Attitudes and views of the general public towards research participation.

BACKGROUND: While the challenges of recruitment into clinical trials are well described, little is known about the public's perceptions towards research. AIMS: We sought to describe the attitudes, beliefs and knowledge of the public towards research and research participation, focusing on clinical trials, contrast these attributes among individuals with different relationships with the healthcare system and to identify predictors of willingness to participate. METHODS: We conducted a self-administered cross-sectional survey of patients and their significant others in two clinics and two intensive care unit waiting rooms and in three public venues. RESULTS: We analysed responses from 417 respondents (102 and 105 in dialysis and oncology clinics, and 106 in intensive care unit (ICU) waiting rooms, 104 in public locations). While most (68.3%) respondents favoured the use of humans in clinical trials, 53% felt that trial participants always or almost always receive the best quality of care, only 30.4% had participated in clinical research. Approximately 70% felt that subjects are always advised of the risks and benefits of participation, and 30% expressed ambiguity regarding whether participants are informed of their involvement. Oncology and dialysis respondents were the most and least informed regarding research methods and ethics. The perceived risks and benefits associated with clinical circumstances influence research participation decisions and vary with healthcare experiences. We identified six predictors of willingness to participate. CONCLUSION: Attitudes of the public towards research participation are beleaguered by misconceptions. Stakeholders in clinical research must educate the general public regarding research methods and ethics.

Timing of continuous renal replacement therapy in severe acute kidney injury patients with fluid overload: A retrospective cohort study.

PURPOSE: We aimed to evaluate the association of early versus late initiation of Continuous renal replacement therapy (CRRT) with mortality in patients with fluid overload. METHODS: This was a retrospective cohort study of patients with fluid overload (FO) treated with CRRT due to severe acute kidney injury (AKI) between January 2015 and December 2017 in a mixed medical intensive care unit of a teaching hospital in Beijing, China. Patients were divided into early (≤15 h) and late (>15 h) groups based on the median time from ICU admission to CRRT initiation. The primary outcome was all-cause mortality at day 60. Multivariable Cox model analysis was used for analysis. RESULTS: The study patients were male predominant (84/150) with a mean age of 64.8 ± 16.7 years. The median FO value before CRRT initiation was 10.1% [6.2-16.1%]. The 60-day mortality rates in the early vs the late CRRT groups were 53.9% and 73%, respectively. On multivariable Cox modelling, the late initiation of CRRT was independently associated with an increased risk of death at 60 days (HR 1.75, 95% CI 1.11-2.74, p = 0.015). CONCLUSIONS: Early initiation of CRRT was independently associated with survival benefits in severe AKI patients with fluid overload.

Long-term assessment of clinical outcomes and disease progression in patients with corrected Tetralogy of Fallot.

OBJECTIVE: Understanding changes of right ventricular (RV) geometry and function in repaired Tetralogy of Fallot (rToF) patients can improve decision-making for pulmonary valve replacement. Therefore, we aimed to assess the magnitude and clinical correlations of RV changes in rToF patients. PATIENTS AND METHODS: Clinical and MRI data of rToF patients who underwent repeated cardiac magnetic resonance imaging (MRI) at two centers between December 2003 and September 2020 were analyzed together with anatomical factors, including RV outflow tract obstruction, pulmonary artery branch stenosis, and tricuspid regurgitation. Adverse cardiac events and/or NYHA class worsening were documented and correlated with MRI changes. QRS length was reported at each MRI. RESULTS: Two-hundred-and-nineteen rToF patients (53% males, aged 20.2 ± 10.1 years) were enrolled. An increase of ventricular dimensions, except LVEDVi, and worsening of right and left ejection fractions were found over an average period of 5 years of follow-up. These changes were statistically significant but within 10% of the initial value. No significant changes were reported on a year-to-year basis, except in a small group of patients (6%) in whom no predictive factors were identified. Despite similar RV dimensions at the first examination, younger patients had a higher RV ejection fraction and a different annual rate of change of ventricular dimensions compared to older ones. Patients with arrhythmias (20%) were more frequently older and had larger RV dimensions but showed no significant correlations with MRI changes/years. CONCLUSIONS:  Changes in RV dimensions and function occur rarely and very slowly in rToF patients. A small percentage of patients experience a significant worsening in a short time interval without any recognized risk factors. Arrhythmias appear to occur in a small percentage of cases in the late follow-up.

