Clinical Presentation of COVID19 in Dementia Patients.

OBJECTIVE: No studies analyzing the role of dementia as a risk factor for mortality in patients affected by COVID-19. We assessed the prevalence, clinical presentation and outcomes of dementia among subjects hospitalized for COVID19 infection. DESIGN: Retrospective study. SETTING: COVID wards in Acute Hospital in Brescia province, Northern Italy. PARTICIPANTS: We used data from 627 subjects admitted to Acute Medical wards with COVID 19 pneumonia. MEASUREMENTS: Clinical records of each patients admitted to the hospital with a diagnosis of COVID19 infection were retrospectively analyzed. Diagnosis of dementia, modalities of onset of the COVID-19 infection, symptoms of presentation at the hospital and outcomes were recorded. RESULTS: Dementia was diagnosed in 82 patients (13.1%). The mortality rate was 62.2% (51/82) among patients affected by dementia compared to 26.2% (143/545) in subjects without dementia (p<0.001, Chi-Squared test). In a logistic regression model age, and the diagnosis of dementia resulted independently associated with a higher mortality, and patients diagnosed with dementia presented an OR of 1.84 (95% CI: 1.09-3.13, p<0.05). Among patients diagnosed with dementia the most frequent symptoms of onset were delirium, especially in the hypoactive form, and worsening of the functional status. CONCLUSION: The diagnosis of dementia, especially in the most advanced stages, represents an important risk factor for mortality in COVID-19 patients. The clinical presentation of COVID-19 in subjects with dementia is atypical, reducing early recognition of symptoms and hospitalization.

Clinical characteristics and risk factors of delirium in demented and not demented elderly medical inpatients.

OBJECTIVES: to evaluate the differences in clinical characteristics and risk factors of delirium in elderly medical inpatients according to the presence or not of dementia. DESIGN: cross-sectional, observational study. SETTING: acute medical care unit (ACU) of a general hospital. PARTICIPANTS: 330 patients aged 65 and older consecutively admitted on a 24-week period. MEASUREMENTS: Functional status, cognitive abilities, severity of acute illness (Acute Physiology, Age and Chronic Health Evaluation (APACHE II) score), Confusion Assessment Method (CAM), Delirium Rating Scale (DRS) and One Day Fluctuation Scale (ODFS). RESULTS: patients with delirium represent 19.1% of the sample, 41.0% of which had also dementia. Hyperactive form of delirium was 41.0%; hypoactive 11.0% and mixed 48.0%. In non demented patients, the delirious patients showed higher APACHE II score, more severe functional decline, poorer cognitive status respect to not delirious. In demented patients no differences were found in APACHE II score and cognitive status among delirious and not delirious subjects. In this group, functional decline (p = .012), acute infection (p = .007), psychotropic drugs use (p = .028) and severe hypoalbuminemia (p = .036) represented risk factors for the onset of delirium. Demented patients had higher perceptual disturbances (p = .040) and less severe delusions (p = .001), while total DRS score do not differs in the two groups. According to ODFS, delirium episode was more fluctuating in patients with dementia. CONCLUSION: clinical characteristics and risk factors of delirium are different in demented and not demented elderly inpatients. Patients with dementia are vulnerable to delirium at lower levels of medical acuity than non-demented patients.

Venlafaxine-induced reset osmostat syndrome: case of a 79-year-old depressed woman.

The presence of hyponatremia, especially in a frail and very old patient, is associated with a greater morbidity and mortality rate. We report the case of a depressed 79-year-old woman who was treated with venlafaxine, in whom a drug-induced hyponatremia occurred in the absence of other possible causes. The case is discussed in the context of the multipotential factors that induce hyponatremia, with particular attention to the geriatric patient.

Correlates of osteoporosis in chronic obstructive pulmonary disease.

