Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study.

BACKGROUND: The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. METHODS: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9-6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40-59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. INTERPRETATION: We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. FUNDING: UK Research and Innovation and National Institute for Health Research.

Respiratory follow-up of patients with COVID-19 pneumonia.

The COVID-19 pandemic has led to an unprecedented surge in hospitalised patients with viral pneumonia. The most severely affected patients are older men, individuals of black and Asian minority ethnicity and those with comorbidities. COVID-19 is also associated with an increased risk of hypercoagulability and venous thromboembolism. The overwhelming majority of patients admitted to hospital have respiratory failure and while most are managed on general wards, a sizeable proportion require intensive care support. The long-term complications of COVID-19 pneumonia are starting to emerge but data from previous coronavirus outbreaks such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) suggest that some patients will experience long-term respiratory complications of the infection. With the pattern of thoracic imaging abnormalities and growing clinical experience, it is envisaged that interstitial lung disease and pulmonary vascular disease are likely to be the most important respiratory complications. There is a need for a unified pathway for the respiratory follow-up of patients with COVID-19 balancing the delivery of high-quality clinical care with stretched National Health Service (NHS) resources. In this guidance document, we provide a suggested structure for the respiratory follow-up of patients with clinicoradiological confirmation of COVID-19 pneumonia. We define two separate algorithms integrating disease severity, likelihood of long-term respiratory complications and functional capacity on discharge. To mitigate NHS pressures, virtual solutions have been embedded within the pathway as has safety netting of patients whose clinical trajectory deviates from the pathway. For all patients, we suggest a holistic package of care to address breathlessness, anxiety, oxygen requirement, palliative care and rehabilitation.

Primary care treatment for child and adolescent neuropsychiatric conditions in remote rural Punjab, Pakistan - a cross-sectional survey.

BACKGROUND: Pakistan is one of the most populous regions of the world. Previous work has demonstrated that there is reliance on traditional healthcare systems when seeking psychiatric care; however, there is a lack of information on help seeking for child and adolescent population. The aim of this study was to describe types of treatments and families' perceptions of the effectiveness of those treatments for childhood neuropsychiatric disorders in remote rural Punjab. METHOD: Cross-sectional survey of consecutive attendees at an advertised mental health consultation day in a remote rural area. RESULTS: The effectiveness of these treatments, as rated by patients and their families, was variable, with highest reported effectiveness for general practitioner treatments. In families with a past history of care from a general practitioner, those who had epilepsy reported treatments to be more effective than those with mental retardation. Carers and users described consulting five different types of primary healthcare practitioners that used both physical and psychotherapeutic treatments. CONCLUSIONS: There is considerable variation in treatments available for child and adolescent neuropsychiatric disorders in remote rural areas of Punjab, a large proportion of which are considered ineffective by the users and carers. This highlights the need to develop effective interventions for child and adolescent neuropsychiatric conditions that can be administered by primary health workers. Our data suggest that the need for this is greatest for mental retardation.

Effects of the plant steroidal hormone, 24-epibrassinolide, on the mitotic index and growth of onion (Allium cepa) root tips.

The purpose of the present study was to determine the effects of the steroidal plant hormone, 24-epibrassinolide (BL), on the mitotic index and growth of onion (Allium cepa) root tips. The classical Allium test was used to gather and quantify data on the rate of root growth, the stages of mitosis, and the number of mitoses in control and BL-treated groups of onions. Low doses of BL (0.005 ppm) nearly doubled the mean root length and the number of mitoses over that of controls. Intermediate doses of BL (0.05 ppm) also produced mean root lengths and number of mitoses that were significantly greater than those of the controls. The highest dose of BL (0.5 ppm) produced mean root lengths and number of mitoses that were less than control values, but the differences were not statistically significant. Examination of longitudinally sectioned root tips produced relatively similar results. This study confirms the suppositions of previous authors who have claimed that exogenously applied BL can increase the number of mitoses in plants, but failed to show cytogenetic data. This is the first report detailing the effects of BL on chromosomes and the cell cycle.

