaccine-type pneumococcal acquisition from 10–14 months of age. Participants and field staff are not masked to group allocation while measurement of the laboratory endpoints is masked. Approximately equal numbers of participants are resident in each of 28 randomly allocated geographic clusters (14 clusters in each group); 784 enrolled for acquisition measurements and 336 for immunogenicity measurements. Purpose: This statistical analysis plan (SAP) describes the PVS-AcqImm cohort and follow-up criteria to be used in different analyses. The SAP defines the endpoints and describes how adherence to the interventions will be presented. We describe the approach to analyses and how we will account for the effect of clustering. Defining the SAP prior to the conduct of analysis will avoid bias in analyses that may arise from prior knowledge of trial findings. Trial registration: ISRCTN, ISRCTN7282161328. Registered on 28 November 2019. https://www.isrctn.com/ISRCTN72821613. Protocol: MRCG SCC number 1670, LSHTM Ref 17683. Current protocol version: 6.0, 24 May 2021. Version: 1.0 (5 April 2023); SAP revisions—none. [ABSTRACT FROM AUTHOR]

Background: Long-term reinforcement in the role of primary care and improvement the healthcare system as a whole requires the involvement of GPs in clinical research processes. However, many clinical studies fail due to failure to achieve sample population targets amongst GPs and their patients. This issue has been identified and discussed, but effective strategies to overcome it are still lacking. One of the reasons is that the positions, requirements, and experiences of GPs on participating in clinical research have hardly been examined up to now. Methods: The years 2021 and 2022 saw three quantitative and qualitative surveys amongst GPs in Germany with the aim of shedding light on the attitudes, experiences, and potential issues regarding the involvement of primary care in clinical research projects and participation in cluster-randomised controlled trials (cRCTs) in a general sense. This overview summarises and abstracts conclusions gained from the exploratory series of studies and compares the results with the current research situation. From here, this contribution will then develop an approach towards optimising the integration of GPs into clinical research. Results: Most of the GPs asked associated clinical research with opportunities and potential such as closing gaps in healthcare, using evidence-based instruments, optimising diagnostic and therapeutic management, and reinforcement of multiprofessional healthcare. Even so, many GPs unsure as to how far primary care in particular would stand to benefit from studies of this type in the long term. Respondents were also divided on willingness to participate in clinical research. GPs having already participated in Innovation Fund projects generally saw a benefit regarding intervention and cost–benefit relationship. However, some also reported major hurdles and stress factors such as excessive documentation and enrolment requirements, greater interference in practice routines, and sometimes poor integration into project processes such as in communication and opportunities to play an active role in the project. Conclusions: Results from the studies presented provide indications as to how GPs perceive clinical research projects and cRCTs as a whole and from their existing project experience, and on the requirements that studies would have to meet for GPs to be willing to participate. In particular, making sure that clinical studies fully conform with GPs would play a major role; this especially applies to freedom to make medical decisions, limitation of documentation obligations, interference in regular practice routine, greater involvement in research planning, and long-term reinforcement in the role of primary care. Clinical research projects and cRCTs should be planned, designed, and communicated for clear and visible relevance to everyday primary care. [ABSTRACT FROM AUTHOR]

Background: The malaria incidence data from a malaria prevention study from the Rift Valley, Central Ethiopia, were reanalysed. The objective was to investigate whether including an administrative structure within the society, which may have required consideration in the protocol or previous analysis, would provide divergent outcomes on the effect measures of the interventions. Methods: A cluster-randomized controlled trial lasting 121 weeks with 176 clusters in four groups with 6071 households with 34,548 persons was done: interventions combining indoor residual spraying (IRS) and insecticide-treated nets (ITNs), IRS alone, ITNs alone and routine use. The primary outcome was malaria incidence. A multilevel negative binomial regression model was employed to examine the impact of the kebele (smallest administrative unit) and the proximity of homes to the primary mosquito breeding sites as potential residual confounders (levels). The study also assessed whether these factors influenced the effect measures of the interventions. Results: The study's initial findings revealed 1183 malaria episodes among 1059 persons, with comparable effects observed across the four intervention groups. In the reanalysis, the results showed that both ITN + IRS (incidence rate ratio [IRR] 0.63, P < 0.001) and ITN alone (IRR 0.78, P = 0.011) were associated with a greater reduction in malaria cases compared to IRS (IRR 0.90; P = 0.28) or the control (reference) group. The combined usage of IRS with ITN yields better outcomes compared to the standalone use of ITN and surpasses the effectiveness of IRS in isolation. Conclusion: The findings indicate that implementing a combination of IRS and ITN and also ITN alone decrease malaria incidence. Furthermore, there was an observed synergistic impact when ITN and IRS were used in combination. Considering relevant social structures as potential residual confounders is of paramount importance. Trial registration: PACTR201411000882128 (08 September 2014). [ABSTRACT FROM AUTHOR]

Abstract Background The cognitive benefits of early non-pharmacological approaches have been demonstrated in older adults with mild cognitive impairment (MCI). However, older adults living in nursing homes have more severe cognitive impairment problems and lower initiative and compliance to participate in complex interventions. Hence, it important to investigate more attractive and sustainable methods to prevent or delay cognitive decline. The present study adopts the self-determination theory (SDT) as a theoretical framework to innovatively develop an integrated art-based intervention for older adults with MCI in nursing homes in China and aims to evaluate its effects on cognitive function, mental health, and other health-related outcomes. Methods The study is a nursing home-based, cluster randomised controlled trial (RCT) that targets older adults (aged ≥ 60 years) with MCI in Fuzhou City, China. All nursing homes in the area covered by Fuzhou City are invited to participate. Eligible nursing homes are randomised to one of two groups: intervention group (receive a 14-week, 27-session intervention) and waitlist control group (receive the usual care). The SDT-based integrated creative art (SDTICA) program reasonably adopts the SDT as a theoretical framework to innovatively develop an integrated art-based intervention for older adults with MCI in nursing homes. The primary (global cognitive function and psychological indicator) and secondary (daily activity function, social function, and specific domains of cognitive function) outcomes will be measured at baseline, after the intervention, and during follow-up. Discussion This study aims to evaluate the effects of SDTICA program on neuropsychological outcomes in older adults with MCI and provide scientific evidence for art-based non-pharmacologic interventions in nursing homes, which may reduce dementia risk in older adults with MCI. Trial registration The trial was prospectively registered at the Chinese Clinical Trials Registry with the registration number ChiCTR2200061681 on 30 June 2022.

Abstract Background Dental service provision in the care home sector is poor, with little emphasis on prevention. Emerging evidence suggests that the use of Dental Care Professionals (dental therapists and dental nurses) as an alternative to dentists has the potential to improve preventive advice, the provision of care and access to services within care homes. However, robust empirical evidence from definitive trials on how to successfully implement and sustain these interventions within care homes is currently lacking. The aim of the study is to determine whether Dental Care Professionals could reduce plaque levels of dentate older adults (65 + years) residing in care homes. Methods This protocol describes a two-arm cluster-randomised controlled trial that will be undertaken in care homes across Wales, Northern Ireland and England. In the intervention arm, the dental therapists will visit the care homes every 6 months to assess and then treat eligible residents, where necessary. All treatment will be conducted within their Scope of Practice. Dental nurses will visit the care homes every month for the first 3 months and then three-monthly afterwards to promulgate advice to improve the day-to-day prevention offered to residents by carers. The control arm will be ‘treatment as usual’. Eligible care homes (n = 40) will be randomised based on a 1:1 ratio (20 intervention and 20 control), with an average of seven residents recruited in each home resulting in an estimated sample of 280. Assessments will be undertaken at baseline, 6 months and 12 months and will include a dental examination and quality of life questionnaires. Care home staff will collect weekly information on the residents’ oral health (e.g. episodes of pain and unscheduled care). The primary outcome will be a binary classification of the mean reduction in Silness-Löe Plaque Index at 6 months. A parallel process evaluation will be undertaken to explore the intervention’s acceptability and how it could be embedded in standard practice (described in a separate paper), whilst a cost-effectiveness analysis will examine the potential long-term costs and benefits of the intervention. Discussion This trial will provide evidence on how to successfully implement and sustain a Dental Care Professional-led intervention within care homes to promote access and prevention. Trial registration ISRCTN16332897 . Registered on 3 December 2021.

