Effect of a multicomponent intervention on achievement and improvements in quality-of-care indices among people with Type 2 diabetes in South Asia: the CARRS trial.

AIMS: To evaluate whether and what combinations of diabetes quality metrics were achieved in a multicentre trial in South Asia evaluating a multicomponent quality improvement intervention that included non-physician care coordinators to promote adherence and clinical decision-support software to enhance physician practices, in comparision with usual care. METHODS: Using data from the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) trial, we evaluated the proportions of trial participants achieving specific and combinations of five diabetes care targets (HbA1c <53 mmol/mol [7%], blood pressure <130/80 mmHg, LDL cholesterol <2.6 mmol/L, non-smoking status, and aspirin use). Additionally, we examined the proportions of participants achieving the following risk factor improvements from baseline: ≥11-mmol/mol (1%) reduction in HbA1c , ≥10-mmHg reduction in systolic blood pressure, and/or ≥0.26-mmol/l reduction in LDL cholesterol. RESULTS: Baseline characteristics were similar in the intervention and usual care arms. Overall, 12.3%, 29.4%, 36.5%, 19.5% and 2.2% of participants in the intervention group and 16.2%, 38.3%, 31.6%, 11.3% and 0.8% of participants in the usual care group achieved any one, two, three, four or five targets, respectively. We noted sizeable improvements in HbA1c , blood pressure and cholesterol, and found that participants in the intervention group were twice as likely to achieve improvements in all three indices at 12 months that were sustained over 28 months of the study [relative risk 2.1 (95% CI 1.5,2.8) and 1.8 (95% CI 1.5,2.3), respectively]. CONCLUSIONS: The intervention was associated with significantly higher achievement of and greater improvements in composite diabetes quality care goals. However, among these higher-risk participants, very small proportions achieved the complete group of targets, which suggests that achievement of multiple quality-of-care goals is challenging and that other methods may be needed in closing care gaps.

Characterizing Agreement in the Level of Interarm Blood Pressure Readings of Adults in the Emergency Department (CALIBRATE Study).

Background: Increased interarm systolic blood pressure difference (IASBPD) is one of the major predictors of cardiovascular disease. An IASBPD of >10 mmHg is of clinical significance. However, studies have reported a high number of patients visiting the emergency department (ED) with high IASBPD and varying correlation of IASBPD to age, ethnic background, and comorbidities such as hypertension and diabetes. Objective: The CALIBRATE study aimed to measure the IABPDs in the multiethnic patient population presenting to the ED in Qatar and to assess the distribution of IASBPD in this population. Methods: In a sitting position, two consecutive blood pressure (BP) measurements were recorded from the right and left arms for each participant using a calibrated automated machine and appropriate cuff sizes. The data were recorded using predefined data fields, including patient demographics, past medical, and social and family history. The continuous variables were reported as mean or median based on the distribution of data. The data were analyzed using Stata MP 14.0. Results: A total of 1800 patients, with a mean age of 34 (10) years, were prospectively recruited from the ED. The median absolute systolic BP difference (ΔSBP) between the right and left arms was 6 (3-10) mmHg, and it was the same for the first (ΔSBP1) and the second readings (ΔSBP2). The absolute average of ΔSBP1 and ΔSBP2 was 7 (4-10) mmHg. The difference in systolic BP difference (SBP) of < 20 mmHg for interarm blood pressure was seen in the 95th percentile of the population. No meaningful association could be detected between the IABPD and the study variables such as age, demographics, regions of interest, and risk factors. Conclusion: In population presenting to the ED, the IASBPD of at least 20 mmHg reached at the 95th percentile, validating the known significant difference. The utility of SBP difference can be improved further by taking the average of two individual readings.

Association between occlusal force distribution in implant overdenture prostheses and residual ridge resorption.

