Increased care at discharge from COVID-19: The association between pre-admission frailty and increased care needs after hospital discharge; a multicentre European observational cohort study.

BACKGROUND: The COVID-19 pandemic has placed significant pressure on health and social care. Survivors of COVID-19 may be left with substantial functional deficits requiring ongoing care. We aimed to determine whether pre-admission frailty was associated with increased care needs at discharge for patients admitted to hospital with COVID-19. METHODS: Patients were included if aged over 18 years old and admitted to hospital with COVID-19 between 27 February and 10 June 2020. The Clinical Frailty Scale (CFS) was used to assess pre-admission frailty status. Admission and discharge care levels were recorded. Data were analysed using a mixed-effects logistic regression adjusted for age, sex, smoking status, comorbidities, and admission CRP as a marker of severity of disease. RESULTS: Thirteen hospitals included patients: 1671 patients were screened, and 840 were excluded including, 521 patients who died before discharge (31.1%). Of the 831 patients who were discharged, the median age was 71 years (IQR, 58-81 years) and 369 (44.4%) were women. The median length of hospital stay was 12 days (IQR 6-24). Using the CFS, 438 (47.0%) were living with frailty (≥ CFS 5), and 193 (23.2%) required an increase in the level of care provided. Multivariable analysis showed that frailty was associated with an increase in care needs compared to patients without frailty (CFS 1-3). The adjusted odds ratios (aOR) were as follows: CFS 4, 1.99 (0.97-4.11); CFS 5, 3.77 (1.94-7.32); CFS 6, 4.04 (2.09-7.82); CFS 7, 2.16 (1.12-4.20); and CFS 8, 3.19 (1.06-9.56). CONCLUSIONS: Around a quarter of patients admitted with COVID-19 had increased care needs at discharge. Pre-admission frailty was strongly associated with the need for an increased level of care at discharge. Our results have implications for service planning and public health policy as well as a person's functional outcome, suggesting that frailty screening should be utilised for predictive modelling and early individualised discharge planning.

Nosocomial COVID-19 infection: examining the risk of mortality. The COPE-Nosocomial Study (COVID in Older PEople).

BACKGROUND: Hospital admissions for non-coronavirus disease 2019 (COVID-19) pathology have decreased significantly. It is believed that this may be due to public anxiety about acquiring COVID-19 infection in hospital and the subsequent risk of mortality. AIM: To identify patients who acquire COVID-19 in hospital (nosocomial COVID-19 infection (NC)) and their risk of mortality compared to those with community-acquired COVID-19 (CAC) infection. METHODS: The COPE-Nosocomial Study was an observational cohort study. The primary outcome was the time to all-cause mortality (estimated with an adjusted hazard ratio (aHR)), and secondary outcomes were day 7 mortality and the time-to-discharge. A mixed-effects multivariable Cox's proportional hazards model was used, adjusted for demographics and comorbidities. FINDINGS: The study included 1564 patients from 10 hospital sites throughout the UK, and one in Italy, and collected outcomes on patients admitted up to April 28th, 2020. In all, 12.5% of COVID-19 infections were acquired in hospital; 425 (27.2%) patients with COVID died. The median survival time in NC patients was 14 days compared with 10 days in CAC patients. In the primary analysis, NC infection was associated with lower mortality rate (aHR: 0.71; 95% confidence interval (CI): 0.51-0.98). Secondary outcomes found no difference in day 7 mortality (adjusted odds ratio: 0.79; 95% CI: 0.47-1.31), but NC patients required longer time in hospital during convalescence (aHR: 0.49, 95% CI: 0.37-0.66). CONCLUSION: The minority of COVID-19 cases were the result of NC transmission. No COVID-19 infection comes without risk, but patients with NC had a lower risk of mortality compared to CAC infection; however, caution should be taken when interpreting this finding.

The distribution of choline acetyltransferase- and acetylcholinesterase-like immunoreactivity in the palmar skin of patients with palmoplantar pustulosis.

