Abstract Purpose A collaborative pharmacist–primary care provider (PharmD-PCP) team approach to medication-therapy management (MTM), with pharmacists initiating and changing medications at separate ...office visits, holds promise for the cost-effective management of hypertension, but has not been evaluated in many systematic trials. The primary objective of this study was to examine blood pressure (BP) control in hypertensive patients managed by a newly formed PharmD-PCP MTM team versus usual care in a university-based primary care clinic. Methods This randomized, pragmatic clinical trial was conducted in hypertensive patients randomly selected for PharmD-PCP MTM or usual care. In the PharmD-PCP MTM group, pharmacists managed drug-therapy initiation and monitoring, medication adjustments, biometric assessments, laboratory tests, and patient education. In the usual-care group, patients continued to see their PCPs. Participants were aged ≥18 years, were diagnosed with hypertension, had a most recent BP measurement of ≥140/≥90 mm Hg (≥130/≥80 mm Hg if codiagnosed with diabetes mellitus), were on at least 1 antihypertensive medication, and were English speaking. The primary outcome was the difference in the mean change from baseline in systolic BP at 6 months. Secondary outcomes included the percentage achieving therapeutic BP goal and the mean changes from baseline in diastolic BP and low- and high-density lipoprotein cholesterol. Findings A total of 166 patients were enrolled (69 men; mean age, 67.7 years; PharmD-PCP MTM group, n = 75; usual-care group, n = 91). Mean reduction in SBP was significantly greater in the PharmD-PCP MTM group at 6 months (–7.1 19.4 vs +1.6 21.0 mm Hg; P = 0.008), but the difference was no longer statistically significant at 9 months (–5.2 16.9 vs –1.7 17.7 mm Hg; P = 0.22), based on an intent-to-treat analysis. In the intervention group, greater percentages of patients who continued to see the MTM pharmacist versus those who returned to their PCP were at goal at 6 months (81% vs 44%) and at 9 months (70% vs 52%). No significant between-group differences in changes in cholesterol were detected at 6 and 9 months; however, the mean baseline values were near recommended levels. The PharmD-PCP MTM group had significantly fewer P CP visits compared with the usual-care group (1.8 1.5 vs 4.2 1.0; P < 0.001). Implications A PharmD-PCP collaborative MTM service was more effective in lowering BP than was usual care at 6 months in all patients and at 9 months in patients who continued to see the pharmacist. Incorporating pharmacists into the primary care team may be a successful strategy for managing medication therapy, improving patient outcomes and possibly extending the capacity of primary care. ClinicalTrials.gov identifier: NCT01973556.
High and variable pre-weaning mortality is a persistent problem in laboratory mouse breeding. Assuming a modest 15% mortality rate across mouse strains, means that approximately 1 million more pups ...are produced yearly in the EU to compensate for those which die. This paper presents the first large study under practical husbandry conditions to determine the risk factors associated with mouse pre-weaning mortality. We analysed historical records from 219,975 pups from two breeding facilities, collected as part of their management routine and including information on number of pups born and weaned per litter, parents' age and identification, and dates of birth and death of all animals. Pups were counted once in their first week of life and at weaning, and once every one or two weeks, depending on the need for cage cleaning. Dead pups were recorded as soon as these were found during the daily cage screening (without opening the cage). It was hypothesized that litter overlap (i.e. the presence of older siblings in the cage when new pups are born), a recurrent social configuration in trio-housed mice, is associated with increased newborn mortality, along with advanced dam age, large litter size, and a high number and age of older siblings in the cage. The estimated probability of pup death was two to seven percentage points higher in cages with litter overlap compared to those without. Litter overlap was associated with an increase in death of the entire litter of five and six percentage points, which represent an increase of 19% and 103% compared to non-overlapped litters in the two breeding facilities, respectively. Increased number and age of older siblings, advanced dam age, small litter size (less than four pups born) and large litter size (over 11 pups born) were associated with increased probability of pup death.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Few studies have assessed predictors of outcome in dogs with thyroid tumors undergoing thyroidectomy.
Objective
To estimate the survival and identify prognostic factors in dogs with ...thyroid tumors treated by thyroidectomy.
Animals
A total of 144 client‐owned dogs with thyroid neoplasia that underwent thyroidectomy.
