EClinicalMedicine最新文献

Background: Children in low and middle-income countries remain vulnerable following hospital-discharge. We estimated the incidence and correlates of hospital readmission among young children admitted to nine hospitals in sub-Saharan Africa and South Asia.

Methods: This was a secondary analysis of the CHAIN Network prospective cohort enrolled between 20th November 2016 and 31st January 2019. Children aged 2-23 months were eligible for enrolment, if admitted for an acute illness to one of the study hospitals. Exclusions were requiring immediate resuscitation, inability to tolerate oral feeds in their normal state of health, had suspected terminal illness, suspected chromosomal abnormality, trauma, admission for surgery, or their parent/caregiver was unwilling to participate and attend follow-up visits. Data from children discharged alive from the index admission were analysed for hospital readmission within 180-days from discharge. We examined ratios of readmission to post-discharge mortality rates. Using models with death as the competing event, we evaluated demographic, nutritional, clinical, and socioeconomic associations with readmission.

Findings: Of 2874 children (1239 (43%) girls, median (IQR) age 10.8 (6.8-15.6) months), 655 readmission episodes occurred among 506 (18%) children (198 (39%) girls): 391 (14%) with one, and 115 (4%) with multiple readmissions, with a rate of: 41.0 (95% CI 38.0-44.3) readmissions/1000 child-months. Median time to readmission was 42 (IQR 15-93) days. 460/655 (70%) and 195/655 (30%) readmissions occurred at index study hospital and non-study hospitals respectively. One-third (N = 213/655, 33%) of readmissions occurred within 30 days of index discharge. Sites with fewest readmissions had the highest post-discharge mortality. Most readmissions to study hospitals (371/450, 81%) were for the same illness as the index admission. Age, prior hospitalisation, chronic conditions, illness severity, and maternal mental health score, but not sex, nutritional status, or physical access to healthcare, were associated with readmission.

Interpretation: Readmissions may be appropriate and necessary to reduce post-discharge mortality in high mortality settings. Social and financial support, training on recognition of serious illness for caregivers, and improving discharge procedures, continuity of care and facilitation of readmission need to be tested in intervention studies. We propose the ratio of readmission to post-discharge mortality rates as a marker of overall post-discharge access and care.

Funding: The Bill & Melinda Gates Foundation (OPP1131320).

Background: Mucositis is a common and highly impactful side effect of conventional and emerging cancer therapy and thus the subject of intense investigation. Although common practice, mucositis assessment is heterogeneously adopted and poorly guided, impacting evidence synthesis and translation. The Multinational Association of Supportive Care in Cancer (MASCC) Mucositis Study Group (MSG) therefore aimed to establish expert recommendations for how existing mucositis assessment tools should be used, in clinical care and trials contexts, to improve the consistency of mucositis assessment.

Methods: This study was conducted over two stages (January 2022-July 2023). The first phase involved a survey to MASCC-MSG members (January 2022-May 2022), capturing current practices, challenges and preferences. These then informed the second phase, in which a set of initial recommendations were prepared and refined using the Delphi method (February 2023-May 2023). Consensus was defined as agreement on a parameter by >80% of respondents.

Findings: Seventy-two MASCC-MSG members completed the first phase of the study (37 females, 34 males, mainly oral care specialists). High variability was noted in the use of mucositis assessment tools, with a high reliance on clinician assessment compared to patient reported outcome measures (PROMs, 47% vs 3%, 37% used a combination). The World Health Organization (WHO) and Common Terminology Criteria for Adverse Events (CTCAE) scales were most commonly used to assess mucositis across multiple settings. Initial recommendations were reviewed by experienced MSG members and following two rounds of Delphi survey consensus was achieved in 91 of 100 recommendations. For example, in patients receiving chemotherapy, the recommended tool for clinician assessment in clinical practice is WHO for oral mucositis (89.5% consensus), and WHO or CTCAE for gastrointestinal mucositis (85.7% consensus). The recommended PROM in clinical trials is OMD/WQ for oral mucositis (93.3% consensus), and PRO-CTCAE for gastrointestinal mucositis (83.3% consensus).

Interpretation: These new recommendations provide much needed guidance on mucositis assessment and may be applied in both clinical practice and research to streamline comparison and synthesis of global data sets, thus accelerating translation of new knowledge into clinical practice.

Funding: No funding was received.

Background: The International Agency for Research on Cancer (IARC) recently classified opium consumption as carcinogenic to humans. This study aimed to estimate the potential reduction in incident cancers by 2035 in Iran, which accounts for 42% of global opium consumption, through decreasing opium use prevalence.

