Assessment of Frailty Among Older Adults in the Physical Activity Daily Trial.

Frailty is common among cardiac patients; however, frailty assessment data from patients with peripheral arterial disease (PAD) are limited. The purpose of this observational study was to identify the prevalence and factors related to frailty in addition to unique frailty marker groupings in a cohort of sedentary adults with PAD. We grouped three PAD-relevant frailty characteristics using Fried's frailty phenotype -1) exhaustion, (2) weakness, and (3) slowness-and observed the prevalence of pre-frailty (1-2 characteristics) and frailty (3 characteristics) in the PAD cohort. Of the 106 participants, 34.9% were robust/non-frail, 53.8% were pre-frail, and 2.8% were frail. Exhaustion (33.3%) was the most occurring characteristic followed by weakness (20.0%) and slowness (5.0%). The grouping of weakness + slowness (10.0%) was the most prevalent followed by exhaustion + weakness (8.3%) and exhaustion + slowness (5.0%). Among pre-frail participants, ankle brachial index was correlated with a reduction in gait speed.

Inflammatory and Cardiovascular Correlates of Physical Activity and Sedentary Behavior in Older Adults Living With HIV.

BACKGROUND: Inflammation is an indicator of oxidative stress that may contribute to cardiovascular diseases in older people living with HIV (OPWH). Physical activity (PA) may reduce these biomarkers in OPWH, but little is known about the association of PA with inflammatory and cardiovascular biomarkers. We sought to examine the inflammatory and cardiovascular biomarker correlates of PA and sedentary behavior in OPWH. METHODS: We included 101 OPWH with complete assessments of PA, sedentary behavior, and biomarker data to examine the association between the volume of PA and inflammatory and cardiovascular biomarkers. RESULTS: In this cohort of OPWH (mean age 55.9 y), 68% were male and 83% were African American/Black. Among OPWH, greater volume of PA (ie, walking, moderate, vigorous, and/or total) was associated with lower systolic (P < .05) and diastolic blood pressure (P < .05), pulse pressure (P < .05), and tumor necrosis factor-alpha (P < .05). Greater duration of sitting was associated with greater triglycerides, interleukin-6, and tumor necrosis factor-alpha (P < .05). CONCLUSIONS: Although adherence to regular PA among OPWH is low and sedentary behavior is high, the associations between biomarkers and PA suggest a greater volume of PA could attenuate the inflammatory and cardiovascular derangements experienced by OPWH.

Cardiometabolic Diseases and Quality-of-Life Outcomes in Adults With HIV in the Deep South: A Cross-sectional Study.

ABSTRACT: The role of cardiometabolic diseases (CMDs) on physical health-related quality of life (P-HRQoL) and quality of sleep was examined among 261 PLWH ≥40 years, recruited from a university-affiliated HIV clinic in the Deep U.S. South. Using a cross-sectional study design, participants completed the Medical Outcomes Study HIV Health Survey (MOS-HIV; P-HRQoL) and Pittsburgh Sleep Quality Index. The overall prevalence of self-reporting ≥1 CMD was 64.4%. P-HRQoL scores were lower in PLWH with ≥1 CMD compared with those with no CMDs (45.53 ± 11.54 vs. 49.67 ± 10.77, p <.01). Poor sleep quality was higher among participants with ≥1 CMD compared with those with no CMDs (9.28 ± 4.42 vs. 7.26 ± 4.17, p <.01). Each additional CMD resulted in a 1.83-point decrease in P-HRQoL and 0.74-point increase in poor sleep quality scores. Interventions that focus on targeting these quality-of-life domains in PLWH with CMDs are needed.

Preserving independence among under-resourced older adults in the Southeastern United States: existing barriers and potential strategies for research.

Disability prevention and preservation of independence is crucial for successful aging of older adults. To date, relatively little is known regarding disparities in independent aging in a disadvantaged older adult population despite widely recognized health disparities reported in other populations and disciplines. In the U.S., the Southeastern region also known as "the Deep South", is an economically and culturally unique region ravaged by pervasive health disparities - thus it is critical to evaluate barriers to independent aging in this region along with strategies to overcome these barriers. The objective of this narrative review is to highlight unique barriers to independent aging in the Deep South and to acknowledge gaps and potential strategies and opportunities to fill these gaps. We have synthesized findings of literature retrieved from searches of computerized databases and authoritative texts. Ultimately, this review aims to facilitate discussion and future research that will help to address the unique challenges to the preservation of independence among older adults in the Deep South region.