Background: The cognitive benefits of early non-pharmacological approaches have been demonstrated in older adults with mild cognitive impairment (MCI). However, older adults living in nursing homes have more severe cognitive impairment problems and lower initiative and compliance to participate in complex interventions. Hence, it important to investigate more attractive and sustainable methods to prevent or delay cognitive decline. The present study adopts the self-determination theory (SDT) as a theoretical framework to innovatively develop an integrated art-based intervention for older adults with MCI in nursing homes in China and aims to evaluate its effects on cognitive function, mental health, and other health-related outcomes. Methods: The study is a nursing home-based, cluster randomised controlled trial (RCT) that targets older adults (aged ≥ 60 years) with MCI in Fuzhou City, China. All nursing homes in the area covered by Fuzhou City are invited to participate. Eligible nursing homes are randomised to one of two groups: intervention group (receive a 14-week, 27-session intervention) and waitlist control group (receive the usual care). The SDT-based integrated creative art (SDTICA) program reasonably adopts the SDT as a theoretical framework to innovatively develop an integrated art-based intervention for older adults with MCI in nursing homes. The primary (global cognitive function and psychological indicator) and secondary (daily activity function, social function, and specific domains of cognitive function) outcomes will be measured at baseline, after the intervention, and during follow-up. Discussion: This study aims to evaluate the effects of SDTICA program on neuropsychological outcomes in older adults with MCI and provide scientific evidence for art-based non-pharmacologic interventions in nursing homes, which may reduce dementia risk in older adults with MCI. Trial registration: The trial was prospectively registered at the Chinese Clinical Trials Registry with the registration number ChiCTR2200061681 on 30 June 2022. [ABSTRACT FROM AUTHOR]

Abstract Background Pneumococcal conjugate vaccines (PCVs) effectively prevent pneumococcal disease, but the global impact of pneumococcal vaccination is hampered by its cost. The evaluation of reduced dose schedules of PCV includes measurement of effects on immunogenicity and carriage acquisition compared to standard schedules. The relevance and feasibility of trials of reduced dose schedules is greatest in middle- and low-income countries, such as The Gambia, where the introduction of PCV resulted in good disease control but where transmission of vaccine-type pneumococci persists. We designed a large cluster-randomised field trial of an alternative reduced dose schedule of PCV compared to the standard schedule, the PVS trial. We will also conduct a sub-study to evaluate the individual-level effect of the two schedules on carriage acquisition, immunogenicity, and co-administration of PCV with yellow fever vaccine, the PVS-AcqImm trial. Methods PVS-AcqImm is a prospective, cluster-randomised trial of one dose of PCV scheduled at age 6 weeks with a booster dose at age 9 months (i.e. alternative ‘1+1’ schedule) compared to three primary doses scheduled at 6, 10, and 14 weeks of age (i.e. standard ‘3+0’ schedule). Sub-groups within the alternative schedule group will receive yellow fever vaccine separately or co-administered with PCV at 9 months of age. The primary endpoints are (a) rate of nasopharyngeal vaccine-type pneumococcal acquisition from 9 to 14 months of age, (b) geometric mean concentration of vaccine-type pneumococcal IgG at 18 months of age, and (c) proportions with yellow fever neutralising antibody titre ≥8 four weeks after administration of yellow fever vaccine. Participants and field staff will not be masked to group allocation while the measurement of laboratory endpoints will be masked. Approximately equal numbers of participants will be resident in each of 28 geographic clusters (14 clusters in alternative and standard schedule groups); 784 enrolled for acquisition measurements and 336 for immunogenicity measurements. Discussion Analysis will account for potential non-independence of measurements by cluster and so interpretation of effects will be at the individual level (i.e. a population of individuals). PVS-AcqImm will evaluate whether acquisition of vaccine-type pneumococci is reduced by the alternative compared to the standard schedule, which is required if the alternative schedule is to be effective. Likewise, evidence of superior immune response at 18 months of age and safety of PCV co-administration with yellow fever vaccine will support decision-making regarding the use of the alternative 1+1 schedule. Acquisition and immunogenicity outcomes will be essential for the interpretation of the results of the large field trial comparing the two schedules. Trial registration International Standard Randomised Controlled Trial Number 72821613 .

Background: Many children would benefit from a diet richer in vegetables and fruit. 'Flavour School' is a programme of 'sensory food education', which aims to increase children's confidence and curiosity in exploring foods and flavours, especially vegetables and fruit. This study will conduct a cluster-randomised controlled trial to assess the outcomes of the Flavour School programme in primary school children aged 4-7 years.Methods: Four hundred plus children from 4+ schools will either complete the Flavour School programme (experimental group) or have no intervention with normal school teaching (control group), cluster-randomised within-schools, by school class. Baseline data collection will consist of video recorded behavioural observation during a tasting activity, and post-intervention data collection will repeat this activity after the experimental group have completed the intervention. Process measures will be assessed using a teacher engagement feedback questionnaire.Discussion: This study will provide causal data on the efficacy of a sensory food education intervention for increasing children's confidence and curiosity in exploring foods and flavours, especially vegetables and fruit. This new knowledge will help educators and policy makers to make evidence based decisions on uptake of sensory food education.Trial Registration: ISRCTN: 40249947 Date assigned 17 March 2020 Last edited 22 September 2021 Version 1.2 Trial Acronym OASES (Outcomes Assessment of Sensory Education in Schools). [ABSTRACT FROM AUTHOR]

Background: Dental service provision in the care home sector is poor, with little emphasis on prevention. Emerging evidence suggests that the use of Dental Care Professionals (dental therapists and dental nurses) as an alternative to dentists has the potential to improve preventive advice, the provision of care and access to services within care homes. However, robust empirical evidence from definitive trials on how to successfully implement and sustain these interventions within care homes is currently lacking. The aim of the study is to determine whether Dental Care Professionals could reduce plaque levels of dentate older adults (65 + years) residing in care homes.Methods: This protocol describes a two-arm cluster-randomised controlled trial that will be undertaken in care homes across Wales, Northern Ireland and England. In the intervention arm, the dental therapists will visit the care homes every 6 months to assess and then treat eligible residents, where necessary. All treatment will be conducted within their Scope of Practice. Dental nurses will visit the care homes every month for the first 3 months and then three-monthly afterwards to promulgate advice to improve the day-to-day prevention offered to residents by carers. The control arm will be 'treatment as usual'. Eligible care homes (n = 40) will be randomised based on a 1:1 ratio (20 intervention and 20 control), with an average of seven residents recruited in each home resulting in an estimated sample of 280. Assessments will be undertaken at baseline, 6 months and 12 months and will include a dental examination and quality of life questionnaires. Care home staff will collect weekly information on the residents' oral health (e.g. episodes of pain and unscheduled care). The primary outcome will be a binary classification of the mean reduction in Silness-Löe Plaque Index at 6 months. A parallel process evaluation will be undertaken to explore the intervention's acceptability and how it could be embedded in standard practice (described in a separate paper), whilst a cost-effectiveness analysis will examine the potential long-term costs and benefits of the intervention.Discussion: This trial will provide evidence on how to successfully implement and sustain a Dental Care Professional-led intervention within care homes to promote access and prevention.Trial Registration: ISRCTN16332897 . Registered on 3 December 2021. [ABSTRACT FROM AUTHOR]