Effects of the plant steroidal hormone, 24-epibrassinolide, on the mitotic index and growth of onion (Allium cepa) root tips

The purpose of the present study was to determine the effects of the steroidal plant hormone, 24-epibrassinolide (BL), on the mitotic index and growth of onion (Allium cepa) root tips. The classical Allium test was used to gather and quantify data on the rate of root growth, the stages of mitosis, and the number of mitoses in control and BL-treated groups of onions. Low doses of BL (0.005 ppm) nearly doubled the mean root length and the number of mitoses over that of controls. Intermediate doses of BL (0.05 ppm) also produced mean root lengths and number of mitoses that were significantly greater than those of the controls. The highest dose of BL (0.5 ppm) produced mean root lengths and number of mitoses that were less than control values, but the differences were not statistically significant. Examination of longitudinally sectioned root tips produced relatively similar results. This study confirms the suppositions of previous authors who have claimed that exogenously applied BL can increase the number of mitoses in plants, but failed to show cytogenetic data. This is the first report detailing the effects of BL on chromosomes and the cell cycle.

Head control strategies during whole-body turns.

Recent reports have described the motion of individual body segments during turns toward visual targets. During a whole-body turn, the head's trajectory in space is determined by both body-in-space rotation and head-on-body rotation. To inform subsequent investigations of head control strategies during turns, we provide a kinematic description of head and pelvis rotation in 20 healthy human subjects as they performed step turns toward a visible target or in the direction of a previously seen target. At the time of peak head velocity in space, the head was moving faster than the pelvis by approximately 54 degrees s(-1) when turning toward a visible target, and approximately 25 degrees s(-1) when turning in a remembered direction. Peak head velocities were slower in the absence of a visual target, but pelvis velocities were not significantly different. The pattern of relative motion between the head and pelvis followed a temporal sequence. Early in the turn, the head rotated with respect to the pelvis in the same direction as the pelvis was rotating in space. During the mid portions of the turn, en bloc rotation of the head and pelvis predominated. Later in the turn, head-in-space velocity was lower than pelvis-in-space velocity, and was thus relatively stabilized. This pattern of head movement during turns is quite similar to eye-in-head movements during large eye-head gaze shifts. This suggests that in addition to saccadic and stabilization mechanisms, a specific control strategy to move segments together should be incorporated into models of gaze reorienting behavior.

Bioavailability and trophic transfer of sediment-bound Ni and U in a southeastern wetland system.

Elemental composition of soil, herbaceous and woody plant species, and the muscle and liver tissue of two common small mammal species were determined in a wetland ecosystem contaminated with Ni and U from nuclear target processing activities at the Savannah River Site, Aiken, SC. Species studied were black willow ( Salix nigra L.), rushes ( Juncus effusus L.), marsh rice rat ( Oryzomys palustris), and cotton rat ( Sigmodon hispidus). Two mature trees were sampled around the perimeter of the former de facto settling basin, and transect lines sampling rushes and trapping small mammals were laid across the wetland area, close to a wooden spillway that previously enclosed the pond. Ni and U concentrations were elevated to contaminant levels; with a total concentration of 1,065 (+/- 54) mg kg(-1) U and 526.7 (+/-18.3) mg kg(-1) Ni within the soil. Transfer of contaminants into woody and herbaceous plant tissues was higher for Ni than for U, which appeared to remain bound to the outside of root tissues, with very little (0.03 +/- 0.001 mg kg(-1)) U detectable within the leaf tissues. This indicated a lower bioavailability of U than the cocontaminant Ni. Trees sampled from the drier margins of the pond area contained more Ni within their leaf tissues than the rushes sampled from the wetter floodplain area, with leaf tissues concentrations of Ni of approximately 75.5 (+/- 3.6) mg kg(-1) Ni. Ni concentrations were also elevated in small mammal tissues. Transfer factors of contaminants indicated that U bioavailability is negligable in this wetland ecosystem.

Cerebrospinal fluid S100B correlates with brain atrophy in Alzheimer's disease.

