Search

Background: Although effective antihypertensive medications have existed for decades, only about half of the hypertensive individuals are considered to have controlled blood pressure. Limited research studies have investigated gender disparity in the utilization and effectiveness of antihypertensive medications treatment. To examine the gender difference in antihypertensive medications’ use and the effect of using antihypertensive medication treatment on blood pressure control among the U.S. adult with hypertension. Methods: Analysis of National Health and Nutrition Examination Survey (NHANES) data from (1999-2012) including individuals≥18 years old with hypertension. Study variables included gender, age, race/ethnicity, obesity, smoking, comorbidities, treatment medication type, and continuity of care. We used multivariate logistic regression in STATA V14. The data is presented as adjusted odds ratios (ORs) and 95% confidence interval (CI). Results: Of the 15719 participants, 52% were female. 49% of the antihypertensive medication users had their blood pressure under control (95% CI). In the adjusted logistic regression analysis, use of antihypertensive medications was found to be 12% greater in females as compared to males (OR=1.12; CI=1.02-1.22; P

In parallel with the decline of renal excretory function, drug dosing of many drugs becomes more challenging. Finding the right dose is even more difficult if kidney replacement therapy is instituted. This is further aggravated by the fact that even for substances with a narrow therapeutic range, drug monitoring is only rarely offered, let alone advocated. This holds also true for gabapentin, an anticonvulsant drug that is increasingly prescribed for indications such as cancer-related pain, restless legs syndrome, migraine, or uremic pruritus. The drug is excreted unchanged in urine, so plasma clearance of gabapentin is directly proportional to creatinine clearance. Hence, renal impairment reduces gabapentin excretion and increases plasma gabapentin concentrations in a linear fashion. Therefore, the elimination half-life of gabapentin is between 5 and 9 h, in patients with normal renal function but increases to 132 h in patients on dialysis. Epidemiological data from the USRDS underline this problem. About 19% of the 140,899 adult USA patients enrolled in Medicare coverage received gabapentin in 2011. Its use was associated with an increased risk of altered mental status, fall, and fracture. We report 2 patients in which overdose of gabapentin occurred. In 1 patient, severe neurological symptoms prompted an extensive diagnostic work up, while the underlying cause of the clinical presentation was a supra-therapeutic drug level of gabapentin. Consequently, symptoms subsided with the discontinuation of the drug. Indication and drug dose of gabapentin in dialysis patients should be tightly controlled, and drug monitoring used to avoid unintended overdose.

Purpose: The COVID-19 pandemic continues to have major and long-lasting impacts on health care delivery and mental health. As health care shifted to telehealth, legislation was adjusted to expand telehealth allowances, creating a unique opportunity to elucidate outcomes. The aim of this study was to assess long-term patient and clinician satisfaction and outcomes with virtual behavioral health. Methods: Data were obtained over 16 months from surveys to patients and clinicians receiving/providing virtual treatment. Outcomes data also were collected from medical records of adults receiving in-person and virtual behavioral health treatment. Data were summarized using descriptive statistics. Groups were compared using various chi-squared tests for categorical variables, Likert response trends over time, and conditional independence, with Wilcoxon rank-sum or Jonckheere trend test used to assess continuous variables. P-values of ≤ 0.05 were considered statistically significant. Results: Patients gave high ratings to virtual treatment and indicated a preference for virtual formats. Both patient and clinician preference for virtual visits increased significantly with time, and many clinicians perceived virtual services to be equally effective to in-person. Virtual programs had higher completion rates, attendance rates, and number of treatment visits, suggesting that virtual behavioral health had equivalent or better outcomes to in-person treatment and that attitudes toward telehealth changed over time. Conclusions: If trends found in this study continue, telehealth may emerge as a preferred option long term This is important considering the increase in mental health needs associated with the COVID-19 pandemic and the eventuality that in-person restrictions ease as the pandemic subsides.

