Association between non-pharmacological therapy and healthcare use and expenditure of patients with diabetes mellitus.

This study explored the sociodemographic and clinical characteristics of patients with diabetes who incorporated two non-pharmacological therapies into their lifestyle and the association between non-pharmacological therapy and healthcare utilization and expenditure. In the USA, 26.4 million people were reportedly diagnosed with diabetes and treated with diet modification or physical activity in the 2019 Medical Expenditure Panel Survey. Physical activity was defined as moderate-to-vigorous physical exercise five times per week, whereas dietary modification involved healthy eating that reduced glucose levels. Only 4.8 million patients with diabetes did not integrate any non-pharmacological intervention into their therapy regimen. Those who did not include non-pharmacological interventions had higher annual total healthcare expenditures (M = $18,428) than those who incorporated either single (M = $17,058) or dual intervention (M = $15,134). A significant difference was observed in prescribed medicine utilization per year for those who did not include lifestyle modifications or non-pharmacological interventions. Propensity score-matched participants revealed significant differences in hospital stays, outpatient visits, and emergency department expenditures. Patients with diabetes who adhered to two non-pharmacological interventions showed significantly lower healthcare utilization. Being active and following a healthy diet can help prevent the progression of diabetes mellitus complications and reduce the cost associated with diabetes.

Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population.

We report the results of clinical exome sequencing (CES) on >2,200 previously unpublished Saudi families as a first-tier test. The predominance of autosomal-recessive causes allowed us to make several key observations. We highlight 155 genes that we propose to be recessive, disease-related candidates. We report additional mutational events in 64 previously reported candidates (40 recessive), and these events support their candidacy. We report recessive forms of genes that were previously associated only with dominant disorders and that have phenotypes ranging from consistent with to conspicuously distinct from the known dominant phenotypes. We also report homozygous loss-of-function events that can inform the genetics of complex diseases. We were also able to deduce the likely causal variant in most couples who presented after the loss of one or more children, but we lack samples from those children. Although a similar pattern of mostly recessive causes was observed in the prenatal setting, the higher proportion of loss-of-function events in these cases was notable. The allelic series presented by the wealth of recessive variants greatly expanded the phenotypic expression of the respective genes. We also make important observations about dominant disorders; these observations include the pattern of de novo variants, the identification of 74 candidate dominant, disease-related genes, and the potential confirmation of 21 previously reported candidates. Finally, we describe the influence of a predominantly autosomal-recessive landscape on the clinical utility of rapid sequencing (Flash Exome). Our cohort's genotypic and phenotypic data represent a unique resource that can contribute to improved variant interpretation through data sharing.

Variants in EXOSC9 Disrupt the RNA Exosome and Result in Cerebellar Atrophy with Spinal Motor Neuronopathy.

The exosome is a conserved multi-protein complex that is essential for correct RNA processing. Recessive variants in exosome components EXOSC3, EXOSC8, and RBM7 cause various constellations of pontocerebellar hypoplasia (PCH), spinal muscular atrophy (SMA), and central nervous system demyelination. Here, we report on four unrelated affected individuals with recessive variants in EXOSC9 and the effect of the variants on the function of the RNA exosome in vitro in affected individuals' fibroblasts and skeletal muscle and in vivo in zebrafish. The clinical presentation was severe, early-onset, progressive SMA-like motor neuronopathy, cerebellar atrophy, and in one affected individual, congenital fractures of the long bones. Three affected individuals of different ethnicity carried the homozygous c.41T>C (p.Leu14Pro) variant, whereas one affected individual was compound heterozygous for c.41T>C (p.Leu14Pro) and c.481C>T (p.Arg161∗). We detected reduced EXOSC9 in fibroblasts and skeletal muscle and observed a reduction of the whole multi-subunit exosome complex on blue-native polyacrylamide gel electrophoresis. RNA sequencing of fibroblasts and skeletal muscle detected significant >2-fold changes in genes involved in neuronal development and cerebellar and motor neuron degeneration, demonstrating the widespread effect of the variants. Morpholino oligonucleotide knockdown and CRISPR/Cas9-mediated mutagenesis of exosc9 in zebrafish recapitulated aspects of the human phenotype, as they have in other zebrafish models of exosomal disease. Specifically, portions of the cerebellum and hindbrain were absent, and motor neurons failed to develop and migrate properly. In summary, we show that variants in EXOSC9 result in a neurological syndrome combining cerebellar atrophy and spinal motoneuronopathy, thus expanding the list of human exosomopathies.

