Lenacapavir Exhibits Atropisomerism-Mechanistic Pharmacokinetics and Disposition Studies of Lenacapavir Reveal Intestinal Excretion as a Major Clearance Pathway.

Lenacapavir (LEN), a long-acting injectable, is the first approved human immunodeficiency virus type 1 capsid inhibitor and one of a few Food and Drug Administration-approved drugs that exhibit atropisomerism. LEN exists as a mixture of two class 2 atropisomers that interconvert at a fast rate (half-life < 2 hours) with a ratio that is stable over time and unaffected by enzymes or binding to proteins in plasma. LEN exhibits low systemic clearance (CL) in nonclinical species and humans; however, in all species, the observed CL was higher than the in vitro predicted CL. The volume of distribution was moderate in nonclinical species and consistent with the tissue distribution observed by whole-body autoradiography in rats. LEN does not distribute to brain, consistent with being a P-glycoprotein (P-gp) substrate. Mechanistic drug disposition studies with [14C]LEN in intravenously dosed bile duct-cannulated rats and dogs showed a substantial amount of unchanged LEN (31%-60% of dose) excreted in feces, indicating that intestinal excretion (IE) was a major clearance pathway for LEN in both species. Coadministration of oral elacridar, a P-gp inhibitor, in rats decreased CL and IE of LEN. Renal excretion was < 1% of dose in both species. In plasma, almost all radioactivity was unchanged LEN. Low levels of metabolites in excreta included LEN conjugates with glutathione, pentose, and glucuronic acid, which were consistent with metabolites formed in vitro in Hµrel hepatocyte cocultures and those observed in human. Our studies highlight the importance of IE for efflux substrates that are highly metabolically stable compounds with slow elimination rates. SIGNIFICANCE STATEMENT: LEN is a long-acting injectable that exists as conformationally stable atropisomers. Due to an atropisomeric interconversion rate that significantly exceeds the in vivo elimination rate, the atropisomer ratio of LEN remains constant in circulation. The disposition of LEN highlights that intestinal excretion has a substantial part in the elimination of compounds that are metabolically highly stable and efflux transporter substrates.

Pharmacokinetics, mass balance, tissue distribution, metabolism, and excretion of [14C]aficamten following single oral dose administration to rats.

The pharmacokinetics, metabolism, excretion, mass balance, and tissue distribution of [14C]aficamten were evaluated following oral administration of an 8 mg/kg dose in Sprague Dawley rats and in a quantitative whole-body autoradiography study in Long Evans rats.[14C]Aficamten accounted for ∼80% and a hydroxylated metabolite (M1) accounted for ∼12% of total radioactivity in plasma over 48-h (AUC0-48). Plasma tmax was 4-h and the t1/2 of total plasma radioactivity was 5.8-h.Tissues showing highest Cmax exposures were myocardium and semitendinosus muscle.Most [14C]aficamten-derived radioactivity was excreted within 48-h post-administration. Mean cumulative recovery in urine and faeces over 168-h was 8.3% and 90.7%, respectively.In urine and bile, unchanged aficamten was detected at <0.1 and <0.2% of dose, respectively; however, based on total radioactivity excreted in urine (8.0%) and bile (51.7%), approximately 60% of dose was absorbed.[14C]Aficamten was metabolised by hydroxylation with subsequent glucuronidation where the most abundant metabolite recovered in bile was M5 (35.2%), the oxygen-linked glucuronide of hydroxylated aficamten (M1a). The major metabolite detected in faeces was a 1,2,4-oxadiazole moiety ring-cleaved metabolite (M18, 35.3%), shown to be formed from the metabolism of M5 in incubations with rat intestinal contents solution.

Functional priorities of individuals with spinal cord injury: a Saudi Arabian perspective.