Methods
Retrospective study. Data for analysis included hospital attended and year of surgery, signalment, thyroxine concentration, thyroid tumor features (lobe involvement, size, invasiveness, histopathological type), thrombosis, metastasis, additional surgery and therapy, administration of adjuvant chemotherapy. The association of predictors with survival (time from surgery to death) were assessed by calculating cause‐specific hazard ratios (HRcs) and 95% confidence intervals (CI). Causes of death were classified as thyroid‐related or because of other cause.
Results
Overall median survival time was 802 days (CI95% = 723‐1015 days); 89 dogs (77.4%) survived >500 days. Metastases were identified at admission in 12 (8.3%) dogs and were associated with higher thyroid cancer‐related fatality (HR = 5.83, CI95% = 1.56‐21.78; P = .009). Thrombosis occurred in 40 dogs and was associated with increased risk of death because of other cause (HR = 2.73, CI95% = 1.18‐6.35; P = .019). Nonfollicular carcinoma (HR = 4.17, CI95% = 1.27‐13.69; P = .018) and administration of chemotherapy (HR = 3.45, CI95% = 1.35‐8.82; P = .01) were associated with higher risk of thyroid cancer‐related death.
Conclusions and Clinical Importance
Dogs with thyroid tumors undergoing thyroidectomy have a long life expectancy. Despite the rare presence of nonfollicular carcinoma and metastases, thyroidectomy should still be considered in some of these dogs.
Inflammation plays a crucial role in Alzheimer's disease (AD). AD neurodegeneration and concurrent involvement of the peripheral immune system may promote leukocyte division and telomere shortening. ...We examined genotypes and plasma levels of two proinflammatory cytokines, IL-1beta and IL-18, and leukocyte telomere length (LTL) in patients with mild cognitive impairment (MCI) and AD. We wanted to determine whether changes in plasma IL-1beta and IL-18 levels, together with LTL shortening, could be diagnostic for disease progression from MCI to AD. Median plasma IL-1beta levels were in the order MCI patients (2.2 pg/ml) < AD patients (4.0 pg/ml), both of which differed significantly from the controls (0.0 pg/ml). In the AD patients, the lowest IL-1beta levels were associated with the presence of the C allele of IL-1beta rs16944 SNP. Median plasma IL-18 levels were in the order MCI patients (116.3 pg/ml) > AD patients (85.8 pg/ml), both of which were significantly higher than in the controls (17.6 pg/ml). Analysis of LTL showed a progressive reduction in the order controls > MCI > AD patients (p < 0.0001). Overall LTL reduction was correlated with increased plasma IL-1beta levels, substantiating the hypothesis that inflammatory processes secondary to neuroinflammation may trigger telomere attrition. Changes in plasma IL-1beta and Il-18 levels, and LTL seem to reflect shifts in AD stage; they may have potential use as blood biomarkers to monitor disease onset and progression from MCI to AD.
•Changes of plasma IL-1beta and IL-18 levels in AD and MCI patients were investigated.•Both interleukins had a distinctive behavior in the MCI group.•LTL in MCI group showed intermediate values between controls and AD groups.•LTL reduction was correlated with increased plasma IL-1beta levels.•Changes in serum IL-1beta and Il-18 levels and LTL seem to reflect shifts in AD stage.
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are novel oral anti-hyperglycemic drugs that demonstrate cardiovascular and metabolic benefits for patients with type 2 diabetes (T2D), heart ...failure (HF), and chronic kidney disease (CKD). There is limited knowledge of real-world data to predict adherence to SGLT-2i in an ambulatory setting. The study aims to predict SGLT-2i adherence in patients with T2D and/or HF and/or CKD by building a prediction model using electronic prescription claims data presented within EPIC datasets. This is a retrospective study of 174 adult patients prescribed SGLT-2i at UC San Diego Health ambulatory pharmacies between 1 January 2020 to 30 April 2021. Adherence was measured by the proportion of days covered (PDC). R packages were used to identify regression and non-linear regression predictive models to predict adherence. Age, gender, race/ethnicity, hemoglobin A1c, and insurance plan were included in the model. Diabetes control based on hemoglobin A1c (HbA1c) and the glomerular filtration rate (GFR) was also evaluated using Welch
-test with a
-value of 0.05. The best predictive model for measuring adherence was the simple decision tree. It had the highest area under the curve (AUC) of 74% and accuracy of 82%. The model accounted for 21 variables with the main node predictors, including glycated hemoglobin, age, gender, and insurance plan payment amount. The adherence rate was inversely proportional to HbA1c and directly proportional to the plan payment amount. As for secondary outcomes, HbA1c values from baseline till 90 days post-treatment duration were consistently higher in the non-compliant group: 7.4% vs. 9.6%,
< 0.001 for the PDC ≥ 0.80 and PDC < 0.80, respectively. Baseline eGFR was 55.18 mL/min/1.73m
vs. 54.23 mL/min/m
at 90 days. The mean eGFR at the end of the study (minimum of 90 days of treatment) was statistically different between the groups: 53.1 vs. 59.6 mL/min/1.73 m
,
< 0.001 for the PDC ≥ 0.80 and PDC < 0.80, respectively. Adherence predictive models will help clinicians to tailor regimens based on non-adherence risk scores.