The furosemide stress test for prediction of worsening acute kidney injury in critically ill patients: A multicenter, prospective, observational study.

PURPOSE: To validate the furosemide stress test (FST) for predicting the progression of acute kidney injury (AKI). MATERIALS AND METHODS: We performed a multicenter, prospective, observational study in patients with stage I or II AKI. The FST (1 mg/kg for loop diuretic naïve patients and 1.5 mg/kg in patients previously exposed to loop diuretics) was administered. Subsequent urinary flow rate (UFR) recorded and predictive ability of urinary output was measured by the area under the curve receiver operatic characteristics (AuROC). Primary outcome was progression to Stage III AKI. Secondary outcomes included in-hospital mortality and adverse events. RESULTS: We studied 92 critically ill patients. 23 patients progressed to stage III AKI and had significantly lower UFR (p < 0.0001). The UFR during the first 2 h was most predictive of progression to stage III AKI (AuROC = 0.87), with an ideal cut-off of less than 200mls, with a sensitivity of 73.9% and specificity of 90.0%. CONCLUSION: In ICU patients without severe CKD with mild AKI, a UFR of less than 200mls in the first 2 h after an FST is predictive of progression to stage III AKI. Future studies should focus on incorporating a FST as part of a clinical decision tool for further management of critically ill patients with AKI.

Nesidioblastosis associated with insulin-mediated hypoglycemia in an adult.

Nesidioblastosis, the process of differentiation of pancreatic islets from ductular epithelium, is a well-described cause of insulin-mediated hypoglycemia in neonates and infants, but not in adults. A 58-yr-old woman with characteristic clinical features of fasting hypoglycemia had inappropriately elevated plasma immunoreactive insulin levels during symptomatic episodes of fasting hypoglycemia. Angiography, palpation at laparotomy, and resection of the distal three-quarters of the pancreas provided no evidence of a tumor. Pathologic examination of the resected pancreas revealed the findings of nesidioblastosis, i.e., budding of islets from the wall of ductules, and also increased number and size of islets and abnormal shape and location of islets. An entire spectrum of islet cell abnormalities including nesidioblastosis can cause insulin-mediated hypoglycemia in adults, as it does in neonates and infants.

Isoproterenol induction of vasodepressor-type reaction in vasodepressor-prone persons.

The ability of isoproterenol to induce symptoms and laboratory findings of a vasodepressor reaction was tested in 48 patients, ages 17 to 74, divided into 4 groups according to the reason for their referral. Group 1 comprised 12 patients with vasodepressor syncope, group 2 had 8 patients with syncope of unknown origin, group 3 included 11 patients with syncope due to seizures in 2 and ventricular tachycardia in 9, group 4 had 17 patients with various arrhythmias not associated with syncope. Isoproterenol boluses were administered starting at 2 micrograms and increased in 2-micrograms steps to a maximum of 8 micrograms at 0 degree and +60 degrees. The responses at 0 degrees were all normal. At +60 degrees a vasodepressor reaction consisting of syncope or near syncope, hypotension and bradycardia was produced by isoproterenol (mean dose 6.0 +/- 0.26 micrograms) in 8 patients from group 1 (66.6%), 4 from group 2 (50%), 0 from group 3 and 4 from group 4 (23.5%). Three of the 4 patients in group 4 had a remote history of classic vasodepressor syncope. The overall sensitivity and specificity of the test were 73 and 85%, respectively, while the predictive accuracy of a test with positive or negative outcome were 69 and 89%, respectively. Muscarinic receptor blockade with atropine in 4 patients prevented isoproterenol-induced bradycardia but not hypotension or symptoms of fainting. Beta-adrenergic receptor blockade with propranolol inhibited all aspects of the isoproterenol-induced faint. Thus, the administration of isoproterenol during a passive upright tilt may identify persons who suffer from or are prone to a vasodepressor reaction.

Vagal techniques for termination of paroxysmal supraventricular tachycardia.

