Early impacts of the COVID-19 pandemic on mental health care and on people with mental health conditions: framework synthesis of international experiences and responses

Purpose

The COVID-19 pandemic has many potential impacts on people with mental health conditions and on mental health care, including direct consequences of infection, effects of infection control measures and subsequent societal changes. We aimed to map early impacts of the pandemic on people with pre-existing mental health conditions and services they use, and to identify individual and service-level strategies adopted to manage these.

Methods

We searched for relevant material in the public domain published before 30 April 2020, including papers in scientific and professional journals, published first person accounts, media articles, and publications by governments, charities and professional associations. Search languages were English, French, German, Italian, Spanish, and Mandarin Chinese. Relevant content was retrieved and summarised via a rapid qualitative framework synthesis approach.

Results

We found 872 eligible sources from 28 countries. Most documented observations and experiences rather than reporting research data. We found many reports of deteriorations in symptoms, and of impacts of loneliness and social isolation and of lack of access to services and resources, but sometimes also of resilience, effective self-management and peer support. Immediate service challenges related to controlling infection, especially in inpatient and residential settings, and establishing remote working, especially in the community. We summarise reports of swiftly implemented adaptations and innovations, but also of pressing ethical challenges and concerns for the future.

Conclusion

Our analysis captures the range of stakeholder perspectives and experiences publicly reported in the early stages of the COVID-19 pandemic in several countries. We identify potential foci for service planning and research.

     

Oral V2 receptor antagonist (RWJ-351647) in patients with cirrhosis and ascites: a randomized, double-blind, placebo-controlled, single ascending dose study

BACKGROUND: RWJ-351647 is a selective V2 receptor antagonist that inhibits vasopressin-induced water reabsorption in the kidney. AIM: To investigate the safety and tolerability of RWJ-351647 compared with placebo after single oral dose administration to patients with cirrhosis and ascites, on a stable treatment with furosemide and spironolactone. METHODS: Single oral doses of 1, 2 and 5 mg of RWJ-351647 were administered to 24 patients with ascites on stable concomitant diuretic treatment. RESULTS: RWJ-351647 had a tmax of 1 to 1.1 h and mean half-life of 10.4-17.4 h. There was no affect on the pharmacokinetics of concomitant diuretics. Increases in cumulative urine volume and free water excretion, and a decrease in urine osmolality were noted in a dose-dependent manner reaching the statistical significance at the 5-mg dose. Four patients exhibited a decrease of > 2 kg in weight in the 24 h after dosing. RWJ-351647 was well tolerated, with no evidence of a dose-related increase in adverse events when compared with placebo. No changes in either serum chemistry or plasma AVP (arginine vasopressin) and renin levels were observed despite the observed aquaresis. CONCLUSION: RWJ-351647 is an effective aquaretic causing dose-dependent increases in urine output and free water clearance, when co-administered with conventional diuretics in patients with cirrhosis and ascites.     

Subclinical cardiomyopathy in Becker muscular dystrophy.

OBJECTIVE--To investigate the prevalence, age distribution, and spectrum of cardiac involvement in a cohort of patients with Becker muscular dystrophy. DESIGN--A prospective non-invasive study with clinical, electrocardiographic, and echocardiographic assessment. PATIENTS--19 patients (age range 16-41 years) with Becker muscular dystrophy attending the Muscle Clinic at Hammersmith Hospital and 22 healthy controls (age range 22-36 years). RESULTS--17 patients (89%) were symptom free; two had exertional dyspnoea. Three had a past history of acute pericarditis. The electrocardiogram was abnormal in 14 patients (74%). Intraventricular conduction delay or right bundle branch block was present in eight (42%). Three (16%) had tall R waves (R/S > 1) in lead V1 in the absence of right bundle branch block and eight (42%) had Q waves in the lateral and inferolateral leads. The PQ interval was significantly shorter in patients with Becker muscular dystrophy (p < 0.01). Echocardiography showed left ventricular dilatation in seven patients (37%) and 12 (63%) had subnormal systolic function caused by global hypokinesia (fractional shortening < 27%). Six of these patients were under the age of 22 years. Patients with Becker muscular dystrophy had significant reduction of both fractional shortening and corrected mean velocity of circumferential shortening compared with controls. No correlation was found between fractional shortening and age. The third filling fraction was significantly reduced in patients with Becker muscular dystrophy (p < 0.05), although other indices of diastolic function (isovolumic relaxation time and E/A ratios) were not significantly different. CONCLUSIONS--Though most patients with Becker muscular dystrophy were symptom free, a high percentage had evidence of a subclinical cardiomyopathy. Electrocardiography showed that the inferolateral and posterior segments of the left ventricle tended to be affected and may show evidence for conduction tissue disease. Echocardiography showed that most patients had left ventricular dilation and global hypokinesia. The severity of left ventricular disease was unrelated to age; some younger patients had severe left ventricular dysfunction. All patients with Becker muscular dystrophy should have echocardiographic assessment of left ventricular function.     

