Health issues and related health-seeking behaviours of snakebite patients after hospital discharge: A cohort study from rural Sri Lanka.

We aimed to assess the unresolved health issues experienced by a cohort of snakebite survivors and their health-seeking behaviours during the first three months after the snakebite. Patients from the Anuradhapura snakebite cohort admitted to the Teaching Hospital Anuradhapura, Sri Lanka, from July 2021 to June 2022 were recruited. Patients were interviewed over the telephone three weeks and three months post-bite to collect data on unresolved health problems post-discharge, patient's adherence to the review plan, newly experienced health issues, health-seeking behaviours and the effect on daily routine. Only snakebite survivors who could be contacted at both three weeks and three months were included. Of 710 eligible patients, 384 (54%) were contactable at both reviews. On discharge from the hospital, 248/384 (65%) had unresolved effects of the snakebite, including 224/384 (58%) who had local effects. The unresolved health problems were reported by patients bitten by H. hypnale (54%), D. russelii (23%), and unidentified snakes (19%). At three weeks and three months, 98/384 (26%) and 52/384 (14%) still had unresolved local effects of envenoming, respectively. Of 144/384 (38%) who were advised to attend review visits post-discharge, mostly to assess renal function, 118 (82%) complied. 112/384 (29%) patients reported self-motivated treatment seeking for unresolved effects of snakebite over the three months. Of them, 87 (78%) visited Sri Lankan indigenous medical practitioners. Patients missed a median of two working days (IQR: 2-4 days) post-discharge. 26 (6.7%) were unable to return to work at 3 weeks, and five patients at 3 months. In rural Sri Lanka, a significant number of viper bite patients leave hospital with mild persistent local effects, which commonly leads to them seeking further treatment. Despite that, almost all snakebite survivors had returned to work at three months post-bite.

A study predicting long-term survival capacity in postoperative advanced gastric cancer patients based on MAOA and subcutaneous muscle fat characteristics.

BACKGROUND: The prognosis of advanced gastric cancer (AGC) is relatively poor, and long-term survival depends on timely intervention. Currently, predicting survival rates remains a hot topic. The application of radiomics and immunohistochemistry-related techniques in cancer research is increasingly widespread. However, their integration for predicting long-term survival in AGC patients has not been fully explored. METHODS: We Collected 150 patients diagnosed with AGC at the Affiliated Zhongshan Hospital of Dalian University who underwent radical surgery between 2015 and 2019. Following strict inclusion and exclusion criteria, 90 patients were included in the analysis. We Collected postoperative pathological specimens from enrolled patients, analyzed the expression levels of MAOA using immunohistochemical techniques, and quantified these levels as the MAOAHScore. Obtained plain abdominal CT images from patients, delineated the region of interest at the L3 vertebral body level, and extracted radiomics features. Lasso Cox regression was used to select significant features to establish a radionics risk score, convert it into a categorical variable named risk, and use Cox regression to identify independent predictive factors for constructing a clinical prediction model. ROC, DCA, and calibration curves validated the model's performance. RESULTS: The enrolled patients had an average age of 65.71 years, including 70 males and 20 females. Multivariate Cox regression analysis revealed that risk (P = 0.001, HR = 3.303), MAOAHScore (P = 0.043, HR = 2.055), and TNM stage (P = 0.047, HR = 2.273) emerged as independent prognostic risk factors for 3-year overall survival (OS) and The Similar results were found in the analysis of 3-year disease-specific survival (DSS). The nomogram developed could predict 3-year OS and DSS rates, with areas under the ROC curve (AUCs) of 0.81 and 0.797, respectively. Joint calibration and decision curve analyses (DCA) confirmed the nomogram's good predictive performance and clinical utility. CONCLUSION: Integrating immunohistochemistry and muscle fat features provides a more accurate prediction of long-term survival in gastric cancer patients. This study offers new perspectives and methods for a deeper understanding of survival prediction in AGC.