CONTEXT/OBJECTIVE: People with spinal cord injury (SCI) are the deciding force behind the rehabilitation program to improve their quality of life (QoL) based on their personal preferences. Here we aimed to determine the preferences perceived most vital by Saudi SCI population to improve their QoL, and explore if these preferences are affected by gender, education, and duration, level, or extent of injury. DESIGN: Participants ranked seven priorities of bodily functions as Rank I-VII with "I" being "Most important," and "VII" being "Least important." SETTING: Inpatient rehabilitation facility. PARTICIPANTS: 120 participants (>18 years of age) of either sex with SCI without polytrauma, acquired brain injury, neurodegenerative disease, and dementia. OUTCOME MEASURES: Ranking scale of seven priorities of bodily functions as Rank I-VII with "I" being "Most important," and "VII" being "Least important." RESULTS: Of 101 individuals (mean age: 35.2 ± 14.8 years) finally included, 70.3% were males, 66.3% had onset of SCI since ≥ 3 years, 48.5% had a complete injury, and 75% had paraplegia. Most (26.7%) participants ranked walking as the first priority followed by hand/arm function (20.8%). Sexual function was the least important priority (39.6%). Hand/arm function was significantly more important for individuals with tetraplegia (p < 0.001). Trunk strength and balance was significantly less important for individuals with complete injury (p = 0.037). Participants with the onset of injury < 3 years and a complete injury reported bladder/bowel function as significantly more important (p = 0.011). Walking was significantly more important for people with incomplete injury and for people with injury duration ≥ 3 years (p = 0.022, p = 0.002 respectively). CONCLUSION: The top priority in our sample of Saudi people with SCI was walking followed by hand/arm function while the least desired function was regaining sexual function. Walking was a prioritized function for people with injury duration ≥ 3 years and people with a complete injury while hand/arm function was highly prioritized by people with tetraplegia.

Absorption, metabolism, and excretion of [14C]-sebetralstat (KVD900) following a single oral dose in healthy male participants.

Sebetralstat is an investigational oral plasma kallikrein inhibitor for the on-demand treatment of hereditary angioedema. Six healthy male participants received one dose of 600 mg (540 µCi) [14C]-sebetralstat. Plasma concentrations of sebetralstat and levels of total radioactivity in plasma, urine, and faeces were determined. Metabolite profiles of radioactivity were generated, and major metabolites structurally characterised.Radioactivity was rapidly absorbed and was excreted with a mean of 95.8% (63.4% faeces; 32.4% urine) recovered by 216 h. Sebetralstat was the major drug-related component in urine and faeces, although metabolism predominated overall (main metabolites: M19 (des-[methoxy-fluoro-methylpyridine]-sebetralstat), M10 (N-des-pyridone-sebetralstat-carboxylic acid), M3 (pyridine O-desmethyl-sebetralstat), and M34 (pyridine dioxy-dihydro-sebetralstat)). Sebetralstat was the main radiolabelled component in plasma (mean of 64.1% of the total radioactivity AUC0-24), followed by relatively low proportions of metabolites: M19 (7.10%), M3 (4.01%), and M10 (4.00%). Although M19 was >10% of the plasma radioactivity AUC0-24, in one participant it comprised a mean of <10% of AUC0-24. Plasma levels of M19 were measured at the NOAEL dose in a rat toxicology study, where higher exposure was observed vs. that in humans.Given these findings and the lack of pharmacological activity of M19, it was concluded that there was no unique or disproportionate circulating metabolite in humans.

The Optimal Parathyroid Hormone Cut-Off Threshold for Early and Safe Management of Hypocalcemia After Total Thyroidectomy.

OBJECTIVE: To define optimal intact parathyroid hormone (iPTH) cut-off threshold predictive of hypocalcemia after total thyroidectomy for safe and effective postoperative management. METHODS: This prospective single center study was done in 2 phases. In phase I, predictors of symptomatic hypocalcemia were analyzed and the receiver operating characteristic curve was used to define the optimal iPTH cut-off threshold predictive of hypocalcemia. Phase II studied giving prompt prophylactic supplemental calcium and vitamin D to all patients who had iPTH levels below the calculated threshold, while phase I patients were given prompt selective supplementation if they had postoperative hypocalcemia or symptoms. RESULTS: Univariate analysis of patients in phase I showed that postoperative iPTH was the only significant variable that can predict symptomatic hypocalcemia. Using receiver operating characteristic curve and Youden index, the confirmed optimal cut-off threshold predictive of hypocalcemia was iPTH 19.95 pg/mL, with area under the curve of 0.903, 100% sensitivity, negative predictive value, and highest Youden index, while iPTH 15 pg/mL and iPTH 10 pg/mL were less optimal. Symptomatic hypocalcemia occurred in 30% of the phase I cohort who received selective supplementation versus 3% of those in the phase II cohort who received prophylactic supplementation. Return to emergency department and need for intravenous calcium were also significantly better in phase II. CONCLUSION: iPTH cut-off for post-thyroidectomy hypocalcemia was 19.95 pg/mL. Low-risk patients were discharged with no supplementation while all high-risk patients received prompt calcium and vitamin D supplementation, which led to effective hypocalcemia management and safe 24-hour discharge.

Non-A non-B aortic dissection: A literature review.

Non-A non-B aortic dissections are an infrequent occurrence and represent a small proportion of aortic dissections. Treating this life-threatening medical emergency often requires surgeons to undertake some one of the most challenging surgical or endovascular cases in medicine. This literature review aims to define and classify non-A non-B dissections, describe their epidemiology as well as their pathology. This review also aims to discuss the range of surgical techniques employed in their treatment and management and to investigate the patient outcomes associated with each technique.

TEVAR for complicated and uncomplicated type B aortic dissection-Systematic review and meta-analysis.

BACKGROUND: Type B aortic dissection (TBAD), is defined as a dissection involving the aorta distal to left subclavian artery with the ascending aorta and the aortic arch not affected. TBAD is classified due to the time frame and presence of complications. Complicated TBAD (co-TBAD) patients have a greater mortality rate than uncomplicated TBAD (un-TBAD) and thoracic endovascular aortic repair (TEVAR) is considered the gold-standard intervention for these clinical challenges. METHODS: We undertook a systematic review of the literature regarding TEVAR intervention in co-TBAD and un-TBAD. A comprehensive search was undertaken across four major databases and was evaluated and assessed until June 2020. RESULTS: A total of 16,104 patients were included in the study (7772 patients co-TBAD and 8352 un-TBAD). A significantly higher proportion of comorbidities were seen in co-TBAD patients compared with un-TBAD. Acute dissection was more frequent in the co-TBAD group (73.55% vs. 66.91%), while chronic dissection was more common in un-TBAD patients (33.8% vs. 70.73%). Postprocedure stroke was higher in co-TBAD (5.85% vs. 3.92%; p < .01), while postprocedural renal failure was higher in un-TBAD patients (7.23 vs. 11.38%; p < .01). No difference was observed in in-hospital mortality however the 30 days mortality was higher in the co-TBAD group. One-year survival was higher in the uncomplicated group but this difference was not observed in the 5-year survival. CONCLUSION: In our analysis we can appreciate that despite significantly higher comorbidities in the co-TBAD cohort, there was no difference in in-hospital mortality between the two groups and the 5-year survival did not have any difference.

Liraglutide in diabetes mellitus: More facts and findings.

Liraglutide exert favorable effects on most of the diabetes associated cardiovascular (CV) risk factors and this study was designed to further explore the benefits of liraglutide by observing its effect on plasma sialic acid (PSA) in diabetic rats. A total of 30 streptozotocin induced (50 mg/Kg; i.p.) diabetic rats were randomized into vehicle treated (1 ml/Kg s.c, twice daily) group I, liraglutide treated groups II and III (30 µg/Kg and 150 µg/Kg, twice daily respectively) and studied for 6 weeks. Liraglutide treated groups showed significant reductions in fructosamine levels (p≤0.05) from baseline. Between groups comparison revealed significant difference (p≤.05) at the end point. Similarly, at week 6, liraglutide treated groups showed significantly low levels of PSA compared to baseline (p<0.03 and p<0.005 for group II and III respectively) and control group I (p<0.002 and p<0.001 for group II and III respectively). However, the difference was non-significant between groups II and III (p<0.09). Other parameters including glucose tolerance, fasting plasma glucose (FPG), blood lipids, systolic blood pressure (SBP) and body weight also improved by liraglutide with the group III showing greater improvement. The study concludes that liraglutide produce favourable effects on PSA and may bea useful choice in protecting against diabetes associated CV complications.

Lower hypoglycemic but higher antiatherogenic effects of bitter melon than glibenclamide in type 2 diabetic patients.

OBJECTIVE: Since antiquity bitter melon has been in use for treating diabetes but clinical trials show conflicting results about its usefulness. The present study aims to asses and compare the hypoglycemic and antiatherogenic effects as well as the safety of two different doses of bitter melon with glibenclamide. METHODS: A total of 95 participants were randomized into 3 groups; group I and group II received bitter melon (2 g/day and 4 g/day respectively) and group III received glibenclamide (5 mg/day) for 10 weeks. Glycemic control and antiatherogenic effects were determined by assessing glycohemoglobin (HbA1-c), fasting plasma glucose (FPG), 2 hour oral glucose tolerance test (OGTT), plasma sialic acid (PSA), systolic blood pressure (SBP), blood lipids and atherogenic index at different time periods. RESULTS: Compared to baseline, mean reduction in HbA1-c at the endpoint was significant among patients of group I, group II and group III (p ≤ 0.05, p ≤ 0.02 and p < 0.005 respectively) and same was the case for FPG (p ≤ 0.05, p < 0.04, p < 0.003 respectively), but the improvement in 2 hour OGTT was significant only in group III (p < 0.03). The decrease in PSA was observed only among group I and group II with the later showing significant reduction from baseline (p < 0.01). In group III, the level slightly increased. Parameters including blood lipids, atherogenic index, body weight and SBP improved among patients of group I and group II but deteriorated among group III patients. CONCLUSIONS: Our study concludes that bitter melon has a weaker hypoglycemic effect but ameliorates the diabetes associated cardiovascular (CV) risk factors more effectively than glibenclamide. TRIAL REGISTRATION: The trial was registered with Naseer Teaching Hospital Clinical Trials Registry number GU2014492233.

Pharmacokinetics and metabolite profiling of fimasartan, a novel antihypertensive agent, in rats.

1. The objectives of this study were to evaluate the pharmacokinetics and metabolism of fimasartan in rats. 2. Unlabeled fimasartan or radiolabeled [(14)C]fimasartan was dosed by intravenous injection or oral administration to rats. Concentrations of unlabeled fimasartan in the biological samples were determined by a validated LC/MS/MS assay. Total radioactivity was quantified by liquid scintillation counting and the radioactivity associated with the metabolites was analyzed by using the radiochemical detector. Metabolite identification was conducted by product ion scanning using LC/MS/MS. 3. After oral administration of [(14)C]fimasartan, total radioactivity was found primarily in feces. In bile duct cannulated rats, 58.8 ± 14.4% of the radioactive dose was excreted via bile after oral dosing. Major metabolites of fimasartan including the active metabolite, desulfo-fimasartan, were identified, yet none represented more than 7.2% of the exposure of the parent drug. Fimasartan was rapidly and extensively absorbed and had an oral bioavailability of 32.7-49.6% in rats. Fimasartan plasma concentrations showed a multi-exponential decline after oral administration. Double peaks and extended terminal half-life were observed, which was likely caused by enterohepatic recirculation. 4. These results provide better understanding on the pharmacokinetics of fimasartan and may aid further development of fimasartan analogs.

Screening for carcinoid heart disease: Trends and future Perspectives.

Background: Screening for carcinoid heart disease (CHD), has historically lacked consensus expert guidelines. In 2017, the North American Neuroendocrine Tumor Society (NANETS) released expert recommendations for CHD screening among NET patients to improve CHD detection. The objective of this study is to evaluate CHD screening trends and utility of screening guidelines over more than two decades at a single tertiary care center. Materials and methods: Patients with NETs referred for abdominal surgical evaluation at a single tertiary care center were included, 300 patients from 1999 to 2018 and 34 patients from 2021 to 2022. Lab values for the following NANETS-proposed criteria at any point during their treatments were recorded: NETs with liver metastasis, blood serotonin >5 times upper limit of normal (>1000 ng/mL), NT-ProBNP >260 pg/mL and clinical features suggestive of CHD. Results: 85 % (285/334) of patients included in this study met one or more expert-recommended CHD screening criteria. However, 40 % (132/285) of patients meeting one or more criteria received CHD screening via echocardiogram at some point following NET diagnosis. While rates of screening for patients increased from the first decade to the second decade (32 % vs 40.6 %), the rates were much higher after guideline publication (70 %, 24/34). Furthermore, patients meeting multiple screening criteria were more likely to have evidence of structural valve disease. Conclusions: Results of this study suggest that utilization of these four expert-recommended screening criteria have greatly increased rates of CHD screening via echocardiogram and could assist in improving early CHD detection, especially for patients meeting multiple criteria.

A prospective longitudinal study of risk factors for abdominal aortic aneurysm.

