Antenatal couples' counselling in Uganda (ACCU): study protocol for a randomised controlled feasibility trial.

BACKGROUND: Common avoidable factors leading to maternal, perinatal and neonatal deaths include lack of birth planning (and delivery in an inappropriate place) and unmet need for contraception. Progress has been slow because routine antenatal care has focused only on women. Yet, in Uganda, many women first want the approval of their husbands. The World Health Organization recommends postpartum family planning (PPFP) as a critical component of health care. The aim of this trial is to test the feasibility of recruiting and retaining participants in a trial of a complex community-based intervention to provide counselling to antenatal couples in Uganda. METHODS: This is a two-group, non-blinded cluster-randomised controlled feasibility trial of a complex intervention. Primary health centres in Uganda will be randomised to receive the intervention or usual care provided by the Ministry of Health. The intervention consists of training village health teams to provide basic counselling to couples at home, encouraging men to accompany their wives to an antenatal clinic, and secondly of training health workers to provide information and counselling to couples at antenatal clinics, to facilitate shared decision-making on the most appropriate place of delivery, and postpartum contraception. We aim to recruit 2 health centres in each arm, each with 10 village health teams, each of whom will aim to recruit 35 pregnant women (a total of 700 women per arm). The village health teams will follow up and collect data on pregnant women in the community up to 12 months after delivery and will directly enter the data using the COSMOS software on a smartphone. DISCUSSION: This intervention addresses two key avoidable factors in maternal, perinatal and neonatal deaths (lack of family planning and inappropriate place of delivery). Determining the acceptability and feasibility of antenatal couples' counselling in this study will inform the design of a fully randomised controlled clinical trial. If this trial demonstrates the feasibility of recruitment and delivery, we will seek funding to conduct a fully powered trial of the complex intervention for improving uptake of birth planning and postpartum family planning in Uganda. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR202102794681952 . Approved on 10 February 2021. ISRCTN Registry ISRCTN97229911. Registered on 23 September 2021

Novel Peptides with Dual Properties for Treating Pseudomonas aeruginosa Keratitis: Antibacterial and Corneal Wound Healing

The corneal epithelium is a layer in the anterior part of eye that contributes to light refraction onto the retina and to the ocular immune defense. Although an intact corneal epithelium is an excellent barrier against microbial pathogens and injuries, corneal abrasions can lead to devastating eye infections. Among them, Pseudomonas aeruginosa-associated keratitis often results in severe deterioration of the corneal tissue and even blindness. Hence, the discovery of new drugs able not only to eradicate ocular infections, which are often resistant to antibiotics, but also to elicit corneal wound repair is highly demanded. Recently, we demonstrated the potent antipseudomonal activity of two peptides, Esc(1-21) and its diastereomer Esc(1-21)-1c. In this study, by means of a mouse model of P. aeruginosa keratitis and an in vivo corneal debridement wound, we discovered the efficacy of these peptides, particularly Esc(1-21)-1c, to cure keratitis and to promote corneal wound healing. This latter property was also supported by in vitro cell scratch and ELISA assays. Overall, the current study highlights Esc peptides as novel ophthalmic agents for treating corneal infection and injury, being able to display a dual function, antimicrobial and wound healing, rarely identified in a single peptide at the same micromolar concentration range

Natural products as starting points for future anti-malarial therapies: going back to our roots?