Long-term outcomes among survivors of childhood osteosarcoma: A report from the Childhood Cancer Survivor Study (CCSS).

PURPOSE: Treatment strategies for osteosarcoma evolving between 1970 and 1999 improved 5-year survival and continue as standard of care today. This report evaluates the impact of these evolving therapies on long-term health outcomes. METHODS: Five-year survivors of childhood osteosarcoma in CCSS treated from 1970 to 1999 were evaluated for late (>5 years from diagnosis) mortality, chronic health conditions (CHCs), and health status using piecewise-exponential and logistical models. Comparisons were made between survivors and siblings without cancer, and among survivors examining historical and current standard chemotherapies (e.g., methotrexate/doxorubicin/cisplatin [MAP] vs. others), specific chemotherapy agents and surgical approaches (amputation vs. limb salvage [LS]). Models were evaluated adjusting for attained age, sex, race, ethnicity, and age at diagnosis. RESULTS: A total of 1257 survivors of osteosarcoma were followed on average for 24.4 years. Twenty-year all-cause late mortality was 13.3% (95% confidence interval [CI]: 11.7%-14.9%) overall and 11.7% (95% CI: 6.9%-16.5%) for the subset treated with MAP plus LS. Survivors were at higher risk of CHCs (rate ratio [RR] 3.7, 95% CI: 3.2-4.3) than the sibling cohort, most notably having more serious cardiac, musculoskeletal, and hearing CHCs. Within the survivor cohort, the risk of severe CHCs was twice as high with MAP versus no chemotherapy (RR 2.1, 95% CI: 1.3-3.4). Compared with primary amputation, serious musculoskeletal CHCs were higher after LS (RR 6.6, 95% CI: 3.6-13.4), without discernable differences in health status. CONCLUSION: Contemporary osteosarcoma therapy with MAP plus LS, while improving 5-year disease-free survival, continues to be associated with a high burden of late mortality, CHCs, and health status limitations.

Giant cell granuloma and neurofibroma in the mandible of a patient with neurofibromatosis type 1: a long-term follow-up case report with radiological and surgical aspects and a review of the literature.

BACKGROUND: Magnetic resonance imaging (MRI) of the brain is frequently performed on patients with neurofibromatosis type 1 (NF1), to detect and follow-up intracranial findings. In addition, NF1-related pathologies can appear in the jaws. This case study investigates if it is advantageous to assess the depicted parts of the jaws in the imaging of NF1 patients with intracranial findings, thereby detecting jaw pathologies in their initial stages. CASE PRESENTATION: We report on the 3-year management with clinical and radiological follow-ups of a central giant cell granuloma and a neurofibroma in the mandible of a patient with NF1 who underwent examinations with brain MRIs. A review of the mandible in the patient's MRIs disclosed lesions with clear differences in progression rates. CONCLUSION: NF1-related jaw pathologies may be detected in the early stages if the depicted parts of the jaws are included in the assessment of the imaging of NF1 patients with intracranial findings. This could impact the treatment of eventual pathologies before lesion progression and further damage to the vicinity.

Evidence for exercise-based interventions across 45 different long-term conditions: an overview of systematic reviews.

Background: Almost half of the global population face significant challenges from long-term conditions (LTCs) resulting in substantive health and socioeconomic burden. Exercise is a potentially key intervention in effective LTC management. Methods: In this overview of systematic reviews (SRs), we searched six electronic databases from January 2000 to October 2023 for SRs assessing health outcomes (mortality, hospitalisation, exercise capacity, disability, frailty, health-related quality of life (HRQoL), and physical activity) related to exercise-based interventions in adults (aged >18 years) diagnosed with one of 45 LTCs. Methodological quality was assessed using AMSTAR-2. International Prospective Resister of Systematic Reviews (PROSPERO) ID: CRD42022319214. Findings: Forty-two SRs plus three supplementary RCTs were included, providing 990 RCTs in 936,825 people across 39 LTCs. No evidence was identified for six LTCs. Predominant outcome domains were HRQoL (82% of SRs/RCTs) and exercise capacity (66%); whereas disability, mortality, physical activity, and hospitalisation were less frequently reported (≤25%). Evidence supporting exercise-based interventions was identified in 25 LTCs, was unclear for 13 LTCs, and for one LTC suggested no effect. No SRs considered multimorbidity in the delivery of exercise. Methodological quality varied: critically-low (33%), low (26%), moderate (26%), and high (12%). Interpretation: Exercise-based interventions improve HRQoL and exercise capacity across numerous LTCs. Key evidence gaps included limited mortality and hospitalisation data and consideration of multimorbidity impact on exercise-based interventions. Funding: This study was funded by the National Institute for Health and Care Research (NIHR; Personalised Exercise-Rehabilitation FOR people with Multiple long-term conditions (multimorbidity)-NIHR202020).

Long-term follow-up in pediatric intensive care-a narrative review.

Pediatric intensive care is a rapidly developing medical specialty and with evolving understanding of pediatric pathophysiology and advances in technology, most children in the developed world are now surviving to intensive care and hospital discharge. As mortality rates for children with critical illness continue to improve, increasing PICU survivorship is resulting in significant long-term consequences of intensive care in these vulnerable patients. Although impairments in physical, psychosocial and cognitive function are well documented in the literature and the importance of establishing follow-up programs is acknowledged, no standardized or evidence-based approach to long-term follow-up in the PICU exists. This narrative review explores pediatric post-intensive care syndrome and summarizes the multifactorial deficits and morbidity that can occur in these patients following recovery from critical illness and subsequent discharge from hospital. Current practices around long-term follow-up are explored with discussion focusing on gaps in research and understanding with suggested ways forward and future directions.

Models of care for pregnant women with multiple long-term conditions and the role of the midwife: A scoping review.

BACKGROUND: More women are experiencing pregnancy with two or more long-term health conditions such as hypertension, depression or HIV (MLTC). Care can be complex and include multiple teams, health professionals and services. The type and range of maternity care models for these women and the role of the midwife within such models is unknown. AIM: To provide an overview of the literature on models of care for pregnant, birthing, and postnatal women with MLTC and the role of the midwife. METHODS: We conducted a scoping review guided by the Joanna Briggs Institute scoping review methodology. Five databases MEDLINE, CINAHL Plus, PsycINFO, EMBASE and The Maternity and Infant Care database were searched from inception until August 2022. A total of 3458 titles and abstracts and 56 full text papers were screened independently by two researchers. Data was extracted from five papers and synthesised narratively. FINDINGS: Multidisciplinary care models are described or recommended in all five papers. Midwives have a varied and core role in the multidisciplinary care of women with MLTC. DISCUSSION: Models of care for those with MLTC covered part or all the maternity journey, primarily antenatal and postnatal care. A focus on delivering high-quality holistic care throughout the maternity journey, including postnatally is needed. There is a lack of evidence on how midwifery continuity of care models may impact experiences of care and outcomes for this group. CONCLUSION: There is a lack of empirical evidence on how best to provide midwifery and multi-disciplinary care for those with MLTC and a need for research to understand this. INCLUSIVITY STATEMENT: Our aims refer to 'pregnant, birthing, and postnatal women and birthing people with MLTC'. We acknowledge that not all those accessing maternity services will identify as a woman. We continually strive to ensure that our research and public involvement is inclusive and sensitive to the needs of everyone. Our search terms did not narrow to either women or birthing people specifically and used broad terms of pregnancy, antenatal, prenatal, childbirth and postnatal care. All included papers use the term woman or women throughout therefore, we have used this terminology when describing their findings. Where the term 'woman' is used this should be taken to include women and people who do not identify as women but are pregnant or have given birth. This builds on our Patient and Public Involvement and Engagement work which has highlighted the need to use inclusive language.

Long-Term Culture of Human Pluripotent Stem Cells in Xeno-Free Condition Using Functional Polymer Films.

Human pluripotent stem cells (hPSCs), encompassing human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), hold immense potential in regenerative medicine, offering new opportunities for personalized cell therapies. However, their clinical translation is hindered by the inevitable reliance on xenogeneic components in culture environments. This study addresses this challenge by engineering a fully synthetic, xeno-free culture substrate, whose surface composition is tailored systematically for xeno-free culture of hPSCs. A functional polymer surface, pGC2 (poly(glycidyl methacrylate-grafting-guanidine-co-carboxylic acrylate)), offers excellent cell-adhesive properties as well as non-cytotoxicity, enabling robust hESCs and hiPSCs growth while presenting cost-competitiveness and scalability over Matrigel. This investigation includes comprehensive evaluations of pGC2 across diverse experimental conditions, demonstrating its wide adaptability with various pluripotent stem cell lines, culture media, and substrates. Crucially, pGC2 supports long-term hESCs and hiPSCs expansion, up to ten passages without compromising their stemness and pluripotency. Notably, this study is the first to confirm an identical proteomic profile after ten passages of xeno-free cultivation of hiPSCs on a polymeric substrate compared to Matrigel. The innovative substrate bridges the gap between laboratory research and clinical translation, offering a new promising avenue for advancing stem cell-based therapies.

Clinically estimated signs of hyposalivation in older adult residents of long-term care.

OBJECTIVE: To assess whether the estimation of clinical signs of hyposalivation is applicable in recognising long-term care facility (LTCF) residents with poor oral health, and which individual characteristics are important in that respect. BACKGROUND: A common inconvenience among older adults, dry mouth, particularly hyposalivation, can cause many complications, such as greater susceptibility to root caries and oral infections, and it can lead to further deterioration of oral health. However, very little is known about the association of clinically assessed signs of hyposalivation with the oral health status of LTCF residents. METHODS: The study sample comprised 362 individuals (dentate n = 266, edentate n = 96) aged 65 or older. The examinations included a questionnaire and clinical oral examination. Participants were categorised into three groups based on clinically assessed oral dryness: normal salivation (n = 83, 22.9%), lower salivation (n = 182, 50.3%) and dry mouth (n = 97, 26.8%). The association between signs of dry mouth with aspects to oral health was evaluated and further tested with logistic regression analysis. RESULTS: The signs of oral dryness were observed among females, those with dementia, and those with longer stays in the current facility. Root caries (odds ratio, OR 1.3) and diagnosis of periodontitis (OR 4.1), together with several individual periodontal parameters, as well as having less than ten occluding pairs of natural teeth (OR 3.5) were associated with dry mouth. Edentate participants showed an increased likelihood of having dry mouth with advancing age, and lesions on the lips were associated with dry mouth with OR 3.0. CONCLUSION: Clinical estimation of signs of oral dryness can be a useful adjunct in evaluating the oral health status of dentate LTCF residents. Poor oral health was a frequent finding, especially among dentate LTCF residents with signs of dry mouth.

Instruments and Warning Signs for Identifying and Evaluating the Frequency of Adverse Events in Intermediate and Long-Term Care Centres: A Narrative Systematic Review.

INTRODUCTION: There is a lack of data about adverse events (AE) in intermediate and long-term care centers (ILCC). We aimed to synthesize the available scientific evidence on instruments used to identify and characterize AEs. We also aimed to describe the most common adverse events in ILCCs. MATERIAL AND METHODS: A narrative systematic review of the literature was conducted according to Prisma recommendations. The PubMed database was searched for articles published between 2000 and 2021. Two reviewers independently screened and reviewed the studies through blind and independent review. We evaluated bias risk with Cochrane's risk of bias tool. Disagreements were resolved by consensus. Discrepancies that were not resolved by discussion were discussed with a third reviewer. Descriptive data was extracted and qualitative content analysis was performed. RESULTS: We found 2191 articles. Based on the inclusion and exclusion criteria, 272 papers were screened by title and abstract, and 66 studies were selected for full review. The instruments used to identify AEs were mostly tools to identify specific AEs or risks of AEs (94%), the remaining 6% were multidimensional. The most frequent categories detected medication-related AEs (n=26, 40%); falls (n=7, 11%); psychiatric AEs (6.9%); malnutrition (4.6%), and infections (4.6%). The studies that used multidimensional tools refer to frailty, dependency, or lack of energy as predictors of AEs. However, they do not take into account the importance of detecting AEs. We found 2-11 adverse drug events (ADE) per resident/month. We found a prevalence of falls (12.5%), delirium (9.6-89%), pain (68%), malnutrition (2-83%), and pressure ulcers (3-30%). Urinary tract infections, lower respiratory tract infections, skin and soft tissue infections, and gastroenteritis were the most common infections in this setting. Transitions between different care settings (from hospitals to ILCC and vice versa) expose AE risk. CONCLUSION: There are many instruments to detect AEs in ILCC, and most have a specific approach. Adverse events affect a significant proportion of patients in ILCC, the nurse-sensitive outcomes, nosocomial infections, and adverse drug events are among the most common. The systematic review was registered with Prospero, ID: CRD42022348168.

Impact of post-hepatectomy biliary leaks on long-term survival in different liver tumors: A single institute experience.

Backgrounds/Aims: A postoperative biliary leak is one of the most morbid complications occurring after a liver resection, the long-term impact of which remains unknown. Methods: Retrospective analysis of consecutive liver resections performed from 1 January 2011 to 31 December 2021. Primary endpoint of disease-free survival (DFS) was compared between patients with and without a bile leak, stratifying for tumor type. Survival curves were plotted using Kaplan-Meier estimates, and differences between them were analyzed using the log-rank test. Results: In toto, 862 patients were analyzed, and included 306 (35.5%) hepatocellular carcinomas, 212 (24.6%) metastatic colorectal cancers, and 111 (12.9%) cholangiocarcinomas (69 intrahepatic cholangiocarcinomas, 42 hilar cholangiocarcinomas). Occurrence of a bile leak was associated with significantly poorer DFS only in patients with cholangiocarcinoma (median DFS 9.9 months vs. 24.9 months, p = 0.013), and further analysis was restricted to this cohort. A Cox regression performed for factors associated with DFS detriment in patients with cholangiocarcinoma showed that apart from node positivity (hazard ratio [HR]: 2.482, p = 0.033) and margin positivity (HR: 2.65, p = 0.021), development of a bile leak was independently associated with worsening DFS on both univariate and multiple regression analyses (HR: 1.896, p = 0.033). Conclusions: Post-hepatectomy biliary leaks are associated with significantly poorer DFS only in patients with cholangiocarcinoma, but not in patients with hepatocellular carcinoma or metastatic colorectal cancer. Methods to mitigate this survival detriment need to be explored.

Long-term stability and bactericidal properties of galenic formulations of Cannabis sativa oils.

The long-term stability in real and accelerated time for galenic oils based on full-spectrum cannabis has been studied, using sesame oil as a dilutant. Sesame oil is one of the most used vehicles in the cannabis pharmaceutical industry due to the costs and increased oral bioavailability of cannabinoids. The real-time assays conducted at 25 °C over twelve months demonstrated high stability and showed no significant changes in the composition of cannabinoids, total polyphenols, flavonoids, or antioxidant capacity. In these studies, it was observed that there was no development of microorganisms compromising the stability of the oils over a year. The three oil varieties exhibited a high bactericidal capacity against E. coli, S. aureus, and P. larvae.

Has Active Surveillance for Prostate Cancer Become Safer? Lessons Learned from a Global Clinical Registry.

