Dysphagia presentation and management following COVID-19: an acute care tertiary centre experience.

OBJECTIVES: As the pathophysiology of COVID-19 emerges, this paper describes dysphagia as a sequela of the disease, including its diagnosis and management, hypothesised causes, symptomatology in relation to viral progression, and concurrent variables such as intubation, tracheostomy and delirium, at a tertiary UK hospital. RESULTS: During the first wave of the COVID-19 pandemic, 208 out of 736 patients (28.9 per cent) admitted to our institution with SARS-CoV-2 were referred for swallow assessment. Of the 208 patients, 102 were admitted to the intensive treatment unit for mechanical ventilation support, of which 82 were tracheostomised. The majority of patients regained near normal swallow function prior to discharge, regardless of intubation duration or tracheostomy status. CONCLUSION: Dysphagia is prevalent in patients admitted either to the intensive treatment unit or the ward with COVID-19 related respiratory issues. This paper describes the crucial role of intensive swallow rehabilitation to manage dysphagia associated with this disease, including therapeutic respiratory weaning for those with a tracheostomy.

Evaluating characteristics of community riparian awareness program interactions.

As part of its mandate to evaluate and monitor program delivery, the Alberta Riparian Habitat Management Society (Cows and Fish) has commissioned independent evaluations to examine the effectiveness and applicability of the community-based riparian awareness and management program. The society's aim is to improve the understanding of landscape function, to better enable landowners and managers to make management decisions. The staff interaction evaluation examined staff ability to deliver certain valued characteristics, and identified whether the program and staff increased awareness and management action. Respondents rated staff highly on all characteristics. Landowners that participated in riparian health programming as part of community/watershed groups were 19% more likely to have learned new information and 21% more likely to implement management change than those that were not part of a group. Repeat interactions are critical to learning new information and influencing management. All those with frequent interactions had learned new information, compared to only 70% of those with very little interaction. A diverse array of interactions led respondents to alter their management, indicating the need for a wide variety of extension tools and activities. The results strongly support the need for a community-based approach in resource management and awareness activities, which enables repeat, ongoing and diverse interactions with extension staff.

Competitive particle concentration fluorescence immunoassays for measuring anti-diabetic drug levels in mouse plasma.

Two competitive particle concentration fluorescence immunoassays were developed to measure blood levels of analogs of anti-diabetic drugs being tested in diabetic mice. Ligands that contained the active pharmacophores were conjugated to PPD for immunization and to beta-phycoerythrin for use as a tracer in the immunoassays. Approximately 90% of 262 compounds assayed were detectable at less than 120 nM in plasma which was well below the estimated therapeutic level of 1 microM for lowering blood glucose. These data were used to define the bioavailability of test compounds and assist in decisions of constructing active analogs. Of additional interest, we noted crossreactivity of one monoclonal antibody for 3 different compound classes that are all known to bind with varying affinities to peroxisome proliferator-activated receptors.

Monoclonal antibodies as surrogate receptors in a high throughput screen for compounds that enhance insulin sensitivity.

Monoclonal antibodies (MoAbs) were made to a known insulin sensitivity enhancer (ISE) compound, CS-045. The MoAbs were characterized with respect to binding other known thiazolidinedione ISE compounds using a CS-045 labeled with b-phycoerythrin in a competitive particle concentration fluorescence immunoassay (PCFIA). By comparing the rank order of IC50 values for each compound to its respective potency as an ISE, one MoAb (13E3) was selected for further characterization. This MoAb was also used as a surrogate receptor in a high throughput screen to identify novel compounds that compete for binding to CS-045. Some of the hits were found to have efficacy in reducing blood glucose. Subsequently, another group reported that several compounds with the core thiazolidinedione structure of the ISE compounds bound with high affinity to peroxisome proliferator-activating receptors (PPAR). Therefore, we used the MoAb assay to test these and other compounds that are known to bind to PPARgamma and noted crossreactivity with some of the compounds.

Effect of aspirin use on death and recurrent myocardial infarction in current and former cigarette smokers. Program on the Surgical Control of the Hyperlipidemias Group.

