Virtual screening of drug materials for pharmaceutical tablet manufacturability with reference to sticking.

The manufacturing of pharmaceutical solid dosage forms, such as tablets involves a large number of successive processing operations including crystallisation of the drug substance, granulation, drying, milling, mixing of the formulation, and compaction. Each step is fraught with manufacturing problems. Undesired adhesion of powders to the surface of the compaction tooling, known as sticking, is a frequent and highly disruptive problem that occurs at the very end of the process chain when the tablet is formed. As an alternative to the mechanistic approaches to address sticking, we introduce two different machine learning strategies to predict sticking directly from the chemical formula of the drug substance, represented by molecular descriptors. An empirical database for sticking behaviour was developed and used to train the machine learning (ML) algorithms to predict sticking properties from molecular descriptors. The ML model has successfully classified sticking/non-sticking behaviour of powders with 100% separation. Predictions were made for materials in the handbook of Pharmaceutical Excipients and a subset of molecules included in the ChemBL database, demonstrating the potential use of machine learning approaches to screen for sticking propensity early at drug discovery and development stages. This is the first-time molecular descriptors and machine learning were used to predict and screen for sticking behaviour. The method has potential to transform the development of medicines by providing manufacturability information at drug screening stage and is potentially applicable to other manufacturing problems controlled by the chemistry of the drug substance.

Risk factors for lung function decline in systemic sclerosis-associated interstitial lung disease in a large single-centre cohort.

OBJECTIVES: The aim of this study was to identify risk factors of percent predicted forced vital capacity (ppFVC) decline in patients with SSc-associated interstitial lung disease (SSc-ILD). METHODS: We identified 484 patients with SSc who had HRCT Chest, of which 312 with ILD. Those with serial pulmonary function tests were included in a longitudinal analysis (n = 184). Linear mixed effect models were fitted to assess the decline in ppFVC over time, and to explore the effect of demographics and baseline characteristics on ppFVC decline. RESULTS: The majority of SSc-ILD patients were female (76.3%) and 51.3% had diffuse cutaneous subset. The mean (s.d.) age was 53.6 (12.7) years, median disease duration since first non-RP symptoms was 2.6 years, and 48.4% of the patients had ILD extent >20% on HRCT. In the univariate analysis, longer disease duration (>2.37 years), ILD extent >20%, and anti-topoisomerase I (ATA) positivity were significantly associated with ppFVC decline. In the multivariate analysis, the only statistically significant variable associated with ppFVC decline was ATA positivity. The overall group's mean decline in ppFVC was -0.28% (P-value 0.029), with -0.13% (n = 163) in those who were alive and -8.28% (P-value 0.0002 for the change in ppFVC trajectory) in patients who died within 2 years. CONCLUSION: Our study confirms that ppFVC is a marker of survival in SSc-ILD, supporting its use for risk stratification to identify patients who may benefit from earlier interventions and treatment. Our study also supports the role of ATA positivity as a predictive marker for ppFVC decline in this population.

The Burden of Cardiac Arrhythmias in Gout: A National Representative Database Study.

The association between gout and arrhythmias has not been thoroughly examined. This study discusses the underappreciated burden, patterns, and outcomes of several arrhythmias, which may have prognostic value in patients with gout. This is a retrospective cohort study that used the US National Inpatient Sample for 2015-2019. Complex samples multivariable logistic and linear regression models were used to assess the incidence and trends in gout-related arrhythmia and consequential inpatient mortality, hospital length of stay (LOS), hospitalization charges, and predictors of mortality. Hospitalizations that included a diagnosis of gout accounted for 60,360 admissions. Arrhythmias affected roughly one-fourth of those. When compared to individuals without arrhythmia, those who experienced arrhythmias were older. Arrhythmias were found to be equally common in both men and women. The most common subtype was AF (88%), followed by atrial flutter (6.2%), conduction disorders (4.7%), and ventricular tachycardia (3.2%). In individuals with gout, there was a rising trend in arrhythmia-related hospital admissions and mortality. The gout-arrhythmia group had more traditional cardiac comorbidities. After adjusting for baseline variables, the arrhythmia group had significantly greater mortality (693 vs 77 per 100,000 hospitalizations), mean LOS (4.3 vs 3.7 days), and hospital costs ($33,057 vs $28,384). In gout, incident arrhythmia dramatically raised the risk of death (adjusted odds ratio, 2.06; 95% CI, 1.95-2.16; P < 0.001). Gout patients who are hospitalized with concurrent arrhythmia have a likelihood of longer stays in the hospital and higher mortality. Early identification and treatment of arrhythmia may benefit outcomes in gout patients.

Rapid Onset and Resolution of Hydroxychloroquine Cardiomyopathy: A Case Report.

