Protocol for systematic review and meta-analysis: magnitude, reasons, associated factors, and implications of the out-of-pocket expenditure during pregnancy.

OBJECTIVES: Health-related out-of-pocket expenditure (OOPE) impedes utilization for maternal health care. We aim to systematically review the magnitude, reasons, associated factors, and implications of OOPE during pregnancy. STUDY DESIGN: The study design is a protocol for systematic review and meta-analysis. METHODS: A comprehensive literature search will be conducted with the electronic databases of PubMed, Web of Science, Scopus, Cochrane, Trip, Social care online, IDEAS, EconPapers, ERIC, and EconStor. A manual search will be carried out for the reference lists of eligible studies and reviews. The search strategy will include combining two key blocks of terms, namely: 'pregnancy' and 'OOPE,' using database-specific subject headings and text words. Two independent reviewers will screen and assess data quality and extract data for synthesis. Any disagreements during any stage will be determined by consensus with the involvement of a third reviewer. The 'Mixed methods appraisal tool' will be adapted for the quality appraisal of the eligible studies. A narrative synthesis will be provided for the reasons, associated factors, and implications of OOPE, and a meta-analysis will be conducted for the magnitude of OOPE. Furthermore, a subgroup analysis will be done with countries with different income levels and health care policies. TRIAL REGISTRATION: PROSPERO 2020 CRD42020168566.

'Why are you not dead yet?' - dimensions and the main driving forces of stigma and discrimination among COVID-19 patients in Sri Lanka.

OBJECTIVES: To explore the experiences, and main driving forces of stigma and discrimination among COVID-19 patients, following hospital discharge, in Sri Lanka. STUDY DESIGN: A qualitative study was used in order to gain insight and explore the depth and complexity of COVID-19 patients' experiences. METHODS: Semi-structured interviews were conducted via telephone in a purposively selected sample of 139 COVID-19 patients. Participants were interviewed during the first 3 weeks following discharge from four main state hospitals that were treating COVID-19 patients during the early phase of the pandemic. Questions on stigma and discrimination were open-ended, enabling patients to provide responses about their different experiences and settings; results were analysed using thematic analysis. RESULTS: The majority of participants were men (n = 80; 57.6%), with a mean age of 43 years (SD = 11.2). In total, up to one-third of the study participants experienced stigma related to COVID-19 and were discriminated against by the community, co-workers and healthcare workers in Sri Lanka. Social discrimination included barriers in accessing basic needs, insulting, blaming, defaming, spreading rumours and receiving no support during emergencies. Workplace discrimination included loss of jobs, not allowing re-entry and loss of earnings due to self-employment. Discrimination by healthcare workers included breaching of confidentiality, lack of respect, not providing health services and communication barriers. Discrimination has led to social isolation, not seeking help and severe psychosocial issues impacting their family relationships. Irresponsible media reporting and sensationalism of news coverage leading to breaching of privacy and confidentiality, defaming, false allegations and reporting household details without consent were perceived as the main factors underlying the views and opinions of the general public. CONCLUSIONS: Stigma and discrimination experienced by COVID-19 patients in society, workplaces and healthcare facilities have serious negative consequences at the individual and family level. Regulations on responsible media reporting, including an effective risk communication strategy to counteract its effects, are strongly recommended.

Trainee experience of 'out of hours' surgical working in the UK: A cross-sectional analysis.

