A comparison of self and proxy quality of life ratings for people with dementia and their carers: a European prospective cohort study.

Objectives: To identify correlates of self-rated and proxy-rated quality of life (QoL) in people with dementia on (i) a dementia-specific and (ii) a capability-wellbeing QoL measure at baseline and 12-month follow-up, and to consider such factors in the context of QoL intervention development.Method: Prospective clinical and demographic data were collected from 451 community-dwelling dyads (mild-moderate dementia) across eight European countries. QoL was measured using the QOL-AD and the ICECAP-O. Multivariate modelling identified correlates of self- and proxy-rated QoL at baseline and at 12-month follow-up.Results: Carer's proxy-ratings of QoL were significantly lower than self-ratings at all time-points for both measures. Proxy-ratings declined over time, but self-ratings remained stable. Baseline predictors of greater self-rated QoL were education, and greater functional ability and relationship quality. Greater proxy-rated QoL was associated with education and greater functional ability, relationship quality, carer social support and carer QoL, lower carer anxiety/depression and less severe neuropsychiatric symptoms in people with dementia. At follow-up, greater self-rated QoL was predicted by greater functional ability, relationship quality, carer social support and having a spousal carer. Greater proxy-rated QoL at follow-up was associated with the same factors as at baseline; however, the dyad living together was an additional predictive factor.Conclusion: Both proxy-ratings and self-ratings of QoL should be interpreted with caution and in the context of each individual caregiving relationship. Different functional, psychosocial, relational and contextual factors influence self- and proxy-ratings, and both sets of factors should be considered in the context of QoL intervention development for the dyad.

A lifestyle intervention as supplement to a physical activity programme in rehabilitation after stroke: a randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of lifestyle group intervention on well-being, occupation and social participation. DESIGN: A randomized controlled trial. SETTING: Senior centres in the community. SUBJECTS: Of 204 stroke survivors screened, 99 (49%) were randomized three months after stroke whereby 86 (87%) participants (mean (SD) age 77.0 (7.1) years) completed all assessments (39 in the intervention group and 47 in the control group). INTERVENTION: A lifestyle course in combination with physical activity (intervention group) compared with physical activity alone (control group). Both programmes were held once a week for nine months. MAIN OUTCOME MEASURE: The Short Form Questionnaire (SF-36), addressing well-being and social participation. Assessments were performed at baseline and at nine months follow-up. RESULTS: We found no statistically significant differences between the groups at the nine months follow-up in the SF-36. Adjusted mean differences in change scores in the eight subscales of SF-36 were; 'mental health' (+1.8, 95% confidence interval (CI) -4.0, +7.6), 'vitality' (-3.0, 95% CI -9.6, +3.6), 'bodily pain' (+3.3, 95% CI -7.8, +14.4), 'general health' (-1.6, 95% CI -8.4, +5.1), 'social functioning' (-2.5, 95% CI -12.8, +7.8), 'physical functioning' (+1.0, 95% CI -6.7, +8.6), 'role physical' (-7.1, 95% CI -22.7, +8.4), 'role emotional' (+11.8, 95% CI -4.4, +28.0). CONCLUSIONS: Improvements were seen in both groups, but no statistically significant differences were found in the intervention group compared to controls. An intervention comprising regular group-based activity with peers may be sufficient in the long-term rehabilitation after stroke.

Delayed diagnosis of foreign body aspiration in children.

AIMS: To assess the diagnostic and therapeutic difficulties as well as the long-term complications of prolonged endobronchial foreign body retention. METHOD: Between January 2000 and May 2021, 794 patients with suspected foreign body aspiration (FBA) were hospitalized in our department. A total of 12 patients with a delayed diagnosis of over 1 month were included. FBAs were confirmed by flexible or rigid endoscopy. A retrospective analysis of medical records was performed. RESULTS: Six male patients and six female patients were hospitalized due to prolonged FBA. The average age was 6.90 years (range: 1-13 years). The average duration of the foreign body retention was 2.60 years (2 months to 9 years). A choking event was found in eight cases. Coughing and wheezing were the main symptoms and signs. A misdiagnosis of asthma was made for five patients. Two atypical clinical presentations led to diagnosis of endobronchial foreign body, unilateral pleurisy, and hemoptysis. We report one case of an occult foreign body externalized spontaneously through a pneumo-pleuro-cutaneous fistula. The most common clinical and radiological findings were of pneumonia and atelectasis. Computed tomography showed localized bronchiectasis in three patients. FBAs were removed with a rigid bronchoscope in eight cases. Other extractions were carried out with a flexible endoscope. The foreign bodies were most frequently of vegetable origin, such as seeds and peanuts. A granulation tissue was observed in seven cases. Bronchial stenosis and bronchiectasis are the most common late complications. Only one patient needed a surgical intervention. CONCLUSIONS: FBA should always be considered in the differential diagnosis of chronic or recurrent respiratory diseases, even in the absence of a previous choking event. Clinical and radiological findings should be carefully evaluated for a possible FBA. Delay in diagnosis and treatment of FBA should be avoided in order to prevent complications. Open surgery may be required when lung abscess has occurred.