The purpose of this study was to examine the effects of aspirin use on mortality and morbidity rates in a subset of the control group of the Program on the Surgical Control of the Hyperlipidemias (POSCH) that was stratified by cigarette smoking status at the time of randomization. The clinical impact of aspirin intake in cigarette smokers and former cigarette smokers has not been well studied. POSCH was a randomized, controlled, clinical trial designed to ascertain the effects of lipid modification by the partial ileal bypass operation on clinical end-points and arteriographic changes in postmyocardial infarction subjects with hypercholesterolemia. Cohorts of cigarette smokers in the diet-control group were evaluated for overall and atherosclerotic coronary heart disease (ACHD) mortality rates and recurrent confirmed nonfatal myocardial infarction rates. In current cigarette smokers at baseline (n = 90) with a mean follow-up of 8.3 years, the overall mortality rate was 45.2% in patients with no aspirin use and 10.4% in patients who reported even infrequent aspirin use (relative risk = 4.3, 95% confidence interval (CI) = 2.4 to 10.6, p < 0.001). For ACHD mortality in this cohort, the relative risk was 17.1 (35.7% vs 2.1%, 95% CI = 1.4 to 125.0, p < 0.001); for the combined end-point of ACHD mortality and nonfatal myocardial infarction, the relative risk was 2.4 (40.5% vs 16.7%, 95% CI = 1.2 to 5.1, p = 0.018).(ABSTRACT TRUNCATED AT 250 WORDS)

Subgroup analyses of the major clinical endpoints in the Program on the Surgical Control of the Hyperlipidemias (POSCH): overall mortality, atherosclerotic coronary heart disease (ACHD) mortality, and ACHD mortality or myocardial infarction.

The Program on the Surgical Control of the Hyperlipidemias (POSCH) was a secondary atherosclerosis intervention trial employing partial ileal bypass surgery as the intervention modality. For this report, we analyzed 105 subgroups in 35 variables in POSCH, chosen predominantly for their potential relationship to the risk of atherosclerotic coronary heart disease (ACHD). We defined potential differential effects as those with: (1) an absolute z-value > or = 2.0 for the subgroup, if the absolute z-value for the overall effect was < 2.0; and (2) an absolute z-value > or = 3.0 for the subgroup and a relative risk < or = 0.5, if the absolute z-value for the overall effect was > or = 2.0. For each of three major POSCH endpoints of overall mortality, ACHD mortality and ACHD mortality or confirmed nonfatal myocardial infarction, we found seven subgroups with a differential risk reduction in the surgery group as compared to the control group. Allowing for identical subgroups for more than one endpoint, there were 13 individual subgroups with differential effects. Of these, seven demonstrated internal consistency across endpoints, and five of these seven displaced external consistency with known ACHD risk factors and for biological plausibility: triglyceride concentration > or = 200 mg/dl; cigarette smoking; overt or borderline diabetes mellitus; a Minnesota ECG Q-QS code of 1-1; and obesity. A greater risk reduction, in comparison to the overall treatment effect, by the reduction of a single risk factor, hypercholesterolemia, in patients with at least two major ACHD risk factors was a provocative and an hypothesis-generating outcome of this analysis. The clinical implications of this finding may lead to more aggressive cholesterol intervention in patients with multiple ACHD risk factors.

Perception of quality of life before and after disclosure of trial results: a report from the Program on the Surgical Control of the Hyperlipidemias (POSCH).

The Program on the Surgical Control of the Hyperlipidemias (POSCH) was a randomized controlled clinical trial designed to ascertain whether cholesterol lowering induced by the partial ileal bypass operation would favorably affect overall mortality and the mortality and morbidity due to coronary heart disease. The trial results provided strong clinical and coronary arteriographic support for the beneficial effects of lipid modification for the reduction of atherosclerosis progression. At the same time, the surgery-assigned group experienced diarrhea and an increased incidence of kidney stones and gallstones compared to the control-assigned group. Identical quality of life determinations were performed in the POSCH study population shortly before disclosure of the trial results to the patients and shortly thereafter. The purpose of this dual assessment was to evaluate the effect of knowledge of outcomes on the patients' subjective evaluation of quality of life. The primary instrument utilized for analysis of the perception of quality of life in POSCH was the McMasters Health Index Questionnaire (MHIQ). In addition, four study-specific questions were asked of the trial patients. The results for the MHIQ before disclosure of trial results showed a difference (p = 0.07) favoring the control-assigned group (diet-treated), for the social function index of the MHIQ. After disclosure of the trial results, the difference was larger (p < 0.05). For the four study-specific questions, all differences favored the control-assigned group (p < 0.01) before and after disclosure of the trial results, with the exception of satisfaction with randomization allocation in the surgery-assigned group (p = 0.08). The intragroup MHIQ indices before and after disclosure of the trial results showed no suggestive significant differences, except in the surgery-assigned group, in which there was an improvement in the emotional function index after disclosure of the trial results (p = 0.03). The intragroup responses to the study-specific questions before and after disclosure of the trial results again showed no significant differences, except in the surgery-assigned group, in which there was an improvement in patient satisfaction with randomization allocation after disclosure of the trial results (p = 0.04).(ABSTRACT TRUNCATED AT 400 WORDS)

Serum creatinine as an independent predictor of coronary heart disease mortality in normotensive survivors of myocardial infarction. POSCH Group.

