Intravaginal lactic acid gel versus oral metronidazole for treating women with recurrent bacterial vaginosis: the VITA randomised controlled trial.

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

Lactic acid gel versus metronidazole for recurrent bacterial vaginosis in women aged 16 years and over: the VITA RCT.

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

Bacterial vaginosis is a common cause of unpleasant vaginal discharge that is caused by an imbalance of vaginal bacteria. The usual treatment is an antibiotic called metronidazole (Flagyl, Sanofi). Although this generally works in the short term, symptoms often return, leading to the repeated use of antibiotics; this can cause side effects as well as increase the risk of antibiotic resistance. Lactic acid gel might be an alternative treatment, but previous studies have not confirmed how clinically effective it is. We wanted to find out if lactic acid gel was better than metronidazole for treating recurrent bacterial vaginosis. Women with typical symptoms and a history of bacterial vaginosis who were taking part in our trial were selected randomly to receive either 7 days of treatment with lactic acid gel inserted into the vagina once per day or 7 days of treatment with metronidazole tablets taken by mouth twice per day. Overall, 518 women took part in the trial. We originally intended to recruit 1900 women but the trial was stopped early because a planned review of the data showed which treatment was better. Most of the women took all of their treatment and 70% reported that symptoms had cleared 2 weeks after taking metronidazole, compared with 47% after using lactic acid gel. Less than half of the women stayed in the trial for the full 6 months; however, the data suggested that the majority of those whose symptoms cleared within 2 weeks with either treatment had symptoms return over the next 6 months. More side effects were reported for metronidazole than for lactic acid gel: nausea 32% compared with 8%, taste changes 18% compared with 1%, and diarrhoea 20% compared with 6%, respectively. Despite thinking that it was less effective, women preferred lactic acid gel because it avoided the need to take an antibiotic and had a soothing effect. The cost-effectiveness analysis found that lactic acid gel was less effective than metronidazole in clearing symptoms by 2 weeks and that the average costs for women whose symptoms resolved were higher (£86.94 with metronidazole vs. £147.00 with lactic acid gel).

Community health workers' efforts to build health system trust in marginalised communities: a qualitative study from South Africa.

INTRODUCTION: Community health workers (CHWs) enable marginalised communities, often experiencing structural poverty, to access healthcare. Trust, important in all patient-provider relationships, is difficult to build in such communities, particularly when stigma associated with HIV/AIDS, tuberculosis and now COVID-19, is widespread. CHWs, responsible for bringing people back into care, must repair trust. In South Africa, where a national CHW programme is being rolled out, marginalised communities have high levels of unemployment, domestic violence and injury. OBJECTIVES: In this complex social environment, we explored CHW workplace trust, interpersonal trust between the patient and CHW, and the institutional trust patients place in the health system. DESIGN, PARTICIPANTS, SETTING: Within the observation phase of a 3-year intervention study, we conducted interviews, focus groups and observations with patients, CHWs, their supervisors and, facility managers in Sedibeng. RESULTS: CHWs had low levels of workplace trust. They had recently been on strike demanding better pay, employment conditions and recognition of their work. They did not have the equipment to perform their work safely, and some colleagues did not trust, or value, their contribution. There was considerable interpersonal trust between CHWs and patients, however, CHWs' efforts were hampered by structural poverty, alcohol abuse and no identification documents among long-term migrants. Those supervisors who understood the extent of the poverty supported CHW efforts to help the community. When patients had withdrawn from care, often due to nurses' insensitive behaviour, the CHWs' attempts to repair patients' institutional trust often failed due to the vulnerabilities of the community, and lack of support from the health system. CONCLUSION: Strategies are needed to build workplace trust including supportive supervision for CHWs and better working conditions, and to build interpersonal and institutional trust by ensuring sensitivity to social inequalities and the effects of structural poverty among healthcare providers. Societies need to care for everyone.

Routine Health Information System (RHIS) improvements for strengthened health system management.

BACKGROUND: A well-functioning routine health information system (RHIS) can provide the information needed for health system management, for governance, accountability, planning, policy making, surveillance and quality improvement, but poor information support has been identified as a major obstacle for improving health system management. OBJECTIVES: To assess the effects of interventions to improve routine health information systems in terms of RHIS performance, and also, in terms of improved health system management performance, and improved patient and population health outcomes. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE Ovid and Embase Ovid in May 2019. We searched Global Health, Ovid and PsycInfo in April 2016. In January 2020 we searched for grey literature in the Grey Literature Report and in OpenGrey, and for ongoing trials using the International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov. In October 2019 we also did a cited reference search using Web of Science, and a 'similar articles' search in PubMed. SELECTION CRITERIA: Randomised and non-randomised trials, controlled before-after studies and time-series studies comparing routine health information system interventions, with controls, in primary, hospital or community health care settings. Participants included clinical staff and management, district management and community health workers using routine information systems. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed records to identify studies for inclusion, extracted data from the included studies and assessed the risk of bias. Interventions and outcomes were too varied across studies to allow for pooled risk analysis. We present a 'Summary of findings' table for each intervention comparisons broadly categorised into Technical and Organisational (or a combination), and report outcomes on data quality and service quality. We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: We included six studies: four cluster randomised trials and two controlled before-after studies, from Africa and South America. Three studies evaluated technical interventions, one study evaluated an organisational intervention, and two studies evaluated a combination of technical and organisational interventions. Four studies reported on data quality and six studies reported on service quality. In terms of data quality, a web-based electronic TB laboratory information system probably reduces the length of time to reporting of TB test results, and probably reduces the overall rate of recording errors of TB test results, compared to a paper-based system (moderate certainty evidence). We are uncertain about the effect of the electronic laboratory information system on the recording rate of serious (misidentification) errors for TB test results compared to a paper-based system (very low certainty evidence). Misidentification errors are inaccuracies in transferring test results between an electronic register and patients' clinical charts. We are also uncertain about the effect of the intervention on service quality (timeliness of starting or changing a patient's TB treatment) (very low certainty evidence). A hand-held electronic device probably improves the length of time to report TB test results, and probably reduces the total frequency of recording errors in TB test results between the laboratory notebook and the electronic information record system, compared to a paper-based system (moderate-certainty evidence). We are, however, uncertain about the effect of the intervention on the frequency of serious (misidentification) errors in recording between the laboratory notebook and the electronic information record, compared to a paper-based system (very low certainty evidence). We are uncertain about the effect of a hospital electronic health information system on service quality (length of time outpatients spend at hospital, length of hospital stay, and hospital revenue collection), compared to a paper-based system (very low certainty evidence). High-intensity brief text messaging (SMS) may make little or no difference to data quality (in terms of completeness of documentation of pregnancy outcomes), compared to low-intensity brief text messaging (low-certainty evidence). We are uncertain about the effect of electronic drug stock notification (with either data management support or product transfer support) on service quality (in terms of transporting stock and stock levels), compared to paper-based stock notification (very low certainty evidence). We are uncertain about the effect of health information strengthening (where it is part of comprehensive service quality improvement intervention) on service quality (health worker motivation, receipt of training by health workers, health information index scores, quality of clinical observation of children and adults) (very low certainty evidence). AUTHORS' CONCLUSIONS: The review indicates mixed effects of mainly technical interventions to improve data quality, with gaps in evidence on interventions aimed at enhancing data-informed health system management. There is a gap in interventions studying information support beyond clinical management, such as for human resources, finances, drug supply and governance. We need to have a better understanding of the causal mechanisms by which information support may affect change in management decision-making, to inform robust intervention design and evaluation methods.

Health workers' perceptions and experiences of using mHealth technologies to deliver primary healthcare services: a qualitative evidence synthesis.

BACKGROUND: Mobile health (mHealth), refers to healthcare practices supported by mobile devices, such as mobile phones and tablets. Within primary care, health workers often use mobile devices to register clients, track their health, and make decisions about care, as well as to communicate with clients and other health workers. An understanding of how health workers relate to, and experience mHealth, can help in its implementation. OBJECTIVES: To synthesise qualitative research evidence on health workers' perceptions and experiences of using mHealth technologies to deliver primary healthcare services, and to develop hypotheses about why some technologies are more effective than others. SEARCH METHODS: We searched MEDLINE, Embase, CINAHL, Science Citation Index and Social Sciences Citation Index in January 2018. We searched Global Health in December 2015. We screened the reference lists of included studies and key references and searched seven sources for grey literature (16 February to 5 March 2018). We re-ran the search strategies in February 2020. We screened these records and any studies that we identified as potentially relevant are awaiting classification. SELECTION CRITERIA: We included studies that used qualitative data collection and analysis methods. We included studies of mHealth programmes that were part of primary healthcare services. These services could be implemented in public or private primary healthcare facilities, community and workplace, or the homes of clients. We included all categories of health workers, as well as those persons who supported the delivery and management of the mHealth programmes. We excluded participants identified as technical staff who developed and maintained the mHealth technology, without otherwise being involved in the programme delivery. We included studies conducted in any country. DATA COLLECTION AND ANALYSIS: We assessed abstracts, titles and full-text papers according to the inclusion criteria. We found 53 studies that met the inclusion criteria and sampled 43 of these for our analysis. For the 43 sampled studies, we extracted information, such as country, health worker category, and the mHealth technology. We used a thematic analysis process. We used GRADE-CERQual to assess our confidence in the findings. MAIN RESULTS: Most of the 43 included sample studies were from low- or middle-income countries. In many of the studies, the mobile devices had decision support software loaded onto them, which showed the steps the health workers had to follow when they provided health care. Other uses included in-person and/or text message communication, and recording clients' health information. Almost half of the studies looked at health workers' use of mobile devices for mother, child, and newborn health. We have moderate or high confidence in the following findings. mHealth changed how health workers worked with each other: health workers appreciated being more connected to colleagues, and thought that this improved co-ordination and quality of care. However, some described problems when senior colleagues did not respond or responded in anger. Some preferred face-to-face connection with colleagues. Some believed that mHealth improved their reporting, while others compared it to "big brother watching". mHealth changed how health workers delivered care: health workers appreciated how mHealth let them take on new tasks, work flexibly, and reach clients in difficult-to-reach areas. They appreciated mHealth when it improved feedback, speed and workflow, but not when it was slow or time consuming. Some health workers found decision support software useful; others thought it threatened their clinical skills. Most health workers saw mHealth as better than paper, but some preferred paper. Some health workers saw mHealth as creating more work. mHealth led to new forms of engagement and relationships with clients and communities: health workers felt that communicating with clients by mobile phone improved care and their relationships with clients, but felt that some clients needed face-to-face contact. Health workers were aware of the importance of protecting confidential client information when using mobile devices. Some health workers did not mind being contacted by clients outside working hours, while others wanted boundaries. Health workers described how some community members trusted health workers that used mHealth while others were sceptical. Health workers pointed to problems when clients needed to own their own phones. Health workers' use and perceptions of mHealth could be influenced by factors tied to costs, the health worker, the technology, the health system and society, poor network access, and poor access to electricity: some health workers did not mind covering extra costs. Others complained that phone credit was not delivered on time. Health workers who were accustomed to using mobile phones were sometimes more positive towards mHealth. Others with less experience, were sometimes embarrassed about making mistakes in front of clients or worried about job security. Health workers wanted training, technical support, user-friendly devices, and systems that were integrated into existing electronic health systems. The main challenges health workers experienced were poor network connections, access to electricity, and the cost of recharging phones. Other problems included damaged phones. Factors outside the health system also influenced how health workers experienced mHealth, including language, gender, and poverty issues. Health workers felt that their commitment to clients helped them cope with these challenges. AUTHORS' CONCLUSIONS: Our findings propose a nuanced view about mHealth programmes. The complexities of healthcare delivery and human interactions defy simplistic conclusions on how health workers will perceive and experience their use of mHealth. Perceptions reflect the interplay between the technology, contexts, and human attributes. Detailed descriptions of the programme, implementation processes and contexts, alongside effectiveness studies, will help to unravel this interplay to formulate hypotheses regarding the effectiveness of mHealth.

Acceptability of and treatment preferences for recurrent bacterial vaginosis-Topical lactic acid gel or oral metronidazole antibiotic: Qualitative findings from the VITA trial.

BACKGROUND: Bacterial vaginosis (BV) is associated with an elevated vaginal pH and the presence of abnormal offensive discharge. It is common, often recurrent, and the most effective treatment regimen is unknown. 'Metronidazole Versus lactic acId for Treating bacterial vAginosis' (VITA) is a UK-based randomised controlled trial assessing clinical and cost-effectiveness of topical lactic acid gel compared to oral metronidazole antibiotic for treating second and subsequent BV episodes. Few BV trials report on women's preferences for treatment in the context of their own experiences. METHOD: This qualitative study investigated the acceptability and tolerability of the two treatments. During the trial, semi-structured telephone interviews were undertaken between January-May 2018. A total of 33 women diagnosed with BV were consecutively sampled then interviewed from six sites across England. Thematic analysis was guided by the acceptability of health interventions framework. Potential causes of BV and its impact on women's lives were explored in addition to women's treatment preference and perceived treatment effectiveness. RESULTS: Although women felt antibiotics treat BV effectively, and were associated with longer time periods between episodes, they generally preferred using the lactic acid gel because of ease of use, once daily application and less side-effects. Women would recommend the lactic acid gel to others for mild cases of BV but to take antibiotics when more severe. The risk of antibiotic drug resistance was a common concern. Self-help medicating or self-decision to not treat was also evident due to prior experience of poor outcomes from treatment. Triggers of BV were attributed to personal hygiene habits-soaps used to wash the vagina and sexual practices such as unprotected sex. CONCLUSION: Acceptability and preference for topical lactic acid gel or oral metronidazole tablets in the treatment of recurrent BV was affected by personal choice relating to affective attitude, burden, ethicality, intervention coherence, opportunity costs, and self-efficacy. These differed depending on ease of use, tolerability and past experiences, but not necessarily based on perceived drug effectiveness. Knowledge of a patient preference for topical lactic acid gel therapy despite lower perceived effectiveness may be useful for clinicians when making treatment decisions.

Rural South African Community Perceptions of Antibiotic Access and Use: Qualitative Evidence from a Health and Demographic Surveillance System Site.

Knowledge and practices of rural South African populations with regard to antibiotic access and use (ABACUS) remain understudied. By using the case of four villages in the north east of the country, our aim was to investigate popular notions and social practices related to antibiotics to inform patient-level social interventions for appropriate antibiotic use. To achieve this, we investigated where community members (village residents) were accessing and sourcing medication, and what they understood antibiotics and antibiotic resistance (ABR) to be. Embedded within the multicountry ABACUS project, this qualitative study uses interviews and focus group discussions. A sample of 60 community members was recruited from the Agincourt Health and Demographic Surveillance System, situated in Mpumalanga Province, from April to August, 2017. We used the five abilities of seek, reach, pay, perceive, and engage in access to healthcare as proposed by Levesque's "Access to Healthcare" framework. Respondents reported accessing antibiotics prescribed from legal sources: by nurses at the government primary healthcare clinics or by private doctors dispensed by private pharmacists. No account of the illegal purchasing of antibiotics was described. There was a mix of people who finished their prescription according to the instructions and those who did not. Some people kept antibiotics for future episodes of infection. The concept of "ABR" was understood by some community members when translated into related Xitsonga words because of knowledge tuberculosis and HIV/AIDS treatment regimens. Our findings indicate that regulation around the sale of antibiotics is enforced. Safer use of antibiotics and why resistance is necessary to understand need to be instilled. Therefore, context-specific educational campaigns, drawing on people's understandings of antibiotics and informed by the experiences of other diseases, may be an important and deployable means of promoting the safe use of antibiotics.

mHealth text and voice communication for monitoring people with chronic diseases in low-resource settings: a realist review.

BACKGROUND: Routine monitoring by patients and healthcare providers to manage chronic disease is vital, though this can be challenging in low-resourced health systems. Mobile health (mHealth) has been proposed as one way to improve management of chronic diseases. Past mHealth reviews have proposed the need for a greater understanding around how the theoretical constructs in mHealth interventions actually work. In response, we synthesised evidence from primary studies on monitoring of chronic diseases using two-way digital text or voice communication between a patient and health worker. We did this in order to understand the important considerations for the design of mHealth interventions. METHOD: Articles retrieved were systematically screened and analysed to elicit explanations of mHealth monitoring interventions. These explanations were consolidated into programme theory and compared with existing theory and frameworks. We identified variation in outcomes to understand how context moderates the outcome. RESULTS: Four articles were identified-monitoring of hypertension and HIV/AIDS from: Kenya, Pakistan, Honduras and Mexico and South Africa. Six components were found in all four interventions: reminders, patient observation of health state, motivational education/advice, provision of support communication, targeted actions and praise and encouragement. Intervention components were mapped to existing frameworks and theory. Variation in outcome identified in subgroup analysis suggests greater impact is achieved with certain patient groups, such as those with low literacy, those with stressful life events or those early in the disease trajectory. There was no other evidence in the included studies of the effect of context on the intervention and outcome. CONCLUSION: mHealth interventions for monitoring chronic disease in low-resource settings, based on existing frameworks and theory, can be effective. A match between what the intervention provides and the needs or social factors relevant to specific patient group increases the effect. It was not possible to understand the impact of context on intervention and outcome beyond these patient-level measures as no evidence was provided in the study reports.

Mobile phone use among patients and health workers to enhance primary healthcare: A qualitative study in rural South Africa.

Mobile phones have the potential to improve access to healthcare information and services in low-resourced settings. This study investigated the use of mobile phones among patients with chronic diseases, pregnant women, and health workers to enhance primary healthcare in rural South Africa. Qualitative research was undertaken in Mpumalanga in 2014. Semi structured in-depth interviews were conducted with 113 patients and 43 health workers from seven primary healthcare clinics and one district hospital. Data were thematically analysed. We found that some health workers and patients used their own mobile phones for healthcare, bearing the cost themselves. Patients used their mobile phones to remind themselves to take medication or attend their clinic visits, and they appreciated receiving voice call reminders. Some patients and health workers accessed websites and used social media to gather health information, but lacked web search strategies. The use of the websites and social media was intermittent due to lack of financial ability to afford airtime among these patients and health workers. Many did not know what to search for and where to search. Doctors have developed their own informal mobile health solutions in response to their work needs and lack of resources due to their rurality. Physical and social factors influence the usability of mobile phones for healthcare, and this can shape communication patterns such as poor eyesight. The bottom-up use of mobile phones has been evolving to fill the gaps to augment primary care services in South Africa; however, barriers to access remain, such as poor digital infrastructure and low digital literacy.