Unravelling patient pathways in the context of antibacterial resistance in East Africa.

BACKGROUND: A key factor driving the development and maintenance of antibacterial resistance (ABR) is individuals' use of antibiotics (ABs) to treat illness. To better understand motivations and context for antibiotic use we use the concept of a patient treatment-seeking pathway: a treatment journey encompassing where patients go when they are unwell, what motivates their choices, and how they obtain antibiotics. This paper investigates patterns and determinants of patient treatment-seeking pathways, and how they intersect with AB use in East Africa, a region where ABR-attributable deaths are exceptionally high. METHODS: The Holistic Approach to Unravelling Antibacterial Resistance (HATUA) Consortium collected quantitative data from 6,827 adult outpatients presenting with urinary tract infection (UTI) symptoms in Kenya, Tanzania, and Uganda between February 2019- September 2020, and conducted qualitative in-depth patient interviews with a subset (n = 116). We described patterns of treatment-seeking visually using Sankey plots and explored explanations and motivations using mixed-methods. Using Bayesian hierarchical regression modelling, we investigated the associations between socio-demographic, economic, healthcare, and attitudinal factors and three factors related to ABR: self-treatment as a first step, having a multi-step treatment pathway, and consuming ABs. RESULTS: Although most patients (86%) sought help from medical facilities in the first instance, many (56%) described multi-step, repetitive treatment-seeking pathways, which further increased the likelihood of consuming ABs. Higher socio-economic status patients were more likely to consume ABs and have multi-step pathways. Reasons for choosing providers (e.g., cost, location, time) were conditioned by wider structural factors such as hybrid healthcare systems and AB availability. CONCLUSION: There is likely to be a reinforcing cycle between complex, repetitive treatment pathways, AB consumption and ABR. A focus on individual antibiotic use as the key intervention point in this cycle ignores the contextual challenges patients face when treatment seeking, which include inadequate access to diagnostics, perceived inefficient public healthcare and ease of purchasing antibiotics without prescription. Pluralistic healthcare landscapes may promote more complex treatment seeking and therefore inappropriate AB use. We recommend further attention to healthcare system factors, focussing on medical facilities (e.g., accessible diagnostics, patient-doctor interactions, information flows), and community AB access points (e.g., drug sellers).

Learning the subtle dance: The experience of therapists who deliver mentalisation-based therapy for borderline personality disorder.

OBJECTIVES: This study aimed to understand therapists' lived experiences of delivering mentalisation-based therapy (MBT), including their experiences of service user change. METHOD: One-to-one semi-structured interviews or focus groups were conducted with 14 MBT therapists and analysed using interpretative phenomenological analysis (IPA). RESULTS: Four superordinate themes were identified: (1) experiencing the challenges and complexities of being with service users during MBT; (2) being on a journey of discovery and change; (3) being an MBT therapist: a new way of working and developing a new therapeutic identity; and (4) being a therapist in the group: seeing it all come together. CONCLUSION: Our findings highlight the complexity, challenges and individualised experience of working therapeutically with service users with a diagnosis of BPD. The study provides a perspective of service use change that is enriched by idiosyncrasies within the therapeutic encounter. We conclude with a consideration of implications for MBT research and clinical practice.

Protocol for an interdisciplinary cross-sectional study investigating the social, biological and community-level drivers of antimicrobial resistance (AMR): Holistic Approach to Unravel Antibacterial Resistance in East Africa (HATUA).

INTRODUCTION: Antimicrobial resistance (AMR) is a global health threat that requires urgent research using a multidisciplinary approach. The biological drivers of AMR are well understood, but factors related to treatment seeking and the social contexts of antibiotic (AB) use behaviours are less understood. Here we describe the Holistic Approach to Unravel Antibacterial Resistance in East Africa, a multicentre consortium that investigates the diverse drivers of drug resistance in urinary tract infections (UTIs) in East Africa. METHODS AND ANALYSIS: This study will take place in Uganda, Kenya and Tanzania. We will conduct geospatial mapping of AB sellers, and conduct mystery client studies and in-depth interviews (IDIs) with drug sellers to investigate AB provision practices. In parallel, we will conduct IDIs with doctors, alongside community focus groups. Clinically diagnosed patients with UTI will be recruited from healthcare centres, provide urine samples and complete a questionnaire capturing retrospective treatment pathways, sociodemographic characteristics, attitudes and knowledge. Bacterial isolates from urine and stool samples will be subject to culture and antibiotic sensitivity testing. Genomic DNA from bacterial isolates will be extracted with a subset being sequenced. A follow-up household interview will be conducted with 1800 UTI-positive patients, where further environmental samples will be collected. A subsample of patients will be interviewed using qualitative tools. Questionnaire data, microbiological analysis and qualitative data will be linked at the individual level. Quantitative data will be analysed using statistical modelling, including Bayesian network analysis, and all forms of qualitative data analysed through iterative thematic content analysis. ETHICS AND DISSEMINATION: Approvals have been obtained from all national and local ethical review bodies in East Africa and the UK. Results will be disseminated in communities, with local and global policy stakeholders, and in academic circles. They will have great potential to inform policy, improve clinical practice and build regional pathogen surveillance capacity.

Effects of vitamin D deficiency on neurobehavioural outcomes in children: a systematic review.

Introduction: Vitamin D plays an important role in brain development in experimental studies; however, the effect of vitamin D deficiency on child development remains inadequately characterized. We aimed to estimate the effects of vitamin D deficiency on neurobehavioural outcomes in children up to 18 years of age. Methods: We searched PubMed, EMBASE, PsycINFO, Scopus, Cochrane Library, Web of Science and Open Grey for published studies up to 10th January 2020. We included all studies that assessed the effects of maternal or child vitamin D status or vitamin D supplementation on neurobehavioural outcomes in children. Study findings were synthesized qualitatively as the high level of heterogeneity in study populations and methodologies precluded a quantitative meta-analysis. Results: Our search identified 5,633 studies, of which 31 studies with 31,375 participants from 18 countries were included in the systematic review. Of the studies identified, one was a randomised controlled trial (RCT) of vitamin D supplementation in children, while 30 were observational. The RCT (n=55) reported a beneficial effect of supplementation with lower doses compared to higher doses of vitamin D on motor development. Twelve mother-child studies (n=17,136) and five studies in children (n=1,091) reported an association between low maternal or child 25-hydroxyvitamin D levels and impaired neurobehavioural outcomes in children, while 15 mother-child studies (n=20,778) and eight studies in children (n=7,496) reported no association. Conclusions: Although animal studies point to an effect of vitamin D deficiency on brain development, there are few studies on the effects of vitamin D deficiency on neurobehavioural outcomes in children and their findings are inconsistent. There is a need for well-conducted, adequately powered studies to further determine these effects in children. Registration: PROSPERO ID CRD42018087619; registered on 15 February 2018.

Does Intensive Treatment Select for Praziquantel Resistance in High-Transmission Settings? Parasitological Trends and Treatment Efficacy Within a Cluster-Randomized Trial.

BACKGROUND: Praziquantel mass drug administration (MDA) is recommended in schistosomiasis-endemic areas. Animal models demonstrate Schistosoma parasite resistance to praziquantel after repeated exposure. METHODS: We conducted a parasitological survey in 26 fishing communities in Uganda after 4 years of quarterly (13 communities) or annual (13 communities) praziquantel MDA, with Schistosoma infection detected by single-stool-sample Kato-Katz. A test of cure was done in participants who were positive on both urine circulating cathodic antigen test and 3-sample Kato-Katz. We calculated cure rates (CRs) and egg reduction rates (ERRs) based on 3-sample Kato-Katz and infection intensity using worm-specific circulating anodic antigen (CAA) in blood, comparing these between quarterly and annually treated participants. RESULTS: Single-sample Kato-Katz Schistosoma mansoni prevalence was 22% in 1,056 quarterly treated participants and 34% in 1,030 annually treated participants (risk ratio, 0.62; 95% confidence interval [CI], 0.40 to 0.94). Among 110 test-of-cure participants, CRs were 65% and 51% in annually and quarterly treated villages, respectively (odds ratio, 0.65; 95% CI, 0.27 to 1.58); ERRs were 94% and 81% (difference, -13%; 95% CI, -48% to 2%). There was no impact of quarterly vs annual praziquantel on S. mansoni by CAA. CONCLUSIONS: In this schistosomiasis hot spot, there was little evidence of decreased praziquantel efficacy. However, in the absence of alternative therapies, there remains a need for continued vigilance of praziquantel efficacy in the MDA era.

The weirdness of having a bunch of other minds like yours in the room: The lived experiences of mentalization-based therapy for borderline personality disorder.

OBJECTIVES: Studies of lived experiences are important for improving treatment effectiveness, but most studies of mentalization-based therapy (MBT) are quantitative. This qualitative study aimed to better understand service users' lived experiences of MBT, including their experiences of change. DESIGN: This is a qualitative study that used one-to-one semi-structured interviews. METHOD: Semi-structured interviews were conducted with eight MBT service users recruited via four NHS trusts. Interviews were analysed using interpretative phenomenological analysis (IPA). FINDINGS: Three superordinate themes were identified: being borderline, being in the group, and being on a journey. 'Experiences of diagnosis' and 'the group' are salient topics in the lived experiences of service users' during the MBT journey, as is the nature/type of 'change' that can create symptom reduction albeit alongside a negative felt experience. CONCLUSION: Our research aligns with current thought regarding the complexity and challenges of treating BPD via psychotherapy and adds a further dimension, that of experiencing MBT and changes during therapy. The participants' experiences of BPD and of experiencing MBT are discussed. PRACTITIONER POINTS: Therapists are observant of how each client gives meaning to their experience of diagnosis, the group, and change, particularly since the experience of recovery is not all positive. Service users' emerging and ongoing construction of their experience of diagnosis is closely monitored and additional appropriate strategies implemented where necessary. The impact of joining MBT, especially the group, becomes a process for formal regular review. Therapists undertake an in-depth exploration of service users' felt experiences to capture less quantifiable dimensions of change.

Effect of Schistosoma mansoni Infection on Innate and HIV-1-Specific T-Cell Immune Responses in HIV-1-Infected Ugandan Fisher Folk.

In Uganda, fisher folk have HIV prevalence rates, about four times higher than the national average, and are often coinfected with Schistosoma mansoni. We hypothesized that innate immune responses and HIV-specific Th1 immune responses might be downmodulated in HIV/S. mansoni-coinfected individuals compared with HIV+/S. mansoni-negative individuals. We stimulated whole blood with innate receptor agonists and analyzed supernatant cytokines by Luminex. We evaluated HIV-specific responses by intracellular cytokine staining for IFN-γ, IL-2, and TNF-α. We found that the plasma viral load and CD4 count were similar between the HIV+SM+ and HIV+SM- individuals. In addition, the TNF-α response to the imidazoquinoline compound CL097 and ß-1, 3-glucan (curdlan), was significantly higher in HIV/S. mansoni-coinfected individuals compared with HIV only-infected individuals. The frequency of HIV-specific IFN-γ+IL-2-TNF-α- CD8 T cells and IFN-γ+IL-2-TNF-α+ CD4 T cells was significantly higher in HIV/S. mansoni-coinfected individuals compared with HIV only-infected individuals. These findings do not support the hypothesis that S. mansoni downmodulates innate or HIV-specific Th1 responses in HIV/S. mansoni-coinfected individuals.

Helminth therapy or elimination: epidemiological, immunological, and clinical considerations.

Deworming is rightly advocated to prevent helminth-induced morbidity. Nevertheless, in affluent countries, the deliberate infection of patients with worms is being explored as a possible treatment for inflammatory diseases. Several clinical trials are currently registered, for example, to assess the safety or efficacy of Trichuris suis ova in allergies, inflammatory bowel diseases, multiple sclerosis, rheumatoid arthritis, psoriasis, and autism, and the Necator americanus larvae for allergic rhinitis, asthma, coeliac disease, and multiple sclerosis. Studies in animals provide strong evidence that helminths can not only downregulate parasite-specific immune responses, but also modulate autoimmune and allergic inflammatory responses and improve metabolic homoeostasis. This finding suggests that deworming could lead to the emergence of inflammatory and metabolic conditions in countries that are not prepared for these new epidemics. Further studies in endemic countries are needed to assess this risk and to enhance understanding of how helminths modulate inflammatory and metabolic pathways. Studies are similarly needed in non-endemic countries to move helminth-related interventions that show promise in animals, and in phase 1 and 2 studies in human beings, into the therapeutic development pipeline.

Guidance on the management of pain in older people.

This guidance document reviews the epidemiology and management of pain in older people via a literature review of published research. The aim of this document is to inform health professionals in any care setting who work with older adults on best practice for the management of pain and to identify where there are gaps in the evidence that require further research. The assessment of pain in older people has not been covered within this guidance and can be found in a separate document (http://www.britishpainsociety.org/pub_professional.htm#assessmentpop). Substantial differences in the population, methods and definitions used in published research makes it difficult to compare across studies and impossible to determine the definitive prevalence of pain in older people. There are inconsistencies within the literature as to whether or not pain increases or decreases in this age group, and whether this is influenced by gender. There is, however, some evidence that the prevalence of pain is higher within residential care settings. The three most common sites of pain in older people are the back; leg/knee or hip and 'other' joints. In common with the working-age population, the attitudes and beliefs of older people influence all aspects of their pain experience. Stoicism is particularly evident within this cohort of people. Evidence from the literature search suggests that paracetamol should be considered as first-line treatment for the management of both acute and persistent pain, particularly that which is of musculoskeletal origin, due to its demonstrated efficacy and good safety profile. There are few absolute contraindications and relative cautions to prescribing paracetamol. It is, however, important that the maximum daily dose (4 g/24 h) is not exceeded. Non-selective non-steroidal anti-inflammatory drugs (NSAIDs) should be used with caution in older people after other safer treatments have not provided sufficient pain relief. The lowest dose should be provided, for the shortest duration. For older adults, an NSAID or cyclooxygenase-2 (COX-2) selective inhibitor should be co-prescribed with a proton pump inhibitor (PPI), and the one with the lowest acquisition cost should be chosen. All older people taking NSAIDs should be routinely monitored for gastrointestinal, renal and cardiovascular side effects, and drug­drug and drug­disease interactions. Opioid therapy may be considered for patients with moderate or severe pain, particularly if the pain is causing functional impairment or is reducing their quality of life. However, this must be individualised and carefully monitored. Opioid side effects including nausea and vomiting should be anticipated and suitable prophylaxis considered. Appropriate laxative therapy, such as the combination of a stool softener and a stimulant laxative, should be prescribed throughout treatment for all older people who are prescribed opioid therapy. Tricyclic antidepressants and anti-epileptic drugs have demonstrated efficacy in several types of neuropathic pain. But, tolerability and adverse effects limit their use in an older population. Intra-articular corticosteroid injections in osteoarthritis of the knee are effective in relieving pain in the short term, with little risk of complications and/or joint damage. Intra-articular hyaluronic acid is effective and free of systemic adverse effects. It should be considered in patients who are intolerant to systemic therapy. Intra-articular hyaluronic acid appears to have a slower onset of action than intra-articular steroids, but the effects seem to last longer. The current evidence for the use of epidural steroid injections in the management of sciatica is conflicting and, until further larger studies become available, no firm recommendations can be made. There is, however, a limited body of evidence to support the use of epidural injections in spinal stenosis. The literature review suggests that assistive devices are widely used and that the ownership of devices increases with age. Such devices enable older people with chronic pain to live in the community. However, they do not necessarily reduce pain and can increase pain if used incorrectly. Increasing activity by way of exercise should be considered. This should involve strengthening, flexibility, endurance and balance, along with a programme of education. Patient preference should be given serious consideration. A number of complementary therapies have been found to have some efficacy among the older population, including acupuncture, transcutaneous electrical nerve stimulation (TENS) and massage. Such approaches can affect pain and anxiety and are worth further investigation. Some psychological approaches have been found to be useful for the older population, including guided imagery, biofeedback training and relaxation. There is also some evidence supporting the use of cognitive behavioural therapy (CBT) among nursing home populations, but of course these approaches require training and time. There are many areas that require further research, including pharmacological management where approaches are often tested in younger populations and then translated across. Prevalence studies need consistency in terms of age, diagnosis and terminology, and further work needs to be done on evaluating non-pharmacological approaches.

Experiences and perceptions of people with headache: a qualitative study.

BACKGROUND: Few qualitative studies of headache have been conducted and as a result we have little in-depth understanding of the experiences and perceptions of people with headache. The aim of this paper was to explore the perceptions and experiences of individuals with headache and their experiences of associated healthcare and treatment. METHODS: A qualitative study of individuals with headache, sampled from a population-based study of chronic pain was conducted in the North-East of Scotland, UK. Seventeen semi-structured interviews were conducted with adults aged 65 or less. Interviews were analysed using the Framework approach utilising thematic analysis. RESULTS: Almost every participant reported that they were unable to function fully as a result of the nature and unpredictability of their headaches and this had caused disruption to their work, family life and social activities. Many also reported a negative impact on mood including feeling depressed, aggressive or embarrassed. Most participants had formed their own ideas about different aspects of their headache and several had searched for, or were seeking, increased understanding of their headache from a variety of sources. Many participants reported that their headaches caused them constant worry and anguish, and they were concerned that there was a serious underlying cause. A variety of methods were being used to manage headaches including conventional medication, complementary therapies and self-developed management techniques. Problems associated with all of these management strategies emerged. CONCLUSION: Headache has wide-ranging adverse effects on individuals and is often accompanied by considerable worry. The development of new interventions or educational strategies aimed at reducing the burden of the disorder and associated anxiety are needed.

HIV risk perception and prevalence in a program for prevention of mother-to-child HIV transmission: comparison of women who accept voluntary counseling and testing and those tested anonymously.

OBJECTIVE: To determine whether data from voluntary counseling and testing (VCT)/prevention of mother-to-child transmission (PMTCT) programs can be used for HIV surveillance. METHODS: Women attending an antenatal clinic at the district hospital in Entebbe, Uganda, from May 2002 to April 2003 were offered counseling and HIV testing with same-day results (VCT) and nevirapine for PMTCT was provided for HIV-positive women and their babies. Those who declined VCT were tested for HIV anonymously. RESULTS: Overall, 2635 women accepted VCT; 883 were tested anonymously. HIV prevalence was higher in VCT than in anonymously tested women in the first month of the program (20% vs. 11%, P=0.05) and in months with <70% VCT uptake (17% vs. 8%, P<0.001) but was similar in months with high uptake. Uptake of VCT was higher in women who had risk factors for HIV, especially those who believed themselves to have been exposed (84% vs. 73%, P<0.001). CONCLUSION: There was a bias to accepting VCT in women with HIV, or risk factors for HIV infection, the former most apparent when there was low coverage. Data from VCT/PMTCT programs cannot replace anonymous surveillance for monitoring of HIV epidemic trends where coverage is incomplete within clinics or communities.

Hand involvement in Schmid metaphyseal chondrodysplasia.

Schmid metaphyseal chondrodysplasia (Schmid MCD, MIM 156500) is caused by mutations in the COL10A1 gene and is clinically characterized by short stature, bowed legs, and a waddling gait. Radiographic findings include anterior cupping, sclerosis and splaying of the ribs, diffuse metaphyseal flaring, and irregularity that is most pronounced at the knees, coxa vara, and femoral bowing. We reviewed the radiographs of Schmid MCD patients at the International Skeletal Dysplasia Registry in Los Angeles for evidence of hand involvement. We found hand involvement in 47% (7/15) of cases included in our analysis. These changes were subtle and consisted of shortening of the tubular bones and metaphyseal cupping of the proximal phalanges and metacarpals. Mild hand involvement is a common feature of Schmid MCD.