Hospital Mortality - a neglected but rich source of information supporting the transition to higher quality health systems in low and middle income countries.

BACKGROUND: There is increasing focus on the strength of primary health care systems in low and middle-income countries (LMIC). There are important roles for higher quality district hospital care within these systems. These hospitals are also sources of information of considerable importance to health systems, but this role, as with the wider roles of district hospitals, has been neglected. KEY MESSAGES: As we make efforts to develop higher quality health systems in LMIC we highlight the critical importance of district hospitals focusing here on how data on hospital mortality offers value: i) in understanding disease burden; ii) as part of surveillance and impact monitoring; iii) as an entry point to exploring system failures; and iv) as a lens to examine variability in health system performance and possibly as a measure of health system quality in its own right. However, attention needs paying to improving data quality by addressing reporting gaps and cause of death reporting. Ideally enabling the collection of basic, standardised patient level data might support at least simple case-mix and case-severity adjustment helping us understand variation. Better mortality data could support impact evaluation, benchmarking, exploration of links between health system inputs and outcomes and critical scrutiny of geographic variation in quality and outcomes of care. Improved hospital information is a neglected but broadly valuable public good. CONCLUSION: Accurate, complete and timely hospital mortality reporting is a key attribute of a functioning health system. It can support countries' efforts to transition to higher quality health systems in LMIC enabling national and local advocacy, accountability and action

Optimization of packing and transportation of the fingerlings of cobia (Rachycentron Canadum (Linnaeus, 1766)) and silver pompano (Trachinotus blochii (Lacepède, 1801)

In mariculture, often the locations of fish hatcheries and farming are distantly situated, and hence, there is a need to transport the seeds/seedlings to a longer distance with maximum survival rate. In the present study, length and weight of fingerlings, duration of starvation, packing density, water volume, water temperature and oxygen level in the packing bags were standardized to ensure maximum survival during transportation. The cobia fingerlings with mean length and weight of 48±12 mm and 3.0±1.0 g, respectively were transported for a duration 48 h at 25 °C with 100 % survival at a packing density of 2.5 fingerlings per litre (L) (7.5±2.5 g/L). Similarly, silver pompano fingerlings with mean length and weight of 24±0.48 mm and 0.6±0.08 g, respectively were transported for a duration of 48 h at 25 °C with 100 % survival at a packing density of 18.75 fingerlings/L (11.25±1.9 g/L). Experiments on bulk transportation of pompano fingerlings in 1000 litres capacity HDPE tanks containing 600 litres of seawater with continuous aeration using oxygen cylinders fitted in a transportation vessel revealed that the silver pompano fingerlings can be transported for a duration of 48 h at 25 °C and 5 – 6 ppm dissolved oxygen concentration with 100 % survival at a packing density of 8.3 fingerlings/L (4.98±0.8 g/L)

Cerebrospinal α-Synuclein Oligomers Reflect Disease Motor Severity in DeNoPa Longitudinal Cohort

Background: Tangible efforts have been made to identify biomarkers for Parkinson's disease (PD) diagnosis and progression, with α-synuclein (α-syn) related biomarkers being at the forefront. Objectives: The objectives of this study were to explore whether cerebrospinal fluid (CSF) levels of total, oligomeric, phosphorylated Ser 129 α-synuclein, along with total tau, phosphorylated tau 181, and β-amyloid 1–42 are (1) informative as diagnostic markers for PD, (2) changed over disease progression, and/or (3) correlated with motor and cognitive indices of disease progression in the longitudinal De Novo Parkinson cohort. Methods: A total of 94 de novo PD patients and 52 controls at baseline and 24- and 48-month follow-up were included, all of whom had longitudinal lumbar punctures and clinical assessments for both cognitive and motor functions. Using our in-house enzymelinked immunosorbent assays and commercially available assays, different forms of α-synuclein, tau, and β-amyloid 1–42 were quantified in CSF samples from the De Novo Parkinson cohort. Results: Baseline CSF total α-synuclein was significantly lower in early de novo PD compared with healthy controls, whereas the ratio of oligomeric/total and phosphorylated/total were significantly higher in the PD group. CSF oligomeric-α-synuclein longitudinally increased over the 4-year follow-up in the PD group and correlated with PD motor progression. Patients at advanced stages of PD presented with elevated CSF oligomeric-α-synuclein levels compared with healthy controls. Conclusions: Longitudinal transitions of CSF biomarkers over disease progression might not occur linearly and are susceptible to disease state. CSF oligomeric-α-synuclein levels appear to increase with diseases severity and reflect PD motor rather than cognitive trajectories. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Designer clown fishes: Unraveling the ambiguities

