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1.
Acta Cardiol ; 78(7): 828-837, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37694719

ABSTRACT

OBJECTIVES: Acute heart failure (AHF) hospitalisation is associated with 10% mortality. Outpatient based management (OPM) of AHF appeared effective in observational studies. We conducted a pilot randomised controlled trial (RCT) comparing OPM with standard inpatient care (IPM). METHODS: We randomised patients with AHF, considered to need IV diuretic treatment for ≥2 days, to IPM or OPM. We recorded all-cause mortality, and the number of days alive and out-of-hospital (DAOH). Quality of life, mental well-being and Hope scores were assessed. Mean NHS cost savings and 95% central range (CR) were calculated from bootstrap analysis. Follow-up: 60 days. RESULTS: Eleven patients were randomised to IPM and 13 to OPM. There was no statistically significant difference in all-cause mortality during the index episode (1/11 vs 0/13) and up to 60 days follow-up (2/11 vs 2/13) [p = .86]. The OPM group accrued more DAOH {47 [36,51] vs 59 [41,60], p = .13}. Two patients randomised to IPM (vs 6 OPM) were readmitted [p = .31]. Hope scores increased more with OPM within 30 days but dropped to lower levels than IPM by 60 days. More out-patients had increased total well-being scores by 60 days (p = .04). OPM was associated with mean cost savings of £2658 (95% CR 460-4857) per patient. CONCLUSIONS: Patients with acute HF randomised to OPM accrued more days alive out of hospital (albeit not statistically significantly in this small pilot study). OPM is favoured by patients and carers and is associated with improved mental well-being and cost savings.


Subject(s)
Heart Failure , Outpatients , Humans , Pilot Projects , Cost Savings , Heart Failure/therapy , Hospitalization
2.
J Neurol ; 270(12): 5889-5902, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37610448

ABSTRACT

BACKGROUND: Approximately one quarter of people with an intellectual disability (PwID) have epilepsy of whom nearly three-quarters are pharmaco-resistant. There are higher reported neuropsychiatric side-effects to anti-seizure medication (ASM) in this group. Levetiracetam (LEV) is a first-line ASM with a stronger association with neuropsychiatric symptoms for PwID than other ASMs. Brivaracetam (BRV) is a newer ASM. Recent studies suggest a beneficial effect of swapping people who experience neuropsychiatric events with LEV to BRV. However, there is limited evidence of this for PwID. This evaluation analyses real world outcomes of LEV to BRV swap for PwID compared to those without ID. METHODS: We performed a multicentre, retrospective review of clinical records. Demographic, clinical characteristics and reported adverse events of patients switched from LEV to BRV (2016-2020) were recorded at 3 months pre and 6- and 12-month post-BRV initiation. Outcomes were compared between PwID and those without and summarised using cross-tabulations and logistic regression models. A Bonferroni correction was applied. RESULTS: Of 77 participants, 46 had ID and 52% had a past psychiatric illness. 71% participants switched overnight from LEV to BRV. Seizure reduction of > 50% was seen in 40% patients. Psychiatric illness history was predictive of having neuropsychiatric side-effects with LEV but not BRV (p = 0.001). There was no significant difference for any primary outcomes between PwID versus without ID. CONCLUSIONS: Switching from LEV to BRV appears as well tolerated and efficacious in PwID as those without ID with over 90% still on BRV after 12 months.


Subject(s)
Drug-Related Side Effects and Adverse Reactions , Epilepsy , Intellectual Disability , Substance Abuse, Intravenous , Humans , Levetiracetam/therapeutic use , Intellectual Disability/complications , Intellectual Disability/drug therapy , Anticonvulsants/adverse effects , Case-Control Studies , Substance Abuse, Intravenous/drug therapy , Epilepsy/complications , Epilepsy/drug therapy , Treatment Outcome
3.
J Perioper Pract ; 33(1-2): 24-29, 2023.
Article in English | MEDLINE | ID: mdl-34380351