BACKGROUND AND OBJECTIVE: Active surveillance (AS) has evolved into a widely applied treatment strategy for many men around the world with low-risk prostate cancer (or in selected cases intermediate-risk disease). Here, we report on the safety and acceptability of AS, and treatment outcomes for low- and intermediate-risk tumours over time in 14 623 men with follow-up of over 6 yr. METHODS: Clinical data from 26 999 men on AS from 25 cohorts in 15 countries have been collected in an international database from 2000 onwards. KEY FINDINGS AND LIMITATIONS: Across our predefined four time periods of 4 yr each (covering the period 2000-2016), there was no significant change in overall survival (OS). However, metastasis-free survival (MFS) rates have improved since the second period and were excellent (>99%). Treatment-free survival rates for earlier periods showed a slightly more rapid shift to radical treatment. Over time, there was a constant proportion of 5% of men for whom anxiety was registered as the reason for treatment alteration. There was, however, also a subset of 10-15% in whom treatment was changed, for which no apparent reason was available. In a subset of men (10-15%), tumour progression was the trigger for treatment. In men who opted for radical treatment, surgery was the most common treatment modality. In those men who underwent radical treatment, 90% were free from biochemical recurrence at 5 yr after treatment. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study confirms that AS was a safe management option over the full duration in this large multicentre cohort with long-term follow-up, given the 84.1% OS and 99.4% MFS at 10 yr. The probability of treatment at 10 yr was 20% in men with initial low-risk tumours and 31% in men with intermediate-risk tumours. New diagnostic modalities may improve the acceptability of follow-up using individual risk assessments, while safely broadening the use of AS in higher-risk tumours. PATIENT SUMMARY: Active surveillance (AS) has evolved into a widely applied treatment strategy for many men with prostate cancer around the world. In this report, we show the long-term safety of following AS for men with low- and intermediate-risk prostate cancer. Our study confirms AS as a safe management option for low- and intermediate-risk prostate cancer. New diagnostic modalities may improve the acceptability of follow-up using individual risk assessments, while safely broadening the use of AS in higher-risk tumours.

Long-term evacuation and obesity: a 12-year follow-up comparative study of residents inside and outside Katsurao Village after the Fukushima nuclear disaster.

Objective: Evacuation, owing to a disaster, impacts various aspects of an individual's life, including health status. This study aimed to determine the prevalence of obesity among residents of Katsurao Village, Fukushima Prefecture, after the evacuation order due to the Fukushima nuclear disaster in 2011 was lifted in 2016 and to compare the prevalence of obesity by place of residence (inside or outside the village). Methods: The number of examinees, sex, age, place of residence, body mass index (BMI), exercise habits, smoking habits, drinking habits, and dietary status were extracted from the results of health checkups since 2016. We compared the BMI of the indigenes of Katsurao Village by place of residence (inside or outside the village) over time. Results: Although 7 years have passed since 2016, ~70% of the registered residents of Katsurao Village still live outside the village. The obesity rates have consistently been higher among people living outside the village compared to those inside, and the place of residence was the only factor significantly associated with obesity. Conclusion: The findings of this study suggest early intervention is necessary to prevent health risks associated with disaster evacuation if the evacuation period is prolonged.

A risk-based approach to the analysis of potential climate change effects on fish communities associated to Posidonia oceanica in the Mediterranean.

The Mediterranean is recognized as a climate change hotspot, with ongoing warming anticipated to impact its habitats and their associated fish fauna. Among these habitats, the seagrass Posidonia oceanica stands out as a foundational species, critical for the stability of coastal fish communities. However, our understanding of climate change consequences on P. oceanica associated fish fauna to date remains limited in part due to a lack of long-term data. This study aimed to highlight potential climate change risks to fish species associated with Posidonia, integrating data on species' thermal envelopes with their habitat and depth preferences into a climate change risk index. Specifically, 9 species, including three pipefish and several wrasse species of the genus Symphodus, emerged as being at higher potential risk from climatic change. A historical time series from Palma Bay (Balearic Islands, Spain), spanning 45 years and providing clear evidence of warming, was employed to evaluate trends in species abundance and occurrence in relation to their relative climate risk score. While certain high-risk species like Symphodus cinereus and Diplodus annularis showed an increase in abundance over time, others, such as the pipefish Syngnathus acus, Syngnathus typhle and Nerophis maculatus experienced declines. The absence of observed declines in some high-risk species could be attributed to several factors, such as acclimation, adaptation, or unmet response thresholds. However, this does not rule out the potential for future changes in these species. Factors such as increased nutrient influx due to growing human populations and changes in fishing regulations may also have contributed to the observed trends. These findings underscore the intricate interplay of environmental and anthropogenic factors and accentuate the pressing need for sustained, long-term data acquisition to fathom the implications of climate change on this highly important marine ecosystem.

