Pattern of strength recovery differences Exist in Adolescent athletes after anterior cruciate ligament reconstruction when using quadriceps versus Hamstring tendon autograft.

OBJECTIVES: To compare the timeline for post-operative quadriceps and hamstrings strength recovery following anterior cruciate ligament reconstruction (ACLR) using either a quadriceps tendon (QT) or hamstring tendon (HT) autograft. METHODS: Patients (≤18 years) who underwent ACLR using autograft QT or HT were included. Isokinetic strength was extracted at 3, 6, and 12 months post-operatively. Effects of time and graft type on quadriceps or hamstring limb symmetry index (qLSI/hLSI) was assessed with two-way repeated measures ANOVA. Between group differences at each time point were assessed with unpaired t-tests. Chi-square and Kaplan-Meir analysis analyzed the proportions of subjects able to achieve ≥90% LSI. RESULTS: A total of 75 subjects (QT n = 38 HT n = 37,15.8 years) were included. There were significant differences in qLSI, with greater symmetry within the HT group at all time points. A higher proportion of subjects with HT grafts were able to achieve ≥90% qLSI within 12 months of surgery (81% vs 45%, p = 0.001). CONCLUSION: Compared to those with HT autografts, adolescents with QT autografts demonstrate a prolonged timeline for quadriceps recovery. While mean strength values above 90% are achieved, a significantly lower percentage of QT patients are able to achieve 90% qLSI by 12 months post-op.

Sustained insulin treatment restoring metabolic status, body weight, and cognition in an anorexia nervosa-like animal model in mice.

INTRODUCTION: Anorexia Nervosa (AN) is a psycho-socio-biological disease characterized by severe weight loss as result of dieting and hyperactivity. Effective treatments are scarce, despite its significant prevalence and mortality. AN patients show lower basal insulin levels and increased metabolic clearance, leading to weight loss, cognitive deficits, and hormonal imbalances. Low-dose polymer insulin could potentially reverse these effects by restoring brain function, reducing fear of weight gain, encouraging food intake, and restoring fat depots. This study evaluates an insulin delivery system designed for sustained release and AN treatment. METHODS: AN-like model was established through dietary restriction (DR). On days 1-25, mice were on DR, and on days 26-31 they were on ad libitum regimen. An insulin-loaded delivery system was administered subcutaneously (1% w/w insulin). The impact of insulin treatment on gene expression in the hippocampus (cognition, regulation of stress, neurogenesis) and hypothalamus (eating behavior, mood) was assessed. Behavioral assays were conducted to evaluate motor activity and cognitive function. RESULTS: The delivery system demonstrated sustained insulin release, maintaining therapeutic plasma levels. Diet restriction mice treated with the insulin delivery system showed body weight restoration. Gene expression analysis revealed enhanced expression of CB1 and CB2 genes associated with improved eating behavior and cognition, while POMC expression was reduced. Insulin-polymer treatment restored cognitive function and decreased hyperactivity in the AN-like model. CONCLUSION: The PSA-RA-based insulin delivery system effectively restores metabolic balance, body weight, and cognitive function in the AN model. Its ability to steadily release insulin makes it a promising candidate for AN treatment."

Deploying a national clinical text processing infrastructure.

OBJECTIVES: Clinical text processing offers a promising avenue for improving multiple aspects of healthcare, though operational deployment remains a substantial challenge. This case report details the implementation of a national clinical text processing infrastructure within the Department of Veterans Affairs (VA). METHODS: Two foundational use cases, cancer case management and suicide and overdose prevention, illustrate how text processing can be practically implemented at scale for diverse clinical applications using shared services. RESULTS: Insights from these use cases underline both commonalities and differences, providing a replicable model for future text processing applications. CONCLUSIONS: This project enables more efficient initiation, testing, and future deployment of text processing models, streamlining the integration of these use cases into healthcare operations. This project implementation is in a large integrated health delivery system in the United States, but we expect the lessons learned to be relevant to any health system, including smaller local and regional health systems in the United States.

