Improving post-stroke dysphagia outcomes through a standardized and multidisciplinary protocol: an exploratory cohort study.

Stroke is a major cause of dysphagia. Few studies to date have reported on standardized multidisciplinary protocolized approaches to the management of post-stroke dysphagia. The aim of this retrospective cohort study was to evaluate the impact of a standardized multidisciplinary protocol on clinical outcomes in patients with post-stroke dysphagia. We performed retrospective chart reviews of patients with post-stroke dysphagia admitted to the neurological ward of Verona University Hospital from 2004 to 2008. Outcomes after usual treatment for dysphagia (T- group) were compared versus outcomes after treatment under a standardized diagnostic and rehabilitative multidisciplinary protocol (T+ group). Outcome measures were death, pneumonia on X-ray, need for respiratory support, and proportion of patients on tube feeding at discharge. Of the 378 patients admitted with stroke, 84 had dysphagia and were enrolled in the study. A significantly lower risk of in-hospital death (odds ratio [OR] 0.20 [0.53-0.78]), pneumonia (OR 0.33 [0.10-1.03]), need for respiratory support (OR 0.48 [0.14-1.66]), and tube feeding at discharge (OR 0.30 [0.09-0.91]) was recorded for the T+ group (N = 39) as compared to the T- group (N = 45). The adjusted OR showed no difference between the two groups for in-hospital death and tube feeding at discharge. Use of a standardized multidisciplinary protocolized approach to the management of post-stroke dysphagia may significantly reduce rates of aspiration pneumonia, in-hospital mortality, and tube feeding in dysphagic stroke survivors. Consistent with the study's exploratory purposes, our findings suggest that the multidisciplinary protocol applied in this study offers an effective model of management of post-stroke dysphagia.

Phospholipase C-ß3 is a key modulator of IL-8 expression in cystic fibrosis bronchial epithelial cells.

Respiratory insufficiency is the major cause of morbidity and mortality in patients affected by cystic fibrosis (CF). An excessive neutrophilic inflammation, mainly orchestrated by the release of IL-8 from bronchial epithelial cells and amplified by chronic bacterial infection with Pseudomonas aeruginosa, leads to progressive tissue destruction. The anti-inflammatory drugs presently used in CF patients have several limitations, indicating the need for identifying novel molecular targets. To address this issue, we preliminarily studied the association of 721 single nucleotide polymorphisms from 135 genes potentially involved in signal transduction implicated in neutrophil recruitment in a cohort of F508del homozygous CF patients with either severe or mild progression of lung disease. The top ranking association was found for a nonsynonymous polymorphism of the phospholipase C-ß3 (PLCB3) gene. Studies in bronchial epithelial cells exposed to P. aeruginosa revealed that PLCB3 is implicated in extracellular nucleotide-dependent intracellular calcium signaling, leading to activation of the protein kinase Cα and Cß and of the nuclear transcription factor NF-κB p65. The proinflammatory pathway regulated by PLCB3 acts by potentiating the Toll-like Receptors' signaling cascade and represents an interesting molecular target to attenuate the excessive recruitment of neutrophils without completely abolishing the inflammatory response.

Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: a protocol for a randomised, independent, pragmatic, multicentre, parallel-group, superiority clinical trial.

BACKGROUND: Data on therapeutic interventions following deliberate self harm (DSH) in patients with treatment-resistant depression (TRD) are very scant and there is no unanimous consensus on the best pharmacological option for these patients. There is some evidence that lithium treatment might be effective in reducing the risk of completed suicide in adult patients with unipolar affective disorders, however no clear cut results have been found so far. The primary aim of the present study is to assess whether adding lithium to standard therapy is an effective treatment strategy to reduce the risk of suicidal behaviour in long term treatment of people with TRD and previous history of DSH. METHODS/DESIGN: We will carry out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode will be allocated to add lithium to current therapy (intervention arm) or not (control arm). Following randomisation, treatment is to be taken daily for 1 year unless some clear reason to stop develops. Suicide completion and acts of DSH during the 12 months of follow-up will constitute the composite primary outcome. To preserve outcome assessor blindness, an independent adjudicating committee, blind to treatment allocation, will anonymously review all outcome events. DISCUSSION: The results of this study should indicate whether lithium treatment is associated with lower risk of completed suicide and DSH in adult patients with treatment resistant unipolar depression, who recently attempted suicide. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00927550.