The aim of this study was to analyse the correlates of reduced bone mineral density in patients with chronic obstructive pulmonary disease (COPD), with special regard to a possible protective role of hypercapnia. One hundred and four consecutive COPD inpatients in stabilized respiratory conditions underwent a comprehensive assessment of their health status. Bone mineral density was measured by X-ray absorptiometry at the lumbar site and at the femoral neck site. Differences in health-related variables between patients with (group O, n=62) and without (group N, n=42) lumbar and/or femoral neck osteoporosis were assessed first by univariate analysis and then by logistic regression analysis aimed to identify independent correlates of osteoporosis. Group O was characterized by worse nutritional status, as reflected by indices exploring either lean or fat mass, and by a trend towards lower forced expiratory volume in 1 sec/forced vital capacity ratio. Arterial tension of carbon dioxide lacked any correlation with bone mineral density. According to the logistic regression analysis, body mass index < or = 22 kg m(-2) qualified as the only and positive independent correlate of osteoporosis (odds ratio=4.18; 95% confidence intervals=1.19-14.71). In conclusion, malnutrition characterizes COPD patients with osteoporosis, while mild to moderate hypercapnia lacks either a positive or negative effect on bone mineral density. Longitudinal studies are needed to identify predictors rather than correlates of bone mineral density.

Influence of factor VIII/von Willebrand complex on the activated protein C-resistance phenotype and on the risk for venous thromboembolism in heterozygous carriers of the factor V Leiden mutation.

High factor VIII plasma levels have been shown to represent a common increased risk for venous thromboembolism (VTE) and may cause an activated protein C (APC) resistance in the absence of the factor V Leiden mutation, but there are no studies specifically aimed to establish if high factor VIII and von Willebrand factor (vWF) concentrations may influence the APC sensitivity ratio (APC-SR) and increase the risk for VTE in the presence of the factor V Leiden mutation. For this purpose, we performed a retrospective case-control study to investigate the influence of the procoagulant factor VIII (VIII:C) and the antigen of vWF (vWF:Ag) on the normalized APC-SR (n-APC-SR) and on the risk for VTE, in two selected groups of 30 symptomatic (Group I) and 32 asymptomatic (Group II) related heterozygotes for the factor V Leiden mutation. Differences between the two groups (Group I versus Group II) were: n-APC-SR, 0.57+/-0.06 versus 0.63+/-0.08, P = 0.001; factor VIII:C, 1.49+/-0.42 versus 1.13+/-0.28 IU/ml, P<0.001; vWF:Ag, 1.46+/-0.53 versus 1.26+/-0.32 IU/ml, NS. As a whole (Group I + Group II), Pearson correlation coefficients were: n-APC-SR versus factor VIII:C, r = -0.410, P = 0.001; n-APC-SR versus vWF:Ag, r = -0.309, P = 0.01; factor VIII:C versus vWF:Ag, r = +0.640, P<0.0001. The relative risk for VTE in individuals with the factor VIII:C concentration > 1.5 IU/ml was 2.5 (95% confidence interval 1.6-3.9). We concluded that high factor VIII:C levels, probably in the effect of vWF, play a determinant role in worsening the APC-resistance phenotype and represent a common additional risk factor for VTE in heterozygous carriers of the factor V Leiden mutation.

Special care units for demented patients: a multicenter study.

The local government of Regione Lombardia, Italy, recently (1994) funded a clinical and research project specifically devoted to dementia (Piano Alzheimer). A central role in this project has been reserved for the special care units (SCUs) for demented patients with behavioral disturbances. In order to evaluate their effectiveness, eight SCUs took part in this study. A specifically designed care program, focusing on environment and staff, was implemented in each SCU. Cognitive, functional, and somatic health status, and use of psychotropic drugs and of physical restraints were assessed at baseline, and after 3 and 6 months in 55 consecutively admitted patients. The data show an overall reduction in behavioral disturbances and a decreased use of psychotropic drugs and physical restraints.