Abstract Objectives In this cluster-randomised controlled study (CoV-Surv Study), four different “active” SARS-CoV-2 testing strategies for general population surveillance are evaluated for their effectiveness in determining and predicting the prevalence of SARS-CoV-2 infections in a given population. In addition, the costs and cost-effectiveness of the four surveillance strategies will be assessed. Further, this trial is supplemented by a qualitative component to determine the acceptability of each strategy. Findings will inform the choice of the most effective, acceptable and affordable strategy for SARS-CoV-2 surveillance, with the most effective and cost-effective strategy becoming part of the local public health department’s current routine health surveillance activities. Investigating its everyday performance will allow us to examine the strategy’s applicability to real time prevalence prediction and the usefulness of the resulting information for local policy makers to implement countermeasures that effectively prevent future nationwide lockdowns. The authors would like to emphasize the importance and relevance of this study and its expected findings in the context of population-based disease surveillance, especially in respect to the current SARS-CoV-2 pandemic. In Germany, but also in many other countries, COVID-19 surveillance has so far largely relied on passive surveillance strategies that identify individuals with clinical symptoms, monitor those cases who then tested positive for the virus, followed by tracing of individuals in close contact to those positive cases. To achieve higher effectiveness in population surveillance and to reliably predict the course of an outbreak, screening and monitoring of infected individuals without major symptoms (about 40% of the population) will be necessary. While current testing capacities are also used to identify such asymptomatic cases, this rather passive approach is not suitable in generating reliable population-based estimates of the prevalence of asymptomatic carriers to allow any dependable predictions on the course of the pandemic. To better control and manage the SARS-CoV-2 pandemic, current strategies therefore need to be complemented by an active surveillance of the wider population, i.e. routinely conducted testing and monitoring activities to identify and isolate infected individuals regardless of their clinical symptoms. Such active surveillance strategies will enable more effective prevention of the spread of the virus as they can generate more precise population-based parameters during a pandemic. This essential information will be required in order to determine the best strategic and targeted short-term countermeasures to limit infection spread locally. Trial design This trial implements a cluster-randomised, two-factorial controlled, prospective, interventional, single-blinded design with four study arms, each representing a different SARS-CoV-2 testing and surveillance strategy. Participants Eligible are individuals age 7 years or older living in Germany’s Rhein-Neckar Region who consent to provide a saliva sample (all four arms) after completion of a brief questionnaire (two arms only). For the qualitative component, different samples of study participants and non-participants (i.e. eligible for study, but refuse to participate) will be identified for additional interviews. For these interviews, only individuals age 18 years or older are eligible. Intervention and comparator Of the four surveillance strategies to be assessed and compared, Strategy A1 is considered the gold standard for prevalence estimation and used to determine bias in other arms. To determine the cost-effectiveness, each strategy is compared to status quo, defined as the currently practiced passive surveillance approach. Strategy A1: Individuals (one per household) receive information and study material by mail with instructions on how to produce a saliva sample and how to return the sample by mail. Once received by the laboratory, the sample is tested for SARS-CoV-2 using Reverse Transcription Loop-mediated Isothermal Amplification (RT-LAMP). Strategy A2: Individuals (one per household) receive information and study material by mail with instructions on how to produce their own as well as saliva samples from each household member and how to return these samples by mail. Once received by the laboratory, the samples are tested for SARS-CoV-2 using RT-LAMP. Strategy B1: Individuals (one per household) receive information by mail on how to complete a brief pre-screening questionnaire which asks about COVID-19 related clinical symptoms and risk exposures. Only individuals whose pre-screening score crosses a defined threshold, will then receive additional study material by mail with instructions on how to produce a saliva sample and how to return the sample by mail. Once received by the laboratory, the saliva sample is tested for SARS-CoV-2 using RT-LAMP. Strategy B2: Individuals (one per household) receive information by mail on how to complete a brief pre-screening questionnaire which asks about COVID-19 related clinical symptoms. Only individuals whose pre-screening score crosses a defined threshold, will then receive additional study material by mail with instructions how to produce their own as well as saliva samples from each household member and how to return these samples by mail. Once received by the laboratory, the samples are tested for SARS-CoV-2 using RT-LAMP. In each strategy, RT-LAMP positive samples are additionally analyzed with qPCR in order to minimize the number of false positives. Main outcomes The identification of the one best strategy will be determined by a set of parameters. Primary outcomes include costs per correctly screened person, costs per positive case, positive detection rate, and precision of positive detection rate. Secondary outcomes include participation rate, costs per asymptomatic case, prevalence estimates, number of asymptomatic cases per study arm, ratio of symptomatic to asymptomatic cases per study arm, participant satisfaction. Additional study components (not part of the trial) include cost effectiveness of each of the four surveillance strategies compared to passive monitoring (i.e. status quo), development of a prognostic model to predict hospital utilization caused by SARS-CoV-2, time from test shipment to test application and time from test shipment to test result, and perception and preferences of the persons to be tested with regard to test strategies. Randomisation Samples are drawn in three batches of three continuous weeks. Randomisation follows a two-stage process. First, a total of 220 sampling points have been allocated to the three different batches. To obtain an integer solution, the Cox-algorithm for controlled rounding has been used. Afterwards, sample points have been drawn separately per batch, following a probability proportional to size (PPS) random sample. Second, for each cluster the same number of residential addresses is randomly sampled from the municipal registries (self-weighted sample of individuals). The 28,125 addresses drawn per municipality are then randomly allocated to the four study arms A1, A2, B1, and B2 in the ratio 5 to 2.5 to 14 to 7 based on the expected response rates in each arm and the sensitivity and specificity of the pre-screening tool as applied in strategy B1 and B2. Based on the assumptions, this allocation should yield 2500 saliva samples in each strategy. Although a municipality can be sampled by multiple batches and the overall number of addresses per municipality might vary, the number of addresses contacted in each arm is kept constant. Blinding (masking) The design is single-blinded, meaning the staff conducting the SARS-CoV-2 tests are unaware of the study arm assignment of each single participant and test sample. Sample sizes Total sample size for the trial is 10,000 saliva samples equally allocated to the four study arms (i.e. 2,500 participants per arm). For the qualitative component, up to 60 in-depth interviews will be conducted with about 30 study participants (up to 15 in each arm A and B) and 30 participation refusers (up to 15 in each arm A and B) purposefully selected from the quantitative study sample to represent a variety of gender and ages to explore experiences with admission or rejection of study participation. Up to 25 asymptomatic SARS-CoV-2 positive study participants will be purposefully selected to explore the way in which asymptomatic men and women diagnosed with SARS-CoV-2 give meaning to their diagnosis and to the dialectic between feeling concurrently healthy and yet also being at risk for transmitting COVID-19. In addition, 100 randomly selected study participants will be included to explore participants’ perspective on testing processes and implementation. Trial Status Final protocol version is “Surveillance_Studienprotokoll_03Nov2020_v1_2” from November 3, 2020. Recruitment started November 18, 2020 and is expected to end by or before December 31, 2020. Trial registration The trial is currently being registered with the German Clinical Trials Register (Deutsches Register Klinischer Studien), DRKS00023271 ( https://www.drks.de/drks_web/navigate.do?navigationId=trial . HTML&TRIAL_ID=DRKS00023271). Retrospectively registered 30 November 2020. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Abstract Background Inappropriate prescribing of antibiotics for acute respiratory infections at the primary care level represents the major source of antibiotic misuse in healthcare, and is a major driver for antimicrobial resistance worldwide. In this study we will develop, pilot and evaluate the effectiveness of a comprehensive antibiotic stewardship programme in China’s primary care hospitals to reduce inappropriate prescribing of antibiotics for acute respiratory infections among all ages. Methods We will use a parallel-group, cluster-randomised, controlled, superiority trial with blinded outcome evaluation but unblinded treatment (providers and patients). We will randomise 34 primary care hospitals from two counties within Guangdong province into the intervention and control arm (1:1 overall ratio) stratified by county (8:9 within-county ratio). In the control arm, antibiotic prescribing and management will continue through usual care. In the intervention arm, we will implement an antibiotic stewardship programme targeting family physicians and patients/caregivers. The family physician components include: (1) training using new operational guidelines, (2) improved management and peer-review of antibiotic prescribing, (3) improved electronic medical records and smart phone app facilitation. The patient/caregiver component involves patient education via family physicians, leaflets and videos. The primary outcome is the proportion of prescriptions for acute respiratory infections (excluding pneumonia) that contain any antibiotic(s). Secondary outcomes will address how frequently specific classes of antibiotics are prescribed, how frequently key non-antibiotic alternatives are prescribed and the costs of consultations. We will conduct a qualitative process evaluation to explore operational questions regarding acceptability, cultural appropriateness and burden of technology use, as well as a cost-effectiveness analysis and a long-term benefit evaluation. The duration of the intervention will be 12 months, with another 24 months’ post-trial long-term follow-up. Discussion Our study is one of the first trials to evaluate the effect of an antibiotic stewardship programme in primary care settings in a low- or middle-income country (LMIC). All interventional activities will be designed to be embedded into routine primary care with strong local ownership. Through the trial we intend to impact on clinical practice and national policy in antibiotic prescription for primary care facilities in rural China and other LMICs. Trial registration ISRCTN, ID: ISRCTN96892547 . Registered on 18 August 2019.

Abstract Background With 7.7 million South Africans currently infected with human immunodeficiency virus (HIV) and 4.8 million currently receiving antiretroviral treatment (ART), the epidemic represents a considerable burden for the country’s resource-limited health system. In response to the health and human resource shortages, task shifting to community health workers (CHWs) and empowering people living with HIV (PLWH) are integral parts of a sustainable ART strategy. Despite the success of the ART programme, South Africa still faces both prevention and treatment challenges. To tackle these challenges, future endeavours need to focus on the role played by the households of PLWH in mediating between the community and PLWH themselves. Building health-enabling “HIV competent” households with the capacity to actively stimulate lifestyles that foster health, offers a potential strategy to tackle South Africa’s HIV-related challenges. The aim of the “Sinako: Households and HIV” study is to investigate to what extent and how an intervention can increase HIV competence in PLWH and their households, and subsequently optimise the impact of CHW support on individual ART outcomes. Methods The “Sinako” study is a cluster-randomised controlled trial with two arms. In the control arm, CHWs offer a standard package of support to PLWH during home visits, focused on the individual. The intervention arm includes both a focus on the individual and the household to enable the patient to self-manage their treatment within an HIV competent household. A longitudinal mixed methods design is adopted to analyse the data. For the quantitative data analysis, methods including latent cross-lagged modelling, multilevel modelling and logistic regression will be used. To assess the acceptability and feasibility of the intervention and to construct a comprehensive picture of the mechanisms underlying the impact on the household and the PLWH, qualitative data (in-depth interviews and focus group discussions) will be collected and analysed. Discussion Stimulating HIV competence in households could be a feasible and sustainable strategy to optimise the outcomes of CHW interventions and thus be important for HIV treatment interventions in resource-limited settings. Trial registration Pan African Clinical Trial Registry, PACTR201906476052236. Registered on 24 June 2019.

Background: Pneumococcal conjugate vaccines (PCVs) effectively prevent pneumococcal disease, but the global impact of pneumococcal vaccination is hampered by its cost. The evaluation of reduced dose schedules of PCV includes measurement of effects on immunogenicity and carriage acquisition compared to standard schedules. The relevance and feasibility of trials of reduced dose schedules is greatest in middle- and low-income countries, such as The Gambia, where the introduction of PCV resulted in good disease control but where transmission of vaccine-type pneumococci persists. We designed a large cluster-randomised field trial of an alternative reduced dose schedule of PCV compared to the standard schedule, the PVS trial. We will also conduct a sub-study to evaluate the individual-level effect of the two schedules on carriage acquisition, immunogenicity, and co-administration of PCV with yellow fever vaccine, the PVS-AcqImm trial.Methods: PVS-AcqImm is a prospective, cluster-randomised trial of one dose of PCV scheduled at age 6 weeks with a booster dose at age 9 months (i.e. alternative '1+1' schedule) compared to three primary doses scheduled at 6, 10, and 14 weeks of age (i.e. standard '3+0' schedule). Sub-groups within the alternative schedule group will receive yellow fever vaccine separately or co-administered with PCV at 9 months of age. The primary endpoints are (a) rate of nasopharyngeal vaccine-type pneumococcal acquisition from 9 to 14 months of age, (b) geometric mean concentration of vaccine-type pneumococcal IgG at 18 months of age, and (c) proportions with yellow fever neutralising antibody titre ≥8 four weeks after administration of yellow fever vaccine. Participants and field staff will not be masked to group allocation while the measurement of laboratory endpoints will be masked. Approximately equal numbers of participants will be resident in each of 28 geographic clusters (14 clusters in alternative and standard schedule groups); 784 enrolled for acquisition measurements and 336 for immunogenicity measurements.Discussion: Analysis will account for potential non-independence of measurements by cluster and so interpretation of effects will be at the individual level (i.e. a population of individuals). PVS-AcqImm will evaluate whether acquisition of vaccine-type pneumococci is reduced by the alternative compared to the standard schedule, which is required if the alternative schedule is to be effective. Likewise, evidence of superior immune response at 18 months of age and safety of PCV co-administration with yellow fever vaccine will support decision-making regarding the use of the alternative 1+1 schedule. Acquisition and immunogenicity outcomes will be essential for the interpretation of the results of the large field trial comparing the two schedules.Trial Registration: International Standard Randomised Controlled Trial Number 72821613 . [ABSTRACT FROM AUTHOR]

Abstract Background Health care employees in Germany and worldwide are exposed to a variety of stressors. However, most of the hospitals in Germany lack a systematic workplace health management. Thus, this study aims at the evaluation of the effects of a behavioural as well as organisational (´complex´) intervention on the mental health and well-being of hospital staff. Methods Mental health in the hospital workplace (SEElische GEsundheit am Arbeitsplatz KrankeNhaus – SEEGEN) is an unblinded, multi-centred cluster-randomised open trial with two groups (intervention group (IG) and waitlist control group (CG)). Study participants in the intervention clusters will receive the complex intervention; study participants in the waitlist control clusters will receive the complex intervention after the last follow-up measurement. The intervention consists of five behavioural and organisational intervention modules that are specifically tailored to hospital employees at different hierarchical and functional levels. Hospital staff may select one specific module according to their position and specific needs or interests. Towards the end of the intervention roundtable discussions with representatives from all professional groups will be held to facilitate organisational change. Primary outcome is the change in emotional and cognitive strain in the working environment, from baseline (T0) to 6 month-follow up (T1), between IG and CG. In addition, employees who do not participate in the modules are included in the trial by answering shorter questionnaires (cluster participants). Furthermore, using mixed methods, a process evaluation will identify uptake of the intervention, and mediators and moderators of the effect. Discussion There seems to be growing psychological strain on people working in the health care sector worldwide. This study will examine whether investing directly in the hospital staff and their interpersonal relationship may lead to measurable benefits in subjective well-being at the workplace and improved economic performance indicators of the hospital. In case of a positive outcome, health promotion strategies looking at behavioural as well as organisational components within the hospital may gain additional importance, especially in regard of the growing financial pressure within the health sector. Trial registration DRKS The SEEGEN study is registered at the German Clinical Trial Register (DRKS) under the DRKS-ID DRKS00017249. Registered 08 October 2019, URL. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00017249.

Objectives: In this cluster-randomised controlled study (CoV-Surv Study), four different “active” SARS-CoV-2 testing strategies for general population surveillance are evaluated for their effectiveness in determining and predicting the prevalence of SARS-CoV-2 infections in a given population. In addition, the costs and cost-effectiveness of the four surveillance strategies will be assessed. Further, this trial is supplemented by a qualitative component to determine the acceptability of each strategy. Findings will inform the choice of the most effective, acceptable and affordable strategy for SARS-CoV-2 surveillance, with the most effective and cost-effective strategy becoming part of the local public health department’s current routine health surveillance activities. Investigating its everyday performance will allow us to examine the strategy’s applicability to real time prevalence prediction and the usefulness of the resulting information for local policy makers to implement countermeasures that effectively prevent future nationwide lockdowns. The authors would like to emphasize the importance and relevance of this study and its expected findings in the context of population-based disease surveillance, especially in respect to the current SARS-CoV-2 pandemic. In Germany, but also in many other countries, COVID-19 surveillance has so far largely relied on passive surveillance strategies that identify individuals with clinical symptoms, monitor those cases who then tested positive for the virus, followed by tracing of individuals in close contact to those positive cases. To achieve higher effectiveness in population surveillance and to reliably predict the course of an outbreak, screening and monitoring of infected individuals without major symptoms (about 40% of the population) will be necessary. While current testing capacities are also used to identify such asymptomatic cases, this rather passive approach is not suitable in generating reliable population-based estimates of the prevalence of asymptomatic carriers to allow any dependable predictions on the course of the pandemic. To better control and manage the SARS-CoV-2 pandemic, current strategies therefore need to be complemented by an active surveillance of the wider population, i.e. routinely conducted testing and monitoring activities to identify and isolate infected individuals regardless of their clinical symptoms. Such active surveillance strategies will enable more effective prevention of the spread of the virus as they can generate more precise population-based parameters during a pandemic. This essential information will be required in order to determine the best strategic and targeted short-term countermeasures to limit infection spread locally. Trial design: This trial implements a cluster-randomised, two-factorial controlled, prospective, interventional, singleblinded design with four study arms, each representing a different SARS-CoV-2 testing and surveillance strategy. Participants: Eligible are individuals age 7 years or older living in Germany’s Rhein-Neckar Region who consent to provide a saliva sample (all four arms) after completion of a brief questionnaire (two arms only). For the qualitative component, different samples of study participants and non-participants (i.e. eligible for study, but refuse to participate) will be identified for additional interviews. For these interviews, only individuals age 18 years or older are eligible. Intervention and comparator: Of the four surveillance strategies to be assessed and compared, Strategy A1 is considered the gold standard for prevalence estimation and used to determine bias in other arms. To determine the cost-effectiveness, each strategy is compared to status quo, defined as the currently practiced passive surveillance approach. Strategy A1: Individuals (one per household) receive information and study material by mail with instructions on how to produce a saliva sample and how to return the sample by mail. Once received by the laboratory, the sample is tested for SARS-CoV-2 using Reverse Transcription Loop-mediated Isothermal Amplification (RT-LAMP). Strategy A2: Individuals (one per household) receive information and study material by mail with instructions on how to produce their own as well as saliva samples from each household member and how to return these samples by mail. Once received by the laboratory, the samples are tested for SARS-CoV-2 using RT-LAMP. Strategy B1: Individuals (one per household) receive information by mail on how to complete a brief pre-screening questionnaire which asks about COVID-19 related clinical symptoms and risk exposures. Only individuals whose prescreening score crosses a defined threshold, will then receive additional study material by mail with instructions on how to produce a saliva sample and how to return the sample by mail. Once received by the laboratory, the saliva sample is tested for SARS-CoV-2 using RT-LAMP. Strategy B2: Individuals (one per household) receive information by mail on how to complete a brief pre-screening questionnaire which asks about COVID-19 related clinical symptoms. Only individuals whose pre-screening score crosses a defined threshold, will then receive additional study material by mail with instructions how to produce their own as well as saliva samples from each household member and how to return these samples by mail. Once received by the laboratory, the samples are tested for SARS-CoV-2 using RT-LAMP. In each strategy, RT-LAMP positive samples are additionally analyzed with qPCR in order to minimize the number of false positives. Main outcomes: The identification of the one best strategy will be determined by a set of parameters. Primary outcomes include costs per correctly screened person, costs per positive case, positive detection rate, and precision of positive detection rate. Secondary outcomes include participation rate, costs per asymptomatic case, prevalence estimates, number of asymptomatic cases per study arm, ratio of symptomatic to asymptomatic cases per study arm, participant satisfaction. Additional study components (not part of the trial) include cost effectiveness of each of the four surveillance strategies compared to passive monitoring (i.e. status quo), development of a prognostic model to predict hospital utilization caused by SARS-CoV-2, time from test shipment to test application and time from test shipment to test result, and perception and preferences of the persons to be tested with regard to test strategies. Randomisation: Samples are drawn in three batches of three continuous weeks. Randomisation follows a twostage process. First, a total of 220 sampling points have been allocated to the three different batches. To obtain an integer solution, the Cox-algorithm for controlled rounding has been used. Afterwards, sample points have been drawn separately per batch, following a probability proportional to size (PPS) random sample. Second, for each cluster the same number of residential addresses is randomly sampled from the municipal registries (self-weighted sample of individuals). The 28,125 addresses drawn per municipality are then randomly allocated to the four study arms A1, A2, B1, and B2 in the ratio 5 to 2.5 to 14 to 7 based on the expected response rates in each arm and the sensitivity and specificity of the pre-screening tool as applied in strategy B1 and B2. Based on the assumptions, this allocation should yield 2500 saliva samples in each strategy. Although a municipality can be sampled by multiple batches and the overall number of addresses per municipality might vary, the number of addresses contacted in each arm is kept constant. Blinding (masking): The design is single-blinded, meaning the staff conducting the SARS-CoV-2 tests are unaware of the study arm assignment of each single participant and test sample. Sample sizes: Total sample size for the trial is 10,000 saliva samples equally allocated to the four study arms (i.e. 2, 500 participants per arm). For the qualitative component, up to 60 in-depth interviews will be conducted with about 30 study participants (up to 15 in each arm A and B) and 30 participation refusers (up to 15 in each arm A and B) purposefully selected from the quantitative study sample to represent a variety of gender and ages to explore experiences with admission or rejection of study participation. Up to 25 asymptomatic SARS-CoV-2 positive study participants will be purposefully selected to explore the way in which asymptomatic men and women diagnosed with SARS-CoV-2 give meaning to their diagnosis and to the dialectic between feeling concurrently healthy and yet also being at risk for transmitting COVID-19. In addition, 100 randomly selected study participants will be included to explore participants’ perspective on testing processes and implementation. Trial Status: Final protocol version is “Surveillance_Studienprotokoll_03Nov2020_v1_2” from November 3, 2020. Recruitment started November 18, 2020 and is expected to end by or before December 31, 2020. [ABSTRACT FROM AUTHOR]

Background: To understand better the success of self-management interventions and to enable tailoring of such interventions at specific subgroups of patients, the nurse-led Activate intervention is developed targeting one component of self-management (physical activity) in a heterogeneous subgroup (patients at risk of cardiovascular disease) in Dutch primary care. Aim: The aim of this study was to evaluate the effectiveness of the Activate intervention and identifying which patient-related characteristics modify the effect. Methods: A two-armed cluster-randomised controlled trial was conducted comparing the intervention with care as usual. The intervention consisted of four nurse-led behaviour change consultations within a 3-month period. Data were collected at baseline, 3 months and 6 months. Primary outcome was the daily amount of moderate to vigorous physical activity at 6 months. Secondary outcomes included sedentary behaviour, self-efficacy for physical activity, patient activation for self-management and health status. Prespecified effect modifiers were age, body mass index, level of education, social support, depression, patient provider relationship and baseline physical activity. Results: Thirty-one general practices (n = 195 patients) were included (intervention group n = 93; control group n = 102). No significant between-group difference was found for physical activity (mean difference 2.49 minutes; 95% confidence interval -2.1; 7.1; P = 0.28) and secondary outcomes. Patients with low perceived social support (P = 0.01) and patients with a low baseline activity level (P = 0.02) benefitted more from the intervention. Conclusion: The Activate intervention did not improve patients' physical activity and secondary outcomes in primary care patients at risk of cardiovascular disease. To understand the results, the intervention fidelity and active components for effective self-management require further investigation. Trial registration: ClinicalTrials.gov NCT02725203. [ABSTRACT FROM AUTHOR]