The aim of this study was to identify risk factors for abdominal aortic aneurysm (AAA) from the largest Welsh screening cohort to date. Patients were recruited from 1993 (to 2015) as part of the South East Wales AAA screening programme through general practitioners. Demographic data and risk factors were collected by means of a self-report questionnaire. Statistical tests were performed to determine whether associations could be observed between AAA and potential risk factors. Odds ratios (OR) were also calculated for each of the risk factors identified. A total of 6879 patients were included in the study. Two hundred and seventy-five patients (4.0%) presented with AAA, of which 16% were female and 84% were male. Patients with AAA were older than the (no AAA) control group (p < 0.0001). The following risk factors were identified for AAA: family history of AAA (p < 0.0001); history of vascular surgery (p < 0.0001), cerebrovascular accident (p < 0.0001), coronary heart disease (p < 0.0001), diabetes (p < 0.0001), medication (p = 0.0018), claudication (p < 0.0001), smoking history (p = 0.0001) and chronic obstructive pulmonary disorder (p = 0.0007). AAA is associated with classical vascular risk factors, in addition to other less-well-documented risk factors including previous vascular surgery. These findings have practical implications with the potential to improve future clinical screening of patients in order to reduce AAA mortality.

Decoding Postinfarction Left Ventricular Pseudoaneurysm.

Recognizing true from pseudo left ventricular aneurysm after myocardial infarction is paramount to guide clinical management and determine need for surgical urgency. We discuss a case of a postinfarction pseudoaneurysm that poses unique anatomic challenges and may hold a secret "DaVinci code" beyond current diagnostic criteria. (Level of Difficulty: Advanced.).

Cellular protection from H2O2 toxicity by Fv-Hsp70: protection via catalase and gamma-glutamyl-cysteine synthase.

Heat shock proteins (HSPs), especially Hsp70 (HSPA1), have been associated with cellular protection from various cellular stresses including heat, hypoxia-ischemia, neurodegeneration, toxins, and trauma. Endogenous HSPs are often synthesized in direct response to these stresses but in many situations are inadequate in protecting cells. The present study addresses the transduction of Hsp70 into cells providing protection from acute oxidative stress by H2O2. The recombinant Fv-Hsp70 protein and two mutant Fv-Hsp70 proteins minus the ATPase domain and minus the ATPase and terminal lid domains were tested at 0.5 and 1.0 µM concentrations after two different concentrations of H2O2 treatment. All three recombinant proteins protected SH-SY5Y cells from acute H2O2 toxicity. This data indicated that the protein binding domain was responsible for cellular protection. In addition, experiments pretreating cells with inhibitors of antioxidant proteins catalase and gamma-glutamylcysteine synthase (GGCS) before H2O2 resulted in cell death despite treatment with Fv-Hsp70, implying that both enzymes were protected from acute oxidative stress after treatment with Fv-Hsp70. This study demonstrates that Fv-Hsp70 is protective in our experiments primarily by the protein-binding domain. The Hsp70 terminal lid domain was also not necessary for protection.

Disposition and Mass Balance of Etrasimod in Healthy Subjects and In Vitro Determination of the Enzymes Responsible for Its Oxidative Metabolism.

Etrasimod (APD334) is an investigational, once-daily, oral, selective sphingosine 1-phosphate receptor 1,4,5 modulator (S1P1,4,5 ) in development for treatment of various immune-mediated inflammatory disorders. The disposition and mass balance of a single 2-mg [14 C]etrasimod dose were evaluated in 8 healthy males. An in vitro study was also conducted to identify etrasimod's oxidative metabolizing enzymes. Peak concentrations of etrasimod and total radioactivity in plasma and whole blood were typically reached 4-7 hours postdose. Etrasimod constituted 49.3% of total radioactivity plasma exposure, with multiple minor/trace metabolites making up the remainder. Etrasimod was slowly cleared mainly via biotransformation, predominantly by oxidative metabolism, with unchanged etrasimod recovered in feces accounting for only 11.2% of the dose and none in urine. The mean apparent terminal half-lives of etrasimod and total radioactivity in plasma were 37.8 and 89.0 hours, respectively. Mean cumulative recovery of radioactivity in excreta over 336 hours was 86.9% of the dose, mostly in feces. The prevalent metabolites eliminated in feces were M3 (hydroxy-etrasimod) and M36 (oxy-etrasimod sulfate), accounting for 22.1% and 18.9% of the dose, respectively. From in vitro reaction phenotyping, the predominant enzymes involved in the oxidation of etrasimod were CYP2C8, CYP2C9, and CYP3A4, with minor contributions from CYP2C19 and CYP2J2.

Knowledge and Attitudes towards Epidural Analgesia among Women of Childbearing Age in Jazan, Saudi Arabia: A Community-Based Cross-Sectional Study to Identify Predictors through Multivariate Modeling.

Epidural analgesia (EA) is a central nerve blockade technique. It is linked to a significant reduction of labor pain and side effects. This study was designed to investigate the knowledge and attitudes towards EA among women of childbearing age (18-45 years) in Jazan, Saudi Arabia, and identify predictors through multivariate modeling. A random sampling technique (n = 680) was used for this cross-sectional, self-administered survey. A previously validated online questionnaire was distributed. After establishing a P value of less than 0.05 to denote statistical significance, SPSS was used to examine the data using descriptive analysis, the chi-square test of homogeneity, and multivariate logistic regression. Six hundred and eighty women were studied. Over 75% of the participants were university educated; less than half (46.3%) were 21-30 years old, students (42.2%), and had never been pregnant (49%). The previous mothers who had never had EA labor accounted for 64.6% (n = 347, 51.0%). "Family/friends" (39%), followed by "internet" (32%), were the most common sources of EA information. Those who correctly defined the EA accounted for 61.8%. Those who reported weak or no contractions after EA accounted for 32.2%. Those who said EA insertion hurt more than labor did accounted for 56.3%. Those women who said one should give consent to EA accounted for 83.1%. Those who believe EA is safe for the baby accounted for 50.1%. Those who knew about EA complications accounted for 24.34%. According to multivariate modeling, attitude score plays a significant role in determining the participant's knowledge level. This study found that childbearing women know a little about EA. Attitudes affected this knowledge level, and demographics did not. Cognitive intervention is needed to change these attitudes and spread EA-related knowledge.

Human leukocyte antigen class II susceptibility conferring alleles among non-insulin dependent diabetes mellitus patients.

OBJECTIVE: To determine the frequency of Human Leukocyte Antigen (HLA) class II susceptibility conferring alleles among type 2 Diabetes mellitus patients, in comparison with healthy controls. STUDY DESIGN: Cross-sectional comparative study. PLACE AND DURATION OF STUDY: Department of Immunology, Armed Forces Institute of Pathology, Rawalpindi, from January 2009 to April 2010. METHODOLOGY: Patients with non-insulin dependent Diabetes mellitus meeting World Health Organization criteria were studied. These were compared with age and gender matched healthy control subjects. For each subject (patients as well as controls), DNA was extracted from ethylene diamine tetra-acetate sample and HLA class II DRB1 typing was carried out at allele group level (DRB1*01-DRB1*16) by sequence specific primers. Human leukocyte antigen DRB1 type was determined by agarose gel electrophoresis and results were recorded. Frequencies were determined as number of an allele divided by total number of alleles per group; p-value was computed using Pearson's chi-square test. RESULTS: Among the 100 patients, there were 63 males and 37 females with 68 controls. A total of 13 different HLA DRB1 alleles were detected, with DRB1*15 being the commonest in both the groups. The allele DRB1*13 had statistically significant higher frequency in patient group as compared to controls (p = 0.005). CONCLUSION: HLA DRB1*13 was found with a significantly increased frequency in non-insulin dependent Diabetes mellitus.

A scientometric analysis on coronaviruses research (1900-2020): Time for a continuous, cooperative and global approach.

Infectious diseases remain a complex, recurring, and challenging public health hazard. Coronaviruses have led to multidimensional consequences on health, mobility, and socio-economic conditions. Despite the significance and magnitude of impact from epidemics to the pandemic, literature is sparse on comprehensive coronaviruses related research performance over time. This study aimed at a scientometric evaluation of coronaviruses related literature including COVID-19. Data related to Coronavirus research was extracted from the Web of Science (WoS). All types of publications (28,846) were included and retrieved. To measure the quantity and quality of the publications, "R-Bibliometrix" package was used for detailed analysis exploring a wide range of indicators. Generally, an increasing trend was observed over time led by the USA and China followed by the United Kingdom, Europe, and few other developed countries. The last two decades contributed around 39.5% of documents while only 06 months of 2020 additionally contributed around 46.5% of total documents. Earlier shorter spikes of increased post epidemic publications followed by decreased productivity were detected in the last 2 decades and showed a lack of continuity-'a research epidemic following a disease epidemic'. Articles (53.4%) were the most common publication type. Journal of Virology, British Medical Journal (BMJ), and Virology were leading sources while BMJ, and Lancet showed increased contributions recently. Overall, similar trends of top authors were observed in terms of productivity, impact, collaborations, funding sources, and affiliations with few exceptions mainly from affected regions. Top 20 countries contributed >89% of documents suggesting a lack of global efforts. Networking was found to be mainly among developed nations with limited contributions from resource-limited countries perhaps requiring more cooperation. Recent post-COVID publications rise is highest, unprecedented, and rapidly growing. Authors strongly recommend recent COVID-19 pandemic as a call for continuous, more cooperative, and collective global research.

Optimal glycaemic and blood pressure but not lipid targets are related to a lower prevalence of diabetic microvascular complications.

BACKGROUND: Diabetic microvascular complications are a major cause of morbidity and are related to glycaemic control and cardiovascular risk factors. AIMS: We sought to determine the association of microvascular complications in relation to control of glycemia, blood pressure and lipids in T2DM patients attending secondary care in Qatar. METHODS: This is a cross-sectional study undertaken in patients with T2DM attending Qatar's National Diabetes Centres. Patients underwent assessment of glycemia, blood pressure and lipids and prevalence of diabetic peripheral neuropathy (DPN), retinopathy and microalbuminuria. RESULTS: We included 1114 subjects aged 52.1 ± 11.3 years with a duration of diabetes 10.0 ± 7.6 years and had a prevalence of 25.8% for DPN, 34.3% for painful DPN, 36.8% for microalbuminuria and 25.1% for retinopathy. Patients who achieved an HbA1c ≤ 7.0% compared to >7% had a significantly lower prevalence of DPN (P < 0.01), painful DPN (P < 0.01), retinopathy (P < 0.01) and microalbuminuria (P < 0.007). Patients who achieved a systolic BP ≤ 140 mmHg compared to >140 mmHg had a significantly lower prevalence of DPN (P < 0.001), painful DPN (P < 0.001), retinopathy (P < 0.001) and microalbuminuria (P < 0.001). Patients who achieved an LDL ≤2.6 mmol/l compared to >2.6 mmol/l had a significantly higher prevalence of DPN (P < 0.03), but no difference in other outcomes. There was no difference in microvascular complications between those who achieved a HDL-C ≥ 1.02 mmol/l, and among those who achieved triglycerides ≤1.7 mmol/l. CONCLUSIONS: Optimal control of glycemia and blood pressure, but not lipids is associated with a lower prevalence of diabetic microvascular complications.

Outcomes of atrial fibrillation hospitalizations in patients with systemic lupus erythematosus: a report from the national inpatient sample.

This study compares outcomes of patients admitted for atrial fibrillation (AF) with and without coexisting systemic lupus erythematosus (SLE). The primary outcome was inpatient mortality. Hospital length of stay (LOS), total hospital charges, odds of undergoing ablation, pharmacologic cardioversion and electrical cardioversion were secondary outcomes of interest. Data were abstracted from the National Inpatient Sample (NIS) 2016 and 2017 database. The NIS was searched for adult hospitalizations with AF as principal diagnosis with and without SLE as secondary diagnosis using International Classification of Diseases, Tenth Revision, Clinical Modification codes. Multivariate logistic and linear regression analysis was used accordingly to adjust for confounders. There were over 71 million discharges included in the combined 2016 and 2017 NIS database. 821,630 hospitalizations were for adult patients, who had a principal diagnosis of AF, out of which, 2645 (0.3%) had SLE as secondary diagnosis. Hospitalizations for AF with SLE had similar inpatient mortality (1.5% vs 0.91%, adjusted OR (AOR): 1.0, 95% CI 0.47 to 2.14, p=0.991), LOS (4.2 vs 3.4 days, p=0.525), total hospital charges ($51,351 vs $39,121, p=0.056), odds of undergoing pharmacologic cardioversion (0.38% vs 0.38%, AOR: 0.90, 95% CI 0.22 to 3.69, p=0.880) and electrical cardioversion (12.9% vs 17.5%, AOR 0.87, 95% CI 0.66 to 1.15, p=0.324) compared with those without SLE. However, SLE group had increased odds of undergoing ablation (6.8% vs 4.2%, AOR: 1.9, 95% CI 1.3 to 2.7, p<0.0001). Patients admitted for AF with SLE had similar inpatient mortality, LOS, total hospital charges, likelihood of undergoing pharmacologic and electrical cardioversion compared with those without SLE. However, SLE group had greater odds of undergoing ablation.