Crisis no epilépticas psicógenas: Semiología en una cohorte de pacientes de una unidad de epilepsia de referencia nacional en Lima, Perú / Non-epileptic psychogenic seizures: semiology in a patient's cohort from a national reference epilepsy unit in Lima, Peru

RESUMEN Objetivo : Describir la semiología de crisis no epilépticas psicógenas (CNEP) en pacientes diagnosticados mediante videoelectroencefalograma (VEEG) en un centro nacional de epilepsia. Material y métodos : Estudio observacional, descriptivo y retrospectivo que incluyó a pacientes mayores de 14 años, ingresados a monitoreo de telemetría en el Hospital Nacional Edgardo Rebagliati Martins en Lima, Perú, entre el 1 de enero de 2017 y el 31 de diciembre de 2022, y definitivamente diagnosticados con CNEP mediante VEEG. Resultados : La mayoría de los 26 pacientes (20 mujeres y 6 varones) presentó pérdida de postura con caída (92 %), así como una instauración gradual (88 %) y cursaron con algún grado de alteración de conciencia o responsividad durante el evento (73 %). Los signos motores más prevalentes fueron movimientos asincrónicos de tronco y/o extremidades (73 %), fluctuación en la actividad motora (73 %), temblor global o en extremidades (54 %) y cierre palpebral forzado (50 %). Las manifestaciones clínicas no motoras fueron, en su mayoría, síntomas subjetivos (34 %). La mayoría (73 %) presentó CNEP motoras (73 %), en comparación con otras manifestaciones no motoras (12 %) y mixtas (15 %). Conclusiones : Los eventos clínicos descritos fueron de larga duración e instauración gradual y mostraron alteraciones de conciencia/responsividad. Los signos clínicos motores más frecuentes fueron movimientos asincrónicos de tronco y/o extremidades, fluctuación motora, temblor y cierre palpebral forzado. Los hallazgos no motores fueron, en su mayoría, síntomas subjetivos. La mayoría de los pacientes presentaron CNEP motoras.

ABSTRACT Objective : To describe the semiology of Psychogenic Non-Epileptic Seizures (PNES) in patients diagnosed by video-electroencephalogram (VEEG) in a national epilepsy center. Methods : An observational, descriptive, and retrospective study of patients older than 14 years, admitted for telemetry monitoring at the Epilepsy Unit of the National Hospital Edgardo Rebagliati Martins in Lima, Peru, between January 1st, 2017, and December 31, 2022. A definitive diagnosis of PNES was reached through VEEG. Results : Twenty of 26 studied patients were female and 6 male. Most patients experienced loss of posture with falls (92%), gradual onset (88%), some degree of altered consciousness or responsiveness during the event (73%). The most prevalent motor signs included asynchronous movements of the trunk and/or extremities (73%), fluctuation in motor activity (73%), global or limb tremors (54%), and forced eyelid closure (50%). Non-motor signs were predominantly subjective symptoms (34%). Most of the patients presented motor PNES (73%) compared to non-motor (12%) and mixed (15%). Conclusions : The described clinical events had a prolonged duration, gradual onset, and altered levels of consciousness/responsiveness. The most frequent clinical motor signs were asynchronous movements of the trunk and/or extremities, motor fluctuation, tremors, and forced eyelid closure. Non-motor findings were, primarily, subjective symptoms. Most of the patients presented motor PNES.

Salivary Epigenetic Measures of Body Mass Index and Social Determinants of Health Across Childhood and Adolescence.