ABSTRACT

BACKGROUND: Dislocation following hip hemiarthroplasty is a major complication with increased mortality and morbidity. Data looking at dislocation following contemporary bipolar stems are lacking in literature. METHODS: Retrospective review of our prospective national hip fracture database over a two-year period. Group 1 comprised of consecutive patients receiving bipolar Furlong prosthesis (N222) while Group 2 was made up of a historical cohort (uncemented; N254). Clinical and radiological records were reviewed to determine dislocation rates, causes and associative factors of dislocations. Data were analysed using SPSS. RESULTS: Following 476 hemiarthroplasties performed during the study period, 12 (2.5%) dislocations were reported (eight in Group 1; four in Group 2). There was no significant difference in dislocation rates (3.6% vs 1.6%) between groups (p = 0.159). Subgroup analysis of Group 1 demonstrated a significant difference in dislocations with Furlong cemented (6%) as compared with Furlong uncemented (0%) hemiarthroplasties (p = 0.024). Following dislocation, death rates increased to 8.3% from 1.7% in both groups. CONCLUSION: There is a statistically significant increase in dislocation rate following use of cemented Furlong prosthesis when compared to similar uncemented prosthesis at the same treatment period. However, when compared to traditional uncemented prosthesis, there is no difference in dislocation rates.


Subject(s)
Arthroplasty, Replacement, Hip , Femoral Neck Fractures , Hemiarthroplasty , Hip Prosthesis , Humans , Hip Prosthesis/adverse effects , Femoral Neck Fractures/surgery , Hemiarthroplasty/adverse effects , Prospective Studies , Treatment Outcome , Prosthesis Design , Arthroplasty, Replacement, Hip/adverse effects
4.
BMC Nephrol ; 22(1): 115, 2021 03 30.
Article in English | MEDLINE | ID: mdl-33784968

ABSTRACT

BACKGROUND: Iron deficiency (ID) is common in patients with chronic kidney disease (CKD). Intravenous (IV) iron in heart failure leads to improvement in exercise capacity and improvement in quality-of-life measurements; however, data in patients with CKD are lacking. METHODS: The Iron and the Heart Study was a prospective double blinded randomised study in non-anaemic CKD stages 3b-5 patients with ID which investigated whether 1000 mg of IV iron (ferric derisomaltose (FDI)) could improve exercise capacity in comparison to placebo measured at 1 and 3 months post infusion. Secondary objectives included effects on haematinic profiles and haemoglobin, safety analysis and quality of life questionnaires (QoL). RESULTS: We randomly assigned 54 patients mean (SD) age for FDI (n = 26) 61.6 (10.1) years vs placebo (n = 28; 57.8 (12.9) years) and mean eGFR (33.2 (9.3) vs. 29.1 (9.6) ml/min/1.73m2) at baseline, respectively. Adjusting for baseline measurements, six-minute walk test (6MWT) showed no statistically significant difference between arms at 1 month (p = 0.736), or 3 months (p = 0.741). There were non-significant increases in 6MWT from baseline to 1 and 3 months in the FDI arm. Haemoglobin (Hb) at 1 and 3 months remained stable. There were statistically significant increases in ferritin (SF) and transferrin saturation (TSAT) at 1 and 3 months (p < 0.001). There was a modest numerical improvement in QoL parameters. There were no adverse events attributable to IV iron. CONCLUSION: This study demonstrated a short-term beneficial effect of FDI on exercise capacity, but it was not significant despite improvements in parameters of iron status, maintenance of Hb concentration, and numerical increases in functional capacity and quality of life scores. A larger study will be required to confirm if intravenous iron is beneficial in iron deficient non-anaemic non-dialysis CKD patients without heart failure to improve the 6MWT. TRIAL REGISTRATION: European Clinical Trials Database (EudraCT) No: 2014-004133-16 REC no: 14/YH/1209 Date First Registered: 2015-02-17 and date of end of trail 2015-05-23 Sponsor ref R1766 and Protocol No: IHI 141.