Systemic lupus erythematosus (SLE) is an autoimmune, chronic, and heterogenous disease with organ damage resulting from immune complex deposition and inflammatory infiltrates. Antimalarial drugs, such as hydroxychloroquine (HCQ), are cornerstone immunomodulators for the treatment of SLE. Rarely, HCQ toxicity can occur, leading to devastating outcomes. We report a case of a patient with SLE on HCQ who presented with a rapid onset of large pericardial effusion and a dramatically decreased left ventricular ejection fraction. Endomyocardial biopsy was positive for curvilinear bodies, confirming the diagnosis of hydroxychloroquine cardiotoxicity. Hydroxychloroquine cardiomyopathy is a rare but life-threatening medication side effect. It is important to consider it in any patient taking the medication who presents with a new onset or worsening symptoms of heart failure.

Practical management of Raynaud's phenomenon - a primer for practicing physicians.

PURPOSE OF REVIEW: Raynaud's phenomenon (RP) is a common vasospastic condition that results in digital hypoperfusion in response to cold and/or emotional stress and is associated with significant pain and disability. The aim of our review is to provide a practical approach for clinicians to inform assessment and management of patients with RP. RECENT FINDINGS: Autoantibodies and nailfold capillaroscopy are key investigations to stratify the risk of progression to systemic sclerosis (SSc) in patients RP, which was recently confirmed in the multicenter, very early diagnosis of systemic sclerosis (VEDOSS) project. Research has explored the complex lived-patient experience of RP including digital vasculopathy in SSc and has highlighted the need for outcome measure development to facilitate research in the field. Pharmacological treatment strategies vary significantly internationally and there is continued interest in developing surgical approaches. SUMMARY: We provide a practical and up-to-date approach to inform the assessment and management of patients with RP including guidance on drug initiation and escalation. Calcium channel blockers are first-line treatment and can be initiated by primary care physicians. We also highlight second-line drug therapies used for refractory RP and the potential role for surgical intervention.

Effect of dust and methods of cleaning on the performance of solar PV module for different climate regions: Comprehensive review.

Recent achievement and progress in solar PV play a significant role in controlling climate change. This study reviewed comprehensively electrical characteristics, life cycle of dust, optical characteristics, and different cleaning techniques related to the effect of dust on the performance of PV modules throughout different climate regions of the world. The power maximum power point (MPP) and curve of PV module under the effect of irradiance and temperature were presented. The effect of dust (shading) on the electrical efficiency of PV module was discussed based on soft, partial, and complete (soiling) shading. The physical properties of dust around the globe such as PM10 concentration, dust loading (mgm-2), and fine dust particles concentration were covered and discussed. Reasons behind the accumulation of dust based on, location and installation factors, dust type, and environmental factors. Environmental reasons causing dust and dust removal in accordance with the life cycle of dust was covered in detail. All the reasons that cause the generation, accumulation and removal of dust during its life cycle were explained. All forces responsible for the adhesion phase of the dust life cycle were presented. The effect of dust on PV module transmittance and electrical parameters module were discussed in detail based on physical properties of the dust at its location and installation conditions. Self-cleaning super hydrophobic surfaces based on methods such as solvents, vapor-assisted coating, powder coating, and polymerization were discussed. All cleaning technologies, including self-cleaning technologies, based on the material coating used, and the manufacturing of PV cells was compared. The future prospective for PV technologies and cleaning methods were also covered.

Hospitalization and Post-hospitalization Outcomes Among Teaching Internal Medicine, Employed Hospitalist, and Locum Tenens Hospitalist Services in a Tertiary Center: a Prospective Cohort Study.

BACKGROUND: There are no prospective studies comparing hospitalization and post-hospitalization outcomes between teaching internal medicine services and non-teaching hospitalists, and no prospective studies comparing these outcomes between locum and employed hospitalists. OBJECTIVE: To compare the length of stay, hospital costs readmission rate, and mortality rate in patients treated by teaching internal medicine services vs. hospitalists and among patients treated by locum vs. employed hospitalists. DESIGN: Prospective cohort study. Propensity score was used to obtain weighted estimates. SETTING: Referral center. PATIENTS: All patients 18 years and older admitted to internal medicine services. INTERVENTION: Treatment by teaching internal medicine services vs. hospitalists. Treatment by locum hospitalists vs. employed hospitalists. MAIN MEASURES: Primary outcome was adjusted length of stay and secondary outcomes included hospital cost, inpatient mortality, 30-day all-cause readmission, and 30-day mortality. KEY RESULTS: A total of 1273 patients were admitted in the study period. The mean patient age was 61 ± 19 years, and the sample was 52% females. Teaching internal medicine physicians admitted 526 patients and non-teaching hospitalists admitted 747 patients. Being seen exclusively by teaching internal medicine physicians comports with a shorter adjusted hospital stay by 0.6 days (95% CI - 1.07 to - 0.22, P = .003) compared to non-teaching hospitalists. Adjusted length of stay was 1 day shorter in patients seen exclusively by locums compared to patients seen exclusively by employed services (95% CI - 1.6 to - 0.43, P < .001) with an adjusted average hospital cost saving of 1339 dollars (95% CI - 2037 to - 642, P < .001). There was no statistically significant difference in other outcomes. CONCLUSIONS: Teaching internal medicine services care was associated with a shorter stay but not with increased costs, readmission, or mortality compared to non-teaching services. In contrary to the "expected," patients treated by locums had shorter stays and decreased hospital costs but no increase in readmissions or mortality.

