Capacity & capability building for applied dementia research in low- & middle-income countries: Two exemplars from South Asia.

BACKGROUND & OBJECTIVES: Cognitive and other neurodegenerative conditions related to ageing have become public health priorities in low- and middle-income countries. However, contextually based, applied research to support the development of awareness, diagnosis and care pathways for people with dementia in South Asia is still largely undeveloped. This study was aimed to use applied research studies for dementia in South Asia as exemplars of how individual-level capacity and capability building for dementia research can be achieved. METHODS: Using Theory of Change as a framework, we embedded capacity and capability building into the studies through six domains: people (human resources), research integrity and governance, study delivery skills, international collaborative working, patient and public involvement (PPI) (awareness raising, stigma and health literacy) and development of 'pathways'. For each aspect, development goals were defined and how they would be achieved. RESULTS: New principal investigators, research assistants (including outcome raters), study coordinators and intervention practitioners were trained across eight study sites in India, Pakistan, and Bangladesh, for dementia research. Training was delivered at study start, and through booster sessions, using workshops, face-to-face sessions, online training and video-link sessions. International collaborations were fostered, leading to a proposal for international funding. Each study site co-created PPI events to raise awareness and to inform the research. The recruitment pathways and study logistics fostered the development dementia diagnosis and care pathways. INTERPRETATION & CONCLUSIONS: Embedding capacity and capability building in applied dementia research in South Asia fosters the sustainability of dementia research, which is essential in developing diagnostic and care pathways.

Intrauterine balloon tamponade for the control of postpartum haemorrhage.

OBJECTIVE: To evaluate the effectiveness of balloon temponade in the management of postpartum haemorrhage. METHODS: The study was conducted at the Dow University of Health Sciences and Civil Hospital Karachi from January to July 18, 2012, and comprised women aged 18-35 years, parity 1-6 and gestational age 31-41 weeks, who developed or were admitted with primary postpartum haemorrhage due to uterine atony in whom medical treatment had failed. SPSS 10 was used to analyse the data. RESULTS: The mean age, parity, gestational age of 139 women was 26.4±4.2 years, 3.4±1.3, 37.81±1.67 respectively. Mean estimated blood loss was 1155.8±350.6 ml, mean systolic blood pressure 90.96±18.1 mmHg, diastolic blood pressure 55±7.5 mmHg and mean pulse was 108.3±10.89 bpm. Balloon tamponade was effective in 126(90.4%) cases. CONCLUSIONS: Condom catheter balloon tamponade was an effective means of controlling postpartum haemorrhage. There should be a low threshold for use of balloon tamponade as it is effective, easy to use, easily available, has low complication rate, and an inexpensive modality to manage non-traumatic postpartum haemorrhage, especially in resource-limited settings, and still maintain reproductive ability.

Frequency of preterm delivery in proteinuric verses non proteinuric pregnancy induced hypertension.

OBJECTIVE: To compare the frequency of preterm labour associated with gestational proteinuric hypertension versus gestational non-proteinuric hypertension. METHODS: The prospective cohort study was conducted at the Department of Obstetrics & Gynaecology, Dow University of Health Sciences and Civil Hospital Karachi, from April 1 to September 30, 2012, and comprised primigravidas of more than or equal to 20th weeks of gestation having blood pressure >140/90 mm Hg. Those with gestational hypertension with proteinuria represented the exposed group, while the non-exposed group had primigravidas with gestational hypertension without proteinuria. SPSS 10 was used to analyse data. RESULTS: There were 112 subjects, with 56(50%) in each of the two groups. Mean maternal age in exposed group was 28.3±4.49 years and in the non-exposed group 26.08±0.04 years. Mean gestational age in the exposed group was 36.89±4.04 weeks and in the non-exposed group 37.75±3.428 weeks. Women with gestational hypertension with proteinuria were more likely to deliver preterm infants compared to women with gestational hypertension without proteinuria (p=0.009). CONCLUSIONS: Gestational proteinuric hypertension increased the risk of preterm labour, therefore vigilant monitoring of gestational proteinuric hypertension is important.

Early Intervention in Psychosis and Management of First Episode Psychosis in Low- and Lower-Middle-Income Countries: A Systematic Review.

BACKGROUND AND HYPOTHESIS: People with first-episode psychosis (FEP) in low- and lower-middle-income countries (LMIC) experience delays in receiving treatment, resulting in poorer outcomes and higher mortality. There is robust evidence for effective and cost-effective early intervention in psychosis (EIP) services for FEP, but the evidence for EIP in LMIC has not been reviewed. We aim to review the evidence on early intervention for the management of FEP in LMIC. STUDY DESIGN: We searched 4 electronic databases (Medline, Embase, PsycINFO, and CINAHL) to identify studies describing EIP services and interventions to treat FEP in LMIC published from 1980 onward. The bibliography of relevant articles was hand-searched. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. STUDY RESULTS: The search strategy produced 5074 records; we included 18 studies with 2294 participants from 6 LMIC countries. Thirteen studies (1553 participants) described different approaches for EIP. Pharmacological intervention studies (n = 4; 433 participants) found a high prevalence of metabolic syndrome among FEP receiving antipsychotics (P ≤ .005). One study found a better quality of life in patients using injectables compared to oral antipsychotics (P = .023). Among the non-pharmacological interventions (n = 3; 308 participants), SMS reminders improved treatment engagement (OR = 1.80, CI = 1.02-3.19). The methodological quality of studies evidence was relatively low. CONCLUSIONS: The limited evidence showed that EIP can be provided in LMIC with adaptations for cultural factors and limited resources. Adaptations included collaboration with traditional healers, involving nonspecialist healthcare professionals, using mobile technology, considering the optimum use of long-acting antipsychotics, and monitoring antipsychotic side effects.

Cognitive therapy for depression in tuberculosis treatment: protocol for multicentre pragmatic parallel arm randomised control trial with an internal pilot.

INTRODUCTION AND OBJECTIVES: There is an unmet need to develop high-quality evidence addressing tuberculosis (TB)-related mental health comorbidity, particularly in the context of lower-middle-income countries. This study aims to examine the effectiveness and cost-effectiveness of cognitive behavioural therapy (CBT) versus enhanced treatment as usual (ETAU) in improving depressive symptoms in people with TB and comorbid depression, enhancing adherence with anti-TB treatment (ATT) and its implementation in the real-world setting of Pakistan. METHODS: We will conduct a pragmatic parallel arm randomised control trial with an internal pilot. A brief psychological intervention based on CBT has been developed using a combination of qualitative and ethnographic studies. The inbuilt pilot trial will have a sample size of 80, while we plan to recruit 560 (280 per arm) participants in the definitive trial. Participants who started on ATT within 1 month of diagnosis for pulmonary and extrapulmonary TB or multidrug resistant TB (MDR-TB) and meeting the criteria for depression on Patient Health Questionnaire-9 (PHQ-9) will be randomised with 1:1 allocation to receive six sessions of CBT (delivered by TB healthcare workers) or ETAU. Data on the feasibility outcomes of the pilot will be considered to proceed with the definitive trial. Participants will be assessed (by a blinded assessor) for the following main trial primary outcomes: (1) severity of depression using PHQ-9 scale (interviewer-administered questionnaire) at baseline, weeks 8, 24 and 32 postrandomisation and (2) ATT at baseline and week 24 at the end of ATT therapy. ETHICS AND DISSEMINATION: Ethical approval has been obtained from Keele University Research Ethics Committee (ref: 2023-0599-792), Khyber Medical University Ethical Review Board (ref: DIR/KMU-EB/CT/000990) and National Bioethics Committee Pakistan (ref: No.4-87/NBC-998/23/587). The results of this study will be reported in peer-reviewed journals and academic conferences and disseminated to stakeholders and policymakers. TRIAL REGISTRATION NUMBER: ISRCTN10761003.

Development and validation of the Montreal cognitive assessment for people with hearing impairment (MoCA-H).

BACKGROUND: Hearing impairment is common among older adults and affects cognitive assessments for identification of dementia which rely on good hearing function. We developed and validated a version of the Montreal Cognitive Assessment (MoCA) for people with hearing impairment. METHODS: We adapted existing MoCA 8.1 items for people with hearing impairment by presenting instructions and stimuli in written rather than spoken format. One Attention domain and two Language domain items required substitution by alternative items. Three and four candidate items respectively were constructed and field-tested along with the items adapted to written form. We used a combination of individual item analysis and item substitution to select the set of alternative items to be included in the final form of the MoCA-H in place of the excluded original items. We then evaluated the performance and reliability of the final tool, including making any required adjustments for demographic factors. RESULTS: One hundred and fifty-nine hearing-impaired participants, including 76 with normal cognition and 83 with dementia, completed the adapted version of the MoCA. A further 97 participants with normal hearing completed the standard MoCA as well as the novel items developed for the MoCA-H to assess score equivalence between the existing and alternative MoCA items and for independence from hearing impairment. Twenty-eight participants were retested between 2-4 weeks after initial testing. After the selection of optimal item set, the final MoCA-H had an area under the curve of 0.973 (95% CI 0.952-0.994). At a cut-point of 24 points or less sensitivity and specificity for dementia was 92.8% and 90.8%, respectively. The intraclass correlation for test-retest reliability was 0.92 (95%CI 0.78-0.97). CONCLUSION: The MoCA-H is a sensitive and reliable means of identifying dementia among adults with acquired hearing impairment.

Traditional healers working with primary care and mental health for early intervention in psychosis in young persons: protocol for the feasibility cluster randomised controlled trial.

OBJECTIVES: In low/middle-income countries (LMICs), more than half of patients with first-episode psychosis initially seek treatment from traditional and religious healers as their first care. This contributes to an excessively long duration of untreated psychosis (DUP). There is a need for culturally appropriate interventions to involve traditional and spiritual healers to work collaboratively with primary care practitioners and psychiatrists through task-shifting for early detection, referral and treatment of first episode of psychosis. METHODS: To prevent the consequences of long DUP in adolescents in LMICs, we aim to develop and pilot test a culturally appropriate and context-bespoke intervention. Traditional HEalers working with primary care and mental Health for early interventiOn in Psychosis in young pErsons (THE HOPE) will be developed using ethnographic and qualitative methods with traditional healers and caregivers. We will conduct a randomised controlled cluster feasibility trial with a nested qualitative study to assess study recruitment and acceptability of the intervention. Ninety-three union councils in district Peshawar, Pakistan will be randomised and allocated using a 1:1 ratio to either intervention arm (THE HOPE) or enhanced treatment as usual and stratified by urban/rural setting. Data on feasibility outcomes will be collected at baseline and follow-up. Patients, carers, clinicians and policymakers will be interviewed to ascertain their views about the intervention. The decision to proceed to the phase III trial will be based on prespecified stop-go criteria. ETHICS AND DISSEMINATION: Ethical approval has been obtained from Keele University Ethical Review Panel (ref: MH210177), Khyber Medical University Ethical Review Board (ref: DIR/KMU-EB/IG/001005) and National Bioethics Committee Pakistan (ref no. 4-87/NBC-840/22/621). The results of THE HOPE feasibility trial will be reported in peer-reviewed journals and academic conferences and disseminated to local stakeholders and policymakers. TRIAL REGISTRATION NUMBER: ISRCTN75347421.

Eosinophilia during natalizumab treatment: Incidence, risk factors and temporal patterns.

Eosinophilia is common during natalizumab treatment for multiple sclerosis but risk factors are unknown. We aimed to identify demographic, clinical and laboratory characteristics predicting eosinophilia. Sustained eosinophilia occurred in 16.8%. Risk factors for sustained eosinophilia included baseline pre-treatment eosinophilia, medical conditions potentially associated with eosinophilia including allergies, and suboptimal compliance. One temporal profile was associated with the highest and most rapidly developing eosinophilia, and was less likely to resolve: in one such case, eosinophilia was symptomatic. Changes in eosinophil and lymphocyte counts were only weakly correlated, suggesting factors other than Very Late Antigen-4 (VLA-4) inhibition drive eosinophilia.

SENSE-Cog Asia: A Feasibility Study of a Hearing Intervention to Improve Outcomes in People With Dementia.

Background: There are few evidence-based non-pharmacological interventions adapted for people with dementia (PwD) in lower- and middle-income countries (LMIC). Thus, there is value in culturally adapting existing interventions from other settings. One such intervention for PwD involves hearing rehabilitation, which may improve dementia-related outcomes. Objective: To culturally adapt and evaluate the feasibility and acceptability of a multi-faceted hearing support intervention to enhance quality of life in PwD for a LMIC setting, Pakistan. Design: This was a study in three phases: (1) training and capacity building to deliver the study, including Patient and Public Involvement (PPI); (2) cultural adaptation of the intervention; and (3) delivery of a single-group feasibility study with a pre-test post-test design. Setting: Home-based intervention, in two cities of Pakistan. Participants: Adults aged ≥ 60 with mild-moderate dementia and uncorrected or partially corrected hearing impairment, and their study partners (n = 14). Intervention: An adapted hearing support intervention (HSI) comprising a full assessment of hearing function, fitting of hearing aids, and home-based support from a "hearing support practitioner." Outcomes: Ratings of the feasibility of the study procedures, and acceptability/tolerability of the adapted intervention were ascertained through questionnaires, participant diaries, therapist logbooks and semi-structured interviews. A signal of effectiveness of the intervention was also explored using a battery of dementia-related outcome measures. Results: Following cultural adaptation and capacity building for study conduct and delivery, we successfully implemented all intervention components in most participants, which were well-received and enacted by participant dyads. Acceptability (i.e., understanding, motivation, sense of achievement) and tolerability (i.e., effort, fatigue) ratings and safety of the intervention were within a priori target ranges. Recruitment and retention targets required improvement, due to the COVID-19 pandemic outbreak, as well as the lack of a clear clinical diagnostic pathway for dementia in both sites. Areas for future modification were clearly identified, including: the assessment/delivery logistics circuit; procedures for arranging visits; communication among referring clinicians and the study team. Conclusion: This is the first study in a LMIC of sensory enhancement to improve dementia outcomes. Positive feasibility, acceptability and tolerability findings suggest that a full-scale effectiveness trial, with certain modifications is warranted.

Patient and Public Involvement for Dementia Research in Low- and Middle-Income Countries: Developing Capacity and Capability in South Asia.

Background: Patient and public involvement (PPI) is an active partnership between the public and researchers in the research process. In dementia research, PPI ensures that the perspectives of the person with "lived experience" of dementia are considered. To date, in many lower- and middle-income countries (LMIC), where dementia research is still developing, PPI is not well-known nor regularly undertaken. Thus, here, we describe PPI activities undertaken in seven research sites across South Asia as exemplars of introducing PPI into dementia research for the first time. Objective: Through a range of PPI exemplar activities, our objectives were to: (1) inform the feasibility of a dementia-related study; and (2) develop capacity and capability for PPI for dementia research in South Asia. Methods: Our approach had two parts. Part 1 involved co-developing new PPI groups at seven clinical research sites in India, Pakistan and Bangladesh to undertake different PPI activities. Mapping onto different "rings" of the Wellcome Trust's "Public Engagement Onion" model. The PPI activities included planning for public engagement events, consultation on the study protocol and conduct, the adaptation of a study screening checklist, development and delivery of dementia training for professionals, and a dementia training programme for public contributors. Part 2 involved an online survey with local researchers to gain insight on their experience of applying PPI in dementia research. Results: Overall, capacity and capability to include PPI in dementia research was significantly enhanced across the sites. Researchers reported that engaging in PPI activities had enhanced their understanding of dementia research and increased the meaningfulness of the work. Moreover, each site reported their own PPI activity-related outcomes, including: (1) changes in attitudes and behavior to dementia and research involvement; (2) best methods to inform participants about the dementia study; (3) increased opportunities to share knowledge and study outcomes; and (4) adaptations to the study protocol through co-production. Conclusions: Introducing PPI for dementia research in LMIC settings, using a range of activity types is important for meaningful and impactful dementia research. To our knowledge, this is the first example of PPI for dementia research in South Asia.

Protocol for the development of versions of the Montreal Cognitive Assessment (MoCA) for people with hearing or vision impairment.

INTRODUCTION: Hearing and vision impairments are highly prevalent among older adults and impact commonly used cognitive assessment tools for the identification of dementia. Adaptations of such tests for people with hearing or vision impairment have not been adequately validated among populations with such sensory impairment. METHODS AND ANALYSIS: We will develop two versions of the Montreal Cognitive Assessment (MoCA) for people with acquired hearing impairment (MoCA-H) or vision impairment (MoCA-V). The MoCA-H and MoCA-V will exclude the existing MoCA items that are presented in spoken or visual format, respectively, and include new suitably adapted items. Participants (n=792) with combinations of hearing, vision and cognitive impairment will complete standard or adapted versions of the MoCA across three language sites (English, French and Greek). Development of the MoCA-H and the MoCA-V will be based on analysis of adapted and standard MoCA items following model-based development to select the combination of items for the MoCA-H and MoCA-V that provide optimal sensitivity and specificity for detection of dementia. ETHICS AND DISSEMINATION: The study has received ethical approval from respective centres in the UK, France, Greece and Cyprus. The results of the study will be disseminated through peer-reviewed publication, conference presentations, the study website (https://www.sense-cog.eu/), the SENSE-Cog Twitter account (@sense_cog) and the MoCA test website (https://www.mocatest.org/). The main outputs of the study will be versions of the MoCA that are appropriate for use with adults with acquired hearing or vision impairment and will contribute significantly to the clinical care of older people.

A roadmap to develop dementia research capacity and capability in Pakistan: A model for low- and middle-income countries.

OBJECTIVE: To produce a strategic roadmap for supporting the development of dementia research in Pakistan. BACKGROUND: While global research strategies for dementia research already exist, none is tailored to the specific needs and challenges of low- and middle-income countries (LMIC) like Pakistan. METHODS: We undertook an iterative consensus process with lay and professional experts to develop a Theory of Change-based strategy for dementia research in Pakistan. This included Expert Reference Groups (ERGs), strategic planning techniques, a "research question" priority survey, and consultations with Key Opinion Leaders. RESULTS: We agreed on ten principles to guide dementia research in Pakistan, emphasizing pragmatic, resource sparing, real-world approaches to support people with dementia, both locally and internationally. Goals included capacity/capability building. Priority research topics included raising awareness and understanding of dementia, and improving quality of life. CONCLUSION: This roadmap may be a model for other LMIC health ecosystems with emerging dementia research cultures.

Recruitment strategies for British South Asians in 5 depression trials: A mixed method study.

BACKGROUND: In the United Kingdom, ethnic minority group's particularly British South Asian women have higher rates of depression than their white counterparts. Despite this they remain under represented in mental health trials. Whilst the US legislation mandates the inclusion of ethnic minorities into research, there are no similar initiatives in the UK. Barriers in recruiting these hard to reach ethnic groups are cited as major reasons behind this under representation. Once these barriers are encountered it becomes a challenge for the researchers to overcome them. As there is paucity of research in this specific area through this paper we want to share our strategies in recruiting British South Asians thus encouraging other researchers to consider ethnic minority inclusion into research. METHODS: Our published systematic review on the barriers to recruitment of ethnic minority participants into mental health research developed a typology of thirty three ethnic recruitment barriers described under five themes. We aimed to find strategies to overcome these barriers from five depression trials for British South Asians conducted by our research group. Firstly we extracted data on recruitment strategies from the published papers. Later researchers involved in these five trials formed a working group to add to these extracted strategies. Finally these strategies were matched to the individual barriers described in the typology. RESULTS: Multiple recruitment strategies were described by the researchers. These strategies were matched to all but two recruitment barriers related to psychopathology/substance misuse by the participants and paucity of healthcare related resources. Multiple strategies were found to be effective against each barrier and appropriate ones could be selected by the researchers after considering available resources at hand. CONCLUSIONS: Findings from this paper have implications for the design of recruitment strategies for hard to recruit ethnic minority groups to health care research. There is need for wider training and support of researchers to give them the skills to recruit these ethnic groups. Further development and evaluation of these strategies will lead to increased recruitment accruals.