More than 1,000 children under 5 years of age die every day from malaria. Cerebral malaria (CM) is the most severe and deadly manifestation of the disease. The occurrence of multiple organ dysfunction syndrome (MODS) has been associated with increased mortality in adult patients with CM. However, little is known about the frequency and severity of MODS in children with CM. This was a retrospective study of 199 pediatric patients with CM admitted to a referral hospital in Blantyre, Malawi, between January 2019 and May 2023. Data were abstracted from charts to calculate scores using four established scoring systems: Pediatric Logistic Organ Dysfunction-2 (PELOD-2), Pediatric Sequential Organ Failure Assessment (pSOFA), Signs of Inflammation in Children that Can Kill (SICK), and Lambaréné Organ Dysfunction Score (LODS). Mortality was 16% (n = 32). All four scoring systems were predictive of mortality, but the PELOD-2 and pSOFA scores outperformed the others with area under the curve values of 0.75 and 0.67, respectively. Multiple organ dysfunction syndrome was diagnosed in 182 patients (91%) using the PELOD-2 score, 172 patients (86%) using the pSOFA score, 99 patients (50%) using the SICK score, and 30 patients (15%) using the LODS. The PELOD-2 and pSOFA identify MODS in children with CM but require laboratory-based testing that is often unavailable in malaria-endemic areas. Furthermore, these scoring systems may identify primary malarial disease pathology rather than true organ dysfunction. Simplified scoring systems designed to recognize and quantify MODS in this patient population may provide opportunities for improved resource allocation and timely, organ-specific treatment.

Background: Fabry disease (FD) is a rare X-linked lysosomal storage disorder marked by alpha-galactosidase-A (α-Gal A) deficiency, caused by pathogenic mutations in the GLA gene, resulting in the accumulation of glycosphingolipids within lysosomes. The current screening test relies on measuring α-Gal A activity. However, this approach is limited to males. Infrared (IR) spectroscopy is a technique that can generate fingerprint spectra of a biofluid's molecular composition and has been successfully applied to screen numerous diseases. Herein, we investigate the discriminating vibration profile of plasma chemical bonds in patients with FD using attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy.

Results: The Fabry disease group (n = 47) and the healthy control group (n = 52) recruited were age-matched (39.2 ± 16.9 and 36.7 ± 10.9 years, respectively), and females were predominant in both groups (59.6% and 65.4%, respectively). All patients had the classic phenotype (100%), and no late-onset phenotype was detected. A generated partial least squares discriminant analysis (PLS-DA) classification model, independent of gender, allowed differentiation of samples from FD vs. control groups, reaching 100% sensitivity, specificity and accuracy.

Conclusion: ATR-FTIR spectroscopy harnessed to pattern recognition algorithms can distinguish between FD patients and healthy control participants, offering the potential of a fast and inexpensive screening test.

The ageing global population is posing a significant challenge to healthcare systems worldwide. Healthcare needs have become more complex and the demand for services is ever increasing. Identification of frailty at the front door of hospitals can prompt comprehensive geriatric assessment and streamline patients to the most suitable clinical area. The United Kingdom has set a priority to develop front door services given the pressure on the National Health Service. A British Geriatrics Society survey has demonstrated that the majority of frailty assessments occur in the emergency department using the Clinical Frailty Scale. This survey prompted the creation of the setting up services guide and its key principles using a collaboration of experience from across the country. Understanding the systems that already exist and creating a network to enable a flow of care towards community teams is crucial to the successful provision of modern frailty attuned care.

Introduction: Breast pain is not typically a symptom of breast cancer, yet nationally 20% of 2-week wait (2WW) breast referrals are breast pain alone. The East Midlands Breast Pain Pathway improves patient experience and frees capacity in secondary care diagnostic breast clinics, managing women with breast pain only in a community setting. We report the results of implementation of community breast pain clinics (CBPCs) at sites in Derbyshire (catchment population ~1 million), with 12 months follow-up data.

Results: 1036 patients were seen at CBPCs between June 2021 and February 2023. The median patient age was 49 (range 16-88) years. 993 patients (95.8%) were discharged from the clinic with breast pain management advice. 43 (4.2%) patients were referred for further assessment at a 2WW breast diagnostic clinic. Objective family history risk assessment identified 124 patients (12.3%) above population risk of breast cancer, who were offered referral to familial cancer services for ongoing management.

Discussion: Seven patients were diagnosed with breast cancer at or within 12 months of CBPC attendance. Five patients were diagnosed through attending the CBPC, one patient was subsequently referred to 2WW clinic with a new symptom and had a mammographically occult tumour and one was diagnosed following a subsequent routine breast screening invitation. Two of the five patients had a personal history of breast cancer which was a stated exclusion criterion for the CBPC. Breast cancer incidence in women with breast pain only and fulfilling CBPC referral criteria was 4.8/1000, confirming that this population is at low risk of developing breast cancer. Patient service satisfaction was high with 99% (n=1022) 'extremely likely or likely' to recommend the service.