BACKGROUND: Serum creatinine has been reported in previous studies to be a prognostic indicator for overall mortality, in particular in a hypertensive population. METHODS: The Program on the Surgical Control of the Hyperlipidemias (POSCH) was a randomized, controlled clinical trial. All patients had survived a single myocardial infarction, were normotensive, were not obese, were not having heart failure, and were free of diabetes mellitus and renal disease at entry into the study. POSCH had followed its control group patients (N = 417) for a minimum of 7.0 years. In this group, a prospective post hoc analysis of the relationship of baseline serum creatinine with subsequent overall and atherosclerotic coronary heart disease mortality was performed. RESULTS: The baseline serum creatinine values in the control group patients ranged from 0.7 to 1.9 mg/dL (60 to 170 mumol/L), and were found to be independent predictors (P < .01) of both overall mortality and atherosclerotic coronary heart disease mortality. Each 0.1 mg/dL (9 mumol/L) increment in the baseline serum creatinine increased the relative risk for subsequent overall mortality by 36% and the relative risk for subsequent atherosclerotic coronary heart disease mortality by 47%. CONCLUSIONS: These results demonstrate that a serum creatinine value, obtained in normotensive, nonobese, normoglycemic survivors of a myocardial infarction without preexistent renal disease or heart failure, provides independent prognostic information regarding subsequent overall and atherosclerotic coronary heart disease mortality.

Women in the POSCH trial. Effects of aggressive cholesterol modification in women with coronary heart disease. The POSCH Group. Program on the Surgical Control of the Hyperlipidemias.

The Program on the Surgical Control of the Hyperlipidemias (POSCH) provided the clearest and the most convincing evidence supporting the beneficial effects of cholesterol lowering in hypercholesterolemic survivors of a myocardial infarction. In POSCH, 78 of the 838 patients (9.3%) were women, with 32 randomized to the diet-control group and 46 to the diet plus partial ileal bypass surgery-intervention group. At 5 years, the mean per cent change from baseline was -23.9% for total plasma cholesterol (p < 0.0001), -36.1% for low-density lipoprotein cholesterol (p < 0.0001), and +8.5% for high-density lipoprotein cholesterol (p = not significant). Because of the small number of women, no statistically significant changes in clinical event rates were observed between the control and the surgery groups. A comparison of 162 coronary arteriography film pairs in the POSCH women, between baseline and 3, 5, 7, and 10 years, consistently showed less disease progression in the surgery group (p = 0.013 for combined assessments of the baseline to the longest follow-up film). Because the lipid and coronary arteriography findings in the POSCH women paralleled these findings in the total POSCH population and in the POSCH men, and because the arteriography changes in POSCH have previously been demonstrated to be statistically significant surrogate end points for certain clinical events and predictors of overall and atherosclerotic coronary heart disease mortality rates, we conclude that the lipid modification achieved in the POSCH women by partial ileal bypass reduced their atherosclerosis progression. The POSCH findings in women support the aggressive treatment of hyperlipidemia in the general management of atherosclerosis in women.

Changes in sequential coronary arteriograms and subsequent coronary events. Surgical Control of the Hyperlipidemias (POSCH) Group.

