308 research outputs found
Topical cystic fibrosis transmembrane conductance regulator gene replacement for cystic fibrosis-related lung disease
BACKGROUND: Cystic fibrosis is caused by a defective gene encoding a protein called the cystic fibrosis transmembrane conductance regulator (CFTR), and is characterised by chronic lung infection resulting in inflammation and progressive lung damage that results in a reduced life expectancy. OBJECTIVES: To determine whether topical CFTR gene replacement therapy to the lungs in people with cystic fibrosis is associated with improvements in clinical outcomes, and to assess any adverse effects. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. Date of most recent search: 05 May 2016. An additional search of the National Institutes for Health (NIH) Genetic Modification Clinical Research Information System (GeMCRIS) was also performed for the years 1992 to 2015. Date of most recent search: 20 April 2016. SELECTION CRITERIA: Randomised controlled studies comparing topical CFTR gene delivery to the lung, using either viral or non‐viral delivery systems, with placebo or an alternative delivery system in people with confirmed cystic fibrosis. DATA COLLECTION AND ANALYSIS: The authors independently extracted data and assessed study quality. Authors of included studies were contacted and asked for any available additional data. Meta‐analysis was limited due to differing study designs. MAIN RESULTS: Four randomised controlled studies met the inclusion criteria for this review, involving a total of 302 participants lasting from 29 days to 13 months; 14 studies were excluded. The included studies differed in terms of CFTR gene replacement agent and study design, which limited the meta‐analysis. One study only enrolled adult males, the remaining studies included both males and females aged 12 years and over. Risk of bias in the studies was moderate. Random sequence generation and allocation concealment was only described in the more recent study; the remaining three studies were judged to have an unclear risk of bias. All four studies documented double‐blinding to the intervention, but there is some uncertainty with regards to participant blinding in one study. Some outcome data were missing from all four studies. There were no differences in either the number of respiratory exacerbations or the number of participants with an exacerbation between replacement therapy or placebo groups at any time point. Meta‐analysis of most respiratory function tests showed no difference between treatment and placebo groups, but the smallest study (n = 16) reported forced vital capacity (litres) increased more in the placebo group at up to 24 hours. A further study reported a significant improvement in forced expiratory volume at one second (litres) at 30 days after participants had received their first dose of favouring the gene therapy agent, but this finding was not confirmed when combined with at second study in the meta‐analysis. The more recent study (n = 140) demonstrated a small improvement in forced vital capacity (per cent predicted) at two and three months and again at 11 and 12 months for participants receiving CFTR gene replacement therapy compared to those receiving placebo. The same study reported a significant difference in the relative change in forced expiratory volume at one second (per cent predicted) at two months, three months and 12 months. One small study reported significant concerns with "influenza‐like" symptoms in participants treated with CFTR gene replacement therapy; this was not reported on repeated use of the same agent in a larger recent study. There was no other evidence of positive impact on outcomes, in particular improved quality of life or reduced treatment burden. Two studies measured ion transport in the lower airways; one (n = 16) demonstrated significant changes toward normal values in the participants who received gene transfer agents (P < 0.0001), mean difference 6.86 (95% confidence interval 3.77 to 9.95). The second study (n = 140) also reported significant changes toward normal values (P = 0.032); however, aggregate data were not available for analysis. In the most recent study, there was also evidence of increased salt transport in cells obtained by brushing the lower airway. These outcomes, whilst important, are not of direct clinical relevance. AUTHORS' CONCLUSIONS: One study of liposome‐based CFTR gene transfer therapy demonstrated some improvements in respiratory function in people with CF, but this limited evidence of efficacy does not support this treatment as a routine therapy at present. There was no evidence of efficacy for viral‐mediated gene delivery. Future studies need to investigate clinically important outcome measures
Serum squamous cell carcinoma antigen as an early indicator of response during therapy of cervical cancer
Association between Computed Tomographic Biomarkers of Cerebral Small Vessel Diseases and Long-Term Outcome after Spontaneous Intracerebral Hemorrhage
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Longitudinal association between CRP levels and risk of psychosis: a meta-analysis of population-based cohort studies.