This study aimed to investigate residual ridge resorption (RRR) of anterior and posterior maxillary and mandibular edentulous ridges, in patients treated with mandibular implant overdentures (IOD) and compare with conventional complete denture (CD) wearers, and to determine at each location, the association of RRR with the occlusal forces distribution and other patients' variables. The anterior and posterior RRR of IOD (six males, 17 females) and CD (12 males, 11 females) groups were determined using baseline and follow-up dental panaromic radiographs (DPT) (mean intervals 4 ± 1·8 years). The bone ratios were calculated using proportional area: anatomic to fixed reference areas and mean difference of ratios between the intervals determined RRR. The ridge locations included anterior and posterior maxillary and posterior mandibular arches. The T-Scan III digital occlusal system was used to record anterior and posterior percentage occlusal force (%OF) distributions. There were significant differences in anterior and posterior %OF between treatment groups. Two-way anova showed RRR was significant for arch locations (P = 0·005), treatment group (IOD versus CD) (P = 0·001), however, no significant interaction (P = 0·799). Multivariate regression analyses showed significant association between RRR and %OF at anterior maxilla (P = 0·000) and posterior mandible (P = 0·023) and for treatment groups at posterior maxilla (P = 0·033) and mandibular areas (P = 0·021). Resorption was observed in IOD compared to CD groups, with 8·5% chance of less resorption in former and 7·8% in the latter location. Depending on arch location, ridge resorption at various locations was associated with occlusal force distribution and/or treatment groups (implant prostheses or conventional complete dentures).

Chromatographic method development and validation for the determination of valsartan in biological fluid.

A swift, precise and simple HPLC bioanalytical technique with UV detection was established and validated for quantitative estimation of valsartan in human plasma. The analyte was separated from plasma by protein precipitation with acetonitrile and chromatographically separated on Zorbax SB-C18 (5µm, 4.6mm × 15cm) column. The solvent mixture system consisting of acetonitrile, water and glacial acetic acid (40:59:1 v/v), was pumped using isocratic mode at 1mL/min flow rate. Samples' detection of drug was made spectrophotometrically at a wavelength of 264nm. The analyte response was instituted to be linear from 0.06 to 8µg/mL with a regression value of 0.999. The accuracy of the proposed method was ranged between 97.2-100.3% with 5% RSD. The analytical recovery (>95%) was consistently observed and satisfactory sample stability was also found at different environmental conditions. In conclusion the reported bio-analytical method is easy and robust that was successfully utilized in estimation of valsartan in a pharmacokinetic study.

Induced pluripotent stem cell model recapitulates pathologic hallmarks of Gaucher disease.

Gaucher disease (GD) is an autosomal recessive disorder caused by mutations in the acid ß-glucocerebrosidase gene. To model GD, we generated human induced pluripotent stem cells (hiPSC), by reprogramming skin fibroblasts from patients with type 1 (N370S/N370S), type 2 (L444P/RecNciI), and type 3 (L444P/L444P) GD. Pluripotency was demonstrated by the ability of GD hiPSC to differentiate to all three germ layers and to form teratomas in vivo. GD hiPSC differentiated efficiently to the cell types most affected in GD, i.e., macrophages and neuronal cells. GD hiPSC-macrophages expressed macrophage-specific markers, were phagocytic, and were capable of releasing inflammatory mediators in response to LPS. Moreover, GD hiPSC-macrophages recapitulated the phenotypic hallmarks of the disease. They exhibited low glucocerebrosidase (GC) enzymatic activity and accumulated sphingolipids, and their lysosomal functions were severely compromised. GD hiPSC-macrophages had a defect in their ability to clear phagocytosed RBC, a phenotype of tissue-infiltrating GD macrophages. The kinetics of RBC clearance by types 1, 2, and 3 GD hiPSC-macrophages correlated with the severity of the mutations. Incubation with recombinant GC completely reversed the delay in RBC clearance from all three types of GD hiPSC-macrophages, indicating that their functional defects were indeed caused by GC deficiency. However, treatment of induced macrophages with the chaperone isofagomine restored phagocytosed RBC clearance only partially, regardless of genotype. These findings are consistent with the known clinical efficacies of recombinant GC and isofagomine. We conclude that cell types derived from GD hiPSC can effectively recapitulate pathologic hallmarks of the disease.

Alfalfa weevils (Coleoptera: Curculionidae) in the western United States are resistant to multiple type II pyrethroid insecticides.

The alfalfa weevil (Hypera postica Gyllenhal (Coleoptera: Curculionidae)), a key pest of alfalfa (Medicago sativa L. (Fabales: Fabacae)) across the US, has developed resistance to pyrethroids lambda-cyhalothrin and zeta-cypermethrin in at least 6 western US states. Unfortunately, 6 pyrethroid active ingredients represent most commercial insecticides registered for alfalfa weevil control in forage alfalfa systems. Thus, the loss of efficacy of this mode of action group due to multiple resistance represents a significant agricultural challenge because of a limited registered alternative mode of actions. To evaluate the extent and severity of resistance among pyrethroids around the United States, laboratory bioassays using larvae from Arizona, California, Montana, Oregon, Washington, and Wyoming, including both the Egyptian and western strains, were conducted. Results indicated that similar degrees of resistance among type II pyrethroids as determined by both laboratory bioassays and field trials exist. The LC50 values of alpha-cypermethrin, beta-cyfluthrin and zeta-cypermethrin produced significant correlations with the LC50 values of lambda-cyhalothrin. In contrast, resistance did not include type I pyrethroid, bifenthrin (registered for seed alfalfa production), whose LC50 values yielded a slope not significantly different from zero when correlated with lambda-cyhalothrin. Field trials conducted in Arizona, Montana, and Washington corroborated laboratory results, as commercial formulations with type II pyrethroid active ingredients failed to adequately control alfalfa weevils resistant to lambda-cyhalothrin. Integrated resistance management recommendations are discussed.

Surgically implanted endovascular, microaxial left ventricular assist device: A single institution study.

Objective: The Impella 5.5 (Abiomed, Inc), a surgically implanted endovascular microaxial left ventricular assist device, is increasingly used worldwide and there have been more than 10,000 implants. The purpose of this study is to describe a large-volume, single-center experience with the use of the Impella 5.5. Methods: Data were obtained retrospectively from patients supported with the Impella 5.5 implanted at our institution from May 1, 2020, to December 31, 2022. Demographic, operative, and postoperative outcomes for each group are described. Results are reported in median (interquartile range) or n (%). The entire cohort was divided into 5 main groups based on the intention to treat at the time of the Impella 5.5 implantation: (1) patients who had a planned Impella 5.5 implanted at the time of high-risk cardiac surgery; (2) patients with cardiogenic shock; (3) patients bridged to a durable left ventricular assist device; (4) patients bridged to transplant; and (5) patients with postcardiotomy shock who received an unplanned Impella 5.5 implant. Results: A total of 126 patients were supported with the Impella 5.5. Overall survival to device explant was 76.2%, with 67.5% surviving to discharge. Midterm survival was assessed with a median follow-up time of 318 days and demonstrated an overall survival of 60.3% and a median of 650 days (549-752). Conclusions: Outcomes after using the Impella 5.5 are variable depending on the indication of use. Patient selection may be of utmost importance and requires further experience with this device to determine who will benefit from insertion.

Alcohol is not a risk factor for oral cancer in nonsmoking, betel quid non-chewing individuals. A meta-analysis update.

BACKGROUND: Alcohol drinking is associated with high oral cancer (OC) risk. This association is particularly evident in tobacco smoking/betel quid (BQ) chewing subjects. In a previous stratified meta-analysis (Petti S et al., Cancer Epidemiol 2012) we reported that drinking was inversely associated with OC in non-smoking BQ non-chewing individuals, while this association was reversed in smoking individuals. However, the previous study could be excessively influenced by a large primary study, which yielded more than 50% of the weight of all the primary studies. Therefore, we updated this analysis using only recent studies. METHODS: Case-control studies published between 2010 and 2012 were searched. In each study, non-smoking/ BQ non-chewing exposed (ever routine drinkers) and unexposed (never drinkers) subjects with (cases)/without (controls) OC were extracted and odds ratio (OR) calculated. Between-study heterogeneity was assessed with Cochran's Q. Publication bias was formally assessed with trim and fill method. Sensitivity analysis to inclusion criteria was made. The pooled OR was assessed with the fixed- and random-effect methods and corrected for publication bias. RESULTS: Seven of these studies met the inclusion criteria: they were not heterogeneous enough. Correction for publication bias was not necessary and provided only one missing study. The OR estimates were 0.70 (95% confidence interval -95CI, 0.51-0.98), 0.70 (95CI, 0.51-0.96), 0.75 (95CI, 0.54-1.03) with the three methods. Sensitivity analysis did not change the OR estimates considerably. CONCLUSIONS: This analysis corroborated the results of the previous analysis, confirming that drinking was inversely associated with OC in non-smoking, BQ non-chewing subjects.

Oral complications associated with metal ion release from oral piercings: a systematic review.

PURPOSE: This systematic review explored dental complications associated with metal ion release from oral piercings using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. METHODS: Item retrieval from October 2022 to December 2022 from databases, such as Cochrane Central Register of Controlled Trials, Medline, PubMed, Embase, Scopus and Web of Science, using predefined search terms was undertaken by two independent reviewers. Data were extracted and risk of bias was assessed using the Joanna Briggs Institute (JBI) critical appraisal checklist. From 1509 identified studies, 25 were included for analysis. RESULTS: Of the 25 studies, 20 included both clinical examination and questionnaire-based data. The remaining five studies were deemed low quality based on the Joanna Briggs Institute criteria. The average time piercings were worn ranged between 5 and 48 months. Most studies did not investigate complications from metal ion release. Only two studies examined the direct effects of metal ion release and showed that metal ions may cause hypersensitivity reactions and mucosal changes. Other soft tissue complications were reported, with gingival recession noted in 16 out of 25 studies, especially due to lip piercings. Studies reporting other complications were as follows: swelling (9), pain (8), infection (6), bleeding (6), inflammation (5), alterations to speech, eating and/or swallowing (5), changes to taste or metallic taste (5), and mucosal changes (4). Ten studies reported tooth chipping from tongue piercings. CONCLUSION: Oral piercings leach metal ions into surrounding tissues which may cause local mucosal changes. Furthermore, oral piercings cause damage to both soft and hard oral tissues, particularly gingival recession for lip piercings and tooth chipping for tongue piercings. Thus, to prevent such adverse injuries, dental professionals should discourage patients against oral piercings.

Ion release from oral piercings from in vitro acidic challenges.

OBJECTIVES: This laboratory-based study measured ion release from metallic piercings when exposed to organic acids (lactic, citric) and inorganic acids (phosphoric, hydrochloric) that could be encountered in the oral cavity. METHODS: Barbell and ring oral piercings composed of stainless steel, titanium or gold-plated titanium were submerged in 2 mL volumes of 0.1% lactic acid, 10% citric acid, 0.2% phosphoric acid, and 0.1% hydrochloric acid for 7 and 34 days. Ion release into the liquid was measured using inductively coupled plasma optical emission spectroscopy (ICPOES) and expressed in relationship to surface area. Surface changes from baseline were assessed using light and backscatter scanning electron microscopy (SEM). RESULTS: ICPOES results showed that hydrochloric and phosphoric acid caused the greatest release of material per surface area. Released elements included (ranked highest to lowest): Fe, P, Ti, Na, Cr, S, Ni, Ca, Mg, K, Si, Al, V, Mn, Ba, and Co. SEM imaging identified qualitative surface changes consistent with corrosion, for most piercing types examined. CONCLUSIONS: Under the exposure conditions used, inorganic acids cause greater metal dissolution than organic acids. Inorganic acids could therefore pose a risk of corrosion and leaching of ions from metallic oral piercings.

Management of severe tricuspid valve regurgitation due to ruptured papillary muscle in a patient with mediastinitis early after heart transplant.

Objective: Even though severe tricuspid regurgitation is not uncommon after cardiac transplantation, primary severe tricuspid regurgitation is rare. We present such a case with additional complexities. Methods: The patient was 44-year-old man with a HeartWare durable left ventricular assist device (Heartware Inc) who received a temporary right ventricular assist device (RVAD) with a ProtekDuo cannula (LivaNova Inc USA) for refractory ventricular fibrillation and underwent a heart transplant as United Network for Organ Sharing Status 1, in the presence of partially compensated cardiogenic shock, renal failure. Given complex re-operative surgery in a volume-overloaded patient with unknown pulmonary vascular resistance, an RVAD cannula was preserved and re- inserted during cardiac transplant. Postoperatively he required hemodialysis, had severe primary tricuspid regurgitation discovered after RVAD removal and developed Enterobacter mediastinitis. He underwent complex tricuspid valve repair for flail tricuspid leaflet due to ruptured papillary muscle likely due to RVAD cannula injury, after multiple mediastinal washouts and was followed by delayed chest reconstruction. Results: The patient is doing well, 6 months after discharge to home, asymptomatic, without re-admissions, on renal recovery path, with no tricuspid regurgitation and good biventricular function. Conclusions: Replacing the tricuspid valve in presence of hemodialysis catheter, immunosuppression and mediastinitis could be high risk for endocarditis. Even though we have short-term follow-up, tricuspid valve repair can be an effective way of managing primary severe regurgitation especially when there is a desire or need to avoid valve replacement.

Predictors of antibiotic use in pregnant women attending Najran University Hospital, Saudi Arabia.

OBJECTIVES: To determine the prevalence of antibiotic use by pregnant women in Najran, Saudi Arabia. METHODS: A total of 125 women aged 18 to 45 with a full-term pregnancy participated from October to December 2019. Age, order of current pregnancy, body mass index (BMI), history of miscarriage, and comorbidity were used to estimate antibiotic use. RESULTS: The majority were Saudis (67.2%), aged 30-35 (39.2%) years, with no history of miscarriage (53.6%), second order of pregnancy (26.4%), and going through weeks 20-25 of pregnancy (21.6%). A total of 26.4% of pregnant women had antibiotic prescriptions in the study population. Pregnant women under 30 years were less likely to receive antibiotics. CONCLUSION: The results found an association between maternal age, order of pregnancy and antibiotic use during pregnancy. An association was observed between maternal BMI and the occurrence of adverse drug reactions after antibiotic use. In addition, a history of miscarriage was negatively associated with the use of antibiotics during pregnancy. These predictors of antibiotic administration have the potential to serve as general health indicators and to direct preventative strategies aimed at increasing the rational use of antibiotics.

Use of libraries to access new chemical space: applications to CRTH2.

The generation of novel CRTH2 ligands in heavily congested chemical space, by de novo design of libraries is disclosed. Novel (1719) compounds across seven libraries were synthesised. More than 100 of these compounds showed binding potency <3 µM against CRTH2, with the most potent being 247 nM. These libraries produced novel series and demonstrated that this approach is a viable one.

Lead diversification. Application to existing drug molecules: mifepristone 1 and antalarmin 8.

A series of C-H functionalisation plate-based chemical screens and other C-H activation protocols were developed for the chemical diversification of drug molecules. In this Letter, metalloporphyrin and other catalytic oxidation systems are described in addition to chlorination. Mifepristone and antalarmin are used as substrates. The products obtained and the biological data demonstrate the potential utility of this approach.

Lead Diversification 2: application to P38, gMTP and lead compounds.

Lead Diversification is a new technology platform developed at Pfizer for the functionalization of drug molecules using C-H activation. We describe its application to some drug programs such as P38 and gMTP and the development of some new plate based screens including a fluorination screen.

Impact of national income and inequality on sugar and caries relationship.

OBJECTIVE: The aim of this study was to examine the impact that national income and income inequality in high and low income countries have on the relationship between dental caries and sugar consumption. METHODS: An ecological study design was used in this study of 73 countries. The mean decayed, missing, or filled permanent teeth (DMFT) for 12-year-old children were obtained from the WHO Oral Health Country/Area Profile Programme. United Nations Food and Agricultural Organization data were used for per capita sugar consumption. Gross national incomes per capita based on purchasing power parity and the Gini coefficient were obtained from World Bank data. Bivariate and multivariate linear regression analysis was performed to estimate the associations between mean DMFT and per capita sugar consumption in different income and income inequality countries. RESULTS: Bivariate and multivariate regression analysis showed that countries with a high national income and low income inequality have a strong negative association between sugar consumption and caries (B = -2.80, R2 = 0.17), whereas countries with a low income and high income inequality have a strong positive relationship between DMFT and per capita sugar consumption (B = -0.89, R2 = 0.20). CONCLUSION: The relationship between per capita consumption of sugar and dental caries is modified by the absolute level of income of the country, but not by the level of income inequality within a country.

Quantitative analysis of specific androgens in serum and urine samples from male, pre, and postmenopausal subjects using LC-MRM-MS.

Androgens are endogenous hormones that play a crucial role in the paracrine and intracrine hormone system to perform and maintain vital physiological functions. Altered levels of androgens are implicated in many diseases such as sexual dysregulation, breast cancer, prostate cancer, and heart diseases etc. In this manuscript we describe a liquid chromatography-mass spectrometry (LC-MS) method using multiple reaction monitoring (MRM) for quantitatively measuring specific androgens such as dehydroepiandrosterone, testosterone, androsterone sulphate, androstenedione, and dihydrotestosterone in serum and urine samples. Serum acquired from nine different subjects (three pre-menopausal women, three postmenopausal women, and three healthy males) were used to evaluate the developed methods. In the sample preparation methods for serum either protein precipitation or liquid-liquid extraction (LLE) was used while the analysis of urinary androgens used LLE. The extracted androgens were quantitatively measured using LC-MRM-MS to which known amounts of stable isotope labeled standards were added. This manuscript also presents a LC-MRM-MS method mode for the analysis of oxime derivatized androgens potentially to enhance the sensitivity of the assay if required, from urine and venous-drawn serum samples.

A preliminary evaluation of tick cement-cone protein extract for a vaccine against Hyalomma infestation.

Background: Vaccines have been widely exploited to prevent tick-borne infections in cattle. Most vaccines have faced failure in the field because of inconsistency in an immune response. It is presumed that the cement-cone proteins of ticks that participate in the acquisition of blood meal for ticks possess strong immune-stimulating properties and, hence, could be a useful candidate in vaccine development. Aims: We evaluated cement-cone proteins of tick Hyalomma anatolicum as a vaccine candidate against infestations of H. anatolicum and H. aegyptium in cattle. Methods: The cement-cone proteins were extracted from H. anatolicum to develop stage-reactive and immunogenic cross-reactive vaccine against the infestation of two species of ticks H. anatolicum and H. aegyptium. The immune response of the vaccine was tested against cement-cone proteins starved, partially fed, and richly fed ticks. Results: The findings of the present study demonstrated the cross-reactivity among the two species of ticks that belonged to the same genus (Hyalomma). The antigenic similarity between the two ticks species suggests that a common antigen may possibly be suitable for a vaccine against the two different species of ticks. The results have also indicated that the 23 kDa cement-cone protein of H. anatolicum and H. aegyptium may be responsible for the induction, or elicitation of immunogenic, common stage reactive, and cross-reactive host immune responses with consistent intensity throughout the life stages of ticks. Conclusion: The vaccine based upon cement-cone proteins of ticks may be a useful deterrent against tick-borne infections in cattle in countries like Pakistan.

Electronic Health Record-Based Deep Learning Prediction of Death or Severe Decompensation in Heart Failure Patients.

BACKGROUND: Surgical mechanical ventricular assistance and cardiac replacement therapies, although life-saving in many heart failure (HF) patients, remain high-risk. Despite this, the difficulty in timely identification of medical therapy nonresponders and the dire consequences of nonresponse have fueled early, less selective surgical referral. Patients who would have ultimately responded to medical therapy are therefore subjected to the risk and life disruption of surgical therapy. OBJECTIVES: The purpose of this study was to develop deep learning models based upon commonly-available electronic health record (EHR) variables to assist clinicians in the timely and accurate identification of HF medical therapy nonresponders. METHODS: The study cohort consisted of all patients (age 18 to 90 years) admitted to a single tertiary care institution from January 2009 through December 2018, with International Classification of Disease HF diagnostic coding. Ensemble deep learning models employing time-series and densely-connected networks were developed from standard EHR data. The positive class included all observations resulting in severe progression (death from any cause or referral for HF surgical intervention) within 1 year. RESULTS: A total of 79,850 distinct admissions from 52,265 HF patients met observation criteria and contributed >350 million EHR datapoints for model training, validation, and testing. A total of 20% of model observations fit positive class criteria. The model C-statistic was 0.91. CONCLUSIONS: The demonstrated accuracy of EHR-based deep learning model prediction of 1-year all-cause death or referral for HF surgical therapy supports clinical relevance. EHR-based deep learning models have considerable potential to assist HF clinicians in improving the application of advanced HF surgical therapy in medical therapy nonresponders.