Maneuvers that reflexly increase vagal tone were deployed to terminate the tachycardia in 68 consecutive patients with paroxysmal supraventricular tachycardia. The order and success rate of the protocol was as follows: 57 episodes were terminated with carotid sinus pressure alone or after pretreatment with edrophonium, 5 were terminated with the Valsalva maneuvers and 6 were terminated with phenylephrine. Potency testing showed that phenylephrine evoked the greatest increase in vagal tone. All cases demonstrated slowing of tachycardia ranging from 40 to 220 ms +/- standard error of the mean (mean 79.0 +/- 3.8 ms) followed by abrupt termination. Pauses after termination ranged from 900 to 3,300 ms (mean 1,683.8 +/- 66.6) with 54 patients showing pauses of 2,000 ms or less. Termination was highly reproducible showing an overall success of 148 (92 percent) of 160 trials among 22 selected cases. The extent of increased vagal tone needed to terminate paroxysmal supraventricular tachycardia was raised by augmented sympathetic tone (infusion of isoproterenol) and decreased by reduced sympathetic tone (pretreatment with propranolol). Thus, paroxysmal supraventricular tachycardia can be rapidly, safety and consistently terminated by maneuvers that reflexly increase vagal tone.

Management of intractable ventricular tachyarrhythmias after myocardial infarction.

Twenty-five patients with recent or old myocardial infarction were studied because they had life-threatening ventricular arrhythmias that required repeated cardioversions and were intractable to medical management. All patients had had a large anterior infarction a mean of 4.6 weeks before the emergence of the arrhythmias and all had severe left ventricular dysfunction. Cardiac catheterization or autopsy revealed a left ventricular aneurysm in 18 of 18 patients and obstruction of the left anterior descending coronary artery in 20 of 20 patients. Of 16 patients treated surgically with aneurysm resection or coronary bypass grafting, or both, 10 (62 percent) were alive after 3 to 39 (mean 26) months of follow-up. The perioperative mortality rate was 31 percent and only one patient died during the postoperative follow-up period 4 months after discharge from the hospital. By contrast, all nine medically treated patients died either in the hospital (four patients) or suddenly within 2 months of discharge (five patients). Ventricular fibrillation was documented as the cause of death in five of these patients. Surgical intervention was found to improve significantly the survival of these patients (P less than 0.02). The perioperative mortality rate was lower when at least 4 weeks had elapsed from acute infarction to surgery (10 versus 67 percent) and when the procedure included coronary bypass grafting (13 versus 50 percent), although these differences were not statistically significant (P greater than 0.05).

Reflex mechanisms responsible for early spontaneous termination of paroxysmal supraventricular tachycardia.

The incidence and possible mechanism of early spontaneous termination of paroxysmal supraventricular tachycardia was studied in 20 consecutive patients. Episodes of induced tachycardia that terminated spontaneously within the 1st minute after initiation were included. Tachycardias ending spontaneously were associated with a reproducible course of hypotension at the onset followed by blood pressure recovery above control levels and termination. Spontaneous termination of tachycardias occurred within the A-V node 18 to 45 seconds (mean +/- standard error of the mean 27.9 +/- 5.3) after their onset. In the supine position (0 degrees) 9 (45 percent) of 20 patients showed spontaneous termination in 36 (16 percent) of 219 episodes of tachycardia. In the head-dependent position (-20 degrees) only 1 (8 percent) of 13 patients manifested spontaneous termination in 2 (4 percent) of 54 episodes. In the head up position (+60 degrees) only 1 (6 percent) of 18 patients exhibited termination in 2 (2 percent) of 102 episodes. After partial cholinergic blockade with intravenous hyoscine butylbromide, 20 mg, or atropine, 0.6 mg, none of five patients showed spontaneous termination in 25 episodes. After beta adrenergic blockade with 10 mg of propranolol intravenously, none of 16 patients showed spontaneous termination in 87 episodes of tachycardia. We conclude that the initial hypotension during tachycardia evokes a sympathetic response that increases blood pressure and this increase in turn causes a rise in vagal tone that breaks the tachycardia.

Enzymatic Capability of HIS-Tagged HIV-1 Integrase Using Oligonucleotide Disintegration Substrates.