Importance: Children who are socioeconomically disadvantaged are at increased risk for high body mass index (BMI) and multiple diseases in adulthood. The developmental origins of health and disease hypothesis proposes that early life conditions affect later-life health in a manner that is only partially modifiable by later-life experiences. Objective: To examine whether epigenetic measures of BMI developed in adults are valid biomarkers of childhood BMI and if they are sensitive to early life social determinants of health. Design, Setting, and Participants: This population-based study of over 3200 children and adolescents aged 8 to 18 years included data from 2 demographically diverse US pediatric cohort studies that combine longitudinal and twin study designs. Analyses were conducted from 2021 to 2022. Exposures: Socioeconomic status, marginalized groups. Main Outcome and Measure: Salivary epigenetic BMI, BMI. Analyses were conducted to validate the use of saliva epigenetic BMI as a potential biomarker of child BMI and to examine associations between epigenetic BMI and social determinants of health. Results: Salivary epigenetic BMI was calculated from 2 cohorts: (1) 1183 individuals aged 8 to 18 years (609 female [51%]; mean age, 13.4 years) from the Texas Twin Project and (2) 2020 children (1011 female [50%]) measured at 9 years of age and 15 years of age from the Future of Families and Child Well-Being Study. Salivary epigenetic BMI was associated with children's BMI (r = 0.36; 95% CI, 0.31-0.40 to r = 0.50; 95% CI, 0.42-0.59). Longitudinal analysis found that epigenetic BMI was highly stable across adolescence but remained both a leading and lagging indicator of BMI change. Twin analyses showed that epigenetic BMI captured differences in BMI between monozygotic twins. Moreover, children from more disadvantaged socioeconomic status (b = -0.13 to -0.15 across samples) and marginalized racial and ethnic groups (b = 0.08-0.34 across samples) had higher epigenetic BMI, even when controlling for concurrent BMI, pubertal development, and tobacco exposure. Socioeconomic status at birth relative to concurrent socioeconomic status best predicted epigenetic BMI in childhood and adolescence (b = -0.15; 95% CI, -0.20 to -0.09). Conclusion and Relevance: This study demonstrated that epigenetic measures of BMI calculated from pediatric saliva samples were valid biomarkers of childhood BMI and may be associated with early-life social inequalities. The findings are in line with the hypothesis that early-life conditions are especially important factors in epigenetic regulation of later-life health. Research showing that health later in life is linked to early-life conditions has important implications for the development of early-life interventions that could significantly extend healthy life span.

The Association of Kidney Function and Inflammatory Biomarkers with Epithelial Ovarian Cancer Risk.

BACKGROUND: One of the mechanisms of ovarian tumorigenesis is through inflammation. Kidney dysfunction is associated with increased inflammation; thus, we assessed its relationship with ovarian cancer risk. METHODS: In prospectively collected samples, we evaluated the association of kidney function markers and C-reactive protein (CRP) with ovarian cancer risk in the UK Biobank. We used multivariable-adjusted Cox proportional hazards models to evaluate quartiles of serum and urine markers with ovarian cancer risk overall and by histology. We assessed effect modification by CRP (≤3.0, >3.0 mg/L). RESULTS: Among 232,908 women (1,110 ovarian cancer cases diagnosed from 2006-2020), we observed no association between estimated glomerular filtration rate and ovarian cancer risk (Q4 vs. Q1: HR, 1.00; 95% confidence intervals, 0.83-1.22). Potassium was associated with endometrioid (Q4 vs. Q1: 0.33, 0.11-0.98) and clear cell (4.74, 1.39-16.16) tumors. Poor kidney function was associated with a nonsignificant increase in ovarian cancer risk among women with CRP>3.0 mg/L (e.g., uric acid Q4 vs. Q1; 1.23, 0.81-1.86), but not CRP≤3.0 mg/L (0.83, 0.66-1.05). Other associations did not vary across CRP categories. CONCLUSIONS: Kidney function was not clearly associated with ovarian cancer risk. Larger studies are needed to evaluate possible histology specific associations. Given the suggestive trend for increased ovarian cancer risk in women with poor kidney function and high CRP, future work is needed, particularly in populations with a high prevalence of inflammatory conditions. IMPACT: This study provided the first evaluation of markers of kidney function in relation to ovarian cancer risk.

Optimizing metaproteomics database construction: lessons from a study of the vaginal microbiome.

Metaproteomics, a method for untargeted, high-throughput identification of proteins in complex samples, provides functional information about microbial communities and can tie functions to specific taxa. Metaproteomics often generates less data than other omics techniques, but analytical workflows can be improved to increase usable data in metaproteomic outputs. Identification of peptides in the metaproteomic analysis is performed by comparing mass spectra of sample peptides to a reference database of protein sequences. Although these protein databases are an integral part of the metaproteomic analysis, few studies have explored how database composition impacts peptide identification. Here, we used cervicovaginal lavage (CVL) samples from a study of bacterial vaginosis (BV) to compare the performance of databases built using six different strategies. We evaluated broad versus sample-matched databases, as well as databases populated with proteins translated from metagenomic sequencing of the same samples versus sequences from public repositories. Smaller sample-matched databases performed significantly better, driven by the statistical constraints on large databases. Additionally, large databases attributed up to 34% of significant bacterial hits to taxa absent from the sample, as determined orthogonally by 16S rRNA gene sequencing. We also tested a set of hybrid databases which included bacterial proteins from NCBI RefSeq and translated bacterial genes from the samples. These hybrid databases had the best overall performance, identifying 1,068 unique human and 1,418 unique bacterial proteins, ~30% more than a database populated with proteins from typical vaginal bacteria and fungi. Our findings can help guide the optimal identification of proteins while maintaining statistical power for reaching biological conclusions. IMPORTANCE Metaproteomic analysis can provide valuable insights into the functions of microbial and cellular communities by identifying a broad, untargeted set of proteins. The databases used in the analysis of metaproteomic data influence results by defining what proteins can be identified. Moreover, the size of the database impacts the number of identifications after accounting for false discovery rates (FDRs). Few studies have tested the performance of different strategies for building a protein database to identify proteins from metaproteomic data and those that have largely focused on highly diverse microbial communities. We tested a range of databases on CVL samples and found that a hybrid sample-matched approach, using publicly available proteins from organisms present in the samples, as well as proteins translated from metagenomic sequencing of the samples, had the best performance. However, our results also suggest that public sequence databases will continue to improve as more bacterial genomes are published.

Multivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders.

Genetic liability to substance use disorders can be parsed into loci that confer general or substance-specific addiction risk. We report a multivariate genome-wide association meta-analysis that disaggregates general and substance-specific loci for published summary statistics of problematic alcohol use, problematic tobacco use, cannabis use disorder, and opioid use disorder in a sample of 1,025,550 individuals of European descent and 92,630 individuals of African descent. Nineteen independent SNPs were genome-wide significant (P < 5e-8) for the general addiction risk factor (addiction-rf), which showed high polygenicity. Across ancestries, PDE4B was significant (among other genes), suggesting dopamine regulation as a cross-substance vulnerability. An addiction-rf polygenic risk score was associated with substance use disorders, psychopathologies, somatic conditions, and environments associated with the onset of addictions. Substance-specific loci (9 for alcohol, 32 for tobacco, 5 for cannabis, 1 for opioids) included metabolic and receptor genes. These findings provide insight into genetic risk loci for substance use disorders that could be leveraged as treatment targets.

The last days: The medical response of United States and allied military teams during the Afghanistan Exodus.

