Explosive nosocomial outbreak of SARS-CoV-2 in a rehabilitation clinic: the limits of genomics for outbreak reconstruction.

BACKGROUND: Nosocomial outbreaks of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are frequent despite implementation of conventional infection control measures. An outbreak investigation was undertaken using advanced genomic and statistical techniques to reconstruct likely transmission chains and assess the role of healthcare workers (HCWs) in SARS-CoV-2 transmission. METHODS: A nosocomial SARS-CoV-2 outbreak in a university-affiliated rehabilitation clinic was investigated, involving patients and HCWs, with high coverage of pathogen whole-genome sequences (WGS). The time-varying reproduction number from epidemiological data (Rt) was estimated, and maximum likelihood phylogeny was used to assess genetic diversity of the pathogen. Genomic and epidemiological data were combined into a Bayesian framework to model the directionality of transmission, and a case-control study was performed to investigate risk factors for nosocomial SARS-CoV-2 acquisition in patients. FINDINGS: The outbreak lasted from 14th March to 12th April 2020, and involved 37 patients (31 with WGS) and 39 employees (31 with WGS), 37 of whom were HCWs. Peak Rt was estimated to be between 2.2 and 3.6. The phylogenetic tree showed very limited genetic diversity, with 60 of 62 (96.7%) isolates forming one large cluster of identical genomes. Despite the resulting uncertainty in reconstructed transmission events, the analyses suggest that HCWs (one of whom was the index case) played an essential role in cross-transmission, with a significantly greater fraction of infections (P<2.2e-16) attributable to HCWs (70.7%) than expected given the number of HCW cases (46.7%). The excess of transmission from HCWs was higher when considering infection of patients [79.0%; 95% confidence interval (CI) 78.5-79.5%] and frail patients (Clinical Frailty Scale score >5; 82.3%; 95% CI 81.8-83.4%). Furthermore, frail patients were found to be at greater risk for nosocomial COVID-19 than other patients (adjusted odds ratio 6.94, 95% CI 2.13-22.57). INTERPRETATION: This outbreak report highlights the essential role of HCWs in SARS-CoV-2 transmission dynamics in healthcare settings. Limited genetic diversity in pathogen genomes hampered the reconstruction of individual transmission events, resulting in substantial uncertainty in who infected whom. However, this study shows that despite such uncertainty, significant transmission patterns can be observed.

Malnutrition in Very Old Hospitalized Patients: A New Etiologic Factor of Anemia?

BACKGROUND: Anemia and malnutrition are highly prevalent, frequently concomitant and associated with negative outcomes and mortality in the elderly. OBJECTIVES: To evaluate the association between these two entities, and test the hypothesis that protein-energy deficit could be etiology of anemia. DESIGN: Prospective case-control study. SETTING: Geriatric and Rehabilitation Hospital, Geneva University Hospitals, Switzerland. PARTICIPANTS: 392 patients (mean age 84.8 years old, 68.6% female). MAIN OUTCOME MEASURES: Hematological (hemoglobin (Hb)), chemical (iron work up, cyanocobalamin, folates, renal function, C-Reactive Protein (CRP)) and nutrition (albumin, prealbumin) parameters, and mini nutritional assessment short form (MNA-SF). RESULTS: The prevalence of anemia (defined as Hb<120 g/l) was 39.3%. Anemic patients were more frequently malnourished or at risk of malnutrition according to the MNA-SF (p=0.047), with lower serum albumin (p <0.001) and prealbumin (p <0.001) levels. Thirty-eight percent of these patients had multiple causes and 14.3% had no cause found for anemia. Among the latter 90.9% of patients with unexplained anemia had albumin levels lower than 35g/l. After exclusion of iron,vitamin B12 and folic acid deficits, anemic patients had lower albumin (p<0.001) and prealbumin (p 0.007) levels. Albumin level explained 84.5% of the variance in anemia. In multivariate analysis albumin levels remain associated with Hb only in anemic patients, explaining 6.4% of Hb variance (adj R2) and 14.7% (adj R2) after excluding inflammatory parameters (CRP>10). CONCLUSIONS: Albumin levels are strongly associated with anemia in the elderly. Screening for undernutrition should be included in anemia assessment in those patients. Further prospective studies are warranted in order to explore the effect of protein and energy supplementation on hemoglobin level.