S100B is a predominantly astrocytic protein with dose-dependent cytotoxic and neurotrophic properties encoded on chromosome 21q22.3. Concentrations of S100B were measured in the cerebrospinal fluid (CSF) of 31 patients with Alzheimer's disease (AD), 36 patients with frontotemporal lobe dementia (FTLD) and 49 patients with other non-inflammatory neurological diseases. Additional CSF S100B concentrations were correlated with normalised brain volume measurements in AD and FTLD. CSF S100B was significantly higher in AD (Mean+/-standard deviation=0.4+/-0.2 ng/ml) and FTLD (0.42+/-0.19 ng/ml) patients when compared with control subjects (0.25+/-0.08, P<0.001). In patients with AD, S100B correlated negatively with normalised brain volume (R(S)=-0.53, P<0.001). No such correlation was found for FTLD patients. This study supports the concept that S100B is of pathological relevance for degeneration of the central nervous system in AD.

Evaluation of cot mattress inner foam as a potential site for microbial generation of toxic gases.

Recent reports of biovolatilisation of phosphorus and antimony by anaerobic bacteria and of leaching of phosphorus and antimony fire-retardant additives from PVC cot mattress covers, indicate that the polyurethane inner-foam of cot mattresses could be a site for generation of toxic gases of group 15 elements. A toxic gas hypothesis for sudden infant death syndrome (SIDS) involving polyurethane foam of cot mattresses was proposed and tested experimentally. Levels of antimony, phosphorus, arsenic and bismuth were determined at four sites for 44 SIDS and 50 control (no death) cot mattress foams. There was no evidence to suggest that the levels of these elements in cot mattress foam have a causal relation to SIDS. Leaching of antimony trioxide from PVC mattress covers could account for detectable levels of this element in 52% of the cot mattress samples analysed. Volatile forms of antimony, phosphorus, arsenic and bismuth was not detected in the headspace of mixed or monoseptic cultures of anaerobic bacteria containing polyurethane foam. Past microbial activity had given rise to involatile methylated species of antimony in some of the cot mattress foams tested (61%, n = 24). Abiotic oxidation of biogenic trimethylantimony together with physical adsorption of methylantimony forms to the polyurethane foam matrix could account for the apparent absence of "escaped" volatile antimony species in culture headspaces of incubation vial. There was no evidence to suggest that levels of trimethylantimony or total methylantimony forms in cot mattress foams have a causal relation to SIDS.

Treatment of hepatocellular carcinoma using doxorubicin/ethiodized oil/gelatin powder chemoembolization.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignancy worldwide with limited effective therapeutic options available or appropriate for cirrhotic patients. METHODS: Chemoembolization, using sequential intra-arterial doxorubicin/ethiodized oil and gelatin sponge particle/ethanol embolization, was used to treat patients with unresectable HCC localized to the liver. Fifty-two patients were treated in this manner from 1988 to 1992. The objective response was determined by sequential computed tomography (CT) scans. RESULTS: Of the 47 patients evaluable for response, 20 (43%) achieved a partial response, and 12 (26%) achieved a minor response. Sixteen patients underwent repeated chemoembolization for locally recurrent disease as many as three times after the initial procedure. All 52 patients were evaluable for survival and toxicity, with a median follow-up of 14 months. Twelve-month survival was 60%, and median survival was 16 months. This compares favorably with values reported in the literature of approximately 20% and 6-14 weeks, respectively. There was a 17% 30-day mortality, with a slightly higher risk for patients with portal vein obstruction. Other toxicities generally were mild and transient, including fever, pain, encephalopathy, and malaise. CONCLUSIONS: Chemoembolization may enhance survival for patients with unresectable, localized HCC. It appears to be an effective alternative to standard treatment, even in cirrhotic patients.

Neoadjuvant therapy for unresectable pancreatic adenocarcinoma.