Subject(s)
Disaccharides/administration & dosage , Functional Status , Hematinics/administration & dosage , Iron Deficiencies/drug therapy , Renal Insufficiency, Chronic/drug therapy , Adult , Aged , Disaccharides/adverse effects , Double-Blind Method , Exercise Tolerance/drug effects , Female , Ferric Compounds/administration & dosage , Ferric Compounds/adverse effects , Hematinics/adverse effects , Hemoglobins/analysis , Humans , Infusions, Intravenous , Iron Deficiencies/etiology , Male , Middle Aged , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/complications , Surveys and Questionnaires
5.
Ann Clin Biochem ; 58(4): 305-310, 2021 07.
Article in English | MEDLINE | ID: mdl-33554608

ABSTRACT

BACKGROUND: Accurate and rapid testing for SARS-COV-2 antibodies could improve the diagnosis and management of COVID-19. In this study, we aim to evaluate the diagnostic accuracy of a commercially available point-of-care lateral flow kit independently and in comparison to an established platform-based system. METHOD: Samples from 144 PCR-confirmed COVID-19 cases and 130 pre-pandemic negative controls were tested in parallel by MP Rapid 2019-NCOV IgM/IgG Combo test and Roche Elecsys. Comparison of results based on serum and capillary blood testing was undertaken. RESULTS: Sensitivity at day 15 onwards was 100% for both methods. Between days 1 and 7 post admission, the IgM/IgG Combo test and Roche Elecsys shown sensitivity of 74% (95%CI: 62%-85%) vs. 67% (95% CI: 55%-79%, P = 0.3947). Combo test specificities were 100% for IgG, 98.5% for IgM vs. Roche Elecsys specificity of 100%. Concordance analysis showed 98.5% agreement to the Roche Elecsys method (Cohen's Kappa 0.96 95% CI [0.92-0.99]). Capillary blood results showed complete agreement with serum samples using the Combo test. CONCLUSION: In comparison to Roche Elecsys, our data show that the MP Rapid 2019-NCOV IgM/IgG Combo test provides a high-confidence assay system for the detection of previous exposure to SARS-COV-2 infection with advantage of affording near-patient testing.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing , COVID-19/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Point-of-Care Systems , SARS-CoV-2/metabolism , Humans , Sensitivity and Specificity
6.
Facts Views Vis Obgyn ; 12(3): 155-161, 2020 Oct 08.
Article in English | MEDLINE | ID: mdl-33123690

ABSTRACT

BACKGROUND: Laparoscopic surgery is the cornerstone of modern gynaecological surgery, with shorter hospital stays and a quicker return to normal activities. However postoperative pain remains problematic. No strategy to reduce phrenic nerve irritation, including heating or humidifying the insufflating gas, alternatives to CO2, and intraperitoneal analgesics, has shown superiority. METHODS: 100 women undergoing laparoscopic surgery were randomly allocated, having either 40ml of 0.25% levobupivacaine or 40ml 0.9% sodium chloride solution administered into the peritoneal cavity following surgery. The patients and the main researcher were blinded. All women received standardised anaesthetic and laparoscopic technique, and postoperative pain control including nursing position and nature of analgesia. Postoperative pain was assessed 3 hours, 8 hours, day 1 and day 4/5 postoperatively. RESULTS: 100 patients were recruited undergoing surgery for benign causes aged 19-73(mean 40.3±13). There was no difference between the groups for age(p=0.64) or length of operation(p=0.56). There were no adverse events related to use of intraperitoneal instillation. There was a significant reduction in shoulder-tip pain scores in the levobupivacaine group at 3 hours(p=0.04). Furthermore, there was a significant reduction in wound-pain scores in the levobupivacaine group at 8hrs(p=0.04) and at day 4(p=0.04). No difference was found in pelvic pain between the two groups. No significant difference was found in the use of post-operative analgesia. CONCLUSIONS: Intraperitoneal instillation of 40ml of levobupivacaine has some benefit in reducing postoperative pain and need for analgesia in the initial hours following gynaecological surgery. However, further well-designed randomised control trials are required to decide the optimum route and concentration of administering local anaesthetic.