Conclusion: The results confirm the pathway is the first to demonstrate women can be safely managed with breast pain alone in a community setting with high levels of patient satisfaction.

Lung cancer is one of the most commonly occurring malignant tumours worldwide. Although some reference methods such as X-ray, computed tomography or bronchoscope are widely used for clinical diagnosis of lung cancer, there is still a need to develop new methods for early detection of lung cancer. Especially needed are approaches that might be non-invasive and fast with high analytical precision and statistically reliable. Herein, we developed a swab "dip" test in saliva whereby swabs were analysed using attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy harnessed to principal component analysis-quadratic discriminant analysis (QDA) and variable selection techniques employing successive projections algorithm (SPA) and genetic algorithm (GA) for feature selection/extraction combined with QDA. A total of 1944 saliva samples (56 designated as lung-cancer positive and 1888 designed as controls) were obtained in a lung cancer-screening programme being undertaken in North-West England. GA-QDA models achieved, for the test set, sensitivity and specificity values of 100.0% and 99.1%, respectively. Three wavenumbers (1422 cm-1, 1546 cm-1 and 1578 cm-1) were identified using the GA-QDA model to distinguish between lung cancer and controls, including ring C-C stretching, CN adenine, Amide II [δ(NH), ν(CN)] and νs(COO-) (polysaccharides, pectin). These findings highlight the potential of using biospectroscopy associated with multivariate classification algorithms to discriminate between benign saliva samples and those with underlying lung cancer

Background: Whether a conservative strategy of medical therapy alone or a strategy of medical therapy plus invasive treatment is more beneficial in older adults with non-ST-segment elevation myocardial infarction (NSTEMI) remains unclear.

Methods: We conducted a prospective, multicenter, randomized trial involving patients 75 years of age or older with NSTEMI at 48 sites in the United Kingdom. The patients were assigned in a 1:1 ratio to a conservative strategy of the best available medical therapy or an invasive strategy of coronary angiography and revascularization plus the best available medical therapy. Patients who were frail or had a high burden of coexisting conditions were eligible. The primary outcome was a composite of death from cardiovascular causes (cardiovascular death) or nonfatal myocardial infarction assessed in a time-to-event analysis.

Results: A total of 1518 patients underwent randomization; 753 patients were assigned to the invasive-strategy group and 765 to the conservative-strategy group. The mean age of the patients was 82 years, 45% were women, and 32% were frail. A primary-outcome event occurred in 193 patients (25.6%) in the invasive-strategy group and 201 patients (26.3%) in the conservative-strategy group (hazard ratio, 0.94; 95% confidence interval [CI], 0.77 to 1.14; P = 0.53) over a median follow-up of 4.1 years. Cardiovascular death occurred in 15.8% of the patients in the invasive-strategy group and 14.2% of the patients in the conservative-strategy group (hazard ratio, 1.11; 95% CI, 0.86 to 1.44). Nonfatal myocardial infarction occurred in 11.7% in the invasive-strategy group and 15.0% in the conservative-strategy group (hazard ratio, 0.75; 95% CI, 0.57 to 0.99). Procedural complications occurred in less than 1% of the patients.

Conclusions: In older adults with NSTEMI, an invasive strategy did not result in a significantly lower risk of cardiovascular death or nonfatal myocardial infarction (the composite primary outcome) than a conservative strategy over a median follow-up of 4.1 years. (Funded by the British Heart Foundation; BHF SENIOR-RITA ISRCTN Registry number, ISRCTN11343602.).

Introduction Currently, there are no agreed-upon investigations and follow-up guidelines for the conservative management of ureteric stones. This study used common themes identified in previous works to investigate whether there is a consensus amongst urology consultants in the United Kingdom. Methods This was a questionnaire-based survey study. An online questionnaire was disseminated nationally to urological consultants practicing in the United Kingdom to explore a range of common factors. The initial sample size was 81 UK-based urological consultants with an interest in endourology and stone surgery. Of the initial 81, 20 participants did not complete the survey and therefore the final sample size was 61. Descriptive analysis was used to analyze the data. Results Our survey found that the main factors influencing the follow-up of conservatively managed ureteric stones were stone size 98% (60), stone location 92% (56), and the degree of altered renal function 79% (48). Regardless of stone size, most participants chose to follow up at 2-4 weeks with asymptomatic patients requiring imaging with discrepancies about the modality. Regarding biochemical markers, most participants only repeated renal function tests if this was deranged on presentation. Calcium and uric acid levels were checked regularly. Diclofenac was the analgesia of choice 93% (55). Regarding the availability of acute ESWL services, over half (59%) were able to offer acute ESWL within the week. The majority offer services at least three or more lists per week. Conclusion Our results demonstrate that there is still no overarching consensus in the follow-up of conservatively managed ureteric stones. Several factors backed by high-level evidence are already consistent across the population of urology consultants and considered "best practice." However, before any all-encompassing national guidelines are formalized, further studies in the form of randomized control trials will be needed to yield high-level evidence.