The morbid genome of ciliopathies: an update.

PURPOSE: Ciliopathies are highly heterogeneous clinical disorders of the primary cilium. We aim to characterize a large cohort of ciliopathies phenotypically and molecularly. METHODS: Detailed phenotypic and genomic analysis of patients with ciliopathies, and functional characterization of novel candidate genes. RESULTS: In this study, we describe 125 families with ciliopathies and show that deleterious variants in previously reported genes, including cryptic splicing variants, account for 87% of cases. Additionally, we further support a number of previously reported candidate genes (BBIP1, MAPKBP1, PDE6D, and WDPCP), and propose nine novel candidate genes (CCDC67, CCDC96, CCDC172, CEP295, FAM166B, LRRC34, TMEM17, TTC6, and TTC23), three of which (LRRC34, TTC6, and TTC23) are supported by functional assays that we performed on available patient-derived fibroblasts. From a phenotypic perspective, we expand the phenomenon of allelism that characterizes ciliopathies by describing novel associations including WDR19-related Stargardt disease and SCLT1- and CEP164-related Bardet-Biedl syndrome. CONCLUSION: In this cohort of phenotypically and molecularly characterized ciliopathies, we draw important lessons that inform the clinical management and the diagnostics of this class of disorders as well as their basic biology.

Further delineation of HIDEA syndrome.

Recently, the genetic cause of HIDEA syndrome (hypotonia, hypoventilation, intellectual disability, dysautonomia, epilepsy, and eye abnormalities) was identified as biallelic pathogenic variants in P4HTM, which encodes an atypical member of the prolyl 4-hydroxylases (P4Hs) family of enzymes. We report seven patients from four new families in whom HIDEA was only diagnosed after whole-exome sequencing (WES) revealed novel disease-causing variants in P4HTM. We note the variable phenotypic expressivity of the syndrome except for cognitive impairment/developmental delay, and hypotonia, which seem to be consistent findings. One patient only presented with hypotonia, developmental delay, and abnormal eye movements, which highlights the challenge in diagnosing milder cases with this new syndrome. Other notable features include mild facial dysmorphism, obesity, and brain dysmyelination and atrophy. We conclude that HIDEA is a highly variable syndrome and suspect that a large fraction of patients will be diagnosed via reverse phenotyping after recessive P4HTM variants are identified by agnostic genomic sequencing assays.

Congenital disorders of glycosylation: The Saudi experience.

We retrospectively reviewed Saudi patients who had a congenital disorder of glycosylation (CDG). Twenty-seven Saudi patients (14 males, 13 females) from 13 unrelated families were identified. Based on molecular studies, the 27 CDG patients were classified into different subtypes: ALG9-CDG (8 patients, 29.5%), ALG3-CDG (7 patients, 26%), COG6-CDG (7 patients, 26%), MGAT2-CDG (3 patients, 11%), SLC35A2-CDG (1 patient), and PMM2-CDG (1 patient). All the patients had homozygous gene mutations. The combined carrier frequency of CDG for the encountered founder mutations in the Saudi population is 11.5 per 10,000, which translates to a minimum disease burden of 14 patients per 1,000,000. Our study provides comprehensive epidemiologic information and prevalence figures for each of these CDG in a large cohort of congenital disorder of glycosylation patients.

Heart Rate Beat-to-Beat Slope Change during Six-Minute Walk Test: a Useful Clinical Tool for Estimating Fitness level.