[Computed tomography in children with cystic fibrosis: The role of an expiratory protocol]. / Scanner thoracique chez l'enfant atteint de mucoviscidose : intérêt d'un protocole en expiration séquentielle pour réduire la dose d'irradiation.

INTRODUCTION: Chest computed tomography (CT) is essential to monitor lung disease in children with cystic fibrosis, but it involves recurrent exposure to ionizing radiation. The aim of this study was to compare the current complete CT protocol (volumetric end-inspiratory plus sequential expiratory acquisition) to a sequential expiratory acquisition protocol alone in terms of image analysis and ionizing radiation dose. METHODS: Seventy-eight CT scans from 57 children aged 5 to 18 years old were scored on the complete protocol images and on the expiratory sequential images only. Each CT protocol was scored independently, using the Brody scoring system, by two paediatric radiologists. RESULTS: Correlations between the Brody global scores of the two different CT protocols were very good (r=0.90 for both observers), for the bronchiectasis score (r=0.72 and 0.86), mucus plugging score (r=0.87 and 0.83), and expiratory trapped air (r=0.96 and 0.92). Total ionizing radiation dose was reduced, with the measured dose length product (DLP) reduced from 103.31mGy.cm (complete protocol) to 3.06mGy.cm (expiratory protocol) (P<0.001). CONCLUSION: An expiratory chest CT protocol was accurate in diagnosing early signs of CF disease and permitted significant reduction of radiation dose. This protocol would allow spacing out of complete CT scanning with its higher radiation dose and should be considered for the monitoring of lung disease severity in children with CF.

Role of novel hormonal therapies in the management of non-metastatic castration-resistant prostate cancer: a literature-based meta-analysis of randomized trials.

BACKGROUND: Novel hormonal therapies have been recently investigated in non-metastatic castration-resistant prostate cancer (CRPC). We performed a meta-analysis to assess the efficacy and safety of novel hormonal therapies in non-metastatic CRPC. MATERIALS AND METHODS: The primary outcome was metastasis-free survival (MFS). The secondary endpoints were overall survival (OS), time to PSA progression and safety. We planned a subgroup analysis according to the PSA doubling time (> 6 vs < 6 months), Eastern Cooperative Oncology Group (ECOG) performance status (1 vs 0) and concomitant use of bone-targeting agent (yes vs no). RESULTS: Pooled analysis of novel hormonal therapies revealed significantly increased MFS compared with placebo (hazard ratio (HR): HR = 0.32, 95% CI 0.25-0.41; p < 0.00001). The subgroup analysis showed a statistically significant MFS advantage in favour of men with the lower ECOG performance status. Other secondary endpoints favoured the novel hormonal therapies. The relative risk (RR) of grade ≥ 3 adverse events and ≥ 3 hypertension was 1.31 and 1.39, respectively. CONCLUSIONS: This study confirmed the efficacy and safety of the novel hormonal therapies in non-metastatic CRPC.

Sudden death by arrythmia in a 4-year-old boy.

Cardiac arrhythmia with sudden death is rare in children but mainly due to ventricular tachycardia. In case of pulseless ventricular tachycardia, prehospital treatment is crucial with immediate cardiopulmonary resuscitation and external electrical cardioversion. We report the case of pulseless ventricular tachycardia in a child with no past medical history. Sinus rhythm was obtained after 12min of cardiorespiratory resuscitation and three external electrical shocks. An exhaustive diagnostic approach allow us to find its origin. The clinical progression was marked by a severe encephalopathy. The authors discuss different etiologies and treatment of arrhythmia in children, reviewing the pediatric algorithm for shockable rhythm.

Reciprocal antagonism between the netrin-1 receptor uncoordinated-phenotype-5A (UNC5A) and the hepatitis C virus.