OBJECTIVES: The objective of this study is to describe the United States and allied military medical response during the withdrawal from Afghanistan. BACKGROUND: The military withdrawal from Afghanistan concluded with severe hostilities resulting in numerous civilian and military casualties. The clinical care provided by coalition forces capitalized on decades of lessons learned and enabled unprecedented accomplishments. METHODS: In this retrospective, observational analysis, casualty numbers, and operative information was collected and reported from military medical assets in Kabul, Afghanistan. The continuum of medical care and the trauma system, from the point of injury back to the United States was captured and described. RESULTS: Prior to a large suicide bombing resulting in a mass casualty event, the international medical teams managed distinct 45 trauma incidents involving nearly 200 combat and non-combat civilian and military patients over the preceding 3 months. Military medical personnel treated 63 casualties from the Kabul airport suicide attack and performed 15 trauma operations. US air transport teams evacuated 37 patients within 15 hours of the attack. CONCLUSION: Lessons learned from the last 20 years of combat casualty care were successfully implemented during the culmination of the Afghanistan conflict. Ultimately, the effort, teamwork, and system adaptability exemplify not only the attitudes and character of service members who provide modern combat casualty care but also the paramount importance of the battlefield learning health care system. A continued posture to maintain military surgical preparedness in unique environments remain crucial as the US military prepares for the future.Retrospective observational analysis. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level V.

Corrigendum: Phylogenomics of the Andean tetraploid clade of the American Amaryllidaceae (subfamily Amaryllidoideae): Unlocking a polyploid generic radiation abetted by continental geodynamics.

[This corrects the article DOI: 10.3389/fpls.2020.582422.].

Efficacy and Safety of Dual Targeted Therapy for Partially or Non-responsive Inflammatory Bowel Disease: A Systematic Review of the Literature.

BACKGROUND: Dual targeted therapy (DTT) has emerged as an attractive therapeutic option for select patients with active inflammatory bowel disease (IBD) who are unable to achieve remission with biologic or small molecule monotherapy. We conducted a systematic review of specific DTT combinations in patients with IBD. METHODS: We conducted a systematic search of MEDLINE, EMBASE, Scopus, CINAHL Complete, Web of Science Core Collection, and Cochrane Library to identify articles related to the use of DTT for the treatment of Crohn Disease (CD) or ulcerative colitis (UC) published before February 2021. RESULTS: Twenty-nine studies were identified comprising 288 patients started on DTT for partially or non-responsive IBD. We identified 14 studies with 113 patients receiving anti-tumor necrosis factor (TNF) and anti-integrin therapies (i.e., vedolizumab and natalizumab), 12 studies with 55 patients receiving vedolizumab and ustekinumab, nine studies with 68 patients receiving vedolizumab and tofacitinib, five studies with 24 patients receiving anti-TNF therapy and tofacitinib, six studies with 18 patients receiving anti-TNF therapy and ustekinumab, and three studies with 13 patients receiving ustekinumab and tofacitinib. CONCLUSION: DTT is a promising approach to improve IBD treatment for patients with incomplete responses to targeted monotherapy. Larger prospective clinical studies are needed to confirm these findings as is additional predictive modeling to identify the patient subgroups most likely to require and benefit from this approach.

Measuring the long arm of childhood in real-time: Epigenetic predictors of BMI and social determinants of health across childhood and adolescence.

Children who are socioeconomically disadvantaged are at increased risk for high body mass index (BMI) and multiple diseases in adulthood. The developmental origins of health and disease hypothesis proposes that early life conditions affect later-life health in a manner that is only partially modifiable by later-life experiences. Epigenetic mechanisms may regulate the influence of early life conditions on later life health. Recent epigenetic studies of adult blood samples have identified DNA-methylation sites associated with higher BMI and worse health (epigenetic-BMI). Here, we used longitudinal and twin study designs to examine whether epigenetic predictors of BMI developed in adults are valid biomarkers of child BMI and are sensitive to early life social determinants of health. Salivary epigenetic-BMI was calculated from two samples: (1) N=1,183 8-to-19-year-olds (609 female, mean age=13.4) from the Texas Twin Project (TTP), and (2) N=2,020 children (1,011 female) measured at 9 and 15 years from the Future of Families and Child Well-Being Study (FFCWS). We found that salivary epigenetic-BMI is robustly associated with children's BMI (r=0.36 to r=0.50). Longitudinal analysis suggested that epigenetic-BMI is highly stable across adolescence, but remains both a leading and lagging indicator of BMI change. Twin analyses showed that epigenetic-BMI captures differences in BMI between monozygotic twins. Moreover, children from more disadvantaged socioeconomic status (SES) and marginalized race/ethnic groups had higher epigenetic-BMI, even when controlling for concurrent BMI, pubertal development, and tobacco exposure. SES at birth relative to concurrent SES best predicted epigenetic-BMI in childhood and adolescence. We show for the first time that epigenetic predictors of BMI calculated from pediatric saliva samples are valid biomarkers of childhood BMI that are sensitive to social inequalities. Our findings are in line with the hypothesis that early life conditions are especially important factors in epigenetic regulation of later life health. Research showing that health later in life is linked to early life conditions have important implications for the development of early-life interventions that could significantly extend healthy life span.