BACKGROUND: The six-minute walk test (6MWT) is one of the most common exercise tests and is used to estimate the level of physical fitness. This study aimed to evaluate the feasibility of the beat-to-beat heart rate 6MWT slope (6MWTS) and recovery slope for predicting and estimating the level of physical fitness during 6MWT, instead of depending on the distance covered during the test. METHODS: Seventy healthy adult male subjects aged 18 to 27 years were recruited randomly from the general Saudi population in Riyadh. Using a 50-m corridor, 6MWT was performed according to standardised American Thoracic Society guidelines. RESULTS: The mean distance walked in 6 minutes (470.5±64.6 m) and beat-to-beat heart rate (HR) were calculated using a HR monitor. In addition, the body mass index, body surface area, Borg Rating of Perceived Exertion, and maximum predicted HR percentage were also calculated. A stepwise regression equation was used to predict the 6MWT distance (6MWTD), 6MWTS, and recovery slope. There was a significant correlation between 6MWTS and the recovery slope (r= -0.575, p<0.001), between 6MWTS and 6MWTD (r= 0.414, p<0.001), and between recovery slope and 6MWTD (r= -0.454, p<0.001). CONCLUSION: Our findings suggest that both 6MWTS and recovery slope can predict 6MWTD.

Prevalence and Severity of Social Anxiety Symptoms and Their Relationship With Body Dysmorphic Symptoms.

Background Social anxiety disorder (SAD) is a subtype of anxiety characterized by avoidance, fear, and physical symptoms such as dry mouth, sweating, palpitations, and blushing. SAD is one of the most common mental disorders. Body dysmorphic disorder (BDD) is a mental disorder marked by a distressing or impairing preoccupation with imagined or minor flaws in one's physical appearance. Both disorders share similar symptoms. No satisfactory data have been provided about the prevalence of social anxiety symptoms in our region. In our study, we measured the prevalence and severity of SAD symptoms among adults in Riyadh City, as well as the sociodemographic factors associated with it. Additionally, the correlation between SAD and BDD was assessed. Methods Our study is quantitative, observational, and cross-sectional. It was conducted by administering a translated Arabic version of the Severity Measure for Social Anxiety Disorder scale and BDD scales in five locations in Riyadh, which include two general hospitals and three shopping malls. Data were analyzed using the SPSS version 22 (IBM Corp., Armonk, NY, USA). Descriptive statistical data are presented through mean values, standard deviations, and percentages. Results A total of 752 responses were received, of which 509 (68.32%) were from females with a mean age of 30.12 years. The majority of the sample had a low to middle family income, with 64% earning less than $2555 monthly. The sample possessed a good educational level; 63% had a bachelor's degree or higher. Our study also shows that 233 subjects (30.98%) had scores indicating a moderate to severe form of SAD. Among these participants, 86 (36.9%) had scores indicating a moderate to severe form of BDD. There was a significant positive correlation between SAD and BDD (r = 0.496). Conclusion The prevalence of SAD was 30.98%, which is higher compared to Western countries. Low income, education, and female gender have roles in the disease condition. Moreover, there was a linear relationship between SAD and BDD.

Pausing behavior of late bilingual and monolingual English speakers.

This study examined the differences in the pausing behavior between native and non-native English speakers. Specifically, it examined the location and duration of pauses in relation to the syntactic and lexical complexity of the clauses in which these pauses occur and the nature of the prosodic phrasing of the utterances containing pauses. Speech samples from 10 native (L1) English and 10 Mandarin non-native English speakers from the Archive of L1 and L2 Scripted and Spontaneous Transcripts and Recordings (ALLSSTAR) were included in the analysis. The results showed that lower-level prosodic boundaries and syntactically complex phrases were associated with significantly longer pause duration in the L2 speech. Additionally, phrases with less frequent words tended to induce longer pauses. These findings suggest that insufficient knowledge of the L2 syntax, lexicon, and prosody might determine the location and duration of pauses and ultimately affect the speech fluency of L2 speakers.

Clinical Reasoning: A Young Woman With Rapidly Progressive Weakness and Paresthesia.

A 24-year-old Middle Eastern woman presented with a 2-month history of rapidly progressive asymmetric weakness and paresthesia that began in her left lower extremity and progressed to involve both legs and arms. It was associated with overflow urinary incontinence and significant weight loss. In addition, she complained of a constant occipital headache that worsened in the supine position and was associated with photophobia, tinnitus, nausea, vomiting, and horizontal binocular diplopia. She also had signs of meningismus, decreased left facial sensation, and right sensorineural hearing loss. Because multifocal localization suggests a wide variety of possible differential diagnoses, this study expands on the differential of a subacute multifocal process while highlighting the importance of identifying appropriate risk factors and performing a relevant yet focused diagnostic workup.

Clinical and molecular features of four families with CLDN10-related HELIX syndrome.

Biallelic pathogenic variants in CLDN10 cause the very rare and distinct multiplex epithelium dysfunction manifested by hypohidrosis and electrolyte imbalance (HELIX) syndrome. HELIX patients often present with heat intolerance and reduced tear secretion. Here, we report on eight new patients (four families) who presented soon after birth with fine scales in the palms and soles and hypohidrosis that was associated with high body temperature. Exome sequencing identified a novel homozygous pathogenic variant in CLDN10 in one family (NM_006984:exon1:c.138G>A:p.W46*) and a previously reported pathogenic founder variant in the other three (NM_006984:exon5:c.653del:P218Lfs*21). The detailed clinical reports of these patients and a review of previously reported patients further delineate the phenotype of this extremely rare disorder.

Metabolomics: A New Era in the Diagnosis or Prognosis of B-Cell Non-Hodgkin's Lymphoma.

A wide range of histological as well as clinical properties are exhibited by B-cell non-Hodgkin's lymphomas. These properties could make the diagnostics process complicated. The diagnosis of lymphomas at an initial stage is essential because early remedial actions taken against destructive subtypes are commonly deliberated as successful and restorative. Therefore, better protective action is needed to improve the condition of those patients who are extensively affected by cancer when diagnosed for the first time. The development of new and efficient methods for early detection of cancer has become crucial nowadays. Biomarkers are urgently needed for diagnosing B-cell non-Hodgkin's lymphoma and assessing the severity of the disease and its prognosis. New possibilities are now open for diagnosing cancer with the help of metabolomics. The study of all the metabolites synthesised in the human body is called "metabolomics." A patient's phenotype is directly linked with metabolomics, which can help in providing some clinically beneficial biomarkers and is applied in the diagnostics of B-cell non-Hodgkin's lymphoma. In cancer research, it can analyse the cancerous metabolome to identify the metabolic biomarkers. This review provides an understanding of B-cell non-Hodgkin's lymphoma metabolism and its applications in medical diagnostics. A description of the workflow based on metabolomics is also provided, along with the benefits and drawbacks of various techniques. The use of predictive metabolic biomarkers for the diagnosis and prognosis of B-cell non-Hodgkin's lymphoma is also explored. Thus, we can say that abnormalities related to metabolic processes can occur in a vast range of B-cell non-Hodgkin's lymphomas. The metabolic biomarkers could only be discovered and identified as innovative therapeutic objects if we explored and researched them. In the near future, the innovations involving metabolomics could prove fruitful for predicting outcomes and bringing out novel remedial approaches.

Sociodemographic characteristics and health-related quality of life of individuals undergoing antidepressant therapy.

An important factor for averting depression and creating awareness about clinical treatment is patient preference. Therefore, investigating health-related quality of life associated with different antidepressants is necessary. A retrospective cohort study was performed using the 2018 Medical Expenditure Panel Survey. The MEPS is a nationally representative database of the civilian and noninstitutionalized population spanning different ages, both sexes, and a wide range of sociodemographic and economic backgrounds. Differences in clinical and sociodemographic characteristics among patients using different antidepressant classes were explored. The differences in Veterans RAND 12-Item Health Survey (VR-12) results among groups were examined. The VR-12 metric was used since it measures a patient's overall perspective of their health. Approximately 34.6 million of the patients reported using at least one antidepressant during 2018. Most patients receiving tricyclic therapy reported substantially better mental HRQoL than patients receiving selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), or combination therapy. Patients receiving atypical antidepressants reported substantially better mental HRQoL than those receiving other types of antidepressants. Most patients reported a substantial decline in HRQoL after SNRIs or combination therapy. This study found that HRQoL varied across antidepressant users. Thus, health care providers could benefit from taking into consideration quality of life when prescribing antidepressant agents. Moreover, further research is needed to explore other factors that could contribute to the quality of care for patients with depression.