A 10-Year Longitudinal Study of Brain Cortical Thickness in People with First-Episode Psychosis Using Normative Models.

BACKGROUND: Clinical forecasting models have potential to optimize treatment and improve outcomes in psychosis, but predicting long-term outcomes is challenging and long-term follow-up data are scarce. In this 10-year longitudinal study, we aimed to characterize the temporal evolution of cortical correlates of psychosis and their associations with symptoms. DESIGN: Structural magnetic resonance imaging (MRI) from people with first-episode psychosis and controls (n = 79 and 218) were obtained at enrollment, after 12 months (n = 67 and 197), and 10 years (n = 23 and 77), within the Thematically Organized Psychosis (TOP) study. Normative models for cortical thickness estimated on public MRI datasets (n = 42 983) were applied to TOP data to obtain deviation scores for each region and timepoint. Positive and Negative Syndrome Scale (PANSS) scores were acquired at each timepoint along with registry data. Linear mixed effects models assessed effects of diagnosis, time, and their interactions on cortical deviations plus associations with symptoms. RESULTS: LMEs revealed conditional main effects of diagnosis and time × diagnosis interactions in a distributed cortical network, where negative deviations in patients attenuate over time. In patients, symptoms also attenuate over time. LMEs revealed effects of anterior cingulate on PANSS total, and insular and orbitofrontal regions on PANSS negative scores. CONCLUSIONS: This long-term longitudinal study revealed a distributed pattern of cortical differences which attenuated over time together with a reduction in symptoms. These findings are not in line with a simple neurodegenerative account of schizophrenia, and deviations from normative models offer a promising avenue to develop biomarkers to track clinical trajectories over time.

Slow wave sleep is associated with forgetting in patients with temporal lobe epilepsy.

While time spent in slow wave sleep (SWS) after learning promotes memory consolidation in the healthy brain, it is unclear if the same benefit is obtained in patients with temporal lobe epilepsy (TLE). Interictal epileptiform discharges (IEDs) are potentiated during SWS and thus may disrupt memory consolidation processes thought to depend on hippocampal-neocortical interactions. Here, we explored the relationship between SWS, IEDs, and overnight forgetting in patients with TLE. Nineteen patients with TLE studied object-scene pairs and memory was tested across a day of wakefulness (6 hrs) and across a night of sleep (16 hrs) while undergoing continuous scalp EEG monitoring. We found that time spent in SWS after learning was related to greater forgetting overnight. Longer duration in SWS and number of IEDs were each associated with greater forgetting, although the number of IEDs did not mediate the relationship between SWS and memory. Further research, particularly with intracranial recordings, is required to identify the mechanisms by which SWS and IEDs can be pathological to sleep-dependent memory consolidation in patients with TLE.

Uncertainty In Long-term Relative Effectiveness Of Medicines In Health Technology Assessment: Comparing Assessments Of Medicines For Spinal Muscular Atrophy, Cystic Fibrosis, And Hypercholesterolemia.