One-year mortality in elderly stable patients with COPD.

A retrospective study was performed to evaluate the risks of one-year mortality in very old hospitalized patients including those suffering from chronic obstructive pulmonary disease (COPD). Six hundred and fifty-eight disabled patients (M = 194, mean age 79.2 +/- 7.4 years) consecutively admitted to and discharged from a Geriatric Evaluation and Rehabilitation Unit (GERU) after a comprehensive rehabilitation program were studied and divided into two groups: COPD (n = 337, 51%) and non-COPD (n = 321, 49%). Multidimensional evaluation including information on demographics, cognitive status [Mini Mental State Examination (MMSE)], physical health [number of diseases, Greenfield's Individual Disease Severity (IDS), and number of drugs used], functional disability [Basic Activity of Daily Living (BADL), Tinetti scale, and Physical Performance Test (PPT)], and nutritional status [Prognostic Nutritional Index (PNI)] were assessed at admission. Survival rate was assessed over a 1-year period following discharge. COPD patients mainly differed from non-COPD in terms of older age, smoking habit, number of associated diseases and drugs used. Aggregating the IDS 2-3-4 COPD classes (symptoms + functional impairment), the risk of one-year mortality was double that of the IDS 1 COPD class (symptoms only) and of non-COPD subjects (IDS 0 class) after adjusting for age, sex, disability, malnutrition, and comorbility. Moreover, IDS 2-3-4 COPD patients suffering from cor pulmonale (CP) had a fourfold 1-year risk of mortality in comparison with the IDS 1 COPD group after adjusting for the same covariates. Hospitalized stable very old COPD patients presenting functional impairment have a higher 1-year risk of mortality than only symptomatic COPD or non-COPD subjects. The presence of cor pulmonale with COPD further increases this risk.

[Algometric approach in the diagnostic evaluation of chest pain]. / Approccio algometrico nella valutazione diagnostica del dolore toracico.

OBJECTIVE: To contribute to a global clinical evaluation of the patients with chest pain, giving a quantitative analysis of the painful experience in the sensory, emotional, value and mixed component and searching significant differences among the different causes of the symptom. MATERIALS AND METHODS: We have administered the "Questionario Italiano del Dolore" by De Benedictis et al. to 92 patients with chest pain, who were divided into 4 diagnostic groups (acute coronary syndrome, coronary artery disease, oesophagus-gastric disease and other) and compared for the quantitative-qualitative features of the associated pain. RESULTS: PRIrcE (Global Value Component) resulted higher in the group "other" (A) compared to the patients with acute ischemic heart disease (CIA), with a statistically significant difference (test U-Mann-Whitney; p = 0.04). This group shows statistically significant differences in the emotional component (PRIrcA; p = 0.01) even compared to pain associated with oesophagus-gastric disease (G). In regard to PRIrcA, the difference between G group and the group of patients with chronic ischemic heart disease (CIC), as well as the "double" category, resulted markedly significant (p = 0.03 and p = 0.01 respectively). We extrapolated the "describers" chosen by at least 50% of patients in every category and obtained the semantics configuration of chest pain for every diagnosis. CONCLUSIONS: PRIrcE resulted lower in CIA group. PRIrcE e PR-IrcA are more represented in CIC group. The same conclusion is valid in the differentiation of pain between CIA and G group and between CIA and A group (the most representative of chronic pain). We found higher values in emotional component compared to pain of new onset as pain becomes chronic.

Is the efficacy of LDL apheresis in ischemic optic neuropathy linked to a reduction in endothelial activation markers?

Endothelial dysfunction of the optic microcirculation is considered to be the main pathogenetic mechanism in nonarteritic ischemic optic neuropathy. The aim of the present work was to assess whether a clinical improvement is correlated with a reduction in the endothelial activation markers by means of LDL apheresis (LDLA). Three weekly sessions of LDLA were administered in 23 patients affected by nonarteritic ischemic optic neuropathy. Statistically significant reductions were achieved in all parameters: total cholesterol (44.6%), LDL cholesterol (54.6%), fibrinogen (60.9%), von Willebrand factor (38.6%), sE-Selectin (22.6%), sICAM-1 (14%) and sVCAM-1 (15.5%), each of which was correlated with an improvement in the mean deviation of the visual field, although statistical significance for the single parameters was not reached. However, analysis of variance between the mean deviation improvement and the set of parameters taken together yielded highly significant results (p < 0.0001). LDLA was effective in reducing the values of all evaluated endothelial activation markers, and this trend was correlated with an improvement in the visual field.

Efficacy of porcine factor VIII in the management of haemophiliacs with inhibitors.

We report our experience with polyelectrolyte-fractionated highly purified porcine factor VIII concentrate (Hyate:C). Porcine factor VIII concentrate was used to treat 14 haemorrhagic episodes including seven severe haemarthroses, three severe haematomata, two episodes of oral bleeding, one traumatic and the other after multiple dental extractions and two life-threatening intestinal haemorrhages. Altogether 60 infusions of Hyate:C were given to five haemophiliacs with inhibitors. At the time of the first infusion with porcine factor VIII the anti-human inhibitor level ranged from 60 to 2.5 modified Bethesda units/ml (MBU 4 h incubation). The porcine cross-reactivity of these inhibitors was 25.6% and 5.4% of the human inhibitor level in two patients and scarcely measurable in the other three patients. We injected an amount of porcine factor VIII concentrate corresponding to the calculated porcine neutralizing units plus the units required for haemostasis. The clinical efficacy was excellent and no adverse effects were encountered, apart from two episodes of mild pyrogenic reactions well controlled by hydrocortisone. The anamnestic antibody response against human factor VIII was of slight degree in all cases, while the porcine cross-reactivity showed no significant variation. Our results emphasize the role of porcine factor VIII in the treatment of haemophiliacs with inhibitors.

Serum cholesterol levels as a measure of frailty in elderly patients.

The authors evaluated the association between serum cholesterol levels and social, clinical, and functional characteristics in 637 elderly hospitalized patients (mean age = 79.1 years, range = 65-97) from the Geriatric Evaluation and Rehabilitation Unit (GERU) at P. Richiedei Hospital in Gussago, Brescia (Italy). Patients consecutively admitted to the GERU during an 18-month period underwent a multidimensional evaluation including information on demographics, cognitive status, physical health (number of chronic diseases and administered drugs), functional disability, and nutritional status. Mean cholesterol levels were significantly lower in men; persons living with others; older individuals; and individuals with cognitive impairment, poorer somatic health, higher disability, and a higher level of malnutrition. Lower serum cholesterol levels may be considered an independent hematologic marker of frailty in elderly hospitalized patients.

Homozygous and heterozygous deletions of the von Willebrand factor gene in patients and carriers of severe von Willebrand disease.

Severe von Willebrand disease is characterized by undetectable or trace quantities of von Willebrand factor in plasma and tissue stores. We have studied the genomic DNA of 10 affected individuals from six families with this disorder using probes from the 5' and 3' ends of the vWF cDNA and with a probe extending from the 5' end into the central region. Southern blots of restriction endonuclease digests and gene dosage analysis measurements carried out with quantitative slot blots of undigested genomic DNA separated these patients into three groups. The first group consisted of a family with complete homozygous deletions of the vWF gene in the four probands. Gene dosage analysis was consistent with heterozygous deletions in both of the asymptomatic parents and four asymptomatic siblings of this kindred (P less than 0.01). The second group was comprised of a family in which there was a complete heterozygous deletion of the vWF gene in the proband and one asymptomatic parent, suggesting that a different type of genetic abnormality was inherited from the other parent. Thus, the patient appeared to be doubly heterozygous for interacting genetic abnormalities affecting vWF expression. In the third group, no gene deletions could be detected. Alloantibodies developed only in the kindred with homozygous deletions. These techniques should prove useful in identifying carriers of severe von Willebrand disease and also in defining patients predictably at risk of developing alloantibodies to vWF.