BACKGROUND: Changes to working practices and increasing service demand have contributed to low morale amongst UK surgical trainees, with pressures particularly acute 'out of hours' (OOH). Surgeons may be expected to be 'on call' for multiple hospitals, or to provide remote consultations, yet healthcare systems may undermine their professional safety and patient care. This cross-sectional study sought to define the perceptions of UK-based Royal College of Surgeons of Edinburgh (RCSEd) affiliated trainees of OOH surgical care and training. METHODS: The RCSEd Trainees' Committee conducted a design-thinking exercise to produce an online questionnaire. Non-consultant grade RCSEd Members and Fellows were invited to participate. Quantitative data was analysed using descriptive statistics, and qualitative data was coded to identify emergent themes. RESULTS: One hundred and fifty-five surgeons participated. Of those surgeons working in multiple hospitals OOH (n = 16), many did not receive access cards (12[75%]) or site-specific induction (13[81%]), and 8(50%) were not confident in using local electronic investigation and records systems. Only 14/114 (12%) of the surgeons providing remote opinion had access to a consultation record system, and most perceived dissatisfaction with the system. Emergent themes from qualitative data revealed that trainee surgeons desire specific training in OOH working, concerns that OOH work experience is diminishing, and that hospital infrastructure such as IT and communications, rest facilities and catering were inadequate in facilitating safe care. CONCLUSIONS: The participants perceived that the systems supporting delivery of safe surgical care OOH were inadequate. Hospital leaders should ensure that systems minimise risk to staff and patients.

Does socioeconomic status influence the epidemiology and outcome of distal radial fractures in adults?

PURPOSE: The aim of this study in adult patients with a distal radial fracture was to determine whether socioeconomic status influenced the epidemiology, mechanism of injury, fracture severity, or the outcome according to function, radiographic assessment, and rate of associated complications. METHODS: We identified 3983 distal radial fractures over a 7-year period. Socioeconomic status was assigned using the Carstairs score, and the population was divided into quintiles depending on deprivation. Patient demographics, mechanism of injury, fracture severity, and radiographic assessment at time of injury were assessed for epidemiological differences according to social quintile. Functional outcome was assessed using grip strength, Moberg pickup test, return to normal use of the hand, and range of movement. Radiographs were assessed at 1 week, 6 weeks, and 1 year. Complications were defined as malunion, carpal tunnel syndrome, complex regional pain syndrome (CRPS), persistent pain, and subjective cosmetic deformity of the wrist. RESULTS: Socioeconomically deprived patients were significantly younger (p < 0.001) and more likely to be male (p = 0.017); after adjusting for confounding factors, deprived patients were 3.1 (95% CI 1.4-4.7) years younger than the most affluent patients (p < 0.001). Deprived patients were more likely to sustain their fracture by a high-energy mechanism (p = 0.004). There were no significant differences between quintiles in outcome. There was a significantly greater prevalence of CRPS in more affluent patients (p = 0.004). CONCLUSIONS: Socioeconomically deprived patients sustaining a distal radial fracture are more likely to be younger and male. Outcome is not influenced by socioeconomic status, but the prevalence of CRPS is greater in more affluent patients.

Dengue NS1 antigen contributes to disease severity by inducing interleukin (IL)-10 by monocytes.

Both dengue NS1 antigen and serum interleukin (IL)-10 levels have been shown to associate with severe clinical disease in acute dengue infection, and IL-10 has also been shown to suppress dengue-specific T cell responses. Therefore, we proceeded to investigate the mechanisms by which dengue NS1 contributes to disease pathogenesis and if it is associated with altered IL-10 production. Serum IL-10 and dengue NS1 antigen levels were assessed serially in 36 adult Sri Lankan individuals with acute dengue infection. We found that the serum IL-10 levels correlated positively with dengue NS1 antigen levels (Spearman's r = 0·47, P < 0·0001), and NS1 also correlated with annexin V expression by T cells in acute dengue (Spearman's r = 0·63, P = 0·001). However, NS1 levels did not associate with the functionality of T cell responses or with expression of co-stimulatory molecules. Therefore, we further assessed the effect of dengue NS1 on monocytes and T cells by co-culturing primary monocytes and peripheral blood mononuclear cells (PBMC), with varying concentrations of NS1 for up to 96 h. Monocytes co-cultured with NS1 produced high levels of IL-10, with the highest levels seen at 24 h, and then declined gradually. Therefore, our data show that dengue NS1 appears to contribute to pathogenesis of dengue infection by inducing IL-10 production by monocytes.

Expansion of highly activated invariant natural killer T cells with altered phenotype in acute dengue infection.