OBJECTIVE: Assessment of the relationship between changes in sequential coronary arteriograms and subsequent clinical coronary events. DESIGN: The Program on the Surgical Control of the Hyperlipidemias, a randomized secondary atherosclerosis intervention trial, obtained coronary arteriograms at baseline, 3, 5, and 7 or 10 years of follow-up. Assessments of changes between pairs of coronary arteriograms were made by two-member panels blinded to the patients' assigned treatment and to the temporal sequence of the films. The relationship of changes between the baseline and the 3-year follow-up arteriograms and subsequent clinical coronary events was examined. SETTING: Three university hospitals and one private primary care facility. PATIENTS: A total of 838 patients, with 417 patients randomized to the control group and 421 to the intervention group. Of all patients, 695 had baseline and 3-year arteriograms. INTERVENTION: The control group received American Heart Association Phase II diet instruction and the intervention group received identical dietary instruction plus a partial ileal bypass operation. MAIN OUTCOME MEASURE: The use of arteriographic changes as a predictor of subsequent clinical coronary events. RESULTS: Changes between the baseline and the 3-year coronary arteriographic overall disease assessment were significantly associated with subsequent overall and atherosclerotic coronary heart disease mortality (P less than .01). For the combined end point of atherosclerotic coronary heart disease mortality or confirmed nonfatal myocardial infarction, a significant relationship between the overall disease assessment and subsequent clinical events was found in the control group (P less than .0001) and in the surgery group (P = .04). For this combined end point, however, the control and the surgery groups were different with respect to clinical coronary events after 3 years, stratified by the baseline to 3-year overall disease assessment (P less than .001, unadjusted; P = .06, adjusted for 3-year clinical covariates). CONCLUSIONS: Coronary arteriographic changes can be used in atherosclerosis intervention trials as a limited surrogate end point for certain clinical coronary events. This relationship is statistically compelling for overall mortality and atherosclerotic coronary heart disease mortality. For an individual patient, changes in the severity of coronary atherosclerosis seen on sequential coronary arteriograms can serve as prognostic indicators for subsequent overall or atherosclerotic coronary heart disease mortality.

Partial ileal bypass in the treatment of hypercholesterolemia.

Partial ileal bypass is a surgical method of lowering circulating cholesterol levels. This article outlines the history of the partial ileal bypass operation and compares the efficacy, durability, compliance, safety, and cost of this operation with currently available diet and drug therapy for hypercholesterolemia. Partial ileal bypass patients have been followed for up to 26 years, and the procedure is employed currently throughout the United States and Europe. Partial ileal bypass has moved beyond the research stage and can be performed in community hospitals by competent general surgeons.

Pathogenesis of nephrolithiasis post-partial ileal bypass surgery: case-control study. The POSCH Group.

Between 1975 and 1983, 838 patients were randomized into the Program on the Surgical Control of Hyperlipidemias (POSCH) trial: 417 to standard medical care and 421 to partial ileal bypass (PIB) surgery. During the course of the trial, an increased incidence of kidney stone formation was found in the surgery group (4%/year) as compared to the control group (0.4%/year). A matched triplet case-control study was conducted to assess the possible causes for the increased incidence of kidney stones. Three groups were studied: PIB stone-formers (S); PIB non-stone formers (N); and non-PIB, non-stone formers in the control group (C). Initially, 162 patients (54 triplets) were selected. Ten percent of the patients declined to participate which resulted in a sample size of 146 patients. The PIB patients had statistically significant (P less than 0.05) lower levels of serum vitamin D metabolites; lower urine volume, pH, citrate, magnesium, carbon dioxide, and sulfate, and higher urinary oxalate, ammonia and relative supersaturation for calcium oxalate and uric acid than the control patients. Although S and N had similar results, those S with no prior history of stones had a higher calcium oxalate supersaturation than similar N with a negative prior history of stones (P less than 0.025). Based on these results, all PIB patients appear to be at risk for kidney stone formation. The combination of reduced urinary volume and calcium oxalate precipitation inhibitor substance with increased calcium oxalate relative supersaturation produced an increase in nephrolithiasis risk in the PIB groups.

Program on the Surgical Control of the Hyperlipidemias (POSCH): patient entry characteristics. The POSCH Group.

The entry characteristics of patients in the Program on the Surgical Control of the Hyperlipidemias (POSCH), a randomized, controlled, clinical trial, are described in this article. The primary objective addressed by POSCH was whether lowering total plasma cholesterol by partial ileal bypass surgery results in a reduction in mortality and morbidity in post-myocardial infarction patients. Between 1975 and 1983, 838 patients between the ages of 30 and 64 years were randomized into POSCH. The mean age at entry was 51 years, and 91% of the patients were men. The mean time between myocardial infarction and entry was 2.2 years. The mean baseline total plasma cholesterol was 251 mg/dl, with a mean LDL-cholesterol of 179 mg/dl and a mean HDL-cholesterol of 40 mg/dl. Significant disease (greater than or equal to 50% occlusion) of one or more major coronary arteries was found in 91% of the patients. In addition to a description of the POSCH patient population at entry, comparisons of the POSCH patient population to populations of participants in other lipid-lowering trials are presented to provide a perspective on how POSCH relates to these trials.

Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. Report of the Program on the Surgical Control of the Hyperlipidemias (POSCH)

BACKGROUND AND METHODS: The Program on the Surgical Control of the Hyperlipidemias (POSCH), a randomized clinical trial, was designed to test whether cholesterol lowering induced by the partial ileal bypass operation would favorably affect overall mortality or mortality due to coronary heart disease. The study population consisted of 838 patients (417 in the control group and 421 in the surgery group), both men (90.7 percent) and women, with an average age of 51 years, who had survived a first myocardial infarction. The mean follow-up period was 9.7 years. RESULTS: When compared with the control group at five years, the surgery group had a total plasma cholesterol level 23.3 percent lower (4.71 +/- 0.91 vs. 6.14 +/- 0.89 mmol per liter [mean +/- SD]; P less than 0.0001), a low-density lipoprotein cholesterol level 37.7 percent lower (2.68 +/- 0.78 vs. 4.30 +/- 0.89 mmol per liter; P less than 0.0001), and a high-density lipoprotein cholesterol level 4.3 percent higher (1.08 +/- 0.26 vs. 1.04 +/- 0.25 mmol per liter; P = 0.02). Overall mortality and mortality due to coronary heart disease were reduced, but not significantly so (deaths overall [control vs. surgery], 62 vs. 49, P = 0.164; deaths due to coronary disease, 44 vs. 32, P = 0.113). The overall mortality in the surgery subgroup with an ejection fraction greater than or equal to 50 percent was 36 percent lower (control vs. surgery, 39 vs. 24; P = 0.021). The value for two end points combined--death due to coronary heart disease and confirmed nonfatal myocardial infarction--was 35 percent lower in the surgery group (125 vs. 82 events; P less than 0.001). During follow-up, 137 control-group and 52 surgery-group patients underwent coronary-artery bypass grafting (P less than 0.0001). A comparison of base-line coronary arteriograms with those obtained at 3, 5, 7, and 10 years consistently showed less disease progression in the surgery group (P less than 0.001). The most common side effect of partial ileal bypass was diarrhea; others included occasional kidney stones, gallstones, and intestinal obstruction. CONCLUSIONS: Partial ileal bypass produces sustained improvement in the blood lipid patterns of patients who have had a myocardial infarction and reduces their subsequent morbidity due to coronary heart disease. The role of this procedure in the management of hypercholesterolemia remains to be determined. These results provide strong evidence supporting the beneficial effects of lipid modification in the reduction of atherosclerosis progression.

Lipid results of partial ileal bypass in patients with heterozygous, type II-A hyperlipoproteinemia. Program on the Surgical Control of the Hyperlipidemias.

Although reduction in total plasma cholesterol has yet to be shown to have a beneficial effect on overall mortality, the weight of experimental and epidemiologic evidence supports efforts to lower total plasma cholesterol levels to reduce the risk of death from coronary heart disease (CHD). This is especially true in patients with heterozygous, type II-A hyperlipoproteinemia, whose total plasma cholesterol levels above the 90th percentile for age and sex place them at markedly increased risk of death from CHD. The lipid results of partial ileal bypass (PIB) were assessed in 110 patients with heterozygous, type II-A hyperlipoproteinemia in the Program on the Surgical Control of the Hyperlipidemias, a randomized, prospective clinical trial assessing the effects of cholesterol reduction on overall mortality and the course of CHD. Compared with dietary control (n = 52), PIB (n = 58) reduced total plasma cholesterol levels 24% +/- 2% (mean +/- SEM), reduced low-density lipoprotein (LDL) cholesterol levels 34% +/- 3%, and increased high-density lipoprotein (HDL) cholesterol levels 5% +/- 5% 5 years after surgery. Very low-density lipoprotein cholesterol levels were 28% +/- 21% higher and plasma triglyceride levels were 24% +/- 11% higher in the surgical group. The HDL cholesterol/total plasma cholesterol and HDL cholesterol/LDL cholesterol ratios were significantly higher after PIB. Apolipoprotein A-I and HDL subfraction 2 levels were significantly higher and apolipoprotein B-100 levels were significantly lower in the surgical group. PIB successfully lowered mean total plasma cholesterol and LDL cholesterol levels below the limits recommended by the National Cholesterol Education Program to minimize the risk of death from CHD. These results confirm the efficacy and support the role of PIB in the management of patients with marked hypercholesterolemia.