Evidence supports a sex disparity in clinical outcomes of COVID-19 patients, with men exhibiting higher mortality rates compared to women. We aimed to test the correlation between serum levels of sex ...hormones total testosterone, estradiol (E2), estradiol to testosterone (E2/T) ratio, progesterone), prolactin and 25-hydroxyvitamin D 25(OH)D and markers of inflammation, coagulation and sepsis at admission in hospitalized men with COVID-19.
We conducted an exploratory retrospective study including symptomatic men with confirmed SARS-CoV-2 infection who were consecutively admitted to our Institution between April 1 and May 31, 2020.
Patients were divided into survivors (n=20) and non-survivors (n=39). As compared to survivors, non-survivors showed significantly higher median neutrophil-to-lymphocyte ratio (NLR) values, D-dimer and procalcitonin (PCT) levels, along with significantly lower median 25(OH)D levels and total testosterone levels. Non-survivors exhibited significantly higher median values of E2/T ratio (a marker of aromatase activity). Spearman's correlation analysis revealed that total testosterone levels were significantly and inversely correlated with NLR, high-sensitivity C-reactive protein (hsCRP), interleukin-6, D-dimer and PCT. Conversely, E2/T ratio values were significantly and positively correlated with the aforementioned markers and with white blood cell (WBC) count. In a multivariate analysis performed by a logistic regression model after adjusting for major confounders (age, body mass index, hypertension and cardiovascular disease, diabetes mellitus and malignancy), total testosterone levels were significantly and inversely associated with risk of COVID-19-related in-hospital mortality.
Low total testosterone levels and elevated E2/T ratio values at admission are associated with hyperinflammatory state in hospitalized men with COVID-19. Low total testosterone levels at admission represent an independent risk factor for in-hospital mortality in such patients. Therefore, total testosterone and E2/T ratio may serve as prognostic markers of disease severity in this population.
Objective
To report complications and long‐term outcomes after submucosal resections of benign and malignant epithelial rectal masses.
Study design
Retrospective multicentric study.
Sample population
...Medical records of 93 dogs at 7 referral hospitals.
Methods
Records were reviewed for surgical time, diagnosis, margins, complications, and recurrences. Survival of dogs was evaluated based on tumor types, categorized as benign, carcinoma in situ, and carcinoma. The Kaplan‐Meier survival curve and Cox proportional hazards analysis were used to determine the association of a range of variables with recurrence and survival time.
Results
Duration of follow up was 708 days (range, 25‐4383). Twenty‐seven dogs (29%) developed complications. Recurrence was identified in 20/93 (21%), with 12/20 recurrent masses treated with repeat submucosal resection. Median survival was not reached in any group. The 1‐,2‐, 5‐year survival rates for carcinomas were 95%, 89%, and 73% respectively. However, overall survival was longer for benign tumors than carcinomas (P = .001). Recurrence was more likely when complications (P = .032) or incomplete margins (P = .023) were present. Recurrence was associated with an increased risk of death (P = .046).
Conclusion
Submucosal resection of both benign and malignant rectal masses was associated with a low rate of severe complications and prolonged survival in the 93 dogs described here.
Clinical significance
Submucosal resection is a suitable technique for resection of selected rectal masses.
The morbidity and mortality from and economic impact of diabetes mellitus in the United States, pathogenesis of microvascular diabetic complications, contribution of poor long-term glycemic control ...to risk for diabetic retinopathy and other microvascular complications, prevalence of diabetic retinopathy, methods for measuring visual acuity, and manifestations of disease progression and etiology of blindness in patients with diabetic retinopathy are discussed.