临床试验安全数据管理介绍

根据药品临床试验质量管理规范要求(GCP),对药品上市前和上市后的临床试验安全信息进行收集、监测、速报和综合分析是临床研究中的重要内容.     

The Protective Effect of Heat Stress Against Reperfusion Arrhythmias in the Rat

Heat stress provides protection against mechanical dysfunction and myocardial necrosis after prolonged ischemia. We have investigated whether this protection extends to reperfusion arrhythmias occurring after a short (non-lethal) ischemic insult. Anaesthetized open chest rats were subjected to a 5-min occlusion of the left coronary artery. The incidence and duration of reperfusion arrhythmias and the duration of sinus rhythm were assessed in the first 5 min of reperfusion. Prior heat stress led to a reduction in the incidence (100-63%, P 0.05) and duration (66.2 ± 15.8 to 9.4 ± 2.9s, P 0.05) of ventricular tachycardia and a non-significant reduction in the incidence (76-50%) and duration (74.3 ± 23.4 to 42.9 ± 24.4s, P = 0.09) of ventricular fibrillation. This resulted in a significant increase in the duration of sinus rhythm (142.1 ± 27.6 to 216.7 ± 24.8s, P 0.05) and reduction in arrhythmia score (P 0.05) in heat stressed rats compared with controls. This protection against reperfusion arrhythmias was associated with a two-fold increase in endogenous catalase activity and expression of the inducible heat stress protein HSP 70. Inhibition of catalase with pre-administered 3-amino triazole resulted in a paradoxical protection in both sham and heat stress hearts. We conclude that heat stress leads to protection against reperfusion arrhythmias; however, we have been unable to resolve whether the changes in catalase activity of HSP expression are the mediators of the demonstrated cardioprotection.     

A meta-analysis of ECG data from healthy male volunteers: diurnal and intra-subject variability, and implications for planning ECG assessments and statistical analysis in clinical pharmacology studies

Objective To evaluate the innate variability in key electrocardiography (ECG) parameters from clinical pharmacology studies.Methods Meta-analysis of ECG data from seven clinical pharmacology studies in healthy male volunteers using model building and stepwise multiple regression analyses.Results Data from 115 male subjects provided over 2,000 observations for all key ECG parameters from baseline (Day−1) and placebo treatment periods (Day 1). Only heart rate and uncorrected QT showed clear and marked changes over the day. QTcB had greater variability compared to QTcF. 1.4% of QTcB and 0.7% QTcF observations were >430 ms and 0.1% of QTcB and 0% of QTcF observations were >450 ms. We estimated that 8.9% of subjects would have at least one out of eight post-observation QTc value in the range 430–450 ms [assuming QTc mean 385 ms, standard deviation (SD) 20 ms] due to intrinsic variability alone. Time-matched within-subjects observations demonstrated that the SD between measurements taken 1 h apart was less than seen with a longer interval, but there was little increase in variability beyond 1 h. The probability of observing an increase in QTc of 30–60 ms in a subject was estimated as 3.0% and 21.8% for one and eight post-dose observations, respectively. The greater the number of observations used to define baseline the narrower the spread; for QTcF the SD of the baseline value was 17.1 ms for a single assessment, 13.3 ms for the mean of three assessements, and 13.2 ms for the mean of all Day−1 assessments.Conclusions The spontaneous variability in QTc measurements must be taken into account when designing studies and interpreting analyses of ECG data. The categorical analysis of QTc change of 30–60 ms is unlikely to be of any additional value to analyses of central tendency. For standard early clinical pharmacology studies, QTcF should be chosen as the primary correction method, while the mean of three measures taken in the afternoon and evening of Day−1 and pre-dose Day 1 should provide a reliable and representative baseline assessment.     