Invariant natural killer T (iNKT) cells are capable of rapid activation and production of cytokines upon recognition of antigenic lipids presented by CD1d molecules. They have been shown to play a significant role in many viral infections and were observed to be highly activated in patients with acute dengue infection. In order to characterize further their role in dengue infection, we investigated the proportion of iNKT cells and their phenotype in adult patients with acute dengue infection. The functionality of iNKT cells in patients was investigated by both interferon (IFN)-γ and interleukin (IL)-4 ex-vivo enzyme-linked immunospot (ELISPOT) assays following stimulation with alpha-galactosyl-ceramide (αGalCer). We found that circulating iNKT cell proportions were significantly higher (P = 0·03) in patients with acute dengue when compared to healthy individuals and were predominantly of the CD4(+) subset. iNKT cells of patients with acute dengue had reduced proportions expressing CD8α and CD161 when compared to healthy individuals. The iNKT cells of patients were highly activated and iNKT activation correlated significantly with dengue virus-specific immunoglobulin (Ig)G antibody levels. iNKT cells expressing Bcl-6 (P = 0·0003) and both Bcl-6 and inducible T cell co-stimulator (ICOS) (P = 0·006) were increased significantly in patients when compared to healthy individuals. Therefore, our data suggest that in acute dengue infection there is an expansion of highly activated CD4(+) iNKT cells, with reduced expression of CD161 markers.

Magnetic resonance imaging findings of patients with suspected tuberculosis from a tertiary care centre in Sri Lanka

Introduction: Spinal tuberculosis (TB) is a relatively common cause for spinal pathology in Sri Lanka and a common indication for magnetic resonance imaging (MRI). Objectives: The objective of the study was to describe the MRI imaging pattern of spinal TB in a series of patients. Methods: One hundred and nine patients with clinically confirmed spinal tuberculosis who had undergone MRI scans at the National Hospital of Sri Lanka from 2012-2016 were included in the study. Results: The commonest vertebral level of spinal TB involvement was at L4/5 level, followed by L5/S1 level. L5 vertebral body involvement was the commonest and L4 was second commonest. Single level involvement (68.8%) was commoner than multiple (31.2%) involvement or contiguous involvement. Wedging (24.8%), erosions (89%), end plate changes (96.3%), canal stenosis (77.1%), paravertebral collection (65.1%), prevertebral collection (39.4%), psoas abscess (23.9%) and epidural collection (45.9%) were noted. No significant difference was seen between females and males. Conclusions: Spinal tuberculosis commonly involves L4/5 level.

Anaemia in pregnancy in the district of Anuradhapura, Sri Lanka--need for updating prevalence data and screening strategies.

OBJECTIVES: To determine the prevalence of anaemia during pregnancy in Anuradhapura district and evaluate present screening methods for anaemia. METHODS: Modified WHO 30 cluster sampling method with increased precision was used to estimate the prevalence of anaemia in the Anuradhapura district, Sri Lanka. Serum haemoglobin was measured using methemoglobin method. Clinical examination was carried out to evaluate the conjunctival method in anaemia screening. Values recorded from haemoglobin colour scale method used in the field antenatal clinics were collected. RESULTS: A total of 990 pregnant women participated in the study. In the first, second and third trimesters, prevalence of anaemia was 7.6%, 19.7% and 19.3% respectively. Gestational age adjusted anaemia prevalence among pregnant women in this study population was 14.1% (95% CI 12.0-16.4%). Mean and median haemoglobin concentration of the study sample was 11.8g/dL (SD 1.02g/dl and IQR 11.2-12.5g/dl). Among anaemic pregnant women, average values for Mean Corpuscular Volume (MCV), Mean Corpuscular Haemoglobin (MCH), and Mean Corpuscular Haemoglobin Concentration (MCHC) were, 82.9 fl (SD 11.5), 27.6 (SD-3.6) pg/cell and 32.9g/dl (SD 1.8) respectively. Sensitivity and specificity of haemoglobin colour scale method was 50% (95% CI 29.0-71.0%) and 76.3% (95% CI 66.9-83.7%) respectively. Sensitivity and specificity of conjunctival method in detecting anaemia during pregnancy was 18.8% (95% CI 11.9-28.4) and 69.3% (95% CI 58.2- 78.6%). CONCLUSIONS: Prevalence of anaemia in the district of Anuradhapura was less than 50% of the estimated prevalence for Sri Lanka. Both haemoglobin colour scale and conjunctival method were having low validity in detecting anaemia in pregnancy.