7.
BMC Psychol ; 8(1): 60, 2020 Jun 12.
Article in English | MEDLINE | ID: mdl-32532354

ABSTRACT

BACKGROUND: Interventions designed to support children with a diagnosis of Autism Spectrum Conditions (ASC) can be time consuming, needing involvement of outside experts. Social Stories™ are a highly personalised intervention aiming to give children with ASC social information or describing an otherwise difficult situation or skill. This can be delivered daily by staff in education settings. Studies examining Social Story™ use have yielded mostly positive results but have largely been single case studies with a lack of randomised controlled trials (RCTs). Despite this numerous schools are utilising Social Stories™, and a fully powered RCT is timely. METHODS: A multi-site pragmatic cluster RCT comparing care as usual with Social Stories™ and care as usual. This study will recruit 278 participants (aged 4-11) with a clinical diagnosis of ASC, currently attending primary school in the North of England. Approximately 278 school based staff will be recruited to provide school based information about participating children with approximately 140 recruited to deliver the intervention. The study will be cluster randomised by school. Potential participants will be screened for eligibility prior to giving informed consent. Follow up data will be collected at 6 weeks and 6 months post randomisation and will assess changes in participants' social responsiveness, goal based outcomes, social and emotional health. The primary outcome measure is the Social Responsiveness Scale Second Edition (SRS-2) completed by school based staff at 6 months. Approvals have been obtained from the University of York's Research Governance Committee, Research Ethics Committee and the Health Research Authority. Study results will be submitted for publication in peer-reviewed journals and disseminated to participating families, educational staff, local authority representatives, community groups and Patient and Participant Involvement representatives. Suggestions will be made to NICE about treatment evidence dependent on findings. DISCUSSION: This study addresses a much used but currently under researched intervention and results will inform school based support for primary school children with a diagnosis of ASC. TRIAL REGISTRATION: The trial is registered on the ISRCTN registry (registration number: ISRCTN11634810). The trial was retrospectively registered on 23rd April 2019.


Subject(s)
Autism Spectrum Disorder/therapy , Narrative Medicine , Psychotherapy/methods , Child , Child, Preschool , Cost-Benefit Analysis , Emotions , England , Female , Humans , Male , Narrative Medicine/economics , Psychotherapy/economics , Schools
8.
Ann Clin Biochem ; 57(4): 316-324, 2020 07.
Article in English | MEDLINE | ID: mdl-32340478

ABSTRACT

BACKGROUND: Calcium circulates bound to albumin and changes in albumin concentration will therefore affect total calcium measurements. In order to mitigate this, correction factors are frequently used. The most widely used correction equation was described by Payne and colleagues in 1973. This equation was derived from well-defined hospitalized patients' data. Current clinical practice is consistent with the general application of the adjusted calcium equation irrespective of clinical setting. This study aims to assess the validity of this approach by the derivation of a community care-specific adjusted calcium equation ('community equation') and the comparison of its performance to a hospitalized patient equation and ionized calcium. METHOD: Retrospective data were collected according to Payne's criteria from an inpatient and community care setting. Data were used to derive the two equations: the in-patient equation and community equation. The outcome of these equations was compared with ionized calcium obtained from 123 healthy participants. RESULTS: The community equation correctly identified the calcium status of 92% of the 123 healthy participants, while the inpatient equation identified 46% only. Regression analysis against ionized calcium showed a higher R2 for the community equation than for the inpatient equation. Furthermore, we have shown that mean albumin and calcium concentrations are significantly different between these two populations. CONCLUSION: In this study, we found that the diagnostic accuracy of the adjusted calcium equation in ambulant patients was improved by the derivation of a population-specific equation for the community care setting.


Subject(s)
Algorithms , Calcium/blood , Data Analysis , Serum Albumin/analysis , Adolescent , Adult , Aged , Female , Healthy Volunteers , Humans , Male , Middle Aged , Prospective Studies , Retrospective Studies , Young Adult
9.
Perioper Med (Lond) ; 8: 8, 2019.
Article in English | MEDLINE | ID: mdl-31406569

ABSTRACT

BACKGROUND: Hip fracture is a procedure with high mortality and complication rates, and there exists a group especially at risk of these outcomes identified by their Nottingham Hip Fracture Score (NHFS). Meta-analysis suggests a possible benefit to this patient group from intravascular volume optimisation. We investigated whether intraoperative fluid and blood pressure optimisation improved complications in this group. METHODS: Patients with a NