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Background:The scale of the 2022 global mpox (formerly known as monkeypox) outbreak has been unprecedented. In less than 6 months, non-endemic countries have reported more than 67 000 cases of a disease that had previously been rare outside of Africa. Mortality has been reported as rare but hospital admission has been relatively common. We aimed to describe the clinical and laboratory characteristics and outcomes of individuals admitted to hospital with mpox and associated complications, including tecovirimat recipients. Methods:In this cohort study, we undertook retrospective review of electronic clinical records and pathology data for all individuals admitted between May 6, and Aug 3, 2022, to 16 hospitals from the Specialist and High Consequence Infectious Diseases Network for Monkeypox. The hospitals were located in ten cities in England and Northern Ireland. Inclusion criteria were clinical signs consistent with mpox and MPXV DNA detected from at least one clinical sample by PCR testing. Patients admitted solely for isolation purposes were excluded from the study. Key outcomes included admission indication, complications (including pain, secondary infection, and mortality) and use of antibiotic and anti-viral treatments. Routine biochemistry, haematology, microbiology, and virology data were also collected. Outcomes were assessed in all patients with available data. Findings:156 individuals were admitted to hospital with complicated mpox during the study period. 153 (98%) were male and three (2%) were female, with a median age of 35 years (IQR 30–44). Gender data were collected from electronic patient records, which encompassed full formal review of clincian notes. The prespecified options for data collection for gender were male, female, trans, non-binary, or unknown. 105 (71%) of 148 participants with available ethnicity data were of White ethnicity and 47 (30%) of 155 were living with HIV with a median CD4 count of 510 cells per mm3(IQR 349–828). Rectal or perianal pain (including proctitis) was the most common indication for hospital admission (44 [28%] of 156). Severe pain was reported in 89 (57%) of 156, and secondary bacterial infection in 82 (58%) of 142 individuals with available data. Median admission duration was 5 days (IQR 2–9). Ten individuals required surgery and two cases of encephalitis were reported. 38 (24%) of the 156 individuals received tecovirimat with early cessation in four cases (two owing to hepatic transaminitis, one to rapid treatment response, and one to patient choice). No deaths occurred during the study period. Interpretation:Although life-threatening mpox appears rare in hospitalised populations during the current outbreak, severe mpox and associated complications can occur in immunocompetent individuals. Analgesia and management of superimposed bacterial infection are priorities for patients admitted to hospital.

Active travel, as a key form of physical activity, can help offset noncommunicable diseases as rapidly urbanising countries undergo epidemiological transition. In Africa a human mobility transition is underway as cities sprawl and motorization rises and preserving active travel modes (walking, cycling and public transport) is important for public health. Across the continent, public transport is dominated by paratransit, privately owned informal modes serving the general public. We reviewed the literature on active travel and paratransit in African cities, published from January 2008 to January 2019. We included 19 quantitative, 14 mixed-method and 8 qualitative studies (n = 41), narratively synthesizing the quantitative data and meta-ethnographically analysing the qualitative data. Integrated findings showed that walking was high, cycling was low and paratransit was a critical mobility option for poor peripheral residents facing long livelihood-generation journeys. As an indigenous solution to dysfunctional mobility systems shaped by colonial and apartheid legacies it was an effective connector, penetrating areas unserved by formal public transport and helping break cycles of poverty. From a public health perspective, it preserved active travel by reducing mode-shifting to private vehicles. Yet many city authorities viewed it as rogue, out of keeping with the 'ideal modern city', adopting official anti-paratransit stances without necessarily considering the contribution of active travel to public health. The studies varied in quality and showed uneven geographic representation, with data from Central and Northern Africa especially sparse; notably, there was a high prevalence of non-local authors and out-of-country funding. Nevertheless, drawing together a rich cross-disciplinary set of studies spanning over a decade, the review expands the literature at the intersection of transport and health with its novel focus on paratransit as a key active travel mode in African cities. Further innovative research could improve paratransit's legibility for policymakers and practitioners, fostering its inclusion in integrated transport plans.