Disintegration, wherein a half-site integration substrate is resolved into separate viral and host DNA components via DNA strand transfer, is one of three well-established in vitro activities of HIV-1 integrase. The role of disintegration in the HIV-1 replicative cycle, however, remains a mystery. In this report, we describe the expression in Escherichia coli and purification of HIV-1 integrase as a fusion protein containing a 6xHis tag at its amino terminus. Integrase resolved dumbbell and Y-substrates optimally at pH 6.8-7.2 in the presence of 2 mM MnCl(2). Substrate requirements for intramolecular disintegration included a 10 base pair viral U5 LTR arm and a CA dinucleotide located at the 3' end of the LTR. Disintegration was not sensitive to changes in the host DNA portion of the substrate. A dumbbell substrate with a 5' oligo-dA tail also underwent disintegration. The released LTR arm with an oligo-dA tail was utilized as a template primer by several DNA polymerases indicating that disintegration occurred via nucleophilic attack on the phosphodiester bond located immediately adjacent to the CA dinucleotide at the 3' end of the LTR. Coupled disintegration-DNA polymerase reactions provided a highly efficient and sensitive means of detecting disintegration activity. Integrase also catalyzed an apparently concerted disintegration-5'-end joining reaction in which an LTR arm was transferred from one dumbbell substrate molecule to another. Copyright 1996 S. Karger AG, Basel

Interactions between the autonomic nervous system and tachycardias in man.

We have endeavoured to present an integrated and dynamic overview of the interaction between the autonomic nervous system and cardiac arrhythmias. Our purpose was not to be comprehensive, detailed, or all inclusive but to present a clinically relevant summary of some of the areas where autonomic tone may be pertinent. Clearly, most arrhythmias are not the result of a primary autonomic nervous system disorder. However, subtle and overt alterations in autonomic tone, interacting with rate, pressure, cardiac volume, contractility, and the intrinsic myocardial electrophysiologic properties likely exert a critical influence on many cardiac arrhythmias. We wish to emphasize that autonomic effects may be temporarily concealed or overwhelmed during certain states or by the administration of drugs. However, the modulating role of neural tone and neurotransmitters is almost always present, contributing significantly to the outcome of therapy.

Visual attention in infant monkeys: effects of dietary fatty acids and age.

Effects of dietary essential fatty acids on visual attention were explored longitudinally in infant rhesus monkeys with a visual paired-comparison paradigm. Sets of primate faces and of patterns were presented at Weeks 2, 5, 9, and 13 to 9 infants deficient in omega-3 fatty acids and 8 fed a standard nursery diet. Familiarization to 1 member of each pair preceded simultaneous presentation of both stimuli. Infants fed the deficient diet showed longer individual looks in both immediate and 24-hr tests. Duration of looks decreased with age to familiar but not to novel stimuli. The proportion of time looking at the novel stimulus (% novel) increased with age but was not affected by diet. Look duration and % novel were differentially affected and may reflect different underlying processes.

A randomized control trial of an Ultra-Short zidovudine regimen in the prevention of perinatal HIV transmission in rural Zimbabwe.

OBJECTIVE: To assess the practicality and effectiveness of an Ultra-Short zidovudine regimen for prevention of perinatal HIV transmission in rural Zimbabwe. DESIGN: Double-blinded placebo-controlled randomized clinical trial. SETTING: The Salvation Army Howard Hospital, a district hospital in rural Zimbabwe. SUBJECTS: 222 HIV positive pregnant women presenting for antenatal care prior to 36 weeks were randomized. Twenty nine women were lost to follow up. INTERVENTION: In the Thai regimen, mothers received zidovudine (300 mg po bid) from 36 weeks gestation until labour, and zidovudine (300 mg po q3h) during labour, and the neonates received a placebo. In the Ultra-Short regimen, the mothers received a placebo from 36 weeks to labour, then zidovudine (300 mg po q3h) in labour. The neonates received zidovudine (2 mg/kg po qid) for the first three days of life. MAIN OUTCOME MEASURE: Infant HIV RNA status at six weeks of life. RESULTS: Results were available for 90 infants from the Thai group and 89 infants from the Ultra-Short group. Infant HIV seroconversion rates at six weeks of life were 18.9% (95%CI 10.8 to 27.0) with the Thai regimen, and 15.7% [95% Confidence Interval (CI) 8.1 to 23.4] with the Ultra-Short regimen. The upper bound of seroconversion in the Ultra-Short group was lower than the 25% seroconversion boundary that was specified to show equivalence. CONCLUSIONS: Although the Ultra-Short regimen has equivalent efficacy to the Thai regimen, it also has many practical advantages. Ultra-Short is thus a preferable protocol.