Metabolic Biomarkers in B-Cell Lymphomas for Early Diagnosis and Prediction, as Well as Their Influence on Prognosis and Treatment.

B-cell lymphomas exhibit a vast variety of clinical and histological characteristics that might complicate the diagnosis. Timely diagnosis is crucial, as treatments for aggressive subtypes are considered successful and frequently curative, whereas indolent B-cell lymphomas are incurable and often need several therapies. The purpose of this review is to explore the current advancements achieved in B-cell lymphomas metabolism and how these indicators help to early detect metabolic changes in B-cell lymphomas and the use of predictive biological markers in refractory or relapsed disease. Since the year 1920, the Warburg effect has been known as an integral part of metabolic reprogramming. Compared to normal cells, cancerous cells require more glucose. These cancer cells undergo aerobic glycolysis instead of oxidative phosphorylation to metabolize glucose and form lactate as an end product. With the help of these metabolic alterations, a novel biomass is generated by the formation of various precursors. An aggressive metabolic phenotype is an aerobic glycolysis that has the advantage of producing high-rate ATP and preparing the biomass for the amino acid, as well as fatty acid, synthesis needed for a rapid proliferation of cells, while aerobic glycolysis is commonly thought to be the dominant metabolism in cancer cells. Later on, many metabolic biomarkers, such as increased levels of lactate dehydrogenase (LDH), plasma lactate, and deficiency of thiamine in B-cell lymphoma patients, were discovered. Various kinds of molecules can be used as biomarkers, such as genes, proteins, or hormones, because they all refer to body health. Here, we focus only on significant metabolic biomarkers in B-cell lymphomas. In conclusion, many metabolic biomarkers have been shown to have clinical validity, but many others have not been subjected to extensive testing to demonstrate their clinical usefulness in B-cell lymphoma. Furthermore, they play an essential role in the discovery of new therapeutic targets.

Effects of Ultra-Long-Acting Insulin Compared to Long-Acting Insulin on Diabetic Ketoacidosis Incidence in Type 1 Diabetes Mellitus Patients.

Purpose: This research was intended to explore the effects of new-generation basal insulin (degludec U100 And glargine U300) versus long-acting basal insulin (glargine U100, detemir) on the incidence of diabetic ketoacidosis episodes and diabetes treatment measures. Patients and methods: This is a cross-sectional, retrospective medical record analysis. The study population included adults with type 1 diabetes mellitus (DM) who were on the hospital records in 2020. Data were collected from 221 eligible participants through review of electronic medical records. Each record was scanned for basal insulin type, total daily insulin dose, diabetic ketoacidosis (DKA) occurrences, and glycated hemoglobin A1C (HbA1c) levels. Data were collected from 6 months before to 6 months after the initiation of ultra-long-acting insulin. Statistical analysis was conducted using R version 3.5.2. The normality of distribution for each independent variable was verified using Shapiro-Wilk tests. The independent paired t-test was used to compare insulin therapy measures between the two insulin regimens. The main outcome measures were the incidence of DKA episodes and clinical outcomes associated with diabetes. Results: The HbA1c did not change significantly before and after ultra-long-acting insulin therapy was initiated (9.9 vs 9.8, respectively; P >0.05). Insulin total daily doses were significantly higher after shifting to ultra-long-acting insulin. Sub-analysis showed higher total daily insulin doses in glargine U300 users compared with degludec U100 users (P =0.0021). However, basal insulin doses did not change after treatment with ultra-long-acting insulin. No statistically significant difference in DKA occurrences was found before and after the start of ultra-long-acting insulin treatment. Conclusion: The frequency of DKA episodes was not affected by changing the treatment to ultra-long-acting insulin. Moreover, the results suggest that insulin dosage and types are not the only cause of uncontrolled diabetes. Additional efforts should be made to cover all factors affecting diabetes complication control.

Implementing an Antimicrobial Stewardship Programme to Improve Adherence to a Perioperative Prophylaxis Guideline.

