Introduction: Non-alcoholic fatty liver disease (NAFLD) is characterized by intra-hepatic fat accumulation, and the mechanisms involved in its pathogenesis are not fully understood. Serum Lysosomal Acid Lipase (LAL) is an essential enzyme involved in lipid metabolism, and its activity has been proposed as a novel mechanism contributing to the disease. We conducted a systematic review and meta-analysis to compare LAL activity levels in patients with NAFLD and patients without NAFLD. Methods: We conducted an extensive literature search using PubMed, EMBASE, and Web of Science databases through April 2023 for all published studies that reported LAL activity levels in patients with NAFLD and patients without NAFLD. Continuous variables (using mean serum levels and standard deviation) were compared, and mean difference (MD) was estimated with a 95% confidence interval (CI), and a P value < 0.05 was considered statistically significant. Meta-analyses were performed using a random-effect model with the inverse variance method. Results: A total of 6 studies involving 1,608 patients were included. A comparison of mean LAL activity levels for NAFLD and non-NAFLD patients was performed in all 6 studies. The pooled mean LAL activity level was 0.80 ± 0.34 and 1.09 ± 0.54 ng/ml for NAFLD and non-NAFLD patients, respectively. The pooled mean LAL activity level was significantly lower in NAFLD patients than in non-NAFLD patients (MD -0.29; 95% CI -0.46, -0.12; P< 0.001, I2=96%; Figure 1A). A leave-one-out sensitivity analysis showed consistent results (Figure 1B). Conclusion: Our meta-analysis demonstrates a significant association between reduced LAL activity and NAFLD incidence. LAL activity may serve as a new non-invasive diagnostic marker to identify patients with NAFLD. Further studies with larger sample sizes, especially in NAFLD patients without genetic causes, are needed to validate our findings.Figure 1.: Study populations and results.
Early cardiopulmonary resuscitation and defibrillation is key to increasing survival following an out-of-hospital-cardiac-arrest (OHCA). However, automated external defibrillators (AEDs) are used in a very small percentage of cases. Despite large numbers of AEDs in the community, the absence of a unified system for registering their locations across the UK's ambulance services may have resulted in missed opportunities to save lives. Therefore, representatives from the resuscitation community worked alongside ambulance services to develop a single repository for data on the location of AEDs in the UK.
BACKGROUNDEarly cardiopulmonary resuscitation and defibrillation is key to increasing survival following an out-of-hospital-cardiac-arrest (OHCA). However, automated external defibrillators (AEDs) are used in a very small percentage of cases. Despite large numbers of AEDs in the community, the absence of a unified system for registering their locations across the UK's ambulance services may have resulted in missed opportunities to save lives. Therefore, representatives from the resuscitation community worked alongside ambulance services to develop a single repository for data on the location of AEDs in the UK.METHODSA national defibrillator network, "The Circuit", was developed by the British Heart Foundation (BHF) in collaboration with the Association of Ambulance Chief Executives (AACE), the UK ambulance services, the Resuscitation Council UK (RCUK) and St John Ambulance (SJA). The database allows "Defibrillator Guardians" to record information about AED location, accessibility, and availability. The database synchronises with ambulance computer aided dispatch (CAD) systems to provide UK ambulance services with real-time information on the nearest, available AED.RESULTSThe Circuit was successfully rolled out to all 14 UK ambulance services. Since 2019, 82,108 AEDs have been registered. Of the AED data collected by The Circuit, 54% were not previously registered to any ambulance service, and are therefore new registrations.CONCLUSIONThe Circuit provides ambulance services with a single point of access to AED locations in the UK. Since the launch of the system the number of defibrillators registered has doubled. Linking the Circuit data with patient outcomes data will help understand whether improving the accessibility to AEDs is associated with increased survival.
Albuminuric and nonalbuminuric pathways contribute to diabetic kidney disease. Proximal tubule and inflammation play important roles in these processes. Urinary biomarker(s) to detect early kidney damage and predict progression are needed.Nine urinary biomarkers were measured at baseline in 400 patients with diabetes. Correlation and multivariate logistic and linear regression analyses were performed to assess the association of biomarkers with chronic kidney disease and progression.In the albumin/creatinine ratio (ACR) <3 cohort, the only biomarker significantly associated with estimated glomerular filtration rate < 60 ml/min was N-acetyl-β-d-glucosaminidase. A combination of ACR and monocyte chemoattractant protein 1 (MCP1) were significantly associated with stage 2 chronic kidney disease in this cohort. Logistic models showed that in patients with all levels of albuminuria, ACR, retinol binding protein (RBP), and MCP1 were associated with progression. A model including MCP1, interleukin 6, and neutrophil gelatinase-associated lipocalin showed significant association with progression to chronic kidney disease 3/4 in the ACR <3 cohort. Linear mixed-model regression analyses demonstrated MCP1, RBP, and ACR as significant proteins associated with progression to stage 3 or worse, whereas MCP1 was the only significant biomarker in the ACR <3 cohort. Time-to-event and Cox proportional hazard models confirmed significant hazard ratios for progression for ACR, RBP, and MCP1, with significant differences noted between quantiles of biomarkers for ACR, RBP, and MCP1.In this study of diabetic patients with single baseline measurements of urinary biomarkers, albumin, RBP, and MCP1 were significantly associated with chronic kidney disease progression at all levels of albuminuria. Inflammatory cytokines, neutrophil gelatinase-associated lipocalin, and MCP1 were associated with progression in patients without albuminuria. N-acetyl-β-d-glucosaminidase demonstrated a significant association with an estimated glomerular filtration rate < 60 ml/min in the ACR <3 cohort.
Background: Most Neisseria gonorrhoea (GC) and Chlamydia trachomatis (CT) infections in men who have sex with men (MSM) are diagnosed at extragenital sites. However, testing at these sites is often lacking. The purpose of this study was to determine if a standardized questionnaire administered by physicians and clinical assistants improves documentation of sex activity and increases extragenital testing and diagnoses of GC and CT among MSM.Methods: A standardized sexual history questionnaire was implemented on 11/1/2022. Electronic medical records of 664 MSM with HIV, including 1064 encounters, were reviewed to compare pre- and post- implementation sexual history documentation, adequacy of documentation, extragenital GC and CT testing, and GC and CT diagnoses. Analysis included Chi-square and exact tests and logistic regression adjusting for physician cluster effects.Results: The standardized questionnaire was used by 53.7% of physicians and 85.9% of coordinators. Documentation of whether sexual activity occurred increased from 79.3% [95%confidence interval (CI) 0.758- 0.828] in the pre-intervention pre-COVID-19 period to 95.2% (95% CI 0.925-0.970) in the post-intervention period with an adjusted odds ratio of 4.7 (95% CI 2.7-8.8). Specific questions about anal and oral sex increased from 42.0% to 88.1% (p < 0.001) and 23.7% to 88.7% (p < 0.001), respectively. Anal and pharyngeal testing increased from 14.4% to 20.2% (p = 0.040) and 17.2% to 23.3% (p = 0.045), respectively.Conclusions: This study demonstrates that using a standardized questionnaire during clinical encounters can improve documentation of sexual activity and testing for GC and CT at extragenital sites.