Modeling Patient Risk for Hospital-Acquired Pressure Injuries During COVID-19: A Retrospective Study.

BACKGROUND: COVID-19 negatively impacts many organ systems including the skin. One of the most significant skin-associated adverse events related to hospitalization are pressure injuries. PURPOSE: The aim of this study was to determine 8 risk factors that would place hospitalized patients at a higher risk for hospital-acquired pressure injuries (HAPIs) during the COVID-19 pandemic. METHODS: A retrospective, descriptive analysis was conducted in an urban academic health science center located in the southeastern United States. RESULTS: There were 247 of 23 093 patients who had pressure injuries and 1053 patients who had a positive COVID-19 diagnosis. Based on the generalized estimating equation model, diagnosis of COVID-19, age, male gender, risk of mortality, severity of illness, and length of stay are statistically significant factors associated with the development of HAPIs. CONCLUSIONS: Further study should explore pathology of COVID-19 skin changes and what interventions are effective against HAPIs in the COVID-19 population taking into consideration current treatments.

Survival in the Real World: A National Analysis of Patients Treated for Early-Stage Breast Cancer.

PURPOSE: Many patient population groups are not proportionally represented in clinical trials, including patients of color, at age extremes, or with comorbidities. It is therefore unclear how treatment outcomes may differ for these patients compared with those who are well-represented in trials. METHODS: This retrospective cohort study included women diagnosed with stage I-III breast cancer between 2005 and 2015 in the national CancerLinQ Discovery electronic medical record-based data set. Patients with comorbidities or concurrent cancer were considered unrepresented in clinical trials. Non-White patients and/or those age < 45 or ≥ 70 years were considered under-represented. Patients who were White, age 45-69 years, and without comorbidities were considered well-represented. Cox proportional hazards models were used to evaluate 5-year mortality by representation group and patient characteristics, adjusting for cancer stage, subtype, chemotherapy, and diagnosis year. RESULTS: Of 11,770 included patients, 48% were considered well-represented in trials, 45% under-represented, and 7% unrepresented. Compared with well-represented patients, unrepresented patients had almost three times the hazard of 5-year mortality (adjusted hazard ratio [aHR], 2.71; 95% CI, 2.08 to 3.52). There were no significant differences in the hazard of 5-year mortality for under-represented patients compared with well-represented patients (aHR, 1.19; 95% CI, 0.98 to 1.45). However, among under-represented patients, those age < 45 years had a lower hazard of 5-year mortality (aHR, 0.63; 95% CI, 0.48 to 0.84) and those age ≥ 70 years had a higher hazard of 5-year mortality (aHR, 2.21; 95% CI, 1.76 to 2.77) compared with those age 45-69 years. CONCLUSION: More than half of the patients were under-represented or unrepresented in clinical trials, because of age, comorbidity, or race. Some of these groups experienced poorer survival compared with those well-represented in trials. Trialists should ensure that study participants reflect the disease population to support evidence-based decision making for all individuals with cancer.

Learning During Crisis: The Impact of COVID-19 on Hospital-Acquired Pressure Injury Incidence.

ABSTRACT: The impact of COVID-19, on the health and safety of patients, staff, and healthcare organizations, has yet to be fully uncovered. Patient adverse events, such as hospital-acquired pressure injuries (HAPIs), have been problematic for decades. The introduction of a pandemic to an environment that is potentially at-risk for adverse events may result in unintended patient safety and quality concerns. We use the learning health system framework to motivate our understanding of the impact of the COVID-19 pandemic on the incidence of HAPIs within our health system. Using a retrospective, observational design, we used descriptive statistics to evaluate trends in HAPI from March to July 2020. Hospital-acquired pressure injury numbers have fluctuated from a steady increase from March-May 2020, hitting a peak high of 90 cases in the month of May. However, the trend in the total all stage HAPIs began to decline in June 2020, with a low of 51 in July, the lowest number since March 2020. Patients evaluated in this study did not have a longitudinal increase in HAPIs from March-July 2020 during the COVID-19 pandemic, despite similarities in illness severity between the two time points. Our experience has demonstrated the ability of our organizational leaders to learn quickly during crisis.

IL-17 patterns in synovium, serum and synovial fluid from treatment-naïve, early rheumatoid arthritis patients.

BACKGROUND: There are actually becoming controversial data regarding the profiles of interleukin-17 (IL-17) in different pathogenical stages of rheumatoid arthritis (RA). OBJECTIVES: To assessing the IL-17 patterns in synovium, serum and synovial fluid from treatment-naïve early RA patients and to identifying potential correlations with disease activity markers and with synovial histopathological profile. MATERIALS AND METHODS: Serum samples from 30 treatment-naïve early RA patients were evaluated for C-reactive protein (CRP), erythrocytes sedimentation rate (ESR), rheumatoid factor (RF), anti-cyclic citrullinated peptide antibodies (anti-CCP). IL-17A levels were also assessed in serum and synovial fluid (SF). Disease activity score (DAS28) calculation was done for all patients. Control serum and SF samples were obtained from 29 patients with osteoarthritis (OA); control synovium specimens were obtained from eight patients with OA and during surgery for knee tear ligaments. Histopathological (Hp) score, immunohistochemical reactivity for IL-17 were also assessed in synovium of early RA patients and controls. Dependencies between serum and synovial profile of IL-17A and the other parameters were statistically tested. RESULTS: In early RA patients, strong correlations of serum and SF IL-17A levels were found with ESR, CRP, RF, anti-CCP, Hp score and IL-17 synovial immunoreactivity; a good correlation was noted with DAS28 score. Also, strong correlation was noted between serum and SF IL-17A levels. CONCLUSIONS: In early stages of untreated RA, simultaneous IL-17 assessment of serum, SF and synovium might be valuable in defining activity and predictive patterns, given that synovium is highly suggestive for an disease aggressivity and might express specific therapeutically targets.

Immunohistochemical study of stellate cells in patients with chronic viral hepatitis C genotype 1.

INTRODUCTION: Hepatic stellate cells (HSC) are key-players in the pathogenesis of liver fibrosis, inducing collagen deposition and abnormal extracellular matrix remodeling. AIM: The purpose of this study was to identify the stellate cells using immunohistochemical techniques and to establish if there is a correlation between the expression of stellate cells and the clinical and histological parameters in patients with chronic viral hepatitis C. MATERIALS AND METHODS: The studied group included 30 patients with chronic viral hepatitis C genotype 1, in whom a liver biopsy was performed previous to the antiviral treatment. After the histological analyze, the biopsy was stained with an anti-SMA antibody (Dako, Carpinteria, CA). The amount of positive stained area was determined using an arbitrary semiquantitative score from 1 to 4. RESULTS: Our observations suggest that there is a strong correlation between the stellate cells activity, evaluated using a semiquantitative score, and the stage of liver fibrosis (rs=0.76, p<0.001). Also, our study revealed a direct correlation, but less intense, with the necro-inflammatory activity (rs=0.39, p=0.03), the steatosis degree (rs=0.428, p=0.01) and the value of alanine aminotransferase (rs=0.4, p=0.03). The age and the viremia level were not correlated with the activity of the stellate cells. CONCLUSIONS: This study suggests that the transition of stellate cells from inactivated state to the state of highly fibrogenic cell is influenced mainly by the histological liver modifications (necroinflammatory activity and steatosis) and less by clinical parameters (age, sex) or the viremia level.

Insulin-dependent diabetes mellitus in homozygous sickle-cell anaemia.

Concurrent sickle-cell disease and diabetes mellitus is rare. The first case of the co-existence of these two disorders to be identified in Nigeria, West Africa, is presented.

Effect of reduced phytate wheat bran on zinc absorption.