What is still missing in acute-phase treatment of stroke: a prospective observational study.

Early recognition of stroke symptoms and activation of emergency medical service (EMS) positively affects prognosis after a stroke. To assess stroke awareness among stroke patients and medical personnel in the catchment area of Verona Hospital and how it affects stroke care, we prospectively studied timing of acute stroke care in relation to patients' characteristics. Patients admitted to Medical Departments of Verona University Hospital between January 1st and December 31st 2009 with a diagnosis of TIA or stroke were enrolled. Outcome measures were: time between (i) symptoms onset and hospital arrival, (ii) hospital arrival and brain CT scan, blood examination, ECG and neurological evaluation. The following patient/event characteristics were also collected: means of hospital arrival, sex, age, degree of disability, type of event (first or recurrent) and acute-phase treatment. Of 578 patients providing complete information, 60 % arrived to the emergency department with the EMS (EMS+ group), while 40 % arrived on their own (EMS-). EMS+ group was older than EMS- (mean age 76.2, SD 13.2, vs. 72.3, SD 13, respectively), displayed more severe symptoms (mRS 4 vs. 2) and shorter time interval between symptoms onset and hospital arrival, hospital arrival and CT scan, ECG, laboratory tests and neurological evaluation (p < 0.0001); 22 % of the EMS+ patients were stroke recurrences versus 29 % of the EMS- (p = 0.058); 85 % of thrombolised patients were EMS+. We conclude that there is a lack of awareness of stroke symptoms and risks of recurrence even among patients who already had a stroke and among medical personnel.

Determinants of ante-partum depression: a multicenter study.

INTRODUCTION: Ante-partum depression (APD) is usually defined as a non-psychotic depressive episode of mild to moderate severity, beginning in or extending into pregnancy. APD has received less attention than postpartum depression. This is a cross-sectional study carried out in the Obstetrics and Gynaecology (OG) departments of four different general hospitals in Italy. METHODS: Women attending consecutively the OG departments for their first ultrasound examination were asked to fill in the Edinburgh Postnatal Depression Scale (EPDS) in its Italian validated version. We used the total scores of the EPDS as a continuous variable for univariate and linear regression analyses; in accordance with the literature, the item analysis of EPDS was carried out by classifying the sample as women with "no depression" (scores 0-9), "possible depression" (scores 10-12), "probable depression" (scores 13+) and "probable APD" (scores 15+). RESULTS: The number of women recruited was 1,608. The EPDS assessment classified 10.9 % of the women as possibly depressed, 8.3 % as probably depressed and 4.7 % probably affected from an APD. EPDS score distribution was associated with nationality (higher scores for foreigners), cohabitation (higher scores for women living with friends or in a community), occupation (higher scores for housewives), past episodes of depression and use of herbal drugs. Non-depressed women had significantly lower values on all ten items as compared with depressed women, however, the pattern of item distribution on the EPDS scale remained similar across depression severity groups. In all four groups item 4 (anxious depression) attained the highest scores, while item 10 (suicidality) attained the lowest scores.

The Impact of Heat on an Emergency Department in Italy: Attributable Visits among Children, Adults, and the Elderly during the Warm Season.

INTRODUCTION: Recent studies suggest that heat is associated with an increase in the number of ambulance calls and emergency department visits. We investigated the association between heat and daily number of emergency department visits at the University Hospital of Verona during the warm seasons 2011-2012 and we assessed the magnitude of the impact in terms of attributable events, focusing on the role of age and triage codification. MATERIALS AND METHODS: We used a Poisson model to analyse the association between daily number of visits and daily mean apparent temperature, accounting for air pollution level and seasonality. The analyses were stratified by age group and were performed both on the total number of emergency department visits and on the subsample of high-priority visits. Impact estimates were obtained only for this subsample, using a Monte Carlo approach to account for sampling variability. Number of attributable events and attributable community rate were calculated. RESULTS: We found a positive and immediate association between event occurrence and mean apparent temperatures exceeding a threshold located around 28-29°C. The estimated percent change in the total number of visits per 1°C increase of exposure above the threshold was equal to 3.75 (90% CI: 3.01; 4.49). Focusing only on high-priority visits, the estimated percent change was larger and the greatest effect was among children. We estimated that apparent temperatures above the threshold were responsible for 1177 high-priority visits during the study period. Due to the record high temperatures observed in 2012 in Italy and in Europe, the impact in 2012 was much larger than in 2011, and consisted in 34 high-priority visits every 10000 children, 30 every 10000 people aged 15-64, and 38 every 10000 people aged 65 and over. DISCUSSION: Our results indicate that heat affects not only the elderly, but also children and non-elderly adults, stressing the need for developing public health preparedness plans for the entire community.

A longitudinal evaluation of two-year outcome in a community-based mental health service using graphical chain models. The South-Verona Outcome Project 9.

The 2-year outcome of 178 patients attending a community-based mental health service was assessed from a multidimensional perspective. The study investigated: (1) the effect of disease-related characteristics (such as diagnosis and illness duration) and of a series of outcome variables measured at baseline (global functioning, psychopathology, social disability, quality of life and satisfaction with services) on total costs of care over 2 years; and (2) the effect of costs of care and outcome variables measured at baseline on the corresponding outcome variables at 2 years. To gain insight into the multivariate longitudinal dependencies among variables, we used graphical Gaussian chain models, a new multivariate method that analyses the relationship between continuous variables taking into account the effect of antecedent and intervening variables, to reveal not only direct but also indirect correlations. Outcome variables showed the tendency to segregate, both at baseline and follow-up, into two distinct groups: a clinician-rated dimension (given by global functioning, social disability and psychopathology) and a patient-rated dimension (given by service satisfaction and subjective quality of life). Higher costs at 2 years were predicted by higher psychopathology at baseline, diagnosis of psychosis and longer duration of illness. Baseline values for each variable were the main predictors of the corresponding values at two years. Improvement in satisfaction with life at follow-up was experienced in those subjects with a lower functioning at baseline. This study throws some light on the complex relationships between clinical, social and economic variables affecting the medium-term outcome of mental health care.

Satisfaction with mental health services among people with schizophrenia in five European sites: results from the EPSILON Study.

Patient satisfaction with services is an important outcome variable that is increasingly used in mental health service evaluation. This study includes 404 people with schizophrenia in five European sites and addresses five questions focused on site, service, and patient characteristics as variables that might explain service satisfaction, using the Verona Service Satisfaction Scale. Patient satisfaction differed significantly across sites (highest in Copenhagen, lowest in London). In all sites, patients were least satisfied with involvement of relatives in care and information about illness. A multiple regression model showed that lower levels of total service satisfaction were associated with living in London or Santander, being retired/unemployed, having more hospital admissions, having more severe psychopathology, having more unmet needs, or having lower satisfaction with life. This model explained 31 percent of variance in service satisfaction. Our data show that service satisfaction can be seen as a result of (1) the ability of the service to provide a standard of care above a certain quality threshold, and (2) the perception of each patient that the care received has been tailored to the patient's own problems.

Subthreshold psychiatric disorders in primary care: prevalence and associated characteristics.

BACKGROUND: The authors analyse the prevalence of subthreshold psychiatric disorders in primary care and their association with the patient's health perception, disability in daily activities and psychological distress. METHODS: Five-hundred and fifty-four primary care patients who completed a two-phase study were administered the Composite International Interview for Primary Health Care (CIDI-PHC) and other self-report measures. Unweighted and weighted prevalence estimates were obtained for ICD-10 formal disorders and subthreshold disorders defined by specific operational criteria. The impact of subthreshold disorders on health perception, disability in daily activities and psychological distress was analysed by using multiple regression models. RESULTS: The overall prevalence of subthreshold disorders exceeded that of ICD-10 disorders. Subjects with subthreshold disorders reported levels of psychological distress, disability in daily activities and perceived health comparable to those of patients with full-fledged ICD-10 disorders. When we analysed the associated health characteristics of individual subthreshold disorders, we found that each subthreshold disorder was characterized by poorer health perception, after adjusting for comorbidity with defined disorders and physical illness, age and gender. Disability in daily activities was increased in individuals with subthreshold depression and agoraphobia. LIMITATIONS: The number of cases with subthreshold panic and somatization is very small and does not allow one to draw any definite conclusions on their associated characteristics. To reduce non-response bias related to sampling design and refusals, adjusted sampling weights were computed. Since the study design in Bologna and Verona was different and Bologna patients scoring <4 on the General Health Questionnaire were not interviewed, individuals with minimal distress come from the Verona sample alone. CONCLUSIONS: Because of the prevalence and associated characteristics of subthreshold disorders, primary care physicians should attach adequate importance to the patient's perceived poor health, distress and inability to fulfil daily tasks. The clinical relevance of subthreshold disorders has also potential implications for ongoing revisions of classification systems.

Identification of depression by medical and surgical general hospital physicians.

Little information is available about identification of mental distress by general hospital physicians (GHPs). We compared, among patients admitted in a General Hospital, depressed patients with patients identified as depressed by the GHPs. A random sample of 1,039 patients were screened with the 12-item General Health Questionnaire. Afterwards, all high scorers and a probability sample of low scorers were interviewed with a variety of measures, including the Composite International Diagnostic Interview-Primary Care version (CIDI-PHC). GHPs recorded the presence of depression on a Physician Encounter Form. Patients were more likely to have depression detected on medical than surgical wards. Of the 195 patients who had a depression, the GHPs assessed 32.5% as depressed. A number of factors associated with CIDI diagnoses were not significantly associated with being identified by the GHPs - female gender, two or more life events in the previous year, and a previous history of depression. The identification by the GHPs was associated with a higher probability of contacts with medical professionals and of antidepressant drug prescriptions during the year which followed the first interview.

Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: results and lessons of an underpowered randomised clinical trial.

BACKGROUND: As lithium treatment might be effective in reducing the risk of deliberate self-harm (DSH) in adult patients with unipolar affective disorders, we designed a pragmatic randomised trial to assess its efficacy in more than 200 patients with treatment-resistant depression. However, we randomised 56 patients only. The aim of this report is therefore twofold: first, to disseminate the results of this underpowered study which may be incorporated into future meta-analytical reviews; second, to analyse some critical aspects of the study which might explain failure to reach the target sample size. METHODS: We carried out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode were allocated to add lithium to usual care (intervention arm) versus usual care alone (control arm). Suicide completion and acts of DSH during the 12 months of follow-up constituted the composite primary outcome. RESULTS: Of 58 patients screened for inclusion, 29 were allocated to lithium plus usual care and 27 were assigned to usual care without lithium. Six patients in the lithium plus usual care group and seven in the usual care group committed acts of DSH during the follow-up phase. The survival probability did not differ between the two treatment arms (Chi2 = 0.17, p =0.676). With regard to changes in the severity of depressive symptomatology from baseline to endpoint, no significant differences were detected. CONCLUSIONS: The present study failed to achieve the minimum sample size needed to detect a clinically meaningful difference between the two treatment arms. Consequently, the finding that lithium, in addition to usual care, did not exert a positive effect in terms of reduction of DSH after 12 months of follow-up is likely due to the lack of sufficient statistical power to detect a difference, if a difference existed. The dissemination of the results of this underpowered study will inform future meta-analytical reviews on lithium and suicide-related outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00927550.

Randomized clinical trial on ivermectin versus thiabendazole for the treatment of strongyloidiasis.