OBJECTIVES: Uncertainty regarding the long-term relative effectiveness is an important factor in health technology assessment (HTA) of medicines. This study investigated how different HTA bodies address this uncertainty in their assessments. METHODS: 49 HTA reports from six national HTA bodies, assessing nine medicines for spinal muscular atrophy, cystic fibrosis, and hypercholesterolemia, were included. In these reports, 81 relative effectiveness assessments (REAs) and 45 cost-effectiveness assessments (CEAs) were performed on an indication level. We collected information on included trials, assessment outcomes, uncertainty regarding the long-term effectiveness, proposed managed entry agreements (MEAs), and reassessments. RESULTS: Uncertainty regarding the long-term effectiveness was an important consideration in almost all CEAs (91%) and three quarters of REAs (74%), despite differences in methodologies between HTA bodies. There were considerable differences in the amount and type of long-term effectiveness data included by HTA bodies due to timing and inclusion criteria. In total 23 MEAs were proposed of which 14 were linked to uncertainty regarding the long-term effectiveness. Additionally, 13 reassessments were performed of which four led to an increase in patient access because of more available long-term effectiveness data. CONCLUSIONS: Uncertainty regarding the long-term effectiveness is an important challenge for HTA bodies. There are large differences in the acceptance of evidence between HTA bodies which leads to heterogeneity in the inclusion of available long-term effectiveness data for decision-making. In cases with large uncertainty regarding the long-term effectiveness, outcome-based agreements and reassessments are used by HTA bodies, but differently between HTA bodies and indications.

Dynamics of Noctiluca scintillans blooms: A 20-year study in Jangmok Bay, Korea.

This 20-year study (2001-2020) conducted in Jangmok Bay, Korea, assessed the intricate relationships between environmental factors and Noctiluca scintillans blooms. Granger causality tests and PCA analysis were used to assess the impact of sea surface temperature (SST), salinity, dissolved oxygen (DO) concentration, wind patterns, rainfall, and chlorophyll-a (Chl-a) concentration on bloom dynamics. The results revealed significant, albeit delayed, influences of these variables on bloom occurrence, with SST exhibiting a notable 2-month lag and salinity a 1-month lag in their impact. Additionally, the analysis highlighted the significant roles of phosphate, ammonium, and silicate, which influenced N. scintillans blooms with lags of 1 to 3 months. The PCA demonstrates how SST and wind speed during spring and summer, along with wind direction and salinity in winter, significantly impact N. scintillans blooms. We noted not only an increase in large-scale N. scintillans blooms but also a cyclical pattern of occurrence every 3 years. These findings underscore the synergistic effects of environmental factors, highlighting the complex interplay between SST, salinity, DO concentration, and weather conditions to influence bloom patterns. This research enhances our understanding of harmful algal blooms (HABs), emphasizing the importance of a comprehensive approach that considers multiple interconnected environmental variables for predicting and managing N. scintillans blooms.

Late Adverse Effects after Treatment for Childhood Acute Leukemia.

The aim of this review is to raise awareness and knowledge among healthcare professionals and policymakers about late adverse effects in survivors of childhood leukemia. With contemporary treatment, over 90% of children with acute lymphoblastic leukemia (ALL) and over 60% with acute myeloid leukemia (AML) are cured. Large cohort studies demonstrate that 20% of ALL and most AML survivors have at least one chronic health condition by 20-25 years after diagnosis. These are life-changing or threatening in some survivors and contribute to increased premature mortality. We describe the frequency, causes, clinical features, and natural history of the most frequent and severe late adverse effects in childhood leukemia survivors, including subsequent malignant neoplasms, metabolic toxicity, gonadotoxicity and impaired fertility, endocrinopathy and growth disturbances, bone toxicity, central and peripheral neurotoxicity, cardiotoxicity, psychosocial late effects, accelerated ageing and late mortality. The wide range of late effects in survivors of haemopoietic stem cell transplant is highlighted. Recent developments informing the approach to long-term survivorship care are discussed, including electronic personalized patient-specific treatment summaries and care plans such as the Survivor Passport (SurPass), surveillance guidelines and models of care. The importance of ongoing vigilance is stressed given the increasing use of novel targeted drugs with limited experience of long-term outcomes. CONCLUSION: It is vital to raise awareness of the existence and severity of late effects of childhood leukemia therapy among parents, patients, health professionals, and policymakers. Structured long-term surveillance recommendations are necessary to standardize follow-up care.