Epigenetics and systemic sclerosis: An answer to disease onset and evolution?

There is growing evidence that implicates epigenetic modification in the pathogenesis of systemic sclerosis (SSc). The complexity of epigenetic regulation and its dynamic nature complicate the investigation of its role in the disease. We will review the current literature for factors that link epigenetics to SSc by discussing DNA methylation, histone acetylation and methylation, and non-coding RNAs (ncRNAs), particularly microRNA changes in endothelial cells, fibroblasts (FBs), and lymphocytes. These three cell types are significantly involved in the early stages and throughout the course of the disease and are particularly vulnerable to epigenetic regulation. The pathogenesis of SSc is likely related to modifications of the epigenome by environmental signals in individuals with a specific genetic makeup. The epigenome is an attractive therapeutic target; however, successful epigenetics-based treatments require a better understanding of the molecular mechanisms controlling the epigenome and its alteration in the disease.

Pancreaticopleural Fistula: A Rare Presentation and a Rare Complication.

Pancreaticopleural fistula (PPF) is a rare complication of pancreatitis that requires a high index of clinical suspicion as patients typically present with pulmonary symptoms related to the pleural effusion rather than pancreatitis. Diagnosis is made by detection of amylase in the pleural fluid. Magnetic resonance cholangiopancreatography can aid in visualizing the fistula. We present a case of massive left pleural effusion secondary to a PPF due to acute on chronic pancreatitis.

Cannabis Smoking-induced Diffuse Alveolar Hemorrhage.

Cannabis smoking is common among adolescents and young adults. Diffuse alveolar hemorrhage (DAH) is a rare and life-threatening complication of cannabis abuse. DAH is characterized by bleeding into alveoli secondary to the disruption of the alveolar-capillary basement membrane as a result of an injury at the level of alveolar microcirculation. The differential diagnosis of DAH includes systemic vasculitis, bland pulmonary hemorrhage, and alveolar damage. The impact of cannabis on the respiratory function includes mucus hypersecretion, inflammatory edema, and increased alveolar permeability. Moreover, in vitro coagulation studies on rats showed that two major cannabinoids, cannabinol and THC, have antithrombotic activity. We present two cases of cannabis use resulting in acute lung injury and diffuse alveolar hemorrhage.

Shortness of Breath: An Unusual Presentation of Bladder Injury. A Case Report and Literature Review of Urinothorax.

Urinothorax is the presence of urine in the pleural space. It can occur at any age and is more common in males. It typically results from obstructive uropathy but can also be caused by malignancy or trauma. Urinothorax is a rare cause of transudative pleural effusion and the only cause of low pH (pH <7.4) transudative effusion. We present the case of a 51-year-old female patient who had recently undergone a urological procedure and came to the emergency department reporting shortness of breath. A chest X-ray revealed a newly developed, large, right-sided pleural effusion. Thoracentesis yielded a transudative yellow fluid of normal pH with a creatinine-to-serum creatinine ratio of 1.7. A computed tomography (CT) cystogram showed extravasated contrast material within the pelvis, from which a diagnosis of urinothorax was confirmed and treated. Urinothorax is a rare diagnosis that requires a multidisciplinary treatment approach, usually including a pulmonologist and a urologist. After the genitourinary disease is treated, the urinothorax usually resolves.

Prevalence and risk factors of obesity and hypertension among students at a central university in the West Bank.

OBJECTIVES: We aimed to determine the prevalence and correlates of obesity and hypertension (HTN) among students at a central university in the West Bank. MATERIALS AND METHODS: This cross-sectional study targeted a cohort of 553 students (59.5% males, 40.5% females) aged 17-26 years (median = 21) from Al-Quds University. Body mass index (BMI) and blood pressure (BP) were measured. Participants completed a questionnaire on physical activity, sedentary behavior, dietary factors, smoking and family history of obesity, HTN, and coronary artery disease. The magnitude of correlation was assessed by Spearman's rho (r(s)) and Chi-square tests. RESULTS: The prevalence of overweight was 25% (31.1% males, 15.6% females) and obesity 7.2% (9.4% males, 4% females). Obesity and overweight were associated with family history of obesity in both genders (p<0.001) and physical activity in males (r(s)= - 0.162, p<0.005). No correlation was demonstrated between participants' BMI and sedentary lifestyle or consumption of fast food. Pre-HTN was detected in 27.1% (38% males, 11.2% females) and HTN in 2.2% (3.3% males, 0.4% females). Pre-HTN and HTN were associated with obesity (r(s)=0.252, p<0.001) and smoking (p<0.05). No relationship was detected between students' BP and sedentary behavior, family history of HTN/CAD, or consumption of fast food. The prevalence of increased BMI and BP among males was significantly higher than females (p<0.001). CONCLUSIONS: We detected a high prevalence of elevated BP and excess weight gain among students at Al-Quds University. An interventional program is urgently needed to control these cardiovascular risk factors in this community.