High-resolution analysis of von Willebrand factor multimeric composition defines a new variant of type I von Willebrand disease with aberrant structure but presence of all size multimers (type IC).

In Type I von Willebrand disease, the whole series of von Willebrand factor (vWF) multimers is present in plasma, but all are decreased in quantity. No structural abnormality of individual multimers has been demonstrated so far in these patients. We now describe five individuals, from two unrelated families, who had this form of the disease and in whom the complex banding pattern of each vWF multimer was markedly abnormal. Inheritance was autosomal dominant and the clinical expression was mild. A bleeding history was elicited in three of the patients and included recurrent epistaxis, menometrorrhagia, and bleeding following tooth extraction. Replacement therapy had never been required. Although vWF levels in plasma were within the normal range in all of them, the ristocetin cofactor activity was decreased in four, and the bleeding time was prolonged in three. Analysis of vWF multimeric structure by agarose gel electrophoresis, including a newly developed high-resolution technique, demonstrated that the main band of each multimer was present, but a second, well-defined band always seen in normal individuals was missing in the patients. Two additional bands had altered mobility and were less well defined than in normal subjects, and a fifth, less intense band was also undetectable in the patients. Treatment with 1-deamino-8-D-arginine vasopressin (DDAVP) was assessed in two patients. It caused the circulating levels of vWF to increase and correct the bleeding time, but did not alter the structural abnormality. This study describes, therefore, a new variant form of Type I von Willebrand disease with aberrant structure of individual repeating multimers and an associated functional abnormality of vWF. In keeping with previously accepted terminology, the designation of Type IC von Willebrand disease has been adopted for this new variant.

Hemophilia B with inhibitor: molecular analysis of the subtotal deletion of the factor IX gene.

The structure of factor IX gene was analyzed in a hemophilia B patient with inhibitor. Genomic DNA, digested with a variety of restriction endonucleases, was hybridized with the cDNA and various genomic factor IX probes. A large subtotal deletion of the gene was observed. The borders of the deletion span from a approximately 125 nucleotide region within the last exon to an unknown domain at least 7.5 kb upstream from the first exon: it thus involves approximately 33 kb of the factor IX locus. The abnormal gene was inherited by the daughter of the propositus, who showed both the normal and the deleted allele.

Evaluation of the effectiveness of DDAVP in surgery and in bleeding episodes in haemophilia and von Willebrand's disease. A study on 43 patients.

1-deamino-8-D-arginine-vasopressin (DDAVP), was used in a wide spectrum of clinical situations employing two different dosages (0.3 and 0.4 microgram/kg b.w.) for the management of 43 patients with factor VIII deficiencies--mild and moderate haemophilia A and von Willebrand's disease (vWD). In most instances, the drug was given in association with antifibrinolytics. Twenty-five dental extractions were carried out with two different protocols: one based upon a single infusion and the other based upon three infusions. Bleeding occurred in three patients regardless of the protocol used. The vasopressin analogue promptly stopped bleeding in 12 'spontaneous' open bleeds (haematuria, epistaxis, menometrorrhagia, gum bleeding) and it appears to be also effective in closed bleeds. DDAVP was used to minimize blood loss during surgical interventions and to avoid haemorrhage in the postoperative period. Nine surgical procedures were carried out in six vWD patients and three haemophiliacs. Bleeding occurred late in the postoperative period on one occasion only. No difference was demonstrated between the two doses of the drug either in terms of clinical benefit or rise of factor VIII coagulant activity. The efficacy of DDAVP and the absence of side-effects make this vasopressin analogue worthy of consideration as a reliable alternative to factor VIII concentrates in a wide variety of clinical situations.