The global marine ornamental fish trade is dominated by wild collected fishes, and the contribution from hatchery production is less than 10% of the total. Hatchery production is considered to be the only long-term sustainable option to reduce the fishing pressure on the wild population and also to safeguard the delicate coral reef ecosystem, which houses most of the marine ornamental species. Among the hatchery-produced fishes that are being traded, clown fishes form a dominant group, and a recent addition to this list is the designer clown fishes, which are costlier than other clown fishes due to their rare and attractive color patterns. However, ambiguities about designer clown fish such as its production (wild caught, captive bred, or genetically modified) and taxonomic identity still exist among the general public and hobbyists, as scientific reports on these aspects have not yet been published, even though few aquaculture companies display the photos of designer clown fishes in their websites. The common names for designer clown fishes (such as Platinum, Picasso, and snowflake) have been given by the aquaculture companies/traders solely based on the color patterns or designs on the fish body. The paper describes in detail the production of designer clown fish through captive breeding, followed by elucidating the taxonomic identity of two easily distinguishable designer clown fishes, viz., Picasso and Platinum. Both classical taxonomic tools and molecular methods were employed to elucidate the taxonomic identity. The morpho-merisitic characteristics of Picasso and Platinum were similar to those of Amphiprion percula. The partial cytochrome c-oxidase subunit I (COI) sequences of Picasso and Platinum clown fishes were submitted to the National Center for Biotechnology Information (NCBI) GenBank with accession numbers MT947238 and MT947239, respectively, which had maximum similarity to sequences of A. percula already deposited in the NCBI GenBank. The designer clown fishes exhibited protandrous hermaphroditism with monogamous mating behavior. Their egg incubation period ranged from 7 to 8 days, and the larval rearing was carried out with live feeds such as rotifers and Artemia under the greenwater technique using microalgae, Nannochloropsis oculata. This paper can thus unravel the ambiguities related to the production of designer clown fishes as well as their taxonomy

Genomic characterization and epidemiology of an emerging SARS-CoV-2 variant in Delhi, India

Delhi, the national capital of India, experienced multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks in 2020 and reached population seropositivity of >50% by 2021. During April 2021, the city became overwhelmed by COVID-19 cases and fatalities, as a new variant, B.1.617.2 (Delta), replaced B.1.1.7 (Alpha). A Bayesian model explains the growth advantage of Delta through a combination of increased transmissibility and reduced sensitivity to immune responses generated against earlier variants (median estimates: 1.5-fold greater transmissibility and 20% reduction in sensitivity). Seropositivity of an employee and family cohort increased from 42% to 87.5% between March and July 2021, with 27% reinfections, as judged by increased antibody concentration after a previous decline. The likely high transmissibility and partial evasion of immunity by the Delta variant contributed to an overwhelming surge in Delhi

Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients

Viral clearance, antibody response and the mutagenic effect of molnupiravir has not been elucidated in at-risk populations. Non-hospitalised participants within 5 days of SARS-CoV-2 symptoms randomised to receive molnupiravir (n = 253) or Usual Care (n = 324) were recruited to study viral and antibody dynamics and the effect of molnupiravir on viral whole genome sequence from 1437 viral genomes. Molnupiravir accelerates viral load decline, but virus is detectable by Day 5 in most cases. At Day 14 (9 days post-treatment), molnupiravir is associated with significantly higher viral persistence and significantly lower anti-SARS-CoV-2 spike antibody titres compared to Usual Care. Serial sequencing reveals increased mutagenesis with molnupiravir treatment. Persistence of detectable viral RNA at Day 14 in the molnupiravir group is associated with higher transition mutations following treatment cessation. Viral viability at Day 14 is similar in both groups with post-molnupiravir treated samples cultured up to 9 days post cessation of treatment. The current 5-day molnupiravir course is too short. Longer courses should be tested to reduce the risk of potentially transmissible molnupiravir-mutated variants being generated. Trial registration: ISRCTN3044803

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

SARS-CoV-2 seroprevalence in three Kenyan health and demographic surveillance sites, December 2020-May 2021