Funder: MQ: Transforming Mental Health; Grant(s): MQDS17/40Meta-analyses of cross-sectional studies suggest that patients with psychosis have higher circulating levels of C-reactive protein (CRP) compared with healthy controls; however, cause and effect is unclear. We examined the prospective association between CRP levels and subsequent risk of developing a psychotic disorder by conducting a systematic review and meta-analysis of population-based cohort studies. Databases were searched for prospective studies of CRP and psychosis. We obtained unpublished results, including adjustment for age, sex, body mass index, smoking, alcohol use, and socioeconomic status and suspected infection (CRP > 10 mg/L). Based on random effect meta-analysis of 89,792 participants (494 incident cases of psychosis at follow-up), the pooled odds ratio (OR) for psychosis for participants with high (>3 mg/L), as compared to low (≤3 mg/L) CRP levels at baseline was 1.50 (95% confidence interval [CI], 1.09-2.07). Evidence for this association remained after adjusting for potential confounders (adjusted OR [aOR] = 1.31; 95% CI, 1.03-1.66). After excluding participants with suspected infection, the OR for psychosis was 1.36 (95% CI, 1.06-1.74), but the association attenuated after controlling for confounders (aOR = 1.23; 95% CI, 0.95-1.60). Using CRP as a continuous variable, the pooled OR for psychosis per standard deviation increase in log(CRP) was 1.11 (95% CI, 0.93-1.34), and this association further attenuated after controlling for confounders (aOR = 1.07; 95% CI, 0.90-1.27) and excluding participants with suspected infection (aOR = 1.07; 95% CI, 0.92-1.24). There was no association using CRP as a categorical variable (low, medium or high). While we provide some evidence of a longitudinal association between high CRP (>3 mg/L) and psychosis, larger studies are required to enable definitive conclusions
Longitudinal association between CRP levels and risk of psychosis: a meta-analysis of population-based cohort studies.
Funder: MQ: Transforming Mental Health; Grant(s): MQDS17/40Meta-analyses of cross-sectional studies suggest that patients with psychosis have higher circulating levels of C-reactive protein (CRP) compared with healthy controls; however, cause and effect is unclear. We examined the prospective association between CRP levels and subsequent risk of developing a psychotic disorder by conducting a systematic review and meta-analysis of population-based cohort studies. Databases were searched for prospective studies of CRP and psychosis. We obtained unpublished results, including adjustment for age, sex, body mass index, smoking, alcohol use, and socioeconomic status and suspected infection (CRP > 10 mg/L). Based on random effect meta-analysis of 89,792 participants (494 incident cases of psychosis at follow-up), the pooled odds ratio (OR) for psychosis for participants with high (>3 mg/L), as compared to low (≤3 mg/L) CRP levels at baseline was 1.50 (95% confidence interval [CI], 1.09-2.07). Evidence for this association remained after adjusting for potential confounders (adjusted OR [aOR] = 1.31; 95% CI, 1.03-1.66). After excluding participants with suspected infection, the OR for psychosis was 1.36 (95% CI, 1.06-1.74), but the association attenuated after controlling for confounders (aOR = 1.23; 95% CI, 0.95-1.60). Using CRP as a continuous variable, the pooled OR for psychosis per standard deviation increase in log(CRP) was 1.11 (95% CI, 0.93-1.34), and this association further attenuated after controlling for confounders (aOR = 1.07; 95% CI, 0.90-1.27) and excluding participants with suspected infection (aOR = 1.07; 95% CI, 0.92-1.24). There was no association using CRP as a categorical variable (low, medium or high). While we provide some evidence of a longitudinal association between high CRP (>3 mg/L) and psychosis, larger studies are required to enable definitive conclusions
Aspiration of parenteral nutrition – a previously unreported complication of central venous access in an infant: a case report
Introduction: The insertion of percutaneous central venous catheters is a common procedure in neonatal intensive care nurseries. Placement of the catheter tip in a large central vein is most desirable. Occasionally, due to difficult venous access, catheter tips are left in places that are less than ideal. Case presentation: A female infant with a complicated gastroschisis developed signs of short bowel syndrome post surgery. She was treated with a combination of parenteral nutrition and enteral feeds. A central venous line was inserted through a scalp vein. The tip was noted to be in a vessel at the level of the mandible. She subsequently became unwell with large milky pharyngeal aspirates and episodes of bradycardia. Chest radiography revealed aspiration. The central venous line was removed because of presumed extravasation. This is the first reported case of parenteral nutrition extravasation into the pharynx causing aspiration in an infant. Conclusion: This complication may have been prevented by recognising that the tip of the catheter was not correctly placed. When catheters are in unusual positions it may be useful to obtain a second radiograph from a different angle or an ultrasound scan to confirm the positioning of the catheter tip