Hepatitis B viruses (HBVs) are compact viruses with circular genomes of ∼3.2 kb in length. Four genes (HBx, Core, Surface, and Polymerase) generating seven products are encoded on overlapping reading frames. Ten HBV genotypes have been characterised (A–J), which may account for differences in transmission, outcomes of infection, and treatment response. However, HBV genotyping is rarely undertaken, and sequencing remains inaccessible in many settings. We set out to assess which amino acid (aa) sites in the HBV genome are most informative for determining genotype, using a machine learning approach based on random forest algorithms (RFA). We downloaded 5,496 genome-length HBV sequences from a public database, excluding recombinant sequences, regions with conserved indels, and genotypes I and J. Each gene was separately translated into aa, and the proteins concatenated into a single sequence (length 1,614 aa). Using RFA, we searched for aa sites predictive of genotype and assessed covariation among the sites with a mutual information–based method. We were able to discriminate confidently between genotypes A–H using ten aa sites. Half of these sites (5/10) sites were identified in Polymerase (Pol), of which 4/5 were in the spacer domain and one in reverse transcriptase. A further 4/10 sites were located in Surface protein and a single site in HBx. There were no informative sites in Core. Properties of the aa were generally not conserved between genotypes at informative sites. Among the highest co-varying pairs of sites, there were fifty-five pairs that included one of these ‘top ten’ sites. Overall, we have shown that RFA analysis is a powerful tool for identifying aa sites that predict the HBV lineage, with an unexpectedly high number of such sites in the spacer domain, which has conventionally been viewed as unimportant for structure or function. Our results improve ease of genotype prediction from limited regions of HBV sequences and may have future applications in understanding HBV evolution.

ObjectiveTo characterise the clinical features of monkeypox infection in humans.DesignDescriptive case series.SettingA regional high consequences infectious disease centre with associated primary and secondary care referrals, and affiliated sexual health centres in south London between May and July 2022.Participants197 patients with polymerase chain reaction confirmed monkeypox infection.ResultsThe median age of participants was 38 years. All 197 participants were men, and 196 identified as gay, bisexual, or other men who have sex with men. All presented with mucocutaneous lesions, most commonly on the genitals (n=111 participants, 56.3%) or in the perianal area (n=82, 41.6%). 170 (86.3%) participants reported systemic illness. The most common systemic symptoms were fever (n=122, 61.9%), lymphadenopathy (114, 57.9%), and myalgia (n=62, 31.5%). 102/166 (61.5%) developed systemic features before the onset of mucocutaneous manifestations and 64 (38.5%) after (n=4 unknown). 27 (13.7%) presented exclusively with mucocutaneous manifestations without systemic features. 71 (36.0%) reported rectal pain, 33 (16.8%) sore throat, and 31 (15.7%) penile oedema. 27 (13.7%) had oral lesions and 9 (4.6%) had tonsillar signs. 70/195 (35.9%) participants had concomitant HIV infection. 56 (31.5%) of those screened for sexually transmitted infections had a concomitant sexually transmitted infection. Overall, 20 (10.2%) participants were admitted to hospital for the management of symptoms, most commonly rectal pain and penile swelling.ConclusionsThese findings confirm the ongoing unprecedented community transmission of monkeypox virus among gay, bisexual, and other men who have sex with men seen in the UK and many other non-endemic countries. A variable temporal association was observed between mucocutaneous and systemic features, suggesting a new clinical course to the disease. New clinical presentations of monkeypox infection were identified, including rectal pain and penile oedema. These presentations should be included in public health messaging to aid early diagnosis and reduce onward transmission.

Hepatitis B viruses (HBV) are compact viruses with circular genomes of ∼3.2kb in length. Four genes (HBx, Core, Surface and Polymerase) generating seven products are encoded on overlapping reading frames. Ten HBV genotypes have been characterised (A-J), which may account for differences in transmission, outcomes of infection, and treatment response. However, HBV genotyping is rarely undertaken, and sequencing remains inaccessible in many settings. We used a machine learning approach based on random forest algorithms (RFA) to assess which amino acid (aa) sites in the genome are most informative for determining genotype. We downloaded 5496 genome-length HBV sequences from a public database, excluding recombinant sequences, regions with conserved indels, and genotypes I/J. Each gene was separately translated into aa, and the proteins concatenated into a single sequence (length 1614aa). Using RFA, we searched for aa sites predictive of genotype, and assessed co-variation among the sites with a Mutual Information (MI)-based method. We were able to discriminate confidently between genotypes A-H using 10 aa sites. 5/10 sites were identified in Polymerase (Pol), of which 4/5 were in the spacer domain, and a single site in reverse transcriptase. A further 4/10 sites were located in Surface protein, and a single site in HBx. There were no informative sites in Core. Properties of the aa were generally not conserved between genotypes at informative sites. Co-variation analysis identified 55 pairs of highly-linked sites. Three RFA-identified sites were represented across all pairs (two sites in spacer, and one in HBx). Residues that co-vary with these sites are concentrated in the small HBV surface gene. We also observe a cluster of sites adjacent to the Surface promoter region that co-vary with a spacer residue. Overall, we have shown that RFA analysis is a powerful tool for identifying aa sites that predict HBV lineage, with an unexpectedly high number of such sites in the spacer domain, which has conventionally been viewed as unimportant for structure or function. Our results improve ease of genotype prediction from limited regions of HBV sequence, and may have implications for understanding HBV evolution and the role of the spacer domain.

Hepatitis B virus (HBV) polymerase is divided into terminal protein, spacer, reverse transcriptase, and RNase domains. Spacer has previously been considered dispensable, merely acting as a tether between other domains or providing plasticity to accommodate deletions and mutations. We explore evidence for the role of spacer sequence, structure, and function in HBV evolution and lineage, consider its associations with escape from drugs, vaccines, and immune responses, and review its potential impacts on disease outcomes.

Travel has individual, societal and planetary health implications. We explored socioeconomic and gendered differences in travel behaviour in Africa, to develop an understanding of travel-related inequity. We conducted a mixed-methods systematic review (PROSPERO CRD42019124802). In 2019, we searched MEDLINE, TRID, SCOPUS, Web of Science, LILACS, SciELO, Global Health, Africa Index Medicus, CINAHL and MediCarib for studies examining travel behaviour by socioeconomic status and gender in Africa. We appraised study quality using Critical Appraisal Skills Programme checklists. We synthesised qualitative data using meta-ethnography, followed by a narrative synthesis of quantitative data, and integrated qualitative and quantitative strands using pattern matching principles. We retrieved 103 studies (20 qualitative, 24 mixed-methods, 59 quantitative). From the meta-ethnography, we observed that travel is: intertwined with social mobility; necessary to access resources; associated with cost and safety barriers; typified by long distances and slow modes; and dictated by gendered social expectations. We also observed that: motorised transport is needed in cities; walking is an unsafe, ‘captive’ mode; and urban and transport planning are uncoordinated. From these observations, we derived hypothesised patterns that were tested using the quantitative data, and found support for these overall. In lower socioeconomic individuals, travel inequity entailed reliance on walking and paratransit (informal public transport), being unable to afford travel, travelling less overall, and travelling long distances in hazardous conditions. In women and girls, travel inequity entailed reliance on walking and lack of access to private vehicles, risk of personal violence, societally-imposed travel constraints, and household duties shaping travel. Limitations included lack of analytical rigour in qualitative studies and a preponderance of cross-sectional quantitative studies (offering a static view of an evolving process). Overall, we found that travel inequity in Africa perpetuates socioeconomic and gendered disadvantage. Proposed solutions focus on improving the safety, efficiency and affordability of public transport and walking., Highlights • Utilised meta-ethnography and pattern-matching principles. • Revealed travel patterns differed by socioeconomic status and gender. • Travel inequity compounded disadvantage. • Females and poor people more likely to rely on walking. • Cost, safety and cultural factors were barriers to travel.

The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in a myriad of interventions with the urgent aim of reducing the public health impact of this virus. However, a wealth of evidence both from high-income and low-income countries is accruing on the broader consequences of such interventions on economic and public health inequalities, as well as on pre-existing programmes targeting endemic pathogens. We provide an overview of the impact of the ongoing COVID-19 pandemic on hepatitis B virus (HBV) programmes globally, focusing on the possible consequences for prevention, diagnosis and treatment. Ongoing disruptions to infrastructure, supply chains, services and interventions for HBV are likely to contribute disproportionately to the short-term incidence of chronic hepatitis B, providing a long-term source of onward transmission to future generations that threatens progress towards the 2030 elimination goals.

IntroductionMaximising efficiency of resources is critical to progressing towards universal health coverage (UHC) and the sustainable development goal (SDG) for health. This study estimates the technical efficiency of national health spending in progressing towards UHC, and the environmental factors associated with efficient UHC service provision.MethodsA two-stage efficiency analysis using Simar and Wilson’s double bootstrap data envelopment analysis investigates how efficiently countries convert health spending into UHC outputs (measured by service coverage and financial risk protection) for 172 countries. We use World Bank and WHO data from 2015. Thereafter, the environmental factors associated with efficient progress towards UHC goals are identified.ResultsThe mean bias-corrected technical efficiency score across 172 countries is 85.7% (68.9% for low-income and 95.5% for high-income countries). High-achieving middle-income and low-income countries such as El Salvador, Colombia, Rwanda and Malawi demonstrate that peer-relative efficiency can be attained at all incomes. Governance capacity, income and education are significantly associated with efficiency. Sensitivity analysis suggests that results are robust to changes.ConclusionWe provide a 2015 baseline for cross-country UHC technical efficiency scores. If countries wish to improve their UHC outputs within existing budgets, they should identify their current efficiency and try to emulate more efficient peers. Policy-makers should focus on strengthening institutions and implementing known best practices to replicate efficient systems. Using resources more efficiently is likely to positively impact UHC coverage goals and health outcomes, and without addressing gaps in efficiency progress towards achieving the SDGs will be impeded.