Background: Inappropriate prescribing of antibiotics for acute respiratory infections at the primary care level represents the major source of antibiotic misuse in healthcare, and is a major driver for antimicrobial resistance worldwide. In this study we will develop, pilot and evaluate the effectiveness of a comprehensive antibiotic stewardship programme in China's primary care hospitals to reduce inappropriate prescribing of antibiotics for acute respiratory infections among all ages.Methods: We will use a parallel-group, cluster-randomised, controlled, superiority trial with blinded outcome evaluation but unblinded treatment (providers and patients). We will randomise 34 primary care hospitals from two counties within Guangdong province into the intervention and control arm (1:1 overall ratio) stratified by county (8:9 within-county ratio). In the control arm, antibiotic prescribing and management will continue through usual care. In the intervention arm, we will implement an antibiotic stewardship programme targeting family physicians and patients/caregivers. The family physician components include: (1) training using new operational guidelines, (2) improved management and peer-review of antibiotic prescribing, (3) improved electronic medical records and smart phone app facilitation. The patient/caregiver component involves patient education via family physicians, leaflets and videos. The primary outcome is the proportion of prescriptions for acute respiratory infections (excluding pneumonia) that contain any antibiotic(s). Secondary outcomes will address how frequently specific classes of antibiotics are prescribed, how frequently key non-antibiotic alternatives are prescribed and the costs of consultations. We will conduct a qualitative process evaluation to explore operational questions regarding acceptability, cultural appropriateness and burden of technology use, as well as a cost-effectiveness analysis and a long-term benefit evaluation. The duration of the intervention will be 12 months, with another 24 months' post-trial long-term follow-up.Discussion: Our study is one of the first trials to evaluate the effect of an antibiotic stewardship programme in primary care settings in a low- or middle-income country (LMIC). All interventional activities will be designed to be embedded into routine primary care with strong local ownership. Through the trial we intend to impact on clinical practice and national policy in antibiotic prescription for primary care facilities in rural China and other LMICs.Trial Registration: ISRCTN, ID: ISRCTN96892547. Registered on 18 August 2019. [ABSTRACT FROM AUTHOR]

Background: With 7.7 million South Africans currently infected with human immunodeficiency virus (HIV) and 4.8 million currently receiving antiretroviral treatment (ART), the epidemic represents a considerable burden for the country's resource-limited health system. In response to the health and human resource shortages, task shifting to community health workers (CHWs) and empowering people living with HIV (PLWH) are integral parts of a sustainable ART strategy. Despite the success of the ART programme, South Africa still faces both prevention and treatment challenges. To tackle these challenges, future endeavours need to focus on the role played by the households of PLWH in mediating between the community and PLWH themselves. Building health-enabling "HIV competent" households with the capacity to actively stimulate lifestyles that foster health, offers a potential strategy to tackle South Africa's HIV-related challenges. The aim of the "Sinako: Households and HIV" study is to investigate to what extent and how an intervention can increase HIV competence in PLWH and their households, and subsequently optimise the impact of CHW support on individual ART outcomes.Methods: The "Sinako" study is a cluster-randomised controlled trial with two arms. In the control arm, CHWs offer a standard package of support to PLWH during home visits, focused on the individual. The intervention arm includes both a focus on the individual and the household to enable the patient to self-manage their treatment within an HIV competent household. A longitudinal mixed methods design is adopted to analyse the data. For the quantitative data analysis, methods including latent cross-lagged modelling, multilevel modelling and logistic regression will be used. To assess the acceptability and feasibility of the intervention and to construct a comprehensive picture of the mechanisms underlying the impact on the household and the PLWH, qualitative data (in-depth interviews and focus group discussions) will be collected and analysed.Discussion: Stimulating HIV competence in households could be a feasible and sustainable strategy to optimise the outcomes of CHW interventions and thus be important for HIV treatment interventions in resource-limited settings.Trial Registration: Pan African Clinical Trial Registry, PACTR201906476052236. Registered on 24 June 2019. [ABSTRACT FROM AUTHOR]

The 'Cuidate' programme for adolescents in Spain has proven to be effective for promoting healthy sexuality (N = 626), but the mechanisms underlying its effects are unknown. This study aimed to identify mediators of the intervention's effects compared to a control group. Participants were students from five areas of Spain, who completed baseline, immediate-posttest, 12-month and 24-month follow-up assessments. Mediation analyses revealed that 'Cuidate' positively affected consistent condom use indirectly through knowledge in serial with the intention to use condoms. The findings underscore the importance of targeting knowledge on HIV and sexually transmitted infections to promote condom use intention and consistent condom use. [ABSTRACT FROM AUTHOR]

Objectives: Reduction in maternal and newborn mortality requires that women deliver in high quality health facilities. However, many facilities provide sub-optimal quality of care, which may be a reason for less than universal facility utilisation. We assessed the impact of a quality improvement project on facility utilisation for childbirth.Methods: In this cluster-randomised experiment in four rural districts in Tanzania, 12 primary care clinics and their catchment areas received a quality improvement intervention consisting of in-service training, mentoring and supportive supervision, infrastructure support, and peer outreach, while 12 facilities and their catchment areas functioned as controls. We conducted a census of all deliveries within the catchment area and used difference-in-differences analysis to determine the intervention's effect on facility utilisation for childbirth. We conducted a secondary analysis of utilisation among women whose prior delivery was at home. We further investigated mechanisms for increased facility utilisation.Results: The intervention led to an increase in facility births of 6.7 percentage points from a baseline of 72% (95% Confidence Interval: 0.6, 12.8). The intervention increased facility delivery among women with past home deliveries by 18.3 percentage points (95% CI: 10.1, 26.6). Antenatal quality increased in intervention facilities with providers performing an additional 0.5 actions across the full population and 0.8 actions for the home delivery subgroup.Conclusions: We attribute the increased use of facilities to better antenatal quality. This increased utilisation would lead to lower maternal mortality only in the presence of improvement in care quality. [ABSTRACT FROM AUTHOR]

Aims: The Drug Education in Victorian Schools (DEVS) programme taught about licit and illicit drugs over two years (2010–2011), with follow up in the third year (2012). It focussed on minimising harm and employed participatory, critical-thinking and skill-focussed pedagogy. This study evaluated the programme’s residual effectiveness at follow up in reducing alcohol-related risk and harm.Methods: A cluster-randomised, controlled trial was conducted with a student cohort during years eight (13–14 years old), nine (14–15 years old) and 10 (15–16 years old). Schools were randomly allocated to the DEVS programme (14 schools,n = 1163), or their usual drug education (7 schools,n = 589). Multi-level models were fitted to the data, which were analysed on an intent-to-treat basis.Statistically significant findings: Over the 3 years, there was a greater increase in intervention students’ knowledge about drugs, including alcohol. Their alcohol consumption did not increase as much as controls. Their alcohol-related harms decreased, while increasing for controls. There were fewer intervention group risky drinkers, and they reduced their consumption compared to controls. Similarly, harms decreased for intervention group risky drinkers, while increasing for controls.Conclusions: Skill-focussed, harm minimisation drug education can remain effective, subsequent to programme completion, in reducing students’ alcohol consumption and harm, even with risky drinkers. [ABSTRACT FROM PUBLISHER]

Background: Despite growing evidence for manualized psychodynamic treatments, there is a lack of studies on their transfer to routine practice. This is the first study to examine the effects of an additional training in manualized Short Term Psychodynamic Psychotherapy (STPP) on the outcome in routine psychotherapy for social anxiety disorder (SAD). The study is an extension to a large RCT comparing STPP to Cognitive-Behavioral Therapy of SAD. Methods: The manualized treatment was designed for a time limited approach with 25 individual sessions of STPP over 6 months. Private practitioners were randomized to training in manualized STPP (mSTPP) vs. treatment as usual without a specific training (tauSTPP). A total of 109 patients were enrolled (105 started treatment; 75 completed at least 20 treatment sessions). Assessments were conducted pre-treatment, after 8 and 15 weeks, after 25 treatment sessions, at the end of treatment, 6 and 12 months after termination of treatment. Remission as primary outcome was defined by the Liebowitz-Social-Anxiety-Scale (LSAS) score ≤30. Secondary outcomes were response (at least 31% reduction in LSAS), treatment duration and number of sessions, changes in social anxiety (LSAS, SPAI), depression (BDI), clinical global impression (CGI), and quality of life (EQ-5D). Results: Remission rates of mSTPP (9%) resp. tauSTPP (16%) and also response rates of 33% resp. 28% were comparable between the two treatment approaches as well as treatment duration and number of sessions. Most of the within-group differences (baseline to 25 sessions) indicated moderate to large improvements in both treatments; within-group differences from baseline to 12 months follow-up (LSAS, SPAI, BDI, CGI) were large ranging from d = -0.605 to d = -2.937. Benefits of mSTPP were limited to single outcomes. Conclusions: Findings are discussed with regard to implementation and dissemination of empirically validated treatments in psychodynamic training and practice. SAD patients with a high comorbidity of personality disorders and a long treatment history may need longer treatments. [ABSTRACT FROM AUTHOR]