Perioperative antimicrobial prophylaxis is effective in reducing the rate of surgical site infections (SSIs); however, non-adherence to surgical antimicrobial prophylaxis protocols can lead to several negative outcomes. We performed a before-and-after intervention study with the aim of improving the process outcome, including adherence to guidelines. Another objective of this study was to investigate improvement in patient outcomes as a result of adherence to a surgical antimicrobial prophylaxis programme. The indicators of improved patient outcomes were a reduction in overall SSI rate and the decreased cost of antibiotics. SSI rate was calculated as a percentage by dividing the number of SSIs by the total number of surgeries and then multiplying the value obtained by 100%. The interventions implemented in the surgical antimicrobial prophylaxis programme included establishment of a guideline, educational sessions, and a monthly revision of prescriptions. Our findings show that implementation of the interventions resulted in reduced antibiotic consumption, a considerable decrease in the cost of prophylaxis, and a decrease in the incidence of SSIs.

Relation between macrophage inflammatory protein-1 and intercellular adhesion molecule-1 and computed tomography findings in critically-ill saudi covid-19 patients.

BACKGROUND: Several, clinical and biochemical factors were suggested as risk factors for more severe forms of Covid-19. Macrophage inflammatory protein-1 alpha (MIP-1α, CCL3) is a chemokine mainly involved in cell adhesion and migration. Intracellular adhesion molecule 1 (ICAM-1) is an inducible cell adhesion molecule involved in multiple immune processes. The present study aimed to assess the relationship between baseline serum MIP-1α and ICAM-1 level in critically-ill Covid-19 patients and the severity of computed tomography (CT) findings. METHODS: The study included 100 consecutive critically-ill patients with Covid-19 infection. Diagnosis of infection was established on the basis of RT-PCR tests. Serum MIP-1α and ICAM-1 levels were assessed using commercially available ELISA kits. All patients were subjected to a high-resolution computed tomography assessment. RESULTS: According to the computed tomography severity score, patients were classified into those with moderate/severe (n=49) and mild (n = 51) pulmonary involvement. Severe involvement was associated with significantly higher MIP-1α and ICAM-1 level. Correlation analysis identified significant positive correlations between MIP-1α and age, D-dimer, IL6, in contrast, there was an inverse correlation with INF-alpha. Additionally, ICAM-1 showed significant positive correlations with age, D-Dimer,- TNF-α, IL6,while an inverse correlation with INF-alpha was observed. CONCLUSIONS: MIP-1α and ICAM-1 level are related to CT radiological severity in Covid-19 patients. Moreover, these markers are well-correlated with other inflammatory markers suggesting that they can be used as reliable prognostic markers in Covid-19 patients.

Assessment of Using the Syndromic Approach in Managing Patients With Sexually Transmitted Diseases Among the National Guard Primary Health Care Physicians, Jeddah City, Saudi Arabia.

Background Sexually transmitted infections (STIs) include a group of clinical syndromes that can be transmitted mainly through sexual activity. Using STIs' syndromic approach for diagnosis and management is widely recommended to control and reduce the burden of these transmissible diseases. Objective The objective of this article is to assess the knowledge and practice of physicians concerning syndromic management of STIs in National Guard Primary Health Care (PHC) centers in Jeddah city, Saudi Arabia. Materials and methods This observational study was conducted at the National Guard PHC centers in Jeddah City, Saudi Arabia. An interview-administered questionnaire was designed. Fifty physicians have met the inclusion criteria, and all of them were included in the present study. Results Of the study population, 47 PHC physicians (response rate was 94%) were interviewed and the questionnaire was completed. Overall, the physicians' knowledge was different from one syndrome to another; it was highest for urethral discharge (72%) and lowest for vaginal discharge in pregnant women (21%). During the last 10 days, the physicians in the present study reported that two-thirds of their cases of STI were urethral discharge cases. However, during the previous 10 days, the practice assessment revealed that most physicians (76%) were correctly prescribed the medications as indicated by specific patients' syndromes. Conclusion Syndromic management is essential guidance to control and reduce the burden of STIs. Overall knowledge and practice of physicians were different from one syndrome to another. There is a need to design continuing medical education programs targeting PHC physicians to be clinically and culturally competent against socially sensitive diseases like STIs.