Local recurrence of rectal cancer in patients not receiving neoadjuvant therapy - the importance of resection margins.

OBJECTIVES: Local recurrence of rectal cancer reduces quality of life and survival. A multi-factorial linear logistic model was used to analyse risk factors for local recurrence in rectal cancer in patients not receiving preoperative chemo-radiation. METHODS: A case-control study of patients with rectal cancer having surgery with curative intent, between 1996 and 2008. Eighteen putative risk factors for local recurrence were subjected to uni-variate analysis. Significant factors were selected for multi-factorial analysis. RESULTS: Twenty-one patients with local recurrence (cases) and 78 controls were selected. Uni-variate analysis showed significant associations with recurrence for nodal stage (N) (p=0.027), metastasis (M) (p=0.009), adjuvant chemotherapy (p=0.039), positive resection margin (R) (p=0.018) and American Joint Committee for Cancer (AJCC) tumours above stage II (p=0.043). Significant uni-variate odds ratios (OR) were obtained for the same factors. Two linear logistic models were fitted as (1) N, M, R1 status and adjuvant chemotherapy and (2) AJCC stage, R1 status and adjuvant chemotherapy. From both models, the only factor significantly associated (p ≤ 0.01) with local recurrence was found to be a positive resection margin (OR 4.81 and 5.51 respectively). CONCLUSIONS: A positive resection margin is the single factor affecting local recurrence of rectal cancer in patients not receiving neo-adjuvant therapy.

Is the 2019 novel coronavirus related to a spike of cosmic rays?

WHO's pronouncement of the 2019 novel coronavirus outbreak as a pandemic disease came months after we published a warning that the present deepest minimum of the sunspot cycle would be likely to facilitate the onset of a viral pandemic. During a deep sunspot minimum (deepest in 100 years) such as we are now witnessing, two space related phenomena could have an effect on the disposition of viral disease and potential pandemics. With the weakening of the magnetic field in the Earth's vicinity, there would be a high flux of mutagenic cosmic rays. These processes would be likely to herald the onset of new pandemics. Neutron counts from Moscow Neutron Monitor show that the flux of cosmic rays reaching Earth in 2019 was indeed at a maximum over a timespan of half a century since 1962. It is of interest to note that immediately prior to the first recorded cases of the novel Corona virus in China a peak of cosmic rays was measured as is indicated by the Huon neutron monitor data. Recent research revealed that estimates of the timing of the most recent common ancestor of COVID-19 made with current sequence data point to emergence of the virus in late November 2019 to early December 2019, compatible with the earliest retrospectively confirmed cases and the cosmic ray spike in late November 2019. In our view, this strong cosmic ray spike was in some way connected with the onset of the outbreak.

A cosmic virosphere.

The concept of a cosmic virosphere that serves as the repository of information for all life on Earth and throughout the Universe is discussed. Recent studies in geology, astronomy and biology point to an intimate connection between the evolution of life and a cosmic virosphere/biosphere.

An internet of microbes straddling the cosmos.

Exchanges of information analogous to a global internet have been known to take place between biological systems on the Earth ranging from bacteria and viruses to plants and animals. We argue that this process can be extended to include a cosmic biosphere within which evolution would seem to be intimately interlinked across astronomical, perhaps cosmological distance scales. Comets and interstellar dust, argued to have a bacterial/viral component, could be involved in establishing these links.

Microbial transfers from Venus to Earth.

The possibility that the clouds of Venus are habitats for microorganisms has been discussed for several decades. Over the past two decades evidence to support this point of view has grown with new data from space probes and space exploration. In this article we argue that microorganisms are likely to be widely present in the clouds of Venus, and may under certain conditions have a ready route to Earth. Such transfers could occur by the action of the solar wind that leads to expulsion of parts of the atmosphere laden with microorganisms. The expelled material forms a comet-like tail in the antisolar direction and during inferior conjunctions of Venus could lead to injections of bacteria and other microorganisms onto the Earth. In situations of very low sunspot activity as now prevails, with a consequent weakening of the magnetopause this flux of microbes will be considerably enhanced. The inferior conjunction of 4 June 2020 together with the prevailing deep minimum in the sunspot cycle provides a combination of circumstances that is particularly favorable to such a process.