An understanding of the health of potential volunteers in Africa is essential for the safe and efficient conduct of clinical trials, particularly for trials of preventive technologies such as vaccines that enroll healthy individuals. Clinical safety laboratory values used for screening, enrolment and follow-up of African clinical trial volunteers have largely been based on values derived from industrialized countries in Europe and North America. This report describes baseline morbidity during recruitment for a multi-center, African laboratory reference intervals study.Asymptomatic persons, aged 18-60 years, were invited to participate in a cross-sectional study at seven sites (Kigali, Rwanda; Masaka and Entebbe, Uganda; Kangemi, Kenyatta National Hospital and Kilifi, Kenya; and Lusaka, Zambia). Gender equivalency was by design. Individuals who were acutely ill, pregnant, menstruating, or had significant clinical findings were not enrolled. Each volunteer provided blood for hematology, immunology, and biochemistry parameters and urine for urinalysis. Enrolled volunteers were excluded if found to be positive for HIV, syphilis or Hepatitis B and C. Laboratory assays were conducted under Good Clinical Laboratory Practices (GCLP).Of the 2990 volunteers who were screened, 2387 (80%) were enrolled, and 2107 (71%) were included in the analysis (52% men, 48% women). Major reasons for screening out volunteers included abnormal findings on physical examination (228/603, 38%), significant medical history (76, 13%) and inability to complete the informed consent process (73, 13%). Once enrolled, principle reasons for exclusion from analysis included detection of Hepatitis B surface antigen (106/280, 38%) and antibodies against Hepatitis C (95, 34%). This is the first large scale, multi-site study conducted to the standards of GCLP to describe African laboratory reference intervals applicable to potential volunteers in clinical trials. Approximately one-third of all potential volunteers screened were not eligible for analysis; the majority were excluded for medical reasons.
'/%3e%3c/defs%3e%3cpath fill='%23fff' d='M-120-80h240V80h-240z'/%3e%3cpath d='M-120-80h240v48h-240z'/%3e%3cpath fill='%23060' d='M-120 32h240v48h-240z'/%3e%3cg id='b'%3e%3cuse xlink:href='%23a' stroke='%23000'/%3e%3cuse xlink:href='%23a' fill='%23fff'/%3e%3c/g%3e%3cuse xlink:href='%23b' transform='scale(-1 1)'/%3e%3cpath fill='%23b00' d='M-120-24v48h101c3 8 13 24 19 24s16-16 19-24h101v-48H19C16-32 6-48 0-48s-16 16-19 24z'/%3e%3cpath id='c' d='M19 24c3-8 5-16 5-24s-2-16-5-24c-3 8-5 16-5 24s2 16 5 24'/%3e%3cuse xlink:href='%23c' transform='scale(-1 1)'/%3e%3cg fill='%23fff'%3e%3cellipse rx='4' ry='6'/%3e%3cpath id='d' d='M1 5.85s4 8 4 21-4 21-4 21z'/%3e%3cuse xlink:href='%23d' transform='scale(-1)'/%3e%3cuse xlink:href='%23d' transform='scale(-1 1)'/%3e%3cuse xlink:href='%23d' transform='scale(1 -1)'/%3e%3c/g%3e%3c/svg%3e)
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)
'%3e%3cpath fill='%23001489' d='M0 0v6h9V0z'/%3e%3cpath fill='%23e03c31' d='M0 0v3h9V0z'/%3e%3cg stroke='%23fff' stroke-width='2'%3e%3cpath id='d' d='m0 0 4.5 3L0 6m4.5-3H9'/%3e%3cuse xlink:href='%23b' stroke='%23ffb81c' clip-path='url(%23c)'/%3e%3c/g%3e%3cuse xlink:href='%23d' fill='none' stroke='%23007749' stroke-width='1.2'/%3e%3c/g%3e%3c/svg%3e)
'%3e%3cg id='b'%3e%3cpath id='a' fill='%23E5BE01' d='M116.1 0 35.692 4.699l76.452 25.35L33.26 13.777l67.286 44.273L28.56 21.915l53.534 60.18-60.18-53.534 36.135 71.985L13.777 33.26l16.272 78.884-25.35-76.452L0 116.1-1-1z'/%3e%3cuse xlink:href='%23a' transform='scale(1 -1)'/%3e%3c/g%3e%3cuse xlink:href='%23b' transform='scale(-1 1)'/%3e%3ccircle r='34.3' fill='%23E5BE01' stroke='%2300A1DE' stroke-width='3.4'/%3e%3c/g%3e%3c/svg%3e)