The rise in plasma zinc after the ingestion of 765 mumol (50 mg) elemental zinc was measured over 6 h in three groups of healthy subjects who, in a second test, also consumed a standard wheat bran, a reduced phytate, high fibre processed bran or rice-based, low phytate, low fibre breakfast cereal (Rice Krispies). Standard bran, reduced phytate bran and Rice Krispies all significantly decreased the area under the plasma zinc time curve (AUC) compared to the zinc alone test. The AUC obtained with standard bran was significantly lower than that after reduced phytate bran (mean +/- s.e.: -5.9 +/- 2.7 vs 18.5 +/- 4.2 mumol.h/l, P less than 0.001). The percentage reductions in AUC produced by the test meals were: standard bran 106.4 +/- 2.4, reduced phytate bran 75.9 +/- 4.8, Rice Krispies 46.3 +/- 10.4 per cent, P less than 0.01). Histidine, taken with standard bran in a small subgroup of subjects, tended to improve zinc absorption but the difference was not statistically significant.

Effects of cimetidine and carbenoxolone on gastric mucus.

The effect of cimetidine on normal human gastric mucus has been compared with that of carbenoxolone, a drug believed to enhance mucus production. Each drug was given for two weeks, the gastric contents aspirated over a timed period and the results assessed in unstimulated and pentagastrin stimulated secretions. The volume, dry weight and the carbohydrate contents of non-diffusable glycoconjugates, high molecular mass glycoproteins and glycopolypeptides were investigated. Both drugs reduced the volumes of stimulated secretions. This was statistically significant after cimetidine. More importantly neither drug affected the amount of non-diffusable glycoconjugates, so that the concentration remained the same or increased. Both drugs reduced the monosaccharide content of the high molecular mass fractions. This reached significance for the stimulated secretion after cimetidine. As the carbohydrate content of the glycopolypeptides was unchanged this indicated the presence of a non-mucin glycoprotein or protein. Overall there was no fundamental difference between the results for cimetidine and carbenoxolone.

Pharmacokinetics of nifedipine after oral administration in chronic liver disease.

Presented are the results of a study in which ten healthy subjects and seven patients with hepatic cirrhosis were given 10 mg nifedipine orally; plasma concentrations of the drug were measured over 24 hours. The drug was also administered intravenously, but those results were unsatisfactory for presentation. The rate of absorption and peak plasma concentrations were similar in the two groups. There was a fourfold increase in the elimination half-life (434 +/- 74 minutes in the cirrhotics compared with 102 +/- 11 minutes in the healthy subjects). A twofold increase in the area under the plasma concentration-time curve occurred in the cirrhotic group. The study confirmed that there is clinically significant alteration in the kinetics of nifedipine in patients who have hepatic cirrhosis and that there is considerable risk of accumulation. No adverse effects were observed despite high plasma levels of nifedipine.

Anti-ulcer drugs and intrinsic factor secretion.

Twelve healthy volunteers were randomly allocated to take two of the following treatments; cimetidine, misoprostol (a prostaglandin E1 analogue) and carbenoxolone, for two weeks. A further four subjects took ranitidine. Gastric aspirates were collected before and on the 14th day of therapy for each drug, and analysed for intrinsic factor concentration and total output. Both randitine and cimetidine inhibited pentagastrin stimulated output by 47% and 27% respectively in comparison to control, but had no effect on stimulated mean intrinsic factor concentrations. No changes were observed with misoprostol and carbenoxolone treatment.

Some aspects of the glycoprotein and glycopolypeptide content of human gastric mucus.

The carbohydrate content of non-diffusable, glycoprotein and glycopolypeptide material has been studied in normal human gastric aspirates. Pentagastrin doubles the volume of secretions but has no effect on the amount of non-diffusable material. Only about 40% of the weight of the non-diffusable material is mucin in nature. Gel-permeation chromatography indicated that about half of the mucin survived as high molecular mass glycoprotein. Monosaccharide differences, for example between secretors and non-secretors, only became manifest at the glycopolypeptide stage. These results emphasize the dangers of attempting to assess mucin changes by simple carbohydrate analyses of unfractionated gastric aspirates.

The natriuresis following oral administration of the calcium antagonists--nifedipine and nitrendipine.

Ten healthy individuals received in random order placebo, nifedipine 10 mg, nifedipine 20 mg, nitrendipine 10 mg and nitrendipine 20 mg as single oral administrations at weekly intervals. On the day before each treatment placebo was administered. Urine was collected for 6 h and then for 18 h after each administration. There was a significant increase in urine volume and sodium excretion after the drugs, but no change in potassium excretion. The effect was most evident in the 6 h after drug administration. The effect was no greater at the higher doses of either drug. A natriuretic-diuretic action of nifedipine and nitrendipine has been confirmed in man. The mechanism of the effect remains unclear.