BACKGROUND: Strongyloidiasis may cause a life-threatening disease in immunosuppressed patients. This can only be prevented by effective cure of chronic infections. Direct parasitologic exams are not sensitive enough to prove cure if negative. We used an indirect immune fluorescent antibody test (IFAT) along with direct methods for patient inclusion and efficacy assessment. METHODOLOGY/PRINCIPAL FINDINGS: Prospective, randomized, open label, phase III trial conducted at the Centre for Tropical Diseases (Verona, Italy) to compare efficacy and safety of ivermectin (single dose, 200 µg/kg) and thiabendazole (two daily doses of 25 mg/Kg for two days) to cure strongyloidiasis. The first patient was recruited on 6(th) December, 2004. Follow-up visit of the last patient was on 11(th) January, 2007. Consenting patients responding to inclusion criteria were randomly assigned to one of the treatment arms. Primary outcome was: negative direct and indirect (IFAT) tests at follow-up (4 to 6 months after treatment) or subjects with negative direct test and drop of two or more IFAT titers. Considering 198 patients who concluded follow-up, efficacy was 56.6% for ivermectin and 52.2% for thiabendazole (p = 0.53). If the analysis is restricted to 92 patients with IFAT titer 80 or more before treatment (virtually 100% specific), efficacy would be 68.1% for ivermectin and 68.9% for thiabendazole (p = 0.93). Considering direct parasitological diagnosis only, efficacy would be 85.7% for ivermectin and 94.6% for thiabendazole (p = 0.21). In ivermectin arm, mild to moderate side effects were observed in 24/115 patients (20.9%), versus 79/108 (73.1%) in thiabendazole arm (p = 0.00). CONCLUSION: No significant difference in efficacy was observed, while side effects were far more frequent in thiabendazole arm. Ivermectin is the drug of choice, but efficacy of single dose is suboptimal. Different dose schedules should be assessed by future, larger studies. TRIAL REGISTRATION: Portal of Clinical Research with Medicines in Italy 2004­004693­87

Improved gait after repetitive locomotor training in children with cerebral palsy.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of repetitive locomotor training with an electromechanical gait trainer in children with cerebral palsy. DESIGN: In this randomized controlled trial, 18 ambulatory children with diplegic or tetraplegic cerebral palsy were randomly assigned to an experimental group or a control group. The experimental group received 30 mins of repetitive locomotor training with an applied technology (Gait Trainer GT I) plus 10 mins of passive joint mobilization and stretching exercises. The control group received 40 mins of conventional physiotherapy. Each subject underwent a total of 10 treatment sessions over a 2-wk period. Performance on the 10-m walk test, 6-min walk test, WeeFIM scale, and gait analysis was evaluated by a blinded rater before and after treatment and at 1-mo follow-up. RESULTS: The experimental group showed significant posttreatment improvement on the 10-m walk test, 6-min walk test, hip kinematics, gait speed, and step length, all of which were maintained at the 1-mo follow-up assessment. No significant changes in performance parameters were observed in the control group. CONCLUSIONS: Repetitive locomotor training with an electromechanical gait trainer may improve gait velocity, endurance, spatiotemporal, and kinematic gait parameters in patients with cerebral palsy.

Dropping out of care: inappropriate terminations of contact with community-based psychiatric services.

BACKGROUND: Few studies have investigated factors which predict inappropriate terminations (drop-out) of clinical contact with mental health services. AIMS: To identify patient and treatment characteristics associated with dropping out of contact with community-based psychiatric services (CPS). METHOD: A 3-month cohort of patients attending the CPS was followed up for 2 years, to identify drop-outs. RESULTS: We identified 495 patients who had had at least one psychiatric contact of whom 261 had complete ratings for the Global Assessment of Functioning and the Verona Service Satisfaction Scale. In the year after the index contact, 70 terminated contact with the CPS; of these, 44 were rated as having inappropriate terminations (the "drop-out" group) and 26 had appropriate terminations of contact. Drop-outs were younger, less likely to be married and their previous length of contact with services was shorter. No drop-outs had a diagnosis of schizophrenia. Multivariate analysis revealed predictors of dropping out. CONCLUSIONS: In a CPS targeted to patients with severe mental illnesses, those who drop out of care are younger patients without psychoses who are generally satisfied with their treatment.