Hepatitis C virus (HCV) infection is a leading cause of hepatocellular carcinoma (HCC), mainly through cirrhosis induction, spurring research for a deeper understanding of HCV versus host interactions in cirrhosis. The present study investigated crosstalks between HCV infection and UNC5A, a netrin-1 dependence receptor that is inactivated in cancer. UNC5A and HCV parameters were monitored in patients samples (n=550) as well as in in vitro. In patients, UNC5A mRNA expression is significantly decreased in clinical HCV(+) specimens irrespective of the viral genotype, but not in (HBV)(+) liver biopsies, as compared to uninfected samples. UNC5A mRNA is downregulated in F2 (3-fold; P=0.009), in F3 (10-fold, P=0.0004) and more dramatically so in F4/cirrhosis (44-fold; P<0.0001) histological stages of HCV(+) hepatic lesions compared to histologically matched HCV(-) tissues. UNC5A transcript was found strongly downregulated in HCC samples (33-fold; P<0.0001) as compared with non-HCC samples. In vivo, association of UNC5A transcripts with polyribosomes is decreased by 50% in HCV(+) livers. Consistent results were obtained in vitro showing HCV-dependent depletion of UNC5A in HCV-infected hepatocyte-like cells and in primary human hepatocytes. Using luciferase reporter constructs, HCV cumulatively decreased UNC5A transcription from the UNC5 promoter and translation in a UNC5A 5'UTR-dependent manner. Proximity ligation assays, kinase assays, as well as knockdown and forced expression experiments identified UNC5A as capable of impeding autophagy and promoting HCV restriction through specific impact on virion infectivity, in a cell death-independent and DAPK-related manner. In conclusion, while the UNC5A dependence receptor counteracts HCV persistence through regulation of autophagy in a DAPK-dependent manner, it is dramatically decreased in all instances in HCC samples, and specifically by HCV in cirrhosis. Such data argue for the evaluation of the implication of UNC5A in liver carcinogenesis.

Valacyclovir prophylaxis for the prevention of Herpes simplex virus reactivation in recipients of progenitor cells transplantation.

HSV can cause oral lesions that exacerbate chemotherapy-related mucositis. Intravenous acyclovir is effective in preventing HSV reactivations, but expensive. Valacyclovir has good bioavailability and has not been studied for prophylaxis of HSV among PCT patients. We compared the efficacy and costs of valacyclovir in preventing HSV reactivation among HSV seropositive autologous progenitor cell transplantation (APCT) patients with historical controls in whom intravenous acyclovir or no HSV prophylaxis were used. Valacyclovir group: From October 1997 to April 1999 108 adult patients received valacyclovir 500 mg twice daily from day -3 of APCT until neutropenia recovery or day +30. Valacyclovir was switched to intravenous acyclovir in cases of oral intolerance (17 patients) or suspected HSV reactivation (five patients). Intravenous acyclovir group: From January 1996 to October 1997 43 patients received 5 mg/kg twice-daily intravenous acyclovir from day -3 until recovery from neutropenia. No prophylaxis group: 38 patients from January 1996 to October 1997 did not receive HSV prophylaxis. HSV reactivations were seen in 2.7%, 2% and 45% of patients in the valacyclovir, intravenous acyclovir, and no prophylaxis groups, respectively. Valacyclovir was well tolerated and was the least expensive strategy. Oral valacyclovir was as effective as intravenous acyclovir for the prophylaxis of HSV reactivation in APCT patients.

Assessment of myocardial sympathetic activity in coronary heart disease.

We measured adrenaline, noradrenaline and dopamine beta-hydroxylase in arterial and in coronary sinus blood in 14 patients with coronary artery disease, at rest and under pacing-induced ischemia. Pacing increased the concentrations of adrenaline and noradrenaline in both arterial and coronary sinus blood. The origin of the adrenaline increase appears to be extramyocardial. The arteriovenous differences indicated that the heart extracts adrenaline and releases noradrenaline. These differences were not significantly changed by pacing, nor by the administration of propranolol. No marked changes in the concentrations of dopamine beta-hydroxylase were observed, except under pacing after propranolol, in which case a release from the heart occurred.

Autologous peripheral blood progenitor cell transplantation mobilized with high-dose cytarabine in acute myeloid leukemia in first complete remission.

BACKGROUND: The aim of this study was to increase disease-free survival (DFS) in AML in CR1 using a high-dose cytarabine consolidation plus G-CSF as in vivo purging and mobilization of CD34+ cells before ablative therapy and peripheral blood autograft. PATIENTS AND METHODS: Fifty-six consecutive AML patients (pts) (including 11 children < 15 years), with a median age of 32 years, were analyzed. After achievement of CR with cytarabine-mitoxantrone (7 + 3) in adults and a BFM-like protocol in children, pts were intensified with cytarabine 2 g/m2 x six doses plus mitoxantrone for adults, or, 3 g/m2 x six doses plus etoposide for children, followed by G-CSF 5 micrograms/kg SC daily. The ablative regimens used were busulfan and cyclophosphamide (Bu/Cy) in standard-risk pts plus etoposide (2400 mg/m2) for high-risk pts. RESULTS: For the 54 pts who underwent autologous transplant, the median time to reach > 1.0 x 10(9)/l neutrophils was 13 days (8-48), and to reach platelets > 25 x 10(9)/l 32 days (8-364), and the median numbers of red blood cell and platelet units transfused were 3 and 5, respectively. Six pts had treatment-related deaths (11%). The disease-free survival and overall survival at 30 months (mos) for the 56 eligible pts were 61% and 62%, respectively. Only two relapses were observed after 21 mos, while there were 12 relapses within 12 mos. CONCLUSIONS: The above treatment results in a similar DFS rate as does rescue with bone marrow cells, with faster neutrophil and platelet recovery.