Background: GPs are often required to make decisions about the management of acute illness in people living with dementia. These decisions are often complex and involve multiple informants.

Aim: We aimed to explore how GPs made decisions about acute illness in people with dementia using a micropolitics approach.

Design & setting: Qualitative, semi-structured interviews with 13 GPs with a range of years of experience working in South Yorkshire, UK.

Method: Interviews were conducted by phone. Interviews focused on GPs' accounts to reflect their own perceptions and choices as portrayed to the interviewer. The analysis used the lens of micro-politics in the analysis and interpretation of the themes, with a focus on decisions between GP, patient, family and carers, other health and social care providers about the management of acute illness in a person with dementia.

Results: The results showed that GPs act as street-level bureaucrats while carrying out their role, using discretion during decision-making in an environment characterised by uncertainties and work pressures. In addition, GPs use the "soft power" skills of diplomacy such as negotiation, persuasion and engagement in navigating through difficult decision-making situations, while building relationships and partnerships with various actors in the health system.

Conclusion: GPs possess and express power and influence decision-making in people living with dementia when navigating biomedical, social, economic and psychological factors. This power comes in the form of soft power (street level diplomacy) and the more formal power of street level bureaucracy.

No abstract available

Objective: To report real-world outcomes for high-risk non-muscle-invasive bladder cancer (HRNMIBC), including bacillus Calmette-Guérin (BCG) and radical cystectomy (RC), as randomised comparisons of these have not been possible.

Methods: We detail consecutive participants screened for the BRAVO randomised controlled trial comparing RC with BCG (International Standard Randomised Controlled Trial Number [ISRCTN]12509361). Patients were prospectively registered and case-note review used for outcomes. The primary outcome was overall survival. Secondary outcomes included recurrence, progression, metastasis, and bladder cancer-specific survival.

Results and limitations: A total of 193 patients were screened, including 106 (54.9%) who received BCG, 43 (22.3%) primary RC, 37 (19.2%) 'other' treatment and seven (3.6%) hyperthermic intravesical mitomycin C. All-cause death occurred in 55 (28.5%) patients at median (interquartile range [IQR]) of 29.0 (19.5-42.0) months. In multivariable analysis, overall mortality was more common in older patients (hazard ratio [HR] 2.63, 95% confidence interval [CI] 1.35-5.13; Cox P = 0.004 for age >70 years), those recruited from district hospitals (HR 0.53, 95% CI 0.3-0.95; P = 0.032) and those who did not undergo RC as their first treatment (HR 2.16, 95% CI 1.17-3.99; P = 0.014). In all, 17 (8.8%) patients died from bladder cancer (BC) at median (IQR) of 22.5 (19-36.25) months. In multivariable analysis, BC-specific mortality was more common in older patients (HR 4.87, 95% CI 1.1-21.6; P = 0.037) and those with Tis/T1 disease (HR 2.26, 95% CI 1.23-4.16; P = 0.008) but did not vary with initial treatment.

Conclusions: Patients with HRNMIBC are at high-risk of mortality. Those choosing RC as their initial treatment have lower risks of mortality than others, although this may reflect fitness and selection.

No abstract available

Lung cancer is one of the most commonly occurring malignant tumours worldwide. Although some reference methods such as X-ray, computed tomography or bronchoscope are widely used for clinical diagnosis of lung cancer, there is still a need to develop new methods for early detection of lung cancer. Especially needed are approaches that might be non-invasive and fast with high analytical precision and statistically reliable. Herein, we developed a swab "dip" test in saliva whereby swabs were analysed using attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy harnessed to principal component analysis-quadratic discriminant analysis (QDA) and variable selection techniques employing successive projections algorithm (SPA) and genetic algorithm (GA) for feature selection/extraction combined with QDA. A total of 1944 saliva samples (56 designated as lung-cancer positive and 1888 designed as controls) were obtained in a lung cancer-screening programme being undertaken in North-West England. GA-QDA models achieved, for the test set, sensitivity and specificity values of 100.0% and 99.1%, respectively. Three wavenumbers (1422 cm-1, 1546 cm-1 and 1578 cm-1) were identified using the GA-QDA model to distinguish between lung cancer and controls, including ring C-C stretching, CN adenine, Amide II [δ(NH), ν(CN)] and νs(COO-) (polysaccharides, pectin). These findings highlight the potential of using biospectroscopy associated with multivariate classification algorithms to discriminate between benign saliva samples and those with underlying lung cancer.