Diabetes, comorbidities and increased long-term mortality in older patients admitted for geriatric inpatient care.

AIMS: To study the specific impact of diabetes on long-term mortality in very old subjects with multiple comorbidities and functional disabilities. METHODS: The prevalence of vascular disorders, global comorbidity load (cumulative illness rating scale [CIRS]) and functional disabilities (activities of daily living [ADL] and Lawton's instrumental ADL [IADL] scores) were determined according to diabetes status in a cohort of 444 patients (mean age 85.3±6.7 years; 74.0% women) admitted to our geriatric service. Also, the specific impact of diabetes on 4-year mortality was analyzed using Cox proportional-hazards models. RESULTS: Diabetic patients had higher BMI scores (27.1±4.9 vs. 23.4±4.7 kg/m(2) in controls; P<0.001), and higher prevalences of hypertension (81.9% vs. 65.1%, respectively; P=0.003) and ischaemic heart disease (33.7% vs. 22.2%, respectively; P=0.033), but not of stroke and renal insufficiency. They also had more comorbidities (CIRS score excluding diabetes: 15.1±4.5 vs. 13.8±4.8, respectively; P=0.016) and functional disabilities. Diabetes was associated with mortality (HR: 1.42, 95% CI: 1.02-1.99; P=0.041) after adjusting for age, gender and BMI, and this persisted after adjusting for individual vascular comorbidities, but disappeared after adjusting for CIRS, ADL or IADL scores. CONCLUSION: Diabetes was associated with 4-year mortality after adjusting for the inverse relationship between mortality and BMI. This association was better accounted for by the global comorbidity load and functional disabilities than by the individual vascular comorbidities. These findings suggest that the active management of all--rather than selected--comorbidities is the key to improving the prognosis for older diabetic patients.

The prevalence, characteristics and metabolic consequences of renal insufficiency in very old hospitalized diabetic patients.

AIMS: We aimed to characterize the determinants and characteristics of renal disease in very old diabetic patients in geriatric care. METHODS: Consecutive diabetic patients (96 women, 38 men) admitted to a geriatric service were studied. Glomerular filtration rate (GFR), albuminuria, vascular and general comorbidities, glycaemic control, malnutrition (using the Mini-Nutritional Assessment [MNA], serum albumin and cholesterol levels), haemoglobin and inflammation (CRP levels) were assessed. RESULTS: (a) 51.2 and 12.4% patients had moderate or severe renal insufficiency. The prevalence of normo-, micro- and macroalbuminuria was 45.0, 38.9 and 16.0% in the whole population, and was similar in patients with or without moderate renal insufficiency. Renal insufficiency was associated with previous stroke (P=0.024), heart failure (P=0.024), and atrial fibrillation (P=0.008), and possibly myocardial infarction (P=0.059, Mann-Whitney test). (b) Albuminaemia was associated with albuminuria, MNA scores, haemoglobin, total and HDL-cholesterol and CRP. However, in multiple linear regression analysis CRP was the only robust determinant of albuminaemia (P<0.0001). (c) Renal insufficiency was not associated with the MNA, serum albumin, haemoglobin and cholesterol levels. CONCLUSION: Renal insufficiency often occurs without albuminuria, suggesting aetiologies distinct from classical diabetic nephropathy, and is strongly associated with vascular comorbidities. Hypoalbuminaemia is more strongly associated with inflammation than with albuminuria and malnutrition. Malnutrition, hypoalbuminaemia, low cholesterol levels and anaemia are not associated with renal insufficiency, likely due to the very high prevalence of these abnormalities in the whole population. These features must be taken into account when organizing the global care of elderly diabetic patients.