On radar and radio exposure and cancer in the military setting.

INTRODUCTION: In 2018, we reported a case series of 47 patients diagnosed with cancer following several years of exposure to high-intensity whole-body radiofrequency radiation (RFR) using the parameter of percentage frequency (PF). Consistent high and statistically significant PFs of hematolymphoid (HL) cancers were found in this group and in four previous reports on RFR-exposed groups in Belgium, Poland and Israel together with increased all-cancers rates. In this paper we report a new series of 46 young cancer patients who were exposed during military service to such radiation. MATERIALS AND METHODS: The new group of patients comprises Israeli soldiers previously exposed to occupational RFR. The patients were self-selected to enroll in the research in cooperation with an NGO assisting patients with administrative counseling and legal and social services. The new group of patients was studied with respect to distribution (proportion) of cancer types using the method of PF. When possible, cancer risk ratios (RR) were estimated too. The results are compared to those of other occupational groups in three countries. RESULTS: Median age at diagnosis was 23 years; duration of exposure was between 1 and 3 years and the latencies were short, median 4.6 years. The PF of HL cancers was 41.3%, 95% CI (27%-57%), versus 22.7% expected in non-exposed subjects matched for age and gender profiles, p = 0.003; 19 out of the 46 patients had HL cancers. The PF of Hodgkin lymphoma cancers was 21.7%, 95%CI (11%-36%), versus 11.6% expected, p = 0.033. For a subgroup of 6 patients, the number of soldiers in the units was known, and we were able estimate approximately the overall cancer risk ratio (RR) after 8 years as being 8.0 with 95% CI (2.9, 17), p < 0.002, with only 0.75 cases expected from the Cancer Registry data. In this subgroup, there were 3 HL cancer cases and 3 non-HL cases. Sarcoma PF was higher than expected, 7 out of the 46 patients were diagnosed with sarcoma, PF = 15.2%, 95%CI (6.3%-28.9%), p = 0.04 versus the expected PF of 7%. CONCLUSION: The HL PF was high and consistent with previous reports. Epidemiological studies on excess risk for HL and other cancers, brain tumors in cellphone users, and experimental studies on RFR and carcinogenicity strongly point to a cause-effect relationship. It is mandatory to reduce the RFR exposure of all personnel to that of the typical community levels, including the peak level of radar pulses. Radiation protection, safety instructions, cancer risk warnings and quantitative data on individual exposure together with regular medical monitoring must be instituted for all personnel exposed to such risks. The findings from our study add to the growing body of evidence underscoring the gross inadequacy of the International Commission on Non-Ionizing Radiation Protection (ICNIRP) thermal standards. Based on our findings and on the previous accumulated research, we endorse the recommendations to reclassify RFR exposure as a human carcinogen, International Agency for Research on Cancer (IARC) group 1.

Multiple Sclerosis Followed by Neuromyelitis Optica Spectrum Disorder: From the National Multiple Sclerosis Society Case Conference Proceedings.

A woman presented at age 18 years with partial myelitis and diplopia and experienced multiple subsequent relapses. Her MRI demonstrated T2 abnormalities characteristic of multiple sclerosis (MS) (white matter ovoid lesions and Dawson fingers), and CSF demonstrated an elevated IgG index and oligoclonal bands restricted to the CSF. Diagnosed with clinically definite relapsing-remitting MS, she was treated with various MS disease-modifying therapies and eventually began experiencing secondary progression. At age 57 years, she developed an acute longitudinally extensive transverse myelitis and was found to have AQP4 antibodies by cell-based assay. Our analysis of the clinical course, radiographic findings, molecular diagnostic methods, and treatment response characteristics support the hypothesis that our patient most likely had 2 CNS inflammatory disorders: MS, which manifested as a teenager, and neuromyelitis optica spectrum disorder, which evolved in her sixth decade of life. This case emphasizes a key principle in neurology practice, which is to reconsider whether the original working diagnosis remains tenable, especially when confronted with evidence (clinical and/or paraclinical) that raises the possibility of a distinctively different disorder.

Combined epigenetic and immunotherapy for blastic and classical mantle cell lymphoma.

Classical MCL (cMCL) constitutes 6-8% of all B cell NHL. Despite recent advances, MCL is incurable except with allogeneic stem cell transplant. Blastic mantle cell lymphoma (bMCL) is a rarer subtype of cMCL associated with an aggressive clinical course and poor treatment response, frequent relapse and poor outcomes. We treated 13 bMCL patients with combined epigenetic and immunotherapy treatment consisting of vorinostat, cladribine and rituximab (SCR). We report an increased OS greater than 40 months with several patients maintaining durable remissions without relapse for longer than 5 years. This is remarkably better then current treatment regimens which in bMCL range from 14.5-24 months with conventional chemotherapy regimens. We demonstrate that the G/A870 CCND1 polymorphism is predictive of blastic disease, nuclear localization of cyclinD1 and response to SCR therapy. The major resistance mechanisms to SCR therapy are loss of CD20 expression and evasion of treatment by sanctuary in the CNS. These data indicate that administration of epigenetic agents improves efficacy of anti-CD20 immunotherapies. This approach is promising in the treatment of MCL and potentially other previously treatment refractory cancers.

Comparisons in polypharmacy over a decade in community-dwelling older adults-findings from Israel national health and nutrition surveys.

BACKGROUND: Polypharmacy increases with age and is associated with serious health and economic costs. This study reports changes over a decade in medication-use patterns and polypharmacy, in Israeli community-dwelling older adults aged ≥ 65 years. METHODS: Demographic and health data from two representative national health cross-sectional surveys - MABAT ZAHAV 1 (MZ1) in 2005-2006, and MZ2 in 2014-2015 were analyzed. Polypharmacy was defined as use of ≥ 5 medications. Risk factors for polypharmacy were estimated by multivariable logistic regression with adjusted odds ratios (aOR) and their 95% confidence intervals (CI). RESULTS: Self-reported data on medications taken were available for 1647 participants (91.5%) in MZ1, and for 833 participants (80.2%) in MZ2, 55% women, and about 20% aged ≥ 80, in both surveys. The prevalence of polypharmacy was significantly lower in MZ2 than in MZ1: 64.2% versus 56.3%, p = .0001; with an aOR (95%CI) of 0.64 (0.52, 0.80). The most commonly taken drugs were for hypertension (27.0%, 25.3%), dyslipidemia (9.7%, 12.4%) and anticoagulation (9.2%, 9.8%). For approximately 10% of drugs, indications were either unknown or incorrect. Polypharmacy was significantly associated with poor self-health assessment 2.47 (1.99, 3.06), ≥ 4 versus 1-3 chronic illnesses 6.36 (3.85, 10.50), and age ≥ 80 versus younger 1.72 (1.32, 2.24). Similar associations were observed with major polypharmacy of ≥ 8 medications. CONCLUSION: Polypharmacy, although reduced in the last decade, requires constant attention, especially concerning lack of knowledge of indications which leads to poor adherence and adverse side effects. Health-care teams should carry out regular medicine reconciliation in at-risk elderly patients.