Diabetic retinopathy and other microvascular and macrovascular complications of diabetes cause considerable morbidity and mortality and have a large economic impact in the United States. Patients with poor long-term glycemic control are more vulnerable to diabetic retinopathy than to other microvascular complications of diabetes. Diabetic retinopathy is the third leading cause of all cases of blindness in the United States and the leading cause of new cases in adults. Retinopathy is already present at the time of diagnosis in 20% of patients with type 2 diabetes. Retinopathy and other micro-vascular complications are attributed to chronic hyperglycemia, vascular damage and leakage, edema, capillary basement membrane thickening, neovascularization, hemorrhage, and ischemia. Measurements of visual acuity loss are expressed in terms of the distance at which a person with normal vision can see what the test subject can see from 20 feet away. Diabetic retinopathy begins as nonproliferative abnormalities and progresses to proliferative diabetic retinopathy. Macular edema can develop at any time in the progression of diabetic retinopathy. Macular ischemia, retinal and vitreous hemorrhage, and retinal detachment are the primary causes of blindness in patients with diabetic retinopathy.
Diabetic retinopathy is a costly and progressive condition associated with chronic hyperglycemia. It is potentially vision-threatening.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Research is uncovering the genetic and biochemical effects of consuming large quantities of alcohol. One prime example is the J- or U-shaped relationship between the levels of alcohol consumption and ...the risk of atherosclerotic cardiovascular disease. Moderate alcohol consumption in humans (about 30 g ethanol/d) is associated with reduced risk of coronary heart disease, while abstinence and heavier alcohol intake is linked to increased risk. However, the hepatic consequences of moderate alcohol drinking are largely unknown. Previous data from alcohol-preferring (P) rats showed that chronic consumption does not produce significant hepatic steatosis in this well-established model. Therefore, free-choice alcohol drinking in P rats may mimic low risk or nonhazardous drinking in humans, and chronic exposure in P animals can illuminate the molecular underpinnings of free-choice drinking in the liver. To address this gap, we captured the global, steady-state liver transcriptome following a 23 week free-choice, moderate alcohol consumption regimen (∼ 7.43 g ethanol/kg/day) in inbred alcohol-preferring (iP10a) rats. Chronic consumption led to down-regulation of nine genes in the cholesterol biosynthesis pathway, including HMG-CoA reductase, the rate-limiting step for cholesterol synthesis. These findings corroborate our phenotypic analyses, which indicate that this paradigm produced animals whose hepatic triglyceride levels, cholesterol levels and liver histology were indistinguishable from controls. These findings explain, at least in part, the J- or U-shaped relationship between cardiovascular risk and alcohol intake, and provide outstanding candidates for future studies aimed at understanding the mechanisms that underlie the salutary cardiovascular benefits of chronic low risk and nonhazardous alcohol intake.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The use of zebrafish (Danio rerio) as an animal model is growing and occurs in a wide range of scientific areas. Therefore, researchers need better and more appropriate anaesthetics for stressful ...and/or painful procedures to prevent unpleasant experiences. Thus, we aimed to study if adult zebrafish displayed aversion-associated behaviours (conditioned place aversion) and alterations in cortisol levels when exposed to equipotent concentrations of MS222, propofol/lidocaine, clove oil, or etomidate. Adult AB zebrafish (mixed-sex, N = 177) were randomly assigned to MS222 (150 mg/L), Propofol/Lidocaine (5 mg/L propofol + 150 mg/L lidocaine), Clove Oil (45 mg/L), or Etomidate (2 mg/L) groups. The conditioned place aversion test was used to assess behavioural aversion. Only etomidate resulted in a similar aversion to the positive control group (HCl; pH = 3). Cortisol levels were measured 5 and 15 min after loss of equilibrium. Etomidate induced low levels of cortisol by impairing its synthesis, whereas all the other groups had similar cortisol levels. Based on our data, etomidate was ruled out as an alternative to MS222, as it showed an aversive profile. The remaining protocols were not innocuous, displaying a weak aversive profile when compared to the positive control. In conclusion, a combination of propofol with lidocaine, clove oil, and MS222 were valid candidates for use as anaesthetic protocols.
PDF