Methods: The population attributable fraction (PAF) of opium-related cancers was projected using national cancer incidence, age- and gender-specific opium use prevalence, relative cancer risks associated with opium use, and annual percentage changes in cancer incidence rates in Iran. Opium-related cancers were defined based on IARC monographs as cancers of lung, larynx, bladder, esophagus, stomach, pancreas, and pharynx. The number of preventable cancer cases under different opium prevalence scenarios was determined by subtracting attributable cases in each year based on current prevalence from those in alternative scenarios.

Findings: By 2035, an estimated 3,001,421 new cancer cases are expected in Iran, with 904,013 (30.1%) occurring in opium-related sites. Maintaining the current opium prevalence (5.6%) is projected to cause 111,130 new cancer cases (3.7% of all cancers, 12.3% of opium-related). A 10%, 30%, and 50% reduction in opium prevalence could prevent 9,016, 28,161, and 49,006 total incident cancers by 2035 in Iran, respectively. Reducing opium use prevalence by 10%-50% is projected to have the highest impact on lung cancer (prevention of 2,946-15,831 cases), stomach cancer (prevention of 2,404-12,593 cases), and bladder cancer (prevention of 1,725-9,520 cases).

Interpretation: Our results highlight the significant benefits that can be achieved through effective cancer prevention policies targeting opium use in Iran. Neglecting this risk factor is estimated to pose a significant burden on cancer incidence in the next decade in this population.

Funding: None.

Research has examined the relationship between interoception and anxiety, depression, and psychosis; however, it is unclear which aspects of interoception have been systematically examined, what the combined findings are, and which areas require further research. To answer these questions, we systematically searched and narratively synthesised relevant reviews, meta-analyses, and theory papers (total n = 34). Existing systematic reviews and meta-analyses (anxiety n = 2; depression n = 2; psychosis n = 0), focus on cardiac interoceptive accuracy (heartbeat perception), and indicate that heartbeat perception is not systematically impaired in anxiety or depression. Heartbeat perception might be poorer in people with psychosis, but further evidence is needed. Other aspects of interoception, such as different body systems and processing levels, have been studied but not systematically reviewed. We highlight studies examining these alternative bodily domains and levels, review the efficacy of interoception-based psychological interventions, and make suggestions for future research.

Funding: Wellcome Trust UK.

There is a growing body of data describing a high burden of respiratory morbidity amongst pulmonary TB patients and survivors, with up to half thought to experience residual respiratory symptoms, abnormal spirometry, or structural pathology after TB treatment completion. Many patients experiencing marked impacts on their lives and livelihoods. However, there remain no guidelines or evidence-based frameworks for integrated TB-respiratory care during or post TB treatment completion. In this scoping review, completed in collaboration with the WHO Global Tuberculosis Programme, we have identified a lack of primary data on the clinical efficacy, cost effectiveness or feasibility of six potential interventions for the prevention and management of TB-associated respiratory impairment and disability, with a lack of studies in children and adolescents. There is a need for robust interventional trials to improve the long-term respiratory outcomes of people affected by pulmonary TB disease, and to explore how these might be implemented within resource-limited settings.

Background: The popularity of tattoos has increased dramatically over the last few decades. Tattoo ink often contains carcinogenic chemicals, e.g., primary aromatic amines, polycyclic aromatic hydrocarbons, and metals. The tattooing process invokes an immunologic response that causes translocation of tattoo ink from the injection site. Deposition of tattoo pigment in lymph nodes has been confirmed but the long-term health effects remain unexplored. We used Swedish National Authority Registers with full population coverage to investigate the association between tattoo exposure and overall malignant lymphoma as well as lymphoma subtypes.

Methods: We performed a case-control study where we identified all incident cases of malignant lymphoma diagnosed between 2007 and 2017 in individuals aged 20-60 years in the Swedish National Cancer Register. Three random age- and sex-matched controls per case were sampled from the Total Population Register using incidence density sampling. We assessed exposure through a questionnaire in 2021, and data on potential confounders were retrieved from registers. We used multivariable logistic regression to estimate the incidence rate ratio (IRR) of malignant lymphoma in tattooed individuals.

Findings: The study population consisted of 11,905 individuals, and the response rate was 54% among cases (n = 1398) and 47% among controls (n = 4193). The tattoo prevalence was 21% among cases and 18% among controls. Tattooed individuals had a higher adjusted risk of overall lymphoma (IRR = 1.21; 95% CI 0.99-1.48). The risk of lymphoma was highest in individuals with less than two years between their first tattoo and the index year (IRR = 1.81; 95% CI 1.03-3.20). The risk decreased with intermediate exposure duration (three to ten years) but increased again in individuals who received their first tattoo ≥11 years before the index year (IRR = 1.19; 95% CI 0.94-1.50). We found no evidence of increasing risk with a larger area of total tattooed body surface. The risk associated with tattoo exposure seemed to be highest for diffuse large B-cell lymphoma (IRR 1.30; 95% CI 0.99-1.71) and follicular lymphoma (IRR 1.29; 95% CI 0.92-1.82).

Interpretation: Our findings suggested that tattoo exposure was associated with an increased risk of malignant lymphoma. More epidemiologic research is urgently needed to establish causality.

Funding: The Swedish Research Council for Health, Working Life and Welfare.

Background: Caesarean section (CS) is the most performed major surgery worldwide. Surgical techniques used for CS vary widely and there is no internationally accepted standardization. We conducted an overview of systematic reviews (SR) of randomized controlled trials (RCT) to summarize the evidence on surgical techniques or procedures related to CS.

Methods: Searches were conducted from database inception to 31 January 2024 in Cochrane Database of Systematic Reviews, PubMed, EMBASE, Lilacs and CINAHL without date or language restrictions. AMSTAR 2 and GRADE were used to assess the methodological quality of the SRs and the certainty of evidence at outcome level, respectively. We classified each procedure-outcome pair into one of eight categories according to effect estimates and certainty of evidence. The overview was registered at PROSPERO (CRD 42023208306).

Findings: The analysis included 38 SRs (16 Cochrane and 22 non-Cochrane) published between 2004-2024 involving 628 RCT with a total of 190,349 participants. Most reviews were of low or critically low quality (AMSTAR 2). The SRs presented 345 procedure-outcome comparisons (237 procedure versus procedure, 108 procedure versus no treatment/placebo). There was insufficient or inconclusive evidence for 256 comparisons, clear evidence of benefit for 40, possible benefit for 17, no difference of effect for 13, clear evidence of harm for 14, and possible harm for 5. We found no SRs for 7 pre-defined procedures. Skin cleansing with chlorhexidine, Joel-Cohen-based abdominal incision, uterine incision with blunt dissection and cephalad-caudal expansion, cord traction for placental extraction, manual cervical dilatation in pre-labour CS, changing gloves, chromic catgut suture for uterine closure, non-closure of the peritoneum, closure of subcutaneous tissue, and negative pressure wound therapy are procedures associated with benefits for relevant outcomes.

Interpretation: Current evidence suggests that several CS surgical procedures improve outcomes but also reveals a lack of or inconclusive evidence for many commonly used procedures. There is an urgent need for evidence-based guidelines standardizing techniques for CS, and trials to fill existing knowledge gaps.

Funding: UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), a cosponsored programme executed by the World Health Organization (WHO).

Background: Diarrhoeal disease poses a significant global health challenge, especially in children under three years old. Despite the effectiveness of oral rehydration therapy (ORT), its adoption remains low. Glucose-based ORS (GORS) is the standard, but novel formulations like glucose-free amino acid-based VS002A have emerged as potential alternatives. This study aimed to compare the safety and efficacy of VS002A against the standard WHO-ORS in treating non-cholera acute watery diarrhoea in children.

Methods: A triple-blind, randomized trial enrolled 310 male infants and children aged 6-36 months, who were assigned to receive WHO-ORS or VS002A over a 16-month period, from June 2021 to September 2022. Both groups received standard of care, including zinc supplementation. The Primary study outcome measured was the duration of diarrhoea. Secondary outcomes included stool output, treatment failure and adverse events. Exploratory endpoints included urinary output, body weight changes, blood biochemistry, stool microbiology and gut health biomarkers.

Findings: Both VS002A and WHO-ORS were well-tolerated with a low adverse event rate. While not different statistically (p = 0.10), duration of diarrhoea was shorter in children treated with VS002A vs. WHO-ORS (65.4 h vs. 72.6 h). Similarly, stool output was also lower vs. WHO-ORS in children treated with VS002A, though not statistically different (p = 0.40). Serum citrulline levels, an indicator of gut health, were higher in the VS002A group at 24 h suggesting a potential protective effect (p = 0.06).

Interpretation: The findings of this study support the non-inferiority of VS002A, a glucose-free amino acid-based ORS compared to the WHO-ORS standard of care. VS002A was shown to be safe and effective in treating non-cholera acute watery diarrhoea in young children. VS002A may offer advantages in pathogen-driven diarrhoea, supported by trends toward a lower duration of diarrhoea and stool output within the per protocol group. Furthermore, individuals with prolonged diarrhoea, severe malnutrition, environmental enteric dysfunction or have issues with obesity or insulin resistance, could benefit from a glucose-free ORS. This research contributes to addressing the persistent challenge of childhood diarrhoea by presenting an alternative glucose-free ORS formulation with potential advantages in select scenarios, offering a promising avenue for improving paediatric diarrhoea management worldwide.

Funding: The study was funded by Entrinsic Bioscience, LLC., Norwood, MA, USA.