Abstract Background The discovery and development of new anti-malarials are at a crossroads. Fixed dose artemisinin combination therapy is now being used to treat a hundred million children each year, with a cost as low as 30 cents per child, with cure rates of over 95%. However, as with all anti-infective strategies, this triumph brings with it the seeds of its own downfall, the emergence of resistance. It takes ten years to develop a new medicine. New classes of medicines to combat malaria, as a result of infection by Plasmodium falciparum and Plasmodium vivax are urgently needed. Results Natural product scaffolds have been the basis of the majority of current anti-malarial medicines. Molecules such as quinine, lapachol and artemisinin were originally isolated from herbal medicinal products. After improvement with medicinal chemistry and formulation technologies, and combination with other active ingredients, they now make up the current armamentarium of medicines. In recent years advances in screening technologies have allowed testing of millions of compounds from pharmaceutical diversity for anti-malarial activity in cellular assays. These initiatives have resulted in thousands of new sub-micromolar active compounds – starting points for new drug discovery programmes. Against this backdrop, the paucity of potent natural products identified has been disappointing. Now is a good time to reflect on the current approach to screening herbal medicinal products and suggest revisions. Nearly sixty years ago, the Chinese doctor Chen Guofu, suggested natural products should be approached by dao-xing-ni-shi or ‘acting in the reversed order’, starting with observational clinical studies. Natural products based on herbal remedies are in use in the community, and have the potential unique advantage that clinical observational data exist, or can be generated. The first step should be the confirmation and definition of the clinical activity of herbal medicinal products already used by the community. This first step forms a solid basis of observations, before moving to in vivo pharmacological characterization and ultimately identifying the active ingredient. A large part of the population uses herbal medicinal products despite limited numbers of well-controlled clinical studies. Increased awareness by the regulators and public health bodies of the need for safety information on herbal medicinal products also lends support to obtaining more clinical data on such products. Conclusions The relative paucity of new herbal medicinal product scaffolds active against malaria results discovered in recent years suggest it is time to re-evaluate the ‘smash and grab’ approach of randomly testing purified natural products and replace it with a patient-data led approach. This will require a change of perspective form many in the field. It will require an investment in standardisation in several areas, including: the ethnopharmacology and design and reporting of clinical observation studies, systems for characterizing anti-malarial activity of patient plasma samples ex vivo followed by chemical and pharmacological characterisation of extracts from promising sources. Such work falls outside of the core mandate of the product development partnerships, such as MMV, and so will require additional support. This call is timely, given the strong interest from researchers in disease endemic countries to support the research arm of a malaria eradication agenda. Para-national institutions such as the African Network for Drugs and Diagnostics Innovation (ANDi) will play a major role in facilitating the development of their natural products patrimony and possibly clinical best practice to bring forward new therapeutics. As in the past, with quinine, lapinone and artemisinin, once the activity of herbal medicinal products in humans is characterised, it can be used to identify new molecular scaffolds which will form the basis of the next generation of anti-malarial therapies.</p

To what extent can traditional medicine contribute a complementary or alternative solution to malaria control programmes?

Recent studies on traditional medicine (TM) have begun to change perspectives on TM effects and its role in the health of various populations. The safety and effectiveness of some TMs have been studied, paving the way to better collaboration between modern and traditional systems. Traditional medicines still remain a largely untapped health resource: they are not only sources of new leads for drug discoveries, but can also provide lessons and novel approaches that may have direct public-health and economic impact. To optimize such impact, several interventions have been suggested, including recognition of TM's economic and medical worth at academic and health policy levels; establishing working relationships with those prescribing TM; providing evidence for safety and effectiveness of local TM through appropriate studies with malaria patients; spreading results for clinical recommendations and health policy development; implementing and evaluating results of new health policies that officially integrate TM

Management of uncomplicated malaria in febrile under five-year-old children by community health workers in Madagascar: reliability of malaria rapid diagnostic tests

<p>Abstract</p> <p>Background</p> <p>Early diagnosis, as well as prompt and effective treatment of uncomplicated malaria, are essential components of the anti-malaria strategy in Madagascar to prevent severe malaria, reduce mortality and limit malaria transmission. The purpose of this study was to assess the performance of the malaria rapid diagnostic tests (RDTs) used by community health workers (CHWs) by comparing RDT results with two reference methods (microscopy and Polymerase Chain Reaction, PCR).</p> <p>Methods</p> <p>Eight CHWs in two districts, each with a different level of endemic malaria transmission, were trained to use RDTs in the management of febrile children under five years of age. RDTs were performed by CHWs in all febrile children who consulted for fever. In parallel, retrospective parasitological diagnoses were made by microscopy and PCR. The results of these different diagnostic methods were analysed to evaluate the diagnostic performance of the RDTs administered by the CHWs. The stability of the RDTs stored by CHWs was also evaluated.</p> <p>Results</p> <p>Among 190 febrile children with suspected malaria who visited CHWs between February 2009 and February 2010, 89.5% were found to be positive for malaria parasites by PCR, 51.6% were positive by microscopy and 55.8% were positive by RDT. The performance accuracy of the RDTs used by CHWs in terms of sensitivity, specificity, positive and negative predictive values was greater than 85%. Concordance between microscopy and RDT, estimated by the Kappa value was 0.83 (95% CI: 0.75-0.91). RDTs stored by CHWs for 24 months were capable of detecting <it>Plasmodium falciparum </it>in blood at a level of 200 parasites/μl.</p> <p>Conclusion</p> <p>Introduction of easy-to-use diagnostic tools, such as RDTs, at the community level appears to be an effective strategy for improving febrile patient management and for reducing excessive use of anti-malarial drugs.</p

Inappropriate prescribing and adverse drug events in older people

Inappropriate prescribing (IP) in older patients is highly prevalent and is associated with an increased risk of adverse drug events (ADEs), morbidity, mortality and healthcare utilisation. Consequently, IP is a major safety concern and with changing population demographics, it is likely to become even more prevalent in the future. IP can be detected using explicit or implicit prescribing indicators. Theoretically, the routine clinical application of these IP criteria could represent an inexpensive and time efficient method to optimise prescribing practice. However, IP criteria must be sensitive, specific, have good inter-rater reliability and incorporate those medications most commonly associated with ADEs in older people. To be clinically relevant, use of prescribing appropriateness tools must translate into positive patient outcomes, such as reduced rates of ADEs. To accurately measure these outcomes, a reliable method of assessing the relationship between the administration of a drug and an adverse clinical event is required. The Naranjo criteria are the most widely used tool for assessing ADE causality, however, they are often difficult to interpret in the context of older patients. ADE causality criteria that allow for the multiple co-morbidities and prescribed medications in older people are required. Ultimately, the current high prevalence of IP and ADEs is unacceptable. IP screening criteria need to be tested as an intervention to assess their impact on the incidence of ADEs in vulnerable older patients. There is a role for IP screening tools in everyday clinical practice. These should enhance, not replace good clinical judgement, which in turn should be based on sound pharmacogeriatric training

Clinical presentation and predictors of outcome in patients with severe acute exacerbation of chronic obstructive pulmonary disease requiring admission to intensive care unit

BACKGROUND: Severe acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) is a common reason for emergency room (ER) visit about which little has been documented from India. METHODS: Prospective study of the clinical presentation and predictors of outcome in 116 patients presenting with severe AE-COPD requiring admission to the medical intensive care unit between January 2000 and December 2004. RESULTS: Their mean age was 62.1 ± 9.8 years. There were 102 males. Mean duration of COPD was 7.2 ± 5.8 years. All males were smokers (22.3 ± 11.2 pack years); 35.2% smoked cigarettes and 64.8% smoked bidis. All women were exposed to domestic fuel. Associated co-morbid illnesses were present in 81 patients (69.8%); 53(45.7%) had one co-morbid illness and the remaining 28 (54.3%) had two or more co-morbid illnesses. Evidence of past pulmonary tuberculosis (PTB) was present in 28.4% patients; 5 patients who also had type II diabetes mellitus had active PTB. Arterial blood gas analysis revealed respiratory failure in 40 (33.8%) patients (type I 17.5% and type II 82.5%). Invasive mechanical ventilation was required in 18 patients. Sixteen (13.7%) patients died. Stepwise multivariate logistic regression analysis revealed need for invasive ventilation (OR 45.809, 95%CI 607.46 to 3.009;p < 0.001); presence of co-morbid illness (OR 0.126, 95%CI 0.428 to 0.037;p < 0.01) and hypercapnia (OR 0.114, 95%CI 1.324 to 0.010;p < 0.05) were predictors of death. CONCLUSION: Co-morbid conditions and metabolic abnormalities render the diagnosis of AE-COPD difficult and also contribute to mortality. High prevalence of past PTB and active PTB in patients with AE-COPD suggests an intriguing relationship between smoking, PTB and COPD which merits further study

Malaria Rapid Testing by Community Health Workers Is Effective and Safe for Targeting Malaria Treatment: Randomised Cross-Over Trial in Tanzania

Early diagnosis and prompt, effective treatment of uncomplicated malaria is critical to prevent severe disease, death and malaria transmission. We assessed the impact of rapid malaria diagnostic tests (RDTs) by community health workers (CHWs) on provision of artemisinin-based combination therapy (ACT) and health outcome in fever patients. Twenty-two CHWs from five villages in Kibaha District, a high-malaria transmission area in Coast Region, Tanzania, were trained to manage uncomplicated malaria using RDT aided diagnosis or clinical diagnosis (CD) only. Each CHW was randomly assigned to use either RDT or CD the first week and thereafter alternating weekly. Primary outcome was provision of ACT and main secondary outcomes were referral rates and health status by days 3 and 7. The CHWs enrolled 2930 fever patients during five months of whom 1988 (67.8%) presented within 24 hours of fever onset. ACT was provided to 775 of 1457 (53.2%) patients during RDT weeks and to 1422 of 1473 (96.5%) patients during CD weeks (Odds Ratio (OR) 0.039, 95% CI 0.029-0.053). The CHWs adhered to the RDT results in 1411 of 1457 (96.8%, 95% CI 95.8-97.6) patients. More patients were referred on inclusion day during RDT weeks (10.0%) compared to CD weeks (1.6%). Referral during days 1-7 and perceived non-recovery on days 3 and 7 were also more common after RDT aided diagnosis. However, no fatal or severe malaria occurred among 682 patients in the RDT group who were not treated with ACT, supporting the safety of withholding ACT to RDT negative patients. RDTs in the hands of CHWs may safely improve early and well-targeted ACT treatment in malaria patients at community level in Africa.\ud \ud \ud \u

Participant experiences of mindfulness-based childbirth education: a qualitative study

Background: Childbirth is an important transitional life event, but one in which many women are dissatisfied stemming in part from a sense that labour is something that happens to them rather than with them. Promoting maternal satisfaction with childbirth means equipping women with communication and decision making skills that will enhance their ability to feel involved in their labour. Additionally, traditional antenatal education does not necessarily prepare expectant mothers and their birth support partner adequately for birth. Mindfulness-based interventions appear to hold promise in addressing these issues. Mindfulness-based Child Birth Education (MBCE) was a pilot intervention combining skills-based antenatal education and Mindfulness Based Stress Reduction. Participant experiences of MBCE, both of expectant mothers and their birth support partners are the focus of this article. Methods: A generic qualitative approach was utilised for this study. Pregnant women between 18 and 28 weeks gestation, over 18 years of age, nulliparous with singleton pregnancies and not taking medication for a diagnosed mental illness or taking illicit drugs were eligible to undertake the MBCE program which was run in a metropolitan city in Australia. Focus groups with 12 mothers and seven birth support partners were undertaken approximately four months after the completion of MBCE. Audio recordings of the groups were transcribed verbatim and analysed thematically using the method of constant comparison by all four authors independently and consensus on analysis and interpretation arrived at through team meetings.Results: A sense of both ‘empowerment’ and ‘community’ were the essences of the experiences of MBCE both for mothers and their birth support partner and permeated the themes of ‘awakening my existing potential’ and ‘being in a community of like-minded parents’. Participants suggested that mindfulness techniques learned during MBCE facilitated their sense of control during birth, and the content and pedagogical approach of MBCE enabled them to be involved in decision making during the birth. The pedagogical approach also fostered a sense of community among participants which extended into the postnatal period. Conclusions: MBCE has the potential to empower women to become active participants in the birthing process, thus addressing common concerns regarding lack of control and satisfaction with labour and facilitate peer support into the postnatal period. Further education of health professionals may be needed to ensure that they respond positively to those women and birth support partners who remain active in decision making during birth

Mental health in the aged: prevalence, covariates and related neuroendocrine, cardiovascular and inflammatory factors of successful aging

<p>Abstract</p> <p>Background</p> <p>Although aging is accompanied by diminished functioning, many elderly individuals preserve a sense of well-being. While the concept of "successful aging" has been popular for many decades, little is known about its psycho-physiologic and endocrine underpinnings. KORA-Age is a population-based, longitudinal study designed to determine the prevalence of successfully aged men and women between 65 and 94 years old in the MONICA/KORA Augsburg cohort of randomly selected inhabitants. Specifically, we aim to identify predictors of successful aging and to elucidate bio-psychosocial mechanisms that maintain mental health and successful adaptation despite adverse experiences of life and aging.</p> <p>Methods/Design</p> <p>Components of successful aging were assessed in a telephone survey of 4,127 participants (2008-2009) enrolled in the MONICA/KORA cohort, on average, 13 years earlier. Psychosocial, somatic and behavioural predictors are used to determine factors that contribute to successful aging. An age-stratified random sub-sample (n = 1,079) participated in a personal interview where further psychological mechanisms that may underlie successful adaptation (resilience, social support, attachment) were examined. The interactions among neuroendocrine systems in the aging process are investigated by studying the cortisol/dehydroepiandrosterone-sulfate ratio, the level of insulin-like growth factor I, and oxytocin.</p> <p>Discussion</p> <p>Longitudinal determinants of successful aging can be assessed based on a follow-up of an average of 13 years. A comprehensive analysis of biological as well as physio-psychological information provides a unique opportunity to investigate relevant outcomes such as resilience and frailty in the elderly population.</p