The distribution of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in involved skin in patients with palmoplantar pustulosis (PPP) and in normal palmar skin in healthy non-smokers and smokers has been studied by immunohistochemistry, especially in relation to the sweat gland apparatus. The sweat gland and its duct showed ChAT- and AChE-like immunoreactivity (LI) of varying intensity in all three groups and with stronger reactivity than in the epidermis. ChAT-LI was present in the coil and in the duct except in the corneal layer. Smokers and patients with PPP displayed significantly fewer ChAT+ acrosyringia than non-smokers. In the patients with PPP, the granulocytes in the pustules and in the papillary dermis displayed ChAT-LI. Western blot analysis of granulocytes from peripheral blood from healthy donors confirmed the presence of ChAT-like proteins in large amounts in neutrophils and small amounts in eosinophils. AChE-LI of varying intensity was found in all parts of the sweat gland apparatus in all three groups. The strongest AChE-LI in the acrosyringia was seen in the lowest part of the stratum corneum, where the PPP pustules are located. No significant differences in staining pattern or intensity were found between the coils, nerve fibres surrounding the coils or ducts. The number of mast cells in the papillary dermis was about four times larger in the patients with PPP than in the control subjects. AChE-LI was observed in about 25% of the mast cells in non-smoking control subjects and in patients with PPP, but only in 10% of those in the smoking control subjects. Our findings indicate that the (non-neuronal) cholinergic system may be involved in cutaneous inflammatory processes.

[Head injury at Reykjavík Hospital, intensive care unit, 1994-1998.].

OBJECTIVE: Reykjavík Hospital is the main trauma hospital in Iceland, receiving all severe head injuries in the country. Incidence of head injury and mortality has been decreasing in the last decades. The aim of this study was to analyse data on admission, treatment and outcome of patients admitted to intensive care unit with severe head injury and compare with other countries. MATERIAL AND METHODS: In this study we looked retrospectively at the incidence of severe head injuries admitted to the intensive care unit at Reykjavik Hospital 1994-1998. Number of patients, type of injury, length of stay, length of ventilator treatment. Glasgow Coma Score (GCS), APACHE II (Acute Physiologic and Chronic Health Evaluation) score and mortality was analysed. RESULTS: A total of 236 patients was admitted with an average of 47 patients per year. Traffic accidents were the most common cause of injury and mortality was 11.7%. Ethanol consumption was seen in many cases where fall was the cause of accident, most often in the year 1998 in 75% of cases. Mortality of patients with GCS 8 that was 40% of the patients was must higher or 24.7% compared with patients with GCS >8 where mortality was 3.4%. There was an increase in admissions in 1998, with more severe injuries and significantly longer length of stay and ventilator treatment. CONCLUSIONS: Number of patients with head injury was decreasing in comparison with older studies. The results of treatment are rather good in comparison with other countries with relatively low mortality, or 11.7% versus 15-20% in nearby countries. There has been improvement of outcome in patients with the most severe head injury (GCS 8) since 20 years ago, where up to 50% of the patients died but in our study mortality was 24.7%. Alcohol consumption was seen in 46% of cases where fall was the cause of head injury. Those that suffer head trauma are most often young people and preventive measures must continue with full strength in order to decrease the incidence of accidents in our society.

Genetic alterations on 3p, 11q13, and 18q in nonfamilial and MEN 1-associated pancreatic endocrine tumors.

Pancreatic endocrine tumors occur sporadically and as part of the multiple endocrine neoplasia type 1 (MEN 1) and von Hippel-Lindau (VHL) syndromes. The MEN1 locus on 11q13 and a candidate tumor suppressor locus on 3p are known to be hemi- or homozygously mutated in a subset of these tumors. Chromosome arm 18q harbors the SMAD4/DPC4 tumor suppressor gene that is frequently deleted and inactivated in tumors of the exocrine pancreas. We have analyzed 22 nonfamilial and 16 MEN 1-associated pancreatic endocrine tumors for loss of heterozygosity (LOH) at 3p, 11q13, and 18q. LOH at 3p was revealed in 45% and 36% of tumors from 31 patients with nonfamilial and MEN 1-associated disease, respectively. The corresponding proportions for 11q13 were 55% and 91%, and for 18q 27% and 25%, respectively. A striking relation between LOH at 11q13 and 3p and a malignant phenotype was found for the nonfamilial tumors. None of the six benign tumors (all of them insulinomas) had allelic loss at 3p or 11q13, whereas 92% (P < 0.01) of the malignant tumors (including malignant insulinomas) had such deletions. Besides the 11q13 abnormality, more than half of the MEN 1-associated tumors had additional genetic lesions affecting 3p or 18q. LOH analysis of several tumors from two MEN 1 patients suggested different clonal origin of the lesions. Sequencing of the SMAD4/DPC4 gene did not identify mutations in coding regions or at exon/intron boundaries in tumors with LOH at 18q. The data indicate involvement of tumor suppressor genes on 3p and 18q, in addition to the MEN1 gene at 11q13, in the tumorigenesis of both nonfamilial and MEN 1-associated pancreatic endocrine tumors.

Clinical efficacy of milbemycin oxime in the treatment of nasal mite infection in dogs.

A multicentric clinical trial was done to evaluate the clinical efficacy of milbemycin oxime in the treatment of nasal mite (Pneumonyssoides caninum) infection in dogs. Milbemycin oxime was given to 70 dogs of different breeds, genders, and ages, with clinical signs associated with nasal mite infection. Twenty-five dogs had a verified infection, and 45 dogs had signs suggestive of nasal mite infection. Milbemycin oxime was given at the dosage of 0.5 to 1.0 mg/kg body weight orally once a week for three consecutive weeks. One month after initiation of treatment, 68 of the dogs had no more clinical signs associated with nasal mite infection.

Targeted superantigens for immunotherapy of haematopoietic tumours.

With the exception of childhood common acute lymphoblastic leukaemia (cALL), treatment of other hematopoietic B cell lineage tumours such as non-Hodgkin's lymphoma (B-NHL), adult ALL and multiple myeloma (MM) is unsatisfactory. Similarly, the therapeutic outcome of acute and chronic myeloid leukaemia (AML, CML) is frequently dismal. At the same time, leukaemia/lymphoma cells represent ideal targets for immunotherapy. The present review summarizes our preclinical experience with a novel type of cytotoxic T cell based immunotherapy for B-lineage and myeloid tumours. Staphylococcal enterotoxin-derived superantigens (SAgs) are among the most potent T cell activators known, linking the T cell receptor to HLA-DR on natural target cells. SAgs were genetically engineered to reduce DR binding and were then fused to Fab parts of tumour-directed monoclonal antibodies (mAbs). Using these "targeted" SAgs, highly efficient lysis of B-lineage (B-NHL, B-CLL, ALL, MM) and myeloid (AML, CML) tumour cells by T-cells was achieved in vitro and in an animal model. We are entering an interesting era of innovative cancer therapy based on novel man-made biotherapeutic agents.

Falling population incidence of eclampsia. A case-control study of short term outcome.

BACKGROUND: Eclampsia remains a serious complication of pregnancy and childbirth and factors related to morbidity require continued evaluation. DESIGN: Retrospective case-control study on the incidence and outcome of eclampsia. SETTING: A defined total island population over 20 years. METHODS: All centrally collected birth registration returns in Iceland for the years 1972-1991 were reviewed to identify women with the diagnosis of eclampsia, selecting women delivering immediately before and after the eclamptic case as controls. Information from all places where women had delivered was obtained to ensure that no case was missed. Maternity records were reviewed to verify the diagnosis and obtain maternal and neonatal data. RESULTS: Forty women had eclampsia (0.046% of deliveries). The incidence diminished between the decades 1972-81 and 1982-91 (p < 0.05), as did the incidence of eclamptic convulsions before delivery. Eclamptic women were more often primiparous, younger and delivered earlier than controls. Preterm delivery and a low ponderal index were more common among offspring of the eclamptic mothers and the male/female ratio was lower. CONCLUSION: The incidence of eclampsia in the population is falling. Common features related to the condition were confirmed. Severe maternal illness is rare, but the babies often appear growth-retarded and are delivered preterm.