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Risk factors for asymptomatic kidney stone passage in adults with recurrent kidney stones.
No full textBACKGROUND
Kidney stones are a common health problem and are characterized by a high risk of recurrence. A certain number of kidney stones passed asymptomatically. Data regarding the frequency of asymptomatic spontaneous stone passages are limited.
METHODS
To assess the frequency of asymptomatic spontaneous stone passage and its covariates, we conducted a post-hoc analysis of the prospective randomized NOSTONE trial. All asymptomatic spontaneous stone passages were identified by comparing the total number of kidney stones on low-dose non-contrast CT imaging at the beginning and end of the study, considering symptomatic stone passages and surgical stone removal. The statistical analysis focused on the association of independent variables and the number of asymptomatic spontaneous stone passages using linear regression analyses.
RESULTS
Of the 416 randomized patients, 383 with both baseline and end-of-study CT were included in this analysis. The median follow-up period was 35 months, the median patient age was 49 years (IQR:40 - 55), and 20% of the patients were female. A total of 442 stone events occurred in 209 out of 383 (55%) patients: 217 out of 442 (49%) were symptomatic spontaneous stone passages, 67 out of 442 (15%) were surgically removed stones, and 158 out of 442 (36%) were asymptomatic spontaneous stone passages. The median size of asymptomatic stones (2.4 mm; IQR:1.95-3.4) and the size of symptomatic stones (2.15 mm; IQR:1.68-2.79) that passed spontaneously were not significantly different (p=0.37). The number of asymptomatic spontaneous stone passages was significantly associated with a higher number of stones on CT at randomization (P=0.001). Limitations include the lack of data on stone size at the time of passage and overrepresentation of White men.
CONCLUSIONS
Asymptomatic stone passage was common in patients with recurrent calcium-containing kidney stones. The higher the number of stones at presentation, the more likely it was that a kidney stone would spontaneously pass over time without causing any symptoms
Fluid accumulation syndrome in sepsis and septic shock: pathophysiology, relevance and treatment-a comprehensive review.
Get PDFIn this review, we aimed to comprehensively summarize current literature on pathophysiology, relevance, diagnosis and treatment of fluid accumulation in patients with sepsis/septic shock. Fluid accumulation syndrome (FAS) is defined as fluid accumulation (any degree, expressed as percentage from baseline body weight) with new onset organ-failure. Over the years, many studies have described the negative impact of FAS on clinically relevant outcomes. While the relationship between FAS and ICU outcomes is well described, uncertainty exists regarding its diagnosis, monitoring and treatment. A stepwise approach is suggested to prevent and treat FAS in patients with septic shock, including minimizing fluid intake (e.g., by limiting intravenous fluid administration and employing de-escalation whenever possible), limiting sodium and chloride administration, and maximizing fluid output (e.g., with diuretics, or renal replacement therapy). Current literature implies the need for a multi-tier, multi-modal approach to de-resuscitation, combining a restrictive fluid management regime with a standardized early active de-resuscitation, maintenance fluid reduction (avoiding fluid creep) and potentially using physical measures such as compression stockings.Trial registration: Not applicable
A Descriptive Review of the Healthcare System and the Provision of Oral Healthcare in the Republic of Sudan.
Get PDFOral health constitutes a significant public health concern in Sub-Saharan Africa. The precise burden of oral diseases and the adequacy of oral healthcare provision remain often unknown. The present study aims to evaluate key components of the healthcare system in Sudan and the delivery of oral healthcare across eight dimensions: Healthcare System Framework, Financing, Service Delivery, Epidemiology, Prevention, Personnel, Dental Education and Training System, and Health Benefit Package. The evaluation of Sudan's healthcare system and oral healthcare provision utilizing the extended World Health Organization building blocks healthcare systems analysis framework. The evolving healthcare landscape in Sudan is characterized by a transition towards a Bismarckian model, a shift facilitated by the implementation of a National Health Insurance Fund. In 2018, Sudan's total healthcare expenditure surged to 2.4 billion US dollars and dental care accounted for less than 1% of this financial allocation. During the period spanning from 2016 to 2019, there was an expansion in the healthcare infrastructure and utilization rates. The number of healthcare facilities and hospital admissions respectively increased from 2,083 to 3,578 and from 14,967,113 to 22,455,772, while the registered number of dentists in 2019 reached 8,964. Within the framework of the national healthcare system, medical consultations and emergency treatments are encompassed in the oral health benefit package. Sudan's healthcare system grapples with endemic vulnerabilities compounded by recurrent political and economic challenges. Nevertheless, strides towards an insurance-based healthcare system and the upward trend observed in oral healthcare provision and infrastructure assets offer promising prospects for future generations
Condensin I folds the Caenorhabditis elegans genome.
No full textThe structural maintenance of chromosome (SMC) complexes-cohesin and condensins-are crucial for chromosome separation and compaction during cell division. During the interphase, mammalian cohesins additionally fold the genome into loops and domains. Here we show that, in Caenorhabditis elegans, a species with holocentric chromosomes, condensin I is the primary, long-range loop extruder. The loss of condensin I and its X-specific variant, condensin IDC, leads to genome-wide decompaction, chromosome mixing and disappearance of X-specific topologically associating domains, while reinforcing fine-scale epigenomic compartments. In addition, condensin I/IDC inactivation led to the upregulation of X-linked genes and unveiled nuclear bodies grouping together binding sites for the X-targeting loading complex of condensin IDC. C. elegans condensin I/IDC thus uniquely organizes holocentric interphase chromosomes, akin to cohesin in mammals, as well as regulates X-chromosome gene expression
Sodium valproate is associated with cortical thinning of disease-specific areas in juvenile myoclonic epilepsy.
No full textBACKGROUND
Juvenile myoclonic epilepsy (JME) is associated with cortical thinning of the motor areas. The relative contribution of antiseizure medication to cortical thickness is unknown. We aimed to investigate how valproate influences the cortical morphology of JME.
METHODS
In this cross-sectional study, individuals with JME with and without valproate, with temporal lobe epilepsy (TLE) with valproate and controls were selected through propensity score matching. Participants underwent T1-weighted brain imaging and vertex-wise calculation of cortical thickness.
RESULTS
We matched 36 individuals with JME on valproate with 36 individuals with JME without valproate, 36 controls and 19 individuals with TLE on valproate. JME on valproate showed thinning of the precentral gyri (left and right, p<0.001) compared with controls and thinning of the left precentral gyrus when compared with JME not on valproate (p<0.01) or to TLE on valproate (p<0.001). Valproate dose correlated negatively with the thickness of the precentral gyri, postcentral gyri and superior frontal gyrus in JME (left and right p<0.0001), but not in TLE.
CONCLUSIONS
Valproate was associated with JME-specific and dose-dependent thinning of the cortical motor regions. This suggests that valproate is a key modulator of cortical morphology in JME, an effect that may underlie its high efficacy in this syndrome
Identification of a non-canonical chemokine-receptor pathway suppressing regulatory T cells to drive atherosclerosis.
Get PDFCCL17 is produced by conventional dendritic cells (cDCs), signals through CCR4 on regulatory T cells (Tregs), and drives atherosclerosis by suppressing Treg functions through yet undefined mechanisms. Here we show that cDCs from CCL17-deficient mice display a pro-tolerogenic phenotype and transcriptome that is not phenocopied in mice lacking its cognate receptor CCR4. In the plasma of CCL17-deficient mice, CCL3 was the only decreased cytokine/chemokine. We found that CCL17 signaled through CCR8 as an alternate high-affinity receptor, which induced CCL3 expression and suppressed Treg functions in the absence of CCR4. Genetic ablation of CCL3 and CCR8 in CD4+ T cells reduced CCL3 secretion, boosted FoxP3+ Treg numbers, and limited atherosclerosis. Conversely, CCL3 administration exacerbated atherosclerosis and restrained Treg differentiation. In symptomatic versus asymptomatic human carotid atheroma, CCL3 expression was increased, while FoxP3 expression was reduced. Together, we identified a non-canonical chemokine pathway whereby CCL17 interacts with CCR8 to yield a CCL3-dependent suppression of atheroprotective Tregs
Re-irradiation to the prostate using stereotactic body radiotherapy (SBRT) after initial definitive radiotherapy - A systematic review and meta-analysis of recent trials.
Get PDFBACKGROUND
There is increasing data on re-irradiation to the prostate using stereotactic body radiotherapy (SBRT) after definitive radiotherapy for prostate cancer, with increasing evidence on prostate re-irradiation using a C-arm LINAC or an MR LINAC in recent years. We therefore conducted this systematic review and meta-analysis on prostate re-irradiation including studies published from 2020 to 2023, to serve as an update on existing meta-analysis.
METHODS
We searched the PubMed and Embase databases in October 2023 with queries including combinations of "repeat", "radiotherapy", "prostate", "re-irradiation", "reirradiation", "re treatment", "SBRT", "retreatment". Publication date was set to be from 2020 to 2023. There was no limitation regarding language. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. After data extraction, heterogeneity testing was done by calculating the I2. A random effects model with a restricted maximum likelihood estimator was used to estimate the combined effect. Funnel plot asymmetry was assessed visually and using Egger's test to estimate the presence of publication and/or small study bias.
RESULTS
14 publications were included in the systematic review. The rates of acute ≥ grade 2 (G2) genitourinary (GU) and gastrointestinal (GI) toxicities reported in the included studies ranged from 0.0-30.0 % and 0.0-25.0 % respectively. For late ≥ G2 GU and GI toxicity, the ranges are 4.0-51.8 % and 0.0-25.0 %. The pooled rate of acute GU and GI toxicity ≥ G2 were 13 % (95 % CI: 7-18 %) and 2 % (95 % CI: 0-4 %). For late GU and GI toxicity ≥ G2 the pooled rates were 25 % (95 % CI: 14-35 %) and 5 % (95 % CI: 1-9 %). The pooled 2-year biochemical recurrence-free survival was 72 % (95 % CI: 64-92 %).
CONCLUSIONS
SBRT in the re-irradiation of radiorecurrent prostate cancer is safe and effective. Further prospective data are warranted
Association of Preoperative Copeptin Levels with Risk of All-Cause Mortality in a Prospective Cohort of Adult Cardiac Surgery Patients.
Get PDFWe aimed to investigate the association of preoperative copeptin, a new cardiovascular biomarker, with short- and long-term mortality in a cohort of adult patients undergoing cardiac surgery, including its potential as a prognostic marker for clinical outcome. Preoperative blood samples of the Bern Perioperative Biobank, a prospective cohort of adults undergoing cardiac surgery during 2019, were analyzed. The primary and secondary outcome measures were 30-day and 1-year all-cause mortality. Optimal copeptin thresholds were calculated with the Youden Index. Associations of copeptin levels with the two outcomes were examined with multivariable logistic regression models; their discriminatory capacity was assessed with the area under the receiver operating characteristic (AUROC). A total of 519 patients (78.4% male, median age 67 y (IQR: 60-73 y)) were included, with a median preoperative copeptin level of 7.6 pmol/L (IQR: 4.7-13.2 pmol/L). We identified an optimal threshold of 15.9 pmol/l (95%-CI: 7.7 to 46.5 pmol/L) for 30-day mortality and 15.9 pmol/L (95%-CI: 9.0 to 21.3 pmol/L) for 1-year all-cause mortality. Regression models featured an AUROC of 0.79 (95%-CI: 0.56 to 0.95) for adjusted log-transformed preoperative copeptin for 30-day mortality and an AUROC of 0.76 (95%-CI: 0.64 to 0.88) for 1-year mortality. In patients undergoing cardiac surgery, the baseline levels of copeptin emerged as a strong marker for 1-year all-cause death. Preoperative copeptin levels might possibly identify patients at risk for a complicated, long-term postoperative course, and therefore requiring a more rigorous postoperative observation and follow-up
Dose-response of daridorexant in insomnia disorder: An analysis of Phase 2 and 3 studies.
Get PDFOBJECTIVE
Daridorexant is approved for the treatment of insomnia at two dose levels (25 and 50 mg). Dose-efficacy and -safety response relationships were evaluated using Phase 2 and 3 data.
METHODS
Data (N = 2153) from one Phase 2 (daridorexant 5, 10, 25, 50 mg, placebo once daily for 1 month) and two Phase 3 studies (daridorexant 10 and 25 or 25 and 50 mg, placebo once daily for 3 months) were pooled. Dose-response analyses at 1 month of double-blind treatment were performed using a linear regression and a two-stage meta-analysis approach. Efficacy endpoints were polysomnography-derived wake after sleep onset, latency to persistent sleep (LPS), self-reported total sleep time and the Insomnia Daytime Symptoms and Impacts Questionnaire total score (only Phase 3 data for the latter). Safety endpoints were the incidence of total adverse events (AEs) and AEs corresponding to somnolence/fatigue.
RESULTS
Dose-responses for all efficacy endpoints were significant in the observed dose range (both statistical approaches, p 0.05). The incidence of AEs corresponding to somnolence/fatigue was low at all doses and, without linear assumption (two-stage meta-analysis) there was no dose-dependency (p = 0.369).
CONCLUSIONS
The data support the use of 50 mg as the preferred daridorexant dose in patients with insomnia disorder to provide the greatest opportunity for efficacy with no increased risk for AEs, including somnolence/fatigue, compared to lower doses
Tailored Basic Life Support Training for Specific Layperson Populations-A Scoping Review.
Get PDFBackground: Basic life support (BLS) is a life-saving link in the out-of-hospital cardiac arrest chain of survival. Most members of the public are capable of providing BLS but are more likely to do so confidently and effectively if they undertake BLS training. Lay members of the public comprise diverse and specific populations and may benefit from tailored BLS training. Data on this topic are scarce, and it is completely unknown if there are any benefits arising from tailored courses or for whom course adaptations should be developed. Methods: The primary objective of this scoping review was to identify and describe differences in patient, clinical, and educational outcomes when comparing tailored versus standard BLS courses for specific layperson populations. This review was undertaken as part of the continuous evidence evaluation process of the International Liaison Committee on Resuscitation. Results: A primary search identified 1307 studies and after title, abstract, and full-text screening, we included eight publications reporting on tailored courses for specific populations. There were no studies reporting direct comparisons between tailored and standardized training. Seven (88%) studies investigated courses tailored for individuals with a disability, and only one study covered another specific population group (refugees). Overall, the quality of evidence was low as the studies did not compare tailored vs. non-tailored approaches or consisted of observational or pre-post-designed investigations. Conclusions: Tailored BLS education for specific populations is likely feasible and can include such groups into the pool of potential bystander resuscitation providers. Research into comparing tailored vs. standard courses, their cost-to-benefit ratio, how to best adapt courses, and how to involve members of the respective communities should be conducted. Additionally, tailored courses for first responders with and without a duty to respond could be explored
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