The purposes of this study were to determine whether continuous infusion of fluorouracil combined with external-beam radiation therapy improved the resectability and survival of patients with pancreatic carcinoma. Sixteen patients with unresectable disease confined to the pancreas and celiac nodes were treated, and their outcome was compared with that of 24 patients with potentially resectable disease who were treated concurrently. The neoadjuvant therapy was completed with acceptably few toxic effects but with only a minor decrease in tumor size. Two patients underwent resection and remained free of disease 20 and 22.5 months later. However, the median survival of the entire neoadjuvant group was 8 months. All 24 patients with potentially resectable carcinoma underwent surgical exploration. Fifteen of the 24 patients underwent resection and survived a median of 12.5 months. Neoadjuvant chemoradiation may have improved outcome and resectability for two (12.5%) of 16 patients with unresectable pancreatic carcinoma, but more effective therapy options must be developed to improve outcome.

Cognitive distraction and relaxation training for the control of side effects due to cancer chemotherapy.

Sixty cancer chemotherapy patients were randomly assigned to one of six conditions formed by a 3(cognitive distraction, relaxation training, no intervention) x 2(high anxiety, low anxiety) factorial design. All patients were followed for five consecutive chemotherapy sessions. Outcome measures included patient reports, nurse observations, and physiological indices. Results indicated that distraction patients reported less nausea prior to chemotherapy and lower systolic blood pressures after chemotherapy than controls. Relaxation training patients reported less nausea prior to chemotherapy and exhibited lower systolic and diastolic blood pressures after chemotherapy than control patients. There were no significant differences between distraction and relaxation training patients on any measure. Patients with high initial levels of anxiety exhibited continually elevated levels of distress throughout the chemotherapy experience; however, anxiety level did not interact with the effectiveness of the treatment interventions. Overall, the data support the use of both cognitive distraction and relaxation training for reducing the distress of chemotherapy with both high and low-anxiety patients and suggest that at least some of the effects of relaxation training can be achieved with distraction alone.

Studies on the acute lethality of diethylcarbamazine in the rat.

In spite of its effectiveness against microfilariae, very little is known about diethylcarbamazine's (DEC) therapeutic mechanism of action or the toxic sequelae which can result from overdose. In preliminary studies, a precipitous decrease in heart rate was noted in rats receiving 1000 mg DEC/kg ip. This effect was less pronounced at 750 mg/kg and was non-existent at 500 mg/kg. In the present study, attempts to attenuate DEC's cardiopulmonary insult by pretreating animals with cyproheptadine failed. Atropine pretreatment failed to block the negative chronotropic effects of DEC, but did restore respiratory function and reduce the lethality associated with the drug. Biochemical studies showed that ATP:ADP ratios in the hearts from rats given high dosages of DEC were elevated over those in controls (11:1 versus 5:1). Inosine levels decreased in cardiac tissues taken from DEC-treated rats. Subsequent enzyme studies revealed that DEC has a potent inhibitory effect on calcium-dependent ATPases from a variety of tissues. Taken together, our data indicate that the mode of acute DEC-lethality involves cardiopulmonary suppression. Furthermore, the cardiac depressant effect of DEC appears related to inhibition of calcium ATPases in cardiac myocytes. To our knowledge, this is the first report of ATPase sensitivity to DEC, a finding that has interesting toxicologic and pharmacologic ramifications.

Elevated muscle vitamin E does not attenuate eccentric exercise-induced muscle injury.

The purpose of this study was to evaluate the effect of elevated muscle vitamin E content on skeletal muscle damage from eccentric exercise. Sixty Sprague-Dawley rats were put on a normal (40 IU vitamin E/kg food) or supplemented (10,000 IU vitamin E/kg food) diet for 5 wk. Injury in soleus muscle was determined using several criteria: reductions in maximal tetanic force and number of intact fibers per square millimeter and elevations in muscle glucose 6-phosphate dehydrogenase activity and plasma creatine kinase activity, either immediately (0 h) or 2 days (48 h) after a downhill walking protocol. Sedentary animals were also tested but did not exercise. Muscle vitamin E levels were significantly elevated (approximately 3- to 4-fold), and susceptibility of the muscles to oxidant stress was decreased, after supplementation. However, vitamin E supplementation did not attenuate injury by any of the criteria employed. Maximal tetanic force decreased approximately 20% at 0 and 48 h after exercise in both groups. The number of intact fibers per square millimeter decreased approximately 30-35% in both groups at 0 and 48 h. Glucose 6-phosphate dehydrogenase activity increased approximately 50-100% in both groups at 48 h, and plasma creatine kinase activity was elevated approximately 2- to 2.5-fold at 0 h in both groups. These findings do not support a major role for free radical damage to muscle membranes in the initiation of injury from eccentric exercise, although they do not disprove free radical involvement in the etiology.