Mantle cell lymphoma management trends and novel agents: where are we going?

The heterogeneity in disease pathology, the unpredictability in disease prognosis, and the variability in response to therapy make mantle cell lymphoma (MCL) a focus of novel therapeutic development. MCL is characterized by dysregulated expression of cyclin D1 through a chromosome t(11;14) translocation. MCL international prognostic index (MIPI), ki-67 proliferation index, and TP53 mutation status are currently utilized for prognostication. With advances in pharmacokinetic analysis and drug discovery, treatment strategy has evolved from chemotherapy to combination of targeted, epigenetic, and immune therapies. In this review, we discuss investigational and newly approved treatment approaches. In a short time, the US Food and Drug Administration (FDA) has approved five agents for the treatment of MCL: lenalidomide, an immunomodulatory agent; bortezomib, a proteasome inhibitor; and ibrutinib, acalabrutinib, and zanubrutinib, all Bruton kinase inhibitors. Epigenetic agents (e.g. cladribine and vorinostat), mammalian target of rapamycin (mTOR) inhibitors (e.g. temsirolimus and everolimus), and monoclonal antibodies and/or antibody-drug conjugates (e.g. obinutuzumab, polatuzumab, and ublituximab) are promising therapeutic agents currently under clinical trial investigation. Most recently, chimeric antigen receptor (CAR)-T cell therapy and bispecific T-cell engager (BiTE) therapy even open a new venue for MCL treatment. However, due to its intricate pathology nature and high relapse incidence, there are still unmet needs in developing optimal therapeutic strategies for both frontline and relapsed/refractory settings. The ultimate goal is to develop innovative personalized combination therapy approaches for the purpose of delivering precision medicine to cure this disease.

The Relationship Between Opioid Use and Healthcare Utilization in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Pain is commonly experienced by patients with inflammatory bowel disease (IBD). Unfortunately, pain management is a challenge in IBD care, as currently available analgesics are associated with adverse events. Our understanding of the impact of opioid use on healthcare utilization among IBD patients remains limited. METHODS: A systematic search was completed using PubMed, Embase, the Cochrane Library, and Scopus through May of 2020. The exposure of interest was any opioid medication prescribed by a healthcare provider. Outcomes included readmissions rate, hospitalization, hospital length of stay, healthcare costs, emergency department visits, outpatient visits, IBD-related surgeries, and IBD-related medication utilization. Meta-analysis was conducted on study outcomes reported in at least 4 studies using random-effects models to estimate pooled relative risk (RR) and 95% confidence interval (CI). RESULTS: We identified 1969 articles, of which 30 met inclusion criteria. Meta-analysis showed an association between opioid use and longer length of stay (mean difference, 2.25 days; 95% CI, 1.29-3.22), higher likelihood of prior IBD-related surgery (RR, 1.72; 95% CI, 1.32-2.25), and higher rates of biologic use (RR, 1.38; 95% CI, 1.13-1.68) but no difference in 30-day readmissions (RR, 1.17; 95% CI, 0.86-1.61), immunomodulator use (RR, 1.13; 95% CI, 0.89-1.44), or corticosteroid use (RR, 1.36; 95% CI, 0.88-2.10) in patients with IBD. On systematic review, opioid use was associated with increased hospitalizations, healthcare costs, emergency department visits, outpatient visits, and polypharmacy. DISCUSSION: Opioids use among patients with IBD is associated with increased healthcare utilization. Nonopioid alternatives are needed to reduce burden on the healthcare system and improve patient outcomes.

Pain control in inflammatory bowel disease presents a challenge due to the potential for adverse effects of opioids in this population. This systematic review and meta-analysis demonstrates that opioid use in inflammatory bowel disease is associated with increased healthcare utilization.