Background: Up to 90 % of people living with dementia in care homes experience one or more behaviours that staff may describe as challenging to support (BSC). Of these agitation is the most common and difficult to manage. The presence of agitation is associated with fewer visits from relatives, poorer quality of life and social isolation. It is recommended that agitation is treated through psychosocial interventions. Dementia Care Mapping™ (DCM™) is an established, widely used observational tool and practice development cycle, for ensuring a systematic approach to providing person-centred care. There is a body of practice-based literature and experience to suggests that DCM™ is potentially effective but limited robust evidence for its effectiveness, and no examination of its cost-effectiveness, as a UK health care intervention. Therefore, a definitive randomised controlled trial (RCT) of DCM™ in the UK is urgently needed.Methods/design: A pragmatic, multi-centre, cluster-randomised controlled trial of Dementia Care Mapping (DCM™) plus Usual Care (UC) versus UC alone, where UC is the normal care delivered within the care home following a minimum level of dementia awareness training. The trial will take place in residential, nursing and dementia-specialist care homes across West Yorkshire, Oxfordshire and London, with residents with dementia. A random sample of 50 care homes will be selected within which a minimum of 750 residents will be registered. Care homes will be randomised in an allocation ratio of 3:2 to receive either intervention or control. Outcome measures will be obtained at 6 and 16 months following randomisation. The primary outcome is agitation as measured by the Cohen-Mansfield Agitation Inventory, at 16 months post randomisation. Key secondary outcomes are other BSC and quality of life. There will be an integral cost-effectiveness analysis and a process evaluation.Discussion: The protocol was refined following a pilot of trial procedures. Changes include replacement of a questionnaire, whose wording caused some residents distress, to an adapted version specifically designed for use in care homes, a change to the randomisation stratification factors, adaption in how the staff measures are collected to encourage greater compliance, and additional reminders to intervention homes of when mapping cycles are due, via text message.Trial Registration: Current Controlled Trials ISRCTN82288852 . Registered on 16 January 2014. Full protocol version and date: v7.1: 18 December 2015. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of an intervention including psychoeducation and yoga for depression management at the primary healthcare level in one district in the Hà Nam province, Vietnam.Method: The Patient Health Questionnaire-9 (PHQ-9) was used for depression screening and follow-up. Screened patients were further diagnosed with the Mini-International Neuropsychiatric Diagnostic Interview, by a trained general doctor. A linear regression model, adjusted for age, gender and baseline PHQ-9 score was used to assess whether the intervention leads to decreased depression severity compared to standard care in the control communes.Results: Both groups had similar PHQ-9 scores at baseline. The intervention group had on average significantly lower PHQ-9 scores after the intervention than the control group. Almost half of the patients in the intervention group recovered from depression, whereas nobody did in the control group.Conclusion: The results indicate that the intervention can be more effective than standard care in treating depression. The mean change of the PHQ-9 score after the intervention is deemed to be of clinical relevance. [ABSTRACT FROM AUTHOR]

Background Chronic heart failure, a common pathology, is increasing due to the aging population and improvements in heart disease detection and management. The prevalence is estimated at ~10% of the French general practice patient population over 59 years old. The primary objective of this study is to improve the quality of life for heart failure patients though a complex intervention involving patient and general practitioner (GP) education in primary care. Methods A randomised, cluster controlled trial, stratified over 4 areas of the Auvergne region in France comparing intervention and control groups. The inclusion criteria are: patients older than 50 years with New York Heart Association stage I, II, or III heart failure, with reduced ejection fraction or with preserved ejection fraction. Heart failure should be confirmed by the patient?s cardiologist according to the European Society of Cardiology guidelines criteria. The exclusion criteria include: severe cognitive disorders, living in an institution, participating in another clinical trial, having New York Heart Association stage IV heart failure, or a lack of French language skills. The complex intervention consists of training at the GP practice with an interactive 2-day workshop to provide a patient?s education programme. GPs are trained to perform case management, lifestyle counselling and motivational interviewing, to educate patients on the main topics including clinical alarm signs, physical activity, diet and cardiovascular risk factors. The patients? education sessions are scheduled at 1, 4, 7, 10, 13 and 19 months following the start of the trial. The primary outcome to be assessed is the impact on the quality of life as determined using two questionnaires: the Minnesota Living with Heart Failure Questionnaire and SF-36. To detect a difference in the mean quality of life at 19 months, we anticipate studying a minimum of 400 patients from 80 GPs. Discussion This trial will provide insight into the effectiveness of a complex intervention to educate patients with heart failure including a 2-day GP workshop and patients? education programme in the setting of a GP consultation to improve the quality of life in patients with chronic heart failure. This complex intervention tool could be used during initial and further medical training. [ABSTRACT FROM AUTHOR]

Common mental disorders (CMDs) are a major cause of sickness absence. Twenty to 30% of the workers who return to work after sickness absence due to CMDs experience recurrent sickness absence. We developed the Stimulating Healthy participation And Relapse Prevention (SHARP)-at work intervention, a problem solving intervention delivered by occupational physicians (OPs), to prevent recurrent sickness absence in this worker population in The Netherlands. A process evaluation was conducted alongside a cluster-randomised controlled trial to (1) evaluate whether the SHARP-at work intervention was implemented according to the protocol and differed from treatment in the control group, and (2) to investigate the relationship between the key elements of the intervention and the effect outcome (i.e. recurrent sickness absence). We collected process data for both the intervention and control group on recruitment, reach, dose delivered, dose received, fidelity, context and satisfaction. Data on recurrent sickness absence was collected through the registry system of the collaborating occupational health service. The study was performed in the Netherlands, and between 2010 and 2012, 154 OPs and 158 participants participated. Compared to the control group, participants in the intervention group more frequently had two or more consultations with the OP (odds ratio [OR] = 3.2, 95% confidence interval [CI] = 1.2-8.8) and completed more assignments (OR = 33.8, 95% CI = 10.4-109.5) as recommended in the intervention protocol. OPs and participants were satisfied with the intervention and rated it as applicable. Several individual intervention components were linked to the effect outcome. The process evaluation showed that the SHARP-at work intervention was conducted according to the protocol for the majority of the participants and well-received by OPs and participants. Furthermore, the intervention differed from treatment in the control group. Overall, the results provide support for implementing the intervention in practice. [ABSTRACT FROM AUTHOR]

Background: Process evaluations are recommended to open the 'black box' of complex interventions evaluated in trials, but there is limited guidance to help researchers design process evaluations. Much current literature on process evaluations of complex interventions focuses on qualitative methods, with less attention paid to quantitative methods. This discrepancy led us to develop our own framework for designing process evaluations of cluster-randomised controlled trials. Methods: We reviewed recent theoretical and methodological literature and selected published process evaluations; these publications identified a need for structure to help design process evaluations. We drew upon this literature to develop a framework through iterative exchanges, and tested this against published evaluations. Results: The developed framework presents a range of candidate approaches to understanding trial delivery, intervention implementation and the responses of targeted participants. We believe this framework will be useful to others designing process evaluations of complex intervention trials. We also propose key information that process evaluations could report to facilitate their identification and enhance their usefulness. Conclusion: There is no single best way to design and carry out a process evaluation. Researchers will be faced with choices about what questions to focus on and which methods to use. The most appropriate design depends on the purpose of the process evaluation; the framework aims to help researchers make explicit their choices of research questions and methods. [ABSTRACT FROM AUTHOR]