Aim The aim of this study was to investigate the financial implications of the inpatient management of open lower limb fractures in adults over 65 years old. Further, the study compares the calculated cost to the income received by the hospital for these patients and to the existing body of literature. Methods This study employed direct inpatient costing analysis to estimate the cost of treating the open lower limb fractures incurred by 58 patients over the age of 65 years treated in our centre (Addenbrooke's Hospital, Cambridge University Hospitals NHS Trust) between March 2014 and March 2019. Results The median cost of inpatient care calculated in this study was £20,398 per patient, resulting in a financial loss to the hospital of £5113 per patient. When the results were disaggregated by sex, the median cost for an open lower limb fracture in a male patient was £20,886 compared to £19,304 in a female patient. Data were also disaggregated by the site of injury, which produced a median cost for an open femur fracture of £23,949, and £24,549 and £15,362 for open tibia and ankle fractures, respectively. Conclusion This study provides a valuable estimate of the expense of treating open lower limb fractures in patients over the age of 65 years in a Major Trauma Centre in England. The study highlights the large losses incurred by hospitals in treating these cases, and supports revision of the remuneration structures in the National Health Service to adequately cover their cost.

Normothermic ex situ liver perfusion might allow viability assessment of livers before transplantation. Perfusion characteristics were studied in 47 liver perfusions, of which 22 resulted in transplants. Hepatocellular damage was reflected in the perfusate transaminase concentrations, which correlated with posttransplant peak transaminase levels. Lactate clearance occurred within 3 hours in 46 of 47 perfusions, and glucose rose initially during perfusion in 44. Three livers required higher levels of bicarbonate support to maintain physiological pH, including one developing primary nonfunction. Bile production did not correlate with viability or cholangiopathy, but bile pH, measured in 16 of the 22 transplanted livers, identified three livers that developed cholangiopathy (peak pH < 7.4) from those that did not (pH > 7.5). In the 11 research livers where it could be studied, bile pH > 7.5 discriminated between the 6 livers exhibiting >50% circumferential stromal necrosis of septal bile ducts and 4 without necrosis; one liver with 25‐50% necrosis had a maximum pH 7.46. Liver viability during normothermic perfusion can be assessed using a combination of transaminase release, glucose metabolism, lactate clearance, and maintenance of acid‐base balance. Evaluation of bile pH may offer a valuable insight into bile duct integrity and risk of posttransplant ischemic cholangiopathy., The authors describe a series of ex situ normothermic liver perfusions in which they examine biochemical markers of hepatocyte and cholangiocyte biochemistry in an effort to predict posttransplant viability.

Intellectual property law is a crucial determinant of global public health, capable of both endangering and facilitating advances in the health of populations. This Viewpoint explains the most important aspects of the interaction between intellectual property law and public health. We use the plain packaging of tobacco products to illustrate how public health policies may be subject to scrutiny under existing trade and investment law structures. Plain packaging of tobacco products is challenging to implement due to legal complexities and uncertainties surrounding the status of mandated plain packaging for consumer products. While the tobacco industry and its proponents once relied on the denial of scientific evidence to delay legislation and influence consumers, its tactics have shifted to the use of trade threats and investment disputes, directly challenging the sovereignty of governments to enact bona fide public health measures to improve the health of their population.

Significant numbers of patients in the USA and UK die while waiting for solid organ transplant. Only 1–2% of deaths are eligible as donors with a fraction of the deceased donating organs. The form of consent to donation may affect the organs available. Forms of consent include: opt-in, mandated choice, opt-out, and organ conscription. Opt-in and opt-out are commonly practiced. A systematic review was conducted to determine the effect of opt-in versus opt-out consent on the deceased donation rate (DDR) and deceased transplantation rate (DTR). Literature searches of PubMed and EMBASE between 2006 and 2016 were performed. Research studies were selected based on certain inclusion criteria which include USA, UK, and Spain; compare opt-in versus opt-out; primary data analysis; and reported DDR or DTR. Modeled effect on US transplant activity was conducted using public data from Organ Procurement and Transplantation Network and Centers for Disease Control WONDER from 2006 to 2015. A total of 2400 studies were screened and six studies were included. Four studies reported opt-out consent increases DDR by 21–76% over 5–14 years. These studies compared 13–25 opt-out countries versus 9–23 opt-in countries. Three studies reported opt-out consent increases DTR by 38–83% over 11–13 years. These studies compared 22–25 opt-out versus 22–28 opt-in countries. Modeled opt-out activity on the USA resulted in 4753–17,201 additional transplants annually. Opt-out consent increases DDR and DTR and may be useful in decreasing deaths on the waiting list in the USA and other countries. PROSPERO CRD42019098759.