The world should establish an early warning system for new viral infectious diseases by space-weather monitoring.

With the emergence of several new epidemics of viral infections - SARS, MERS, EBOLA, ZIKA, Influenza A (H1N1) pandemic,Covid-2019 - over the past 3 decades we suggest that a world-wide programme of stratospheric surveillance and space weather monitoring should be urgently put in place without further delay.

Cometary panspermia and origin of life?

A range of astronomical observations are shown to be in accord with the theory of cometary panspermia. This theory posits that comets harbor a viable biological component in the form of bacteria and viruses that led to origin and evolution of life on Earth. The data includes (1) infrared, visual and ultraviolet spectra of interstellar dust, (2) infrared spectra of the dust released from comet Halley in 1986, (3) infrared spectra of comet Hale-Bopp in 1997, (4) near and mid-infrared spectra of comet Tempel I in 2005, (5) the discovery of an amino acid and degradation products attributable to biology in the material recovered from the Stardust Mission in 2009, (6) jets from comet Lovejoy showing both a sugar and Ethyl alcohol and finally, (7) a diverse set of data that has emerged from the Rosetta mission. The conjunction of all the available data points to cometary biology and interstellar panspermia as being inevitable.

The sociology of science and generality of the DNA/RNA/protein paradigm throughout the cosmos.

The theory of cometary panspermia argues that life cannot have originated on Earth in the time available. It must have an ultimate, but still undiscovered cosmological source. The origin of life remains an open question. Life on Earth was introduced by impacting comets, and its further evolution was driven by the subsequent acquisition of cosmically derived genes. Explicit predictions of this theory stating how the acquisition of new genes drives evolution, are compared with recent developments in relation to horizontal gene transfer, and the role of retroviruses in evolution. Precisely stated predictions of the theory of cometary panspermia are shown to have been verified.

The efficient Lamarckian spread of life in the cosmos.

In this Chapter we discuss the various mechanisms that are available for the possible transfer of cosmic microbial living systems from one cosmic habitat to another. With the 100 or so habitable planets that are now known to exist in our galaxy alone transfers of cometary dust carrying life including fragments of icy planetoids/asteroids would be expected to occur on a routine basis. It is thus easy to view the galaxy as a single connected "biosphere" of which our planet Earth is a minor component. The Hoyle-Wickramasinghe Panspermia paradigm provides a cogent biological rationale for the actual widespread existence of Lamarckian modes of inheritance in terrestrial systems (which we review here). Thus the Panspermia paradigm provides the raison d'etre for Lamarckian Inheritance. Under a terrestrially confined neoDarwinian viewpoint such an association may have been thought spurious in the past. Our aim here is to outline the main evidence for rapid terrestrial-based Lamarckian-based evolutionary hypermutation processes dependent on reverse transcription-coupled mechanisms among others. Such rapid adaptation mechanisms would be consistent with the effective cosmic spread of living systems. For example, a viable, or cryo-preserved, living system traveling through space in a protective matrix will of necessity need to adapt rapidly and proliferate on landing in a new cosmic niche. Lamarckian mechanisms thus come to the fore and supersede the slow (blind and random) genetic processes expected under neoDarwinian Earth centred theories.

Experiments to prove continuing microbial ingress from Space to Earth.

A wide range of evidence for pointing to our cosmic origins is close to the point of being overwhelming. Yet the long-entrenched paradigm of Earth-centered biology appears to prevail in scientific culture. A matter of crucial importance is to carry out a decisive experiment that is long overdue-establishing empirically beyond any doubt that extraterrestrial microbiota reaches the surface of the Earth at the present day. Such an experiment may of course happen naturally by the appearance of pandemics of new disease as discussed in an earlier chapter.