Subclinical cardiomyopathy in Becker muscular dystrophy

Objective—To investigate the prevalence, age distribution, and spectrum of cardiac involvement in a cohort of patients with Becker muscular dystrophy.

Design—A prospective non-invasive study with clinical, electrocardiographic, and echocardiographic assessment.

Patients—19 patients (age range 16–41 years) with Becker muscular dystrophy attending the Muscle Clinic at Hammersmith Hospital and 22 healthy controls (age range 22–36 years).

Results—17 patients (89%) were symptom free; two had exertional dyspnoea. Three had a past history of acute pericarditis. The electrocardiogram was abnormal in 14 patients (74%). Intraventricular conduction delay or right bundle branch block was present in eight (42%). Three (16%) had tall R waves (R/S > 1) in lead V1 in the absence of right bundle branch block and eight (42%) had Q waves in the lateral and inferolateral leads. The PQ interval was significantly shorter in patients with Becker muscular dystrophy (p < 0·01). Echocardiography showed left ventricular dilatation in seven patients (37%) and 12 (63%) had subnormal systolic function caused by global hypokinesia (fractional shortening <27%). Six of these patients were under the age of 22 years. Patients with Becker muscular dystrophy had significant reduction of both fractional shortening and corrected mean velocity of circumferential shortening compared with controls. No correlation was found between fractional shortening and age.

The third filling fraction was significantly reduced in patients with Becker muscular dystrophy (p < 0·05), although other indices of diastolic function (isovolumic relaxation time and E/A ratios) were not significantly different.

Conclusions—Though most patients with Becker muscular dystrophy were symptom free, a high percentage had evidence of a subclinical cardiomyopathy. Electrocardiography showed that the inferolateral and posterior segments of the left ventricle tended to be affected and may show evidence for conduction tissue disease. Echocardiography showed that most patients had left ventricular dilation and global hypokinesia. The severity of left ventricular disease was unrelated to age; some younger patients had severe left ventricular dysfunction. All patients with Becker muscular dystrophy should have echocardiographic assessment of left ventricular function.

     

Preconditioning the human myocardium: Recent advances and aspirations for the development of a new means of cardioprotection in clinical practice

Summary Ischemic preconditioning has been shown to be one of the most powerful means of protecting the myocardium from ischemic injury in experimental animal models, although the mechanism is incompletely understood. In this review we discuss the evidence for preconditioning occurring in ischemic syndromes in humans, whether the human myocardium can be preconditioned, and whether preconditioning would have a place as a therapeutic tool in clinical practice. Some studies evaluating patients after acute myocardial infarction have shown a better outcome in patients reporting angina before the onset of the infarction, but this is not a universal finding, and it is difficult to exclude other confounding factors, such as collateral flow, from influencing the results. More controlled prospective studies have evaluated patients undergoing percutaneous transluminal coronary angioplasty and have found less ST-segment change and less reported angina during the second balloon inflation when compared with the first. Again, it is impossible to completely exclude other causes for this effect, but the dependence on mechanisms that are known to be important for preconditioning in animal models does suggest the phenomena are the same. Further experiments using isolated human atrial muscle have shown that human myocardium can be preconditioned and that the mechanisms involved are similar to those elucidated in animal models (adenosine, protein kinase C, and ATP-dependent potassium channels). In clinical medicine preconditioning is most likely to benefit patients when it is used to protect against the ischemia induced by cardiac surgery. In this respect, a study has shown that in patients undergoing coronary artery bypass grafts, the reduction in ATP occurring during the first ischemic period is attenuated in those given an ischemic preconditioning protocol beforehand. Despite these advances, it is likely that the full potential of preconditioning in clinical practice will not be realized until the whole mechanism of protection is understood and a safe pharmacological preconditioning agent becomes available.