A DNA variant at the angiotensin-converting enzyme gene locus associates with coronary artery disease in the Caerphilly Heart Study.

BACKGROUND: We analyzed an insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene in 1226 subjects from the Caerphilly Prospective Heart Disease Study. Amplification of genomic DNA using the polymerase chain reaction yielded the genotypes II, ID, and DD. Distribution of the polymorphism was analyzed among the whole group and within subgroups (specified following multiple risk factor analysis) for coronary artery disease (CAD) and against multiple risk factors. METHODS AND RESULTS: Allele frequencies were I = 0.413 and D = 0.587. No association was observed between the polymorphism and CAD in the whole group. Among subjects defined at lower risk of CAD by total cholesterol/HDL cholesterol (TC/HDL) ratios, we found significant associations of the DD genotype with CAD (P < .0053, n = 586 for TC/HDL < 5.654 [median] and P < .009, n = 385 for TC/HDL < 5.0 [clinical threshold]). On further exclusion of subjects with blood pressures > or = 140/90 or on hypotensive medications, the DD genotype still associated with CAD (P < .07, n = 210, TC/HDL < 5.654 and P < .016, n = 135, TC/HDL < 5.0). Further stratification of risk incorporating other risk factors, except body mass index, did not alter or enhance this association. Although similar association was observed when risk was specified by using HDL and apo B levels instead of TC/HDL, this association was lost when body mass index was included in the low-risk stratification. CONCLUSIONS: The DD genotype is a linkage marker for an etiologic mutation at or near the ACE gene that may confer risk of CAD detectable in subjects previously unidentifiable with "classic" risk factors. However, this risk may be quantitatively small among the general male population.

Prevalence of DSM III schizophrenia among the first-degree relatives of schizophrenic probands.

The extent of the genetic component, if any, in DSM III schizophrenia still remains unresolved. To further examine the issue, the first-degree relatives of 116 DSM III schizophrenic probands in our department were compared with those of an equal number of normal subjects, randomly selected and matched for age and sex. More than three fourths of the surviving relatives of each group were interviewed and rated according to DSM III criteria. Information of varying degrees of completeness was obtained about the remainder (surviving and dead). The gathered data were sufficiently detailed to provide general evidence that schizophrenia, and schizophrenia-related personality disorders were significantly more common in the first-degree relatives of DSM III schizophrenic probands than in the relatives of the controls. These findings suggest that even narrowly defined schizophrenia, such as that obtained by using DSM III criteria, has also a genetic component.

Psychotic depressive disorder. A separate entity?

Two groups of patients suffering from primary unipolar major depressive disorder, one with (n = 145) and one without (n = 119) psychotic disorders were compared, in order to elucidate whether psychotic depressive disorder represents a distinct subtype or a severe variation of the illness. Except for more frequent appearance of psychomotor disturbances among the psychotic depressives, no demographic, family history and course variables were found to distinguish between those with or without psychotic features. The findings from our study are compatible with the view that psychotic depressive disorder is a severe variant of major depressive illness.

Serum calcium and magnesium levels in chronic schizophrenics.

Serum calcium and magnesium levels were studied during neuroleptic treatment in a group of 29 chronic schizophrenic inpatients who had previously remained drug free for at least 4 weeks. The drug-free values of both electrolytes were not significantly different between patients and controls. In three patients who developed catatonic stupor during the drug-free period, calcium was significantly increased at the onset of the catatonic manifestations. Both electrolytes were significantly decreased in the whole group during treatment; the magnitude of the decrease was independent of the neuroleptic used. No correlation was found between the observed increase in prolactin and calcium changes. Patients who remained free of extra-pyramidal symptoms had a higher mean drug-free magnesium to calcium ratio compared to those who developed such symptoms. Our study provides evidence for an interconnection between serum electrolyte changes and neuroleptic drug action.