Do beta blockers differ in their effects on hepatic microsomal enzymes and liver blood flow?

The effects of three beta blockers on liver blood flow and hepatic enzyme activity were investigated. Eight healthy subjects received placebo, 100 mg metoprolol, 40 mg nadolol, and 60 mg propranolol orally three times a day for four days in a randomized block design. On the fourth day of each treatment, beta blockade was measured by inhibition of exercise-induced tachycardia and apparent liver blood flow was measured by indocyanine green clearance. Plasma concentrations of the beta blockers were measured 2 hours after the early morning dose. Metoprolol produced the greatest inhibition of exercise tachycardia. All three drugs appeared to reduce liver blood flow, but this was only statistically significant in the case of propranolol. Enzyme inhibition occurred but to a varying extent. Propranolol produced a 36 per cent fall in antipyrine clearance (P less than 0.1) while metoprolol and nadolol both caused a 12 per cent reduction (P less than 0.05 and P = 0.06, respectively). Wide interindividual variation in the plasma concentrations of the drugs limit interpretation, but the results suggest that at the doses used, metoprolol and nadolol may be less likely to cause significant drug interaction by enzyme inhibition than propranolol.

A study of the potential interactions between azapropazone and frusemide in man.

Ten healthy individuals received frusemide 40 mg orally for 7 days. Following a drug free period of 7 days they received azapropazone 600 mg twice daily for 7 days and then both treatments for a further 7 days. Sodium excretion fell from 141 +/- 16.8 mmol/day to 84.3 +/- 6.8 mmol/day (P less than 0.01) on initiation of azapropazone treatment. The natriuretic response to frusemide was unchanged by premedication with azapropazone. Urate excretion rose from 3.35 +/- 0.249 mmol/day to 4.98 +/- 0.365 mmol/day on initiation of azapropazone therapy but subsequently returned to baseline values. Plasma uric acid fell from 0.289 +/- 0.024 mmol/l to 0.167 +/- 0.0125 mmol/l (P less than 0.001) on azapropazone but rose to 0.186 +/- 0.0116 mmol/l (P less than 0.001) with the addition of frusemide. Azapropazone may cause sodium retention but after repeated administration frusemide still has a marked diuretic action. The hypouricaemic effect of azapropazone is only slightly antagonised by frusemide at the doses studied.

Systemic absorption of ketoconazole from vaginal pessaries.

Eight healthy female subjects were each given (a) ketoconazole 400 mg orally, (b) ketoconazole 400 mg as a single vaginal pessary, (c) ketoconazole 800 mg as two vaginal pessaries, and (d) ketoconazole 1200 mg as three vaginal pessaries. The area under the plasma concentration time curve (AUC) after the oral dose was 51.41 +/- 10.99 mg l-1 h (mean +/- s.d.) and the half-life of ketoconazole was 2.98 +/- 1.41 h. The AUCs after vaginal administration were 0.27 +/- 0.14, 0.52 +/- 0.25, and 0.43 +/- 0.22 mg-1 l h following the 400, 800 and 1200 mg pessaries respectively. Systemic absorption of single doses of vaginally administered ketoconazole appears to be negligible in the absence of vaginal infection. There were no local or systemic side effects related to ketoconazole in these healthy volunteers.

Effects of chronic oral cimetidine on apparent liver blood flow and hepatic microsomal enzyme activity in man.

Cimetidine 200 mg three times daily and 400 mg at night was given to 10 subjects for four weeks. Apparent liver blood flow was measured by indocyanine green clearance and microsomal enzyme activity by antipyrine clearance, before and after cimetidine. There was no reduction in indocyanine green clearance but antipyrine clearance, as expected, was significantly reduced by 15% at four weeks. Chronic cimetidine treatment does not reduce apparent liver blood flow and is therefore unlikely to be of use in the treatment of portal hypertension. The cimetidine associated hepatic enzyme inhibition appears to persist with prolonged treatment. Therefore patients on chronic cimetidine remain vulnerable to certain drug interactions.