Newcastle upon Tyne NHS Hospitals Foundation Trust

Newcastle upon Tyne, United Kingdom

Newcastle upon Tyne NHS Hospitals Foundation Trust

Newcastle upon Tyne, United Kingdom
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Usmani Z.A.,The Queen Elizabeth Hospital | Usmani Z.A.,University of Adelaide | Carson K.V.,University of Adelaide | Heslop K.,Newcastle upon Tyne NHS Hospitals Foundation Trust | And 3 more authors.
Cochrane Database of Systematic Reviews | Year: 2017

Background: Chronic obstructive pulmonary disease (COPD) (commonly referred to as chronic bronchitis and emphysema) is a chronic lung condition characterised by the inflammation of airways and irreversible destruction of pulmonary tissue leading to progressively worsening dyspnoea. It is a leading international cause of disability and death in adults. Evidence suggests that there is an increased prevalence of anxiety disorders in people with COPD. The severity of anxiety has been shown to correlate with the severity of COPD, however anxiety can occur with all stages of COPD severity. Coexisting anxiety and COPD contribute to poor health outcomes in terms of exercise tolerance, quality of life and COPD exacerbations. The evidence for treatment of anxiety disorders in this population is limited, with a paucity of evidence to support the efficacy of medication-only treatments. It is therefore important to evaluate psychological therapies for the alleviation of these symptoms in people with COPD. Objectives: To assess the effects of psychological therapies for the treatment of anxiety disorders in people with chronic obstructive pulmonary disease. Search methods: We searched the specialised registers of two Cochrane Review Groups: Cochrane Common Mental Disorders (CCMD) and Cochrane Airways (CAG) (to 14 August 2015). The specialised registers include reports of relevant randomised controlled trials from The Cochrane Library, MEDLINE, Embase, and PsycINFO. We carried out complementary searches on PsycINFO and CENTRAL to ensure no studies had been missed. We applied no date or language restrictions. Selection criteria: We considered all randomised controlled trials (RCTs), cluster-randomised trials and cross-over trials of psychological therapies for people (aged over 40 years) with COPD and coexisting anxiety disorders (as confirmed by recognised diagnostic criteria or a validated measurement scale), where this was compared with either no intervention or education only. We included studies in which the psychological therapy was delivered in combination with another intervention (co-intervention) only if there was a comparison group that received the co-intervention alone. Data collection and analysis: Two review authors independently screened citations to identify studies for inclusion and extracted data into a pilot-tested standardised template. We resolved any conflicts that arose through discussion. We contacted authors of included studies to obtain missing or raw data. We performed meta-analyses using the fixed-effect model and, if we found substantial heterogeneity, we reanalysed the data using the random-effects model. Main results: We identified three prospective RCTs for inclusion in this review (319 participants available to assess the primary outcome of anxiety). The studies included people from the outpatient setting, with the majority of participants being male. All three studies assessed psychological therapy (cognitive behavioural therapy) plus co-intervention versus co-intervention alone. We assessed the quality of evidence contributing to all outcomes as low due to small sample sizes and substantial heterogeneity in the analyses. Two of the three studies had prespecified protocols available for comparison between prespecified methodology and outcomes reported within the final publications. We observed some evidence of improvement in anxiety over 3 to 12 months, as measured by the Beck Anxiety Inventory (range from 0 to 63 points), with psychological therapies performing better than the co-intervention comparator arm (mean difference (MD) -4.41 points, 95% confidence interval (CI) -8.28 to -0.53; P = 0.03). There was however, substantial heterogeneity between the studies (I2 = 62%), which limited the ability to draw reliable conclusions. No adverse events were reported. Authors' conclusions: We found only low-quality evidence for the efficacy of psychological therapies among people with COPD with anxiety. Based on the small number of included studies identified and the low quality of the evidence, it is difficult to draw any meaningful and reliable conclusions. No adverse events or harms of psychotherapy intervention were reported. A limitation of this review is that all three included studies recruited participants with both anxiety and depression, not just anxiety, which may confound the results. We downgraded the quality of evidence in the 'Summary of findings' table primarily due to the small sample size of included trials. Larger RCTs evaluating psychological interventions with a minimum 12-month follow-up period are needed to assess long-term efficacy. © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.


Sayers J.,Newcastle University | Hynes A.M.,Newcastle University | Srivastava S.,Newcastle University | Dowen F.,Newcastle upon Tyne NHS Hospitals Foundation Trust | And 6 more authors.
Clinical Kidney Journal | Year: 2015

Mutations in CYP24A1, encoding the vitamin D 24-hydroxlase enzyme, are known to cause a range of clinical phenotypes and presentations including idiopathic infantile hypercalcaemia and adult-onset nephrocalcinosis and nephrolithiasis. In the context of raised or borderline high serum calcium levels, suppressed PTH and persistently elevated 1,25 dihydroxy vitamin D levels, this rare condition should be considered.We present a case where this biochemical pattern was seen and mutations in CYP24A1 were confirmed. We were able to successfully control serum calcium levels and reduce urinary calcium excretion by treatment with low-dose fluconazole, which inhibits vitamin D-synthesizing enzymes (including 25-hydroxylases and 1-a- hydroxylase) thereby reducing levels of 1,25-dihydroxy vitamin D. © The Author 2015.


Elliott S.L.,Northumbria University | Crawford C.,Northumbria University | Mulligan E.,Northumbria University | Summerfield G.,Queen Elizabeth Hospital | And 7 more authors.
British Journal of Haematology | Year: 2011

Defects in the DNA damage response pathway [e.g. del(17p)] are associated with drug-resistant B-cell chronic lymphocytic leukaemia (CLL). We previously demonstrated that over-expression of DNA-dependent protein kinase (DNA-PK) correlates with chemo-resistance and that inhibition of DNA-PK sensitizes CLL cells to chemotherapeutics. Here, we investigated expression of DNA-PK and other proteins that impact on drug resistance, and evaluated the effects of a DNA-PK inhibitor (NU7441) on mitoxantrone-induced cytotoxicity in CLL cells. NU7441 sensitized cells from 42/49 CLL samples to mitoxantrone, with sensitization ranging from 2- to 200-fold Co-culture of CLL cells in conditioned stromal medium increased chemoresistance but did not reduce sensitization by NU7441. Mitoxantrone treatment induced γH2AX foci and NU7441 increased their longevity (24 h). NU7441 prevented mitoxantrone-induced autophosphorylation of the DNA-PK catalytic subunit (DNA-PKcs) at Ser 2056, confirming that DNA-PK participates in repair of mitoxantrone-induced DNA damage. del(17p) cases were more resistant to mitoxantrone than del(13q) cases, but were resensitized (7-16 fold) by co-incubation with NU7441. Expression of DNA-PKcs, Ku80, P-glycoprotein and topoisomerase IIβ were significantly higher in del(17p) cases. PRKDC mRNA levels correlated with DNA-PKcs protein expression, which predicted shorter survival. These data confirm the potential of DNA-PK as a therapeutic target in poor prognosis CLL. © 2010 Blackwell Publishing Ltd.


Graham Y.N.H.,University of Sunderland | Graham Y.N.H.,Sunderland Royal Hospital | Mansour D.,Newcastle upon Tyne NHS Hospitals Foundation Trust | Small P.K.,Sunderland Royal Hospital | And 6 more authors.
Obesity Surgery | Year: 2016

Background: Over 80 % of bariatric surgical patients are women with obesity in their reproductive years. Obesity adversely affects fertility; the rapid weight loss following bariatric surgery can increase fecundity. Current guidelines recommend avoiding pregnancy for up to 24 months following surgery, but little is known about current contraceptive care of women who undergo bariatric surgery. Two surveys were undertaken with bariatric surgical and contraceptive practitioners in England to establish current contraceptive practices in both groups. Methods: Two anonymous on-line surveys were sent to all 382 members of the British Obesity and Metabolic Surgery Society (BOMSS) and an estimated 300 contraceptive practitioners in the North East of England. Results: The BOMSS survey elicited a response rate of 17 % (n = 65), mainly from bariatric surgeons (n = 24 (36 %)). Most respondents (97 %) acknowledged the need to educate patients, but contraceptive information was only provided by 7 % (n = 4) of respondents in bariatric surgical clinics. Less than half of respondents were confident discussing contraception, and the majority requested further training, guidance and communication with contraceptive practitioners. The majority of respondents to the contraceptive practitioner survey were general practitioners (28 %, n = 20). Three quarters of respondents reported little knowledge of bariatric surgery, and many reported not seeing women with obesity requiring contraception before (66 %, n = 45) or after surgery (71 %, n = 49). Conclusions: There is a need to increase knowledge levels of contraception within bariatric surgical teams and to understand why, despite increasing levels of bariatric surgery, women do not seem to be appearing for advice in contraceptive settings. © 2016, Springer Science+Business Media New York.


PubMed | Sunderland Royal Hospital, University of Sunderland and Newcastle upon Tyne NHS Hospitals Foundation Trust
Type: Journal Article | Journal: Obesity surgery | Year: 2016

Over 80% of bariatric surgical patients are women with obesity in their reproductive years. Obesity adversely affects fertility; the rapid weight loss following bariatric surgery can increase fecundity. Current guidelines recommend avoiding pregnancy for up to 24months following surgery, but little is known about current contraceptive care of women who undergo bariatric surgery. Two surveys were undertaken with bariatric surgical and contraceptive practitioners in England to establish current contraceptive practices in both groups.Two anonymous on-line surveys were sent to all 382 members of the British Obesity and Metabolic Surgery Society (BOMSS) and an estimated 300 contraceptive practitioners in the North East of England.The BOMSS survey elicited a response rate of 17% (n=65), mainly from bariatric surgeons (n=24 (36%)). Most respondents (97%) acknowledged the need to educate patients, but contraceptive information was only provided by 7% (n=4) of respondents in bariatric surgical clinics. Less than half of respondents were confident discussing contraception, and the majority requested further training, guidance and communication with contraceptive practitioners. The majority of respondents to the contraceptive practitioner survey were general practitioners (28%, n=20). Three quarters of respondents reported little knowledge of bariatric surgery, and many reported not seeing women with obesity requiring contraception before (66%, n=45) or after surgery (71%, n=49).There is a need to increase knowledge levels of contraception within bariatric surgical teams and to understand why, despite increasing levels of bariatric surgery, women do not seem to be appearing for advice in contraceptive settings.


PubMed | Northumbria University and Newcastle upon Tyne NHS Hospitals Foundation Trust
Type: Journal Article | Journal: Clinical kidney journal | Year: 2015

Mutations in CYP24A1, encoding the vitamin D 24-hydroxlase enzyme, are known to cause a range of clinical phenotypes and presentations including idiopathic infantile hypercalcaemia and adult-onset nephrocalcinosis and nephrolithiasis. In the context of raised or borderline high serum calcium levels, suppressed PTH and persistently elevated 1,25 dihydroxy vitamin D levels, this rare condition should be considered. We present a case where this biochemical pattern was seen and mutations in CYP24A1 were confirmed. We were able to successfully control serum calcium levels and reduce urinary calcium excretion by treatment with low-dose fluconazole, which inhibits vitamin D-synthesizing enzymes (including 25-hydroxylases and 1--hydroxylase) thereby reducing levels of 1,25-dihydroxy vitamin D.

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