Effectiveness of biofeedback and relaxation training in reducing the side effects of cancer chemotherapy.

Assessed the effectiveness of electromyographic (EMG) and skin-temperature (ST) biofeedback and relaxation training (RT) in reducing the aversiveness of cancer chemotherapy. Eighty-one cancer patients, equated on several individual-difference variables, were randomized to one of six groups formed by a 3 (EMG Biofeedback, ST Biofeedback, No Biofeedback) x 2 (RT, No RT) factorial design. Outcome was assessed with physiological, patient-reported, and nurse-reported indices taken over five consecutive chemotherapy treatments. RT patients showed decreases in nausea and anxiety during chemotherapy and physiological arousal after chemotherapy. EMG and ST biofeedback reduced some indices of physiological arousal but had no other effects on chemotherapy side effects. These findings suggest that RT can be effective in reducing the adverse consequences of chemotherapy and that the positive effects found for biofeedback in prior research were due to the RT that was given with the biofeedback, not to the biofeedback alone.

Preparing patients for cancer chemotherapy: effect of coping preparation and relaxation interventions.

Sixty cancer chemotherapy patients were randomly assigned to one of four treatments: (a) relaxation training with guided relaxation imagery (RT), (b) general coping preparation package (PREP), (c) both RT and PREP, or (d) routine clinic treatment only. All patients were assessed on self-report, nurse observation, family observation, and physiological measures and were followed for five sequential chemotherapy treatments. Results indicate that the PREP intervention increased patients' knowledge of the disease and its treatment, reduced anticipatory side effects, reduced negative affect, and improved general coping. RT patients showed some decrease in negative affect and vomiting, but not as great as in past studies. The data suggest that a relatively simple, one-session coping preparation intervention can reduce many different types of distress associated with cancer chemotherapy and may be more effective than often-used behavioral relaxation procedures.

Mechanisms of inhibition of mononuclear cell activation by the iron-chelating agent desferrioxamine.

Iron-withholding by the chelating agent desferrioxamine abrogates the proliferative response of human peripheral blood mononuclear cells (PBMC) to phytohaemagglutinin (PHA). The present study investigated whether desferrioxamine operates late in the activation process or, as recently suggested, at an early stage, by inhibiting the appearance of the interleukin-2 (IL-2) receptor. Human PBMC were stimulated with PHA (10 micrograms/ml) and [3H]thymidine ([3H]TdR) incorporation determined after 66 hr of culture. Greater than 90% inhibition was achieved by concentrations of desferrioxamine as low as 5 mumol/l present throughout culture, while IL-2 receptor expression (anti-Tac), analysed by FACS, was maintained at up to 75% of control levels. 300 mumol/l desferrioxamine present throughout culture abrogated [3H]TdR incorporation and additionally suppressed IL-2 receptor to 10-15% of control levels. In contrast, the same high dose of desferrioxamine when added for 2 hr to cells previously cultured for 66 hr produced 80% inhibition of [3H]TdR incorporation but failed to inhibit expression of the IL-2 receptor. Desferrioxamine rapidly achieved equilibrium across the cell membrane (within 60 min) and chelated 59Fe delivered to activated cells by the transferrin endocytic cycle. These results indicate that desferrioxamine can inhibit T-cell activation either early or late in the process by chelating iron and independently of an effect on the IL-2 receptor. In support of a dual effect of the drug is the finding that at 50 mumol/l, desferrioxamine-enhanced expression of the transferrin receptor occurred, an adaptive response made to intracellular iron depletion, while IL-2 receptor expression was inhibited.