Aspiration of parenteral nutrition – a previously unreported complication of central venous access in an infant: a case report
Introduction: The insertion of percutaneous central venous catheters is a common procedure in neonatal intensive care nurseries. Placement of the catheter tip in a large central vein is most desirable. Occasionally, due to difficult venous access, catheter tips are left in places that are less than ideal. Case presentation: A female infant with a complicated gastroschisis developed signs of short bowel syndrome post surgery. She was treated with a combination of parenteral nutrition and enteral feeds. A central venous line was inserted through a scalp vein. The tip was noted to be in a vessel at the level of the mandible. She subsequently became unwell with large milky pharyngeal aspirates and episodes of bradycardia. Chest radiography revealed aspiration. The central venous line was removed because of presumed extravasation. This is the first reported case of parenteral nutrition extravasation into the pharynx causing aspiration in an infant. Conclusion: This complication may have been prevented by recognising that the tip of the catheter was not correctly placed. When catheters are in unusual positions it may be useful to obtain a second radiograph from a different angle or an ultrasound scan to confirm the positioning of the catheter tip
Risks of recurrent stroke and all serious vascular events after spontaneous intracerebral haemorrhage: pooled analyses of two population-based studies
BACKGROUND: Patients with stroke due to spontaneous (non-traumatic) intracerebral haemorrhage (ICH) are at risk of recurrent ICH, ischaemic stroke, and other serious vascular events. We aimed to analyse these risks in population-based studies and compare them with the risks in RESTART, which assessed antiplatelet therapy after ICH. METHODS: We pooled individual patient data from two prospective, population-based inception cohort studies of all patients with an incident firs-in-a-lifetime ICH in Oxfordshire, England (Oxford Vascular Study; April 1, 2002, to Sept 28, 2018) and Lothian, Scotland, UK (Lothian Audit of the Treatment of Cerebral Haemorrhage; June 1, 2010, to May 31, 2013). We quantified the absolute and relative risks of recurrent ICH, ischaemic stroke, or any serious vascular event (non-fatal stroke, non-fatal myocardial infarction, or vascular death), stratified by ICH location (lobar vs non-lobar) and comorbid atrial fibrillation (AF). We compared pooled event rates with those after allocation to avoid antiplatelet therapy in RESTART. FINDINGS: Among 674 patients (mean age 74·7 years [SD 12·6], 320 [47%] men) with 1553 person-years of follow-up, 46 recurrent ICHs (event rate 3·2 per 100 patient-years, 95% CI 2·0-5·1) and 25 ischaemic strokes (1·7 per 100 patient-years, 0·8-3·3) were reported. Patients with lobar ICH (n=317) had higher risk of recurrent ICH (5·1 per 100 patient-years, 95% CI 3·6-7·2) than patients with non-lobar ICH (n=355; 1·8 per 100 patient-years, 1·0-3·3; hazard ratio [HR] 3·2, 95% CI 1·6-6·3; p=0·0010), but there was no evidence of a difference in the risk of ischaemic stroke (1·8 per 100 patient-years, 1·0-3·2, vs 1·6 per 100 patient-years, 0·6-4·4; HR 1·1, 95% CI 0·5-2·8). Conversely, there was no evidence of a difference in recurrent ICH rate in patients with AF (n=147; 3·3 per 100 patient-years, 95% CI 1·0-10·7) compared with those without (n=526; 3·2 per 100 patient-years, 2·2-4·7; HR 0·9, 95% CI 0·4-2·1), but the risk of ischaemic stroke was higher with AF (6·3 per 100 patient-years, 3·7-10·9, vs 0·7 per 100 patient-years, 0·1-5·6; HR 8·2, 3·3-20·3; p<0·0001), resulting in patients with AF having a higher risk of all serious vascular events than patients without AF (15·5 per 100 patient-years, 10·0-24·1, vs 6·8 per 100 patient-years, 3·6-12·5; HR 1·78, 95% CI 1·16-2·74; p=0·0090). Only for patients with lobar ICH without comorbid AF was the risk of recurrent ICH greater than the risk of ischaemic stroke (5·2 per 100 patient-years, 95% CI 3·6-7·5, vs 0·9 per 100 patient-years, 0·2-4·8; p=0·00034). Comparing data from the pooled population-based studies with that from patients allocated to not receive antiplatelet therapy in RESTART, there was no evidence of a difference in the rate of recurrent ICH (3·5 per 100 patient-years, 95% CI 1·9-6·0, vs 4·4 per 100 patient-years, 2·6-6·1) or ischaemic stroke (3·4 per 100 patient-years, 1·9-5·9, vs 5·3 per 100 patient-years, 3·3-7·2). INTERPRETATION: The risks of recurrent ICH, ischaemic stroke, and all serious vascular events after ICH differ by ICH location and comorbid AF. These data enable risk stratification of patients in clinical practice and ongoing randomised trials. FUNDING: UK Medical Research Council, Stroke Association, British Heart Foundation, Wellcome Trust, and the National Institute for Health Research Oxford Biomedical Research Centre
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