Differences in lateral brain ventricular size among various types of chronic schizophrenics. Evidence based on a CT study.

Data from a previous study of ours, based on computerised tomography of the brain in 70 chronic schizophrenics, indicated that a severe degree of lateral brain enlargement was present in a great proportion. No correlation was found between lateral ventricular enlargement and age of patients, length of illness, duration of hospitalization or ECT treatment. In order to elucidate whether other factors (e.g. type of disease) are likely to correlate with the enlargement we divided these patients into three subgroups: hebephrenics, paranoids and undifferentiated. Comparison of the mean values of ventricular brain ratio (VBR) of the above groups showed that paranoids presented a statistically greater enlargement than hebephrenics. There was no statistically significant difference between undifferentiated and hebephrenics. The difference between undifferentiated and paranoids approached statistical significance. This study provides evidence that there exists a difference between the types of schizophrenia in CT images, a finding that may suggest different degrees of underlying disease process.

HLA antigens in schizophrenia: no difference between patients with and without evidence of brain atrophy.

The HLA antigens distribution was studied in 56 chronic schizophrenic in-patients with or without brain atrophy determined by CAT examination, and compared with that of 200 controls. There was no difference in the incidence of HLA-A2 in the whole sample, and an increase in those without brain atrophy (by comparison with normal controls) failed to reach statistical significance. A decrease of Bw35 in the whole sample, more prominent in those without brain atrophy, again failed to be significant after multiplying the probability by the number of antigens studied.

Side effects in preventive maintenance therapy with neuroleptics with special emphasis on tardive dyskinesia.

Neuroleptics induce hypersensitivity reactions, and toxic, systemic and extrapyramidal manifestations. The latter mainly include acute dystonic reactions, other early dyskinesias, akathisia, parkinsonism and TD. These drugs have been implicated for DA antagonism exerted by an adenylate cyclase inhibition. Prolonged blockade of DA receptors is considered as the motivation for a counterbalancing mechanism inducing the DA supersensitivity from which TD results. Recent reports suggest cholinergic and GABA ergic insufficiency as secondary participants. The increasing frequency of TD calls for prevention by modifying treatment practices and searching for effective measures to combat the symptoms.

Seasonality of the episodes of recurrent affective psychoses. Possible prophylactic interventions.

This study is an attempt to ascertain whether evidence for seasonal variations of the episodes of recurrent affective psychoses can be found in patients in Greece. Due allowance has been made for the fact that different socio-cultural and above all climatological factors prevail in Greece as opposed to other countries, which might be relevant in the phenomenon of seasonality. The seasonal distribution of the psychotic episodes, either depressive or manic, has been examined for 533 patients with various forms of affective psychoses, admitted to and treated in the State Mental Hospital of Athens, Greece, during the last 50 years. Statistically significant seasonal variation with peaks in spring was found for both depressive and manic episodes of various subgroups of patients, divided according to the I.C.D.-9.

Clinical observations of the treatment of tardive dyskinesia with haloperidol.

In the present study, after briefly describing the clinical characteristics of the neurologic syndromes provoked by the neuroleptic drugs and most particularly of the syndrome of tardive dyskinesia, we refer to the incidence of this latter syndrome and to the results obtained with the administration of haloperidol for a period of 16 weeks in 10 patients suffering from it. From the detailed analysis of 300 chronic schizophrenic patients, we detected this complication in 10 cases, which gives an incidence of 3,3%. With the administration of haloperidol, on the other hand, we obtained an excellent reduction of both the frequency and the intensity of the peristomal movements in nearly all the patients. This reduction was more remarkable in 2 of the patients who had manifested certain complications of the syndrome, mainly a difficulty in swallowing, followed by a considerable loss of weight in the one patient and by an intense perplexity and a tendency towards suicide in the other. The continued suppression of the above dyskinetic phenomena during the whole period of the trial allows us to conclude that haloperidal may be recommended for the maintenance treatment of the syndrome of tardive dyskinesia.