Background Despite the popularity of hypnotherapy for smoking cessation, the efficacy of this method is unclear. We aimed to investigate the efficacy of a single-session of group hypnotherapy for smoking cessation compared to relaxation in Swiss adult smokers. Methods This was a cluster-randomised, parallel-group, controlled trial. A single session of hypnosis or relaxation for smoking cessation was delivered to groups of smokers (median size = 11). Participants were 223 smokers consuming ≥ 5 cigarettes per day, willing to quit and not using cessation aids (47.1% females, M = 37.5 years [SD = 11.8], 86.1% Swiss). Nicotine withdrawal, smoking abstinence self-efficacy, and adverse reactions were assessed at a 2-week follow-up. The main outcome, self-reported 30-day point prevalence of smoking abstinence, was assessed at a 6-month follow up. Abstinence was validated through salivary analysis. Secondary outcomes included number of cigarettes smoked per day, smoking abstinence self-efficacy, and nicotine withdrawal. Results At the 6-month follow up, 14.7% in the hypnosis group and 17.8% in the relaxation group were abstinent. The intervention had no effect on smoking status (p = .73) or on the number of cigarettes smoked per day (p = .56). Smoking abstinence self-efficacy did not differ between the interventions (p = .14) at the 2-week follow-up, but non-smokers in the hypnosis group experienced reduced withdrawal (p = .02). Both interventions produced few adverse reactions (p = .81). Conclusions A single session of group hypnotherapy does not appear to be more effective for smoking cessation than a group relaxation session. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this impact evaluation was to measure the influence of a government of Ontario, Canada health promotion initiative, the Northern Fruit and Vegetable Pilot Programme (NFVPP), on elementary school-aged children's psychosocial variables regarding fruit and vegetables, and fruit and vegetable consumption patterns. Design: A cluster-randomised controlled trial design was used. The NFVPP consisted of three intervention arms: (i) Intervention I: Free Fruit and Vegetable Snack (FFVS)+Enhanced Nutrition Education; (ii) Intervention II: FFVS-alone; and (iii) Control group. Using the Pro-Children Questionnaire, the primary outcome measure was children's fruit and vegetable consumption, and the secondary outcome measures included differences in children's awareness, knowledge, self-efficacy, preference, intention and willingness to increase fruit and vegetable consumption. Setting/Subjects: Twenty-six elementary schools in a defined area of Northern Ontario were eligible to participate in the impact evaluation. A final sample size of 1277 students in grades five to eight was achieved. Results: Intervention I students consumed more fruit and vegetables at school than their Control counterparts by 0.49 serving/d (P<0.05). Similarly, Intervention II students consumed more fruit and vegetables at school than Control students by 0.42 serving/d, although this difference was not statistically significant. Among students in both intervention groups, preferences for certain fruit and vegetables shifted from 'never tried it' towards 'like it'. Conclusions: The NFVPP resulted in positive changes in elementary school-aged children's fruit and vegetable consumption at school, and favourable preference changes for certain fruit and vegetables. [ABSTRACT FROM AUTHOR]

Background: Potentially inappropriate medication (PIM) is considered to have potentially more harmful than beneficial health effects in elderly patients. A German example for a PIM list is the PRISCUS list that has been available since 2010. PIMs are associated with an increased risk of hospitalisation and adverse health outcomes. Furthermore, drug-drug interactions (DDI) may pose additional risks to patients. It is not yet clear how numbers of PIM and DDI can be reduced in community-dwelling seniors in primary care; nor is it clear whether patients would benefit from such deprescribing., Methods: The cluster-randomised controlled study on the "Reduction of potentially Inappropriate Medication in the Elderly" (RIME study) is designed to examine whether an intervention based on the PRISCUS list can lower the proportion of community-dwelling people of ⩾70 years taking at least one PIM and/or medication inducing at least one dangerous DDI. The intervention consists of professional education and training on the reduction of PIM and DDI, and will be offered to either general practitioners (GPs) alone or GPs and their office staff in the experimental study arm. The control group will be offered professional education and training on more general issues of prescribing in the elderly, not specifically addressing PIM or DDI. The primary endpoint is the difference in the proportion of patients with at least one PIM or DDI between the start of the study and study closure after 12 months as compared between intervention and control group. Secondary endpoints include overall mortality, number of hospitalisations during the course of the study, quality of life and costs. Secondary analyses will be explorative, with the cluster randomisation being factored in., Discussion: The RIME study will contribute to answering the question of whether an intervention based on the PRISCUS list can reduce the proportion of community-dwelling seniors aged ⩾70 years with at least one PIM and/or DDI, and whether this will result in positive health effects, for example, as regards hospitalisations., Trial Registration: The Study has been registered in the German Clinical Trials Register (DRKS) under the number DRKS00003610., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

Introduction: There is a need to evaluate whether, and to what degree, labour inspections or other regulatory tools have the desired effects on psychosocial, organisational and mechanical work environment, and employee health. The Norwegian Labour Inspection Authority (NLIA) uses different tools and strategies to enforce compliance with occupational safety and health (OSH) legislation. The aim of the present study is to evaluate the effects of labour inspections and other regulatory tools employed by the NLIA. The home-care service is one of the fastest growing occupations and a prioritised area for the NLIA, hence the present study will investigate regulatory tools in this sector., Methods and Analysis: The research project has been designed as a longitudinal, cluster-randomised, controlled trial and will be conducted among Norwegian home-care workers. The objective of the research project is to evaluate the effects of the NLIA's regulatory tools (inspection and guidance) on: (1) compliance with OSH legislation and regulation; (2) psychosocial, organisational and mechanical work environment; (3) employee health in terms of musculoskeletal and mental health complaints; and (4) sickness absence. Public home-care services have been randomised to three intervention groups and one control group. Home-care services in the intervention groups will receive one of three intervention activities from the NLIA: (1) inspection from the Labour Inspection Authority; (2) guidance through an online interactive risk-assessment tool; and (3) guidance on psychosocial, organisational and mechanical work environment through workshops. The interventions will be performed at the organisational level (home-care service), and the effects of the interventions on the working environment and health complaints will be measured at the individual level (home-care employees)., Ethics and Dissemination: This project has been approved by the Regional Committees for Medical and Health Research Ethics (REC) in Norway (REC South East) (2018/2003/REK sør-øst C), the Norwegian Center for Research Data (566128), and will be conducted in accordance with the World Medical Association Declaration of Helsinki. The results will be reported in international peer-reviewed journals., Trial Registration Number: NCT03855163., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Childhood obesity in China has increased more rapidly and over a shorter time period than in other countries. However, there is a paucity of rigorously developed and evaluated prevention interventions. We aim to evaluate the clinical and cost-effectiveness as well as the implementation process of a complex multicomponent intervention developed using the UK Medical Research Council (MRC) framework. This study provides one of the first examples of rigorous development and evaluation of a childhood obesity prevention programme in a non-western population using the MRC methods., Methods and Analysis: A cluster-randomised controlled trial in 40 primary schools in Guangzhou, China, including children aged 6-7 years at baseline. Schools will be randomly allocated to either the usual practice (n=20) or intervention arm (n=20). The 12-month intervention consists of four components targeting diet and physical activity behaviours in and outside school, with family involvement. The primary objective is to compare the difference in mean body mass index (BMI) z-score between the intervention and control arms at the end of the intervention (starting March/April 2017). A sample size of 1640 pupils recruited from 40 schools is sufficient to detect a difference of 0.17 units in the mean BMI z-score with a power of 80% (ICC=0.01. ICC, intraclass correlation coefficient) and a significance level of 5%. Treatment effects will be tested using a mixed linear model in STATA adjusting for the child baseline BMI z-score and clustering by school. All analyses will be by intention to treat. Secondary analyses will additionally adjust for prespecified school-level and child-level covariates. The incremental cost-effectiveness ratio for the intervention versus usual practice will be 'cost per quality-adjusted life year (QALY)'. Cost per change in BMI z-score will also be assessed. A range of methods will be used to evaluate intervention implementation, mechanisms of impact and contextual factors., Ethics and Dissemination: Ethical approval was obtained from the Life and Health Sciences Ethical Review Committee at the University of Birmingham and the Ethical Committee of Guangzhou Centre for Disease Control and Prevention. The primary, secondary, process evaluation and economic evaluation results of the trial will be disseminated through relevant international peer-reviewed journals and conferences., Trial Registration Number: ISRCTN11867516; Pre-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)