Abstract Background Heart transplantation (HTx) from brainstem dead (BSD) donors is the gold-standard therapy for severe/end-stage cardiac disease, but is limited by a global donor heart shortage. Consequently, innovative solutions to increase donor heart availability and utilisation are rapidly expanding. Clinically relevant preclinical models are essential for evaluating interventions for human translation, yet few exist that accurately mimic all key HTx components, incorporating injuries beginning in the donor, through to the recipient. To enable future assessment of novel perfusion technologies in our research program, we thus aimed to develop a clinically relevant sheep model of HTx following 24 h of donor BSD. Methods BSD donors (vs. sham neurological injury, 4/group) were hemodynamically supported and monitored for 24 h, followed by heart preservation with cold static storage. Bicaval orthotopic HTx was performed in matched recipients, who were weaned from cardiopulmonary bypass (CPB), and monitored for 6 h. Donor and recipient blood were assayed for inflammatory and cardiac injury markers, and cardiac function was assessed using echocardiography. Repeated measurements between the two different groups during the study observation period were assessed by mixed ANOVA for repeated measures. Results Brainstem death caused an immediate catecholaminergic hemodynamic response (mean arterial pressure, p = 0.09), systemic inflammation (IL-6 - p = 0.025, IL-8 - p = 0.002) and cardiac injury (cardiac troponin I, p = 0.048), requiring vasopressor support (vasopressor dependency index, VDI, p = 0.023), with normalisation of biomarkers and physiology over 24 h. All hearts were weaned from CPB and monitored for 6 h post-HTx, except one (sham) recipient that died 2 h post-HTx. Hemodynamic (VDI - p = 0.592, heart rate - p = 0.747) and metabolic (blood lactate, p = 0.546) parameters post-HTx were comparable between groups, despite the observed physiological perturbations that occurred during donor BSD. All p values denote interaction among groups and time in the ANOVA for repeated measures. Conclusions We have successfully developed an ovine HTx model following 24 h of donor BSD. After 6 h of critical care management post-HTx, there were no differences between groups, despite evident hemodynamic perturbations, systemic inflammation, and cardiac injury observed during donor BSD. This preclinical model provides a platform for critical assessment of injury development pre- and post-HTx, and novel therapeutic evaluation.

Purpose – Happiness levels differ among the Middle East and North African (MENA) countries and follow a downtrend, making such heterogeneity a popular topic to investigate. The paper aims to study the contribution of governance quality on the heterogeneity in happiness levels across MENA countries while controlling for demographic and socioeconomic variables. Design/methodology/approach – The paper applies panel random-effects regression analysis on three samples: full sample, rich and poor subsamples, using data from 20 MENA countries over the 2007–2017 period. Findings – The empirical results for the full sample conclude that better technical quality of governance increases happiness in the region. Furthermore, findings suggest that political stability and absence of violence matters for people's happiness only in rich countries. Whereas, control of corruption is positively associated with happiness level in the full sample and poor subsample. Across all three samples, voice and accountability has no impact on happiness. Research limitations/implications – A possible limitation of the paper is using an index for happiness based on a subjective weight distribution. Therefore, researchers are encouraged to implement a novel method using data envelopment analysis. Practical implications – This paper includes implications for policymakers in the MENA region. Governments should strengthen existing laws and create a comprehensive database of laws, fight corruption and prioritize raising income. Originality/value – This paper is the first to categorize MENA countries into rich and poor to analyze how governance quality contributes to the heterogeneity in happiness levels.

Abstract Background Cerebral regional microcirculation is altered following severe head injury. In addition to tissue disruption, partial pressure of tissue oxygenation is impaired due to an increase in the oxygen tissue gradient. The heterogenic distribution of cerebral microcirculation is multifactorial, and acute anemia challenges further the delivery of oxygen to tissues. Currently, a restrictive transfusion threshold is globally applied; however, it is unclear how anemia modifies regional cerebral microcirculation; hence, it is unclear if by aiming to a global endpoint, specific anatomical regions undergo ischemia. This study aims to quantify the temporal changes in cerebral microcirculation after severe head injury, under the effect of anemia and transfusion. It also aims to assess its effects specifically at the ischemic penumbra compared to contralateral regions and its interactions with axonal integrity in real time. Twelve ovine models were subjected to a severe contusion and acceleration-deceleration injury. Normovolemic anemia to a restrictive threshold was maintained after injury, followed by autologous transfusion. Direct quantification of cerebral microcirculation used cytometric count of color-coded microspheres. Axonal injury was assessed using amyloid precursor protein staining. Results A mixed-effect regression model from pre-transfusion to post-transfusion times with a random intercept for each sheep was used. Cerebral microcirculation amongst subjects with normal intracranial pressure was maintained from baseline and increased further after transfusion. Subjects with high intracranial pressure had a consistent reduction of their microcirculation to ischemic thresholds (20–30 ml/100 g/min) without an improvement after transfusion. Cerebral PtiO2 was reduced when exposed to anemia but increased in a 9.6-fold with transfusion 95% CI 5.6 to 13.6 (p value

Abstract Background Nebulised antibiotics are frequently used for the prevention or treatment of ventilator-associated pneumonia. Many factors may influence pulmonary drug concentrations with inaccurate dosing schedules potentially leading to therapeutic failure and/or the emergence of antibiotic resistance. We describe a research pathway for studying the pharmacokinetics of a nebulised antibiotic during mechanical ventilation using in vitro methods and ovine models, using tobramycin as the study antibiotic. Methods In vitro studies using a laser diffractometer and a bacterial-viral filter were used to measure the effect of the type and size of tracheal tubes and antibiotic concentration on the particle size distribution of the tobramycin 400 mg (4 ml; 100 mg/ml) and 160 mg (4 ml, 40 mg/ml) aerosol and nebulised mass delivered. To compare the regional drug distribution in the lung of two routes (intravenous and nebulised) of drug administration of tobramycin 400 mg, technetium-99m-labelled tobramycin 400 mg with planar nuclear medicine imaging was used in a mechanically ventilated ovine model. To measure tobramycin concentrations by intravenous and nebulised tobramycin 400 mg (4 ml, 100 mg/ml) administration in the lung interstitial space (ISF) fluid and blood of mechanically ventilated sheep, the microdialysis technique was used over an 8-h duration. Results Tobramycin 100 mg/ml achieved a higher lung dose (121.3 mg) compared to 40 mg/ml (41.3 mg) solution. The imaging study with labelled tobramycin indicated that nebulised tobramycin distributed more extensively into each lung zone of the mechanically ventilated sheep than intravenous administration. A higher lung ISF peak concentration of tobramycin was observed with nebulised tobramycin (40.8 mg/l) compared to intravenous route (19.0 mg/l). Conclusions The research methods appear promising to describe lung pharmacokinetics for formulations intended for nebulisation during mechanical ventilation. These methods need further validation in an experimental pneumonia model to be able to contribute toward optimising dosing regimens to inform clinical trials and/or clinical use.

BackgroundCerebral microcirculation after severe head injury is heterogeneous and temporally variable. Microcirculation is dependent upon the severity of injury, and it is unclear how histology relates to cerebral regional blood flow.ObjectiveThis study assesses the changes of cerebral microcirculation blood flow over time after an experimental brain injury model in sheep and contrasts these findings with the histological analysis of the same regions with the aim of mapping cerebral flow and tissue changes after injury.MethodsMicrocirculation was quantified using flow cytometry of color microspheres injected under intracardiac ultrasound to ensure systemic and homogeneous distribution. Histological analysis used amyloid precursor protein staining as a marker of axonal injury. A mapping of microcirculation and axonal staining was performed using adjacent layers of tissue from the same anatomical area, allowing flow and tissue data to be available from the same anatomical region. A mixed effect regression model assessed microcirculation during 4 h after injury, and those results were then contrasted to the amyloid staining qualitative score.ResultsMicrocirculation values for each subject and tissue region over time, including baseline, ranged between 20 and 80 ml/100 g/min with means that did not differ statistically from baseline flows. However, microcirculation values for each subject and tissue region were reduced from baseline, although their confidence intervals crossing the horizontal ratio of 1 indicated that such reduction was not statistically significant. Histological analysis demonstrated the presence of moderate and severe score on the amyloid staining throughout both hemispheres.ConclusionMicrocirculation at the ipsilateral and contralateral site of a contusion and the ipsilateral thalamus and medulla showed a consistent decline over time. Our data suggest that after severe head injury, microcirculation in predefined areas of the brain is reduced from baseline with amyloid staining in those areas reflecting the early establishment of axonal injury.

Bronchoscopy is an important diagnostic and therapeutic intervention for a variety of patients displaying pulmonary pathology. The heterogeneity of the patients undergoing bronchoscopy affords a challenge for providing minimal and safe respiratory support during anesthesia. Currently, options are intubation and general anesthesia versus frequently inadequate sedation or local anaesthesia with low flow oxygen through nasal prongs or mouthpiece. The advent of high flow nasal cannula allows the clinician to have a “middle man” that allows high flow oxygen delivery as well as a degree of respiratory support, which in some cases has been noted to be between 3 and 4 cm of continuous positive airway pressure-like effect. There are minimal data analyzing the use of high flow nasal cannula during anesthesia for bronchoscopy. We present a case report of orthotropic lung transplant recipient undergoing diagnostic bronchoscopy whilst being supported with high flow nasal oxygen in the intensive care unit.

The use of microspheres for the determination of regional microvascular blood flow (RMBF) has previously used different approaches. This study presents for the first time the intracardiac injection of microspheres using transeptal puncture under intracardiac echocardiography guidance. Five Merino sheep were instrumented and cardiovascularly supported according to local guidelines. Two catheter sheaths into the internal jugular vein facilitated the introduction of an intracardiac probe and transeptal catheter, respectively. Five million colour coded microspheres were injected into the left atrium via this catheter. After euthanasia the brain was used as proof of principle and the endpoint for determination of microcirculation at different time points. Homogeneous allocation of microspheres to different regions of the brain was found over time. Alternate slices from both hemispheres showed the following flow ranges: for slice 02; 0.57–1.02 mL/min/g, slice 04; 0.45–1.42 mL/min/g, slice 06; 0.35–1.87 mL/min/g, slice 08; 0.46–1.77 mL/min/g, slice 10; 0.34–1.28 mL/min/g. A mixed effect regression model demonstrated that the confidence interval did include zero suggesting that the apparent variability intra- and intersubject was not statistically significant, supporting the stability and reproducibility of the injection technique. This study demonstrates the feasibility of the transeptal injection of microspheres, showing a homogeneous distribution of blood flow through the brain unchanged over time and has established a new interventional model for the measurement of RMBF in ovine models.