Background Most of the studies that have informed the public health response to the COVID-19 pandemic in Kenya have relied on samples that are not representative of the general population. We conducted population-based serosurveys at three Health and Demographic Surveillance Systems (HDSSs) to determine the cumulative incidence of infection with SARS-CoV-2. Methods We selected random age-stratified population-based samples at HDSSs in Kisumu, Nairobi and Kilifi, in Kenya. Blood samples were collected from participants between 01 Dec 2020 and 27 May 2021. No participant had received a COVID-19 vaccine. We tested for IgG antibodies to SARS-CoV-2 spike protein using ELISA. Locally-validated assay sensitivity and specificity were 93% (95% CI 88–96%) and 99% (95% CI 98–99.5%), respectively. We adjusted prevalence estimates using classical methods and Bayesian modelling to account for the sampling scheme and assay performance. Results We recruited 2,559 individuals from the three HDSS sites, median age (IQR) 27 (10–78) years and 52% were female. Seroprevalence at all three sites rose steadily during the study period. In Kisumu, Nairobi and Kilifi, seroprevalences (95% CI) at the beginning of the study were 36.0% (28.2–44.4%), 32.4% (23.1–42.4%), and 14.5% (9.1–21%), and respectively; at the end they were 42.0% (34.7–50.0%), 50.2% (39.7–61.1%), and 24.7% (17.5–32.6%), respectively. Seroprevalence was substantially lower among children (&lt;16 years) than among adults at all three sites (p≤0.001). Conclusion By May 2021 in three broadly representative populations of unvaccinated individuals in Kenya, seroprevalence of anti-SARS-CoV-2 IgG was 25–50%. There was wide variation in cumulative incidence by location and age. </jats:sec

Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients

Viral clearance, antibody response and the mutagenic effect of molnupiravir has not 77 been elucidated in at-risk populations. Non-hospitalised participants within 5 days of 78 SARS-CoV-2 symptoms randomised to receive molnupiravir (n=253) or Usual Care 79 (n=324) were recruited to study viral and antibody dynamics and the effect of molnupiravir on viral whole genome sequence from 1437 viral genomes. Molnupiravir accelerates viral load decline, but virus is detectable by Day 5 in most cases. At Day 14 (9 days post-treatment), molnupiravir is associated with significantly higher viral persistence and significantly lower anti-SARS-CoV-2 spike antibody titres compared to Usual Care. Serial sequencing reveals increased mutagenesis with molnupiravir treatment. Persistence of detectable viral RNA at Day 14 in the molnupiravir group is associated with higher transition mutations following treatment cessation. Viral viability at Day 14 is similar in both groups with post-molnupiravir treated samples cultured up to 9 days post cessation of treatment. The current 5-day molnupiravir course is too short. Longer courses should be tested to reduce the risk of potentially transmissible molnupiravir-mutated variants being generated

A methodological framework for the improved use of routine health system data to evaluate national malaria control programs : evidence from Zambia

Due to challenges in laboratory confirmation, reporting completeness, timeliness, and health access, routine incidence data from health management information systems (HMIS) have rarely been used for the rigorous evaluation of malaria control program scale-up in Africa.; We used data from the Zambia HMIS for 2009-2011, a period of rapid diagnostic and reporting scale-up, to evaluate the association between insecticide-treated net (ITN) program intensity and district-level monthly confirmed outpatient malaria incidence using a dose-response national platform approach with district-time units as the unit of analysis. A Bayesian geostatistical model was employed to estimate longitudinal district-level ITN coverage from household survey and programmatic data, and a conditional autoregressive model (CAR) was used to impute missing HMIS data. The association between confirmed malaria case incidence and ITN program intensity was modeled while controlling for known confounding factors, including climate variability, reporting, testing, treatment-seeking, and access to health care, and additionally accounting for spatial and temporal autocorrelation.; An increase in district level ITN coverage of one ITN per household was associated with an estimated 27% reduction in confirmed case incidence overall (incidence rate ratio (IRR): 0 · 73, 95% Bayesian Credible Interval (BCI): 0 · 65-0 · 81), and a 41% reduction in areas of lower malaria burden.; When improved through comprehensive parasitologically confirmed case reporting, HMIS data can become a valuable tool for evaluating malaria program scale-up. Using this approach we provide further evidence that increased ITN coverage is associated with decreased malaria morbidity and use of health services for malaria illness in Zambia. These methods and results are broadly relevant for malaria program evaluations currently ongoing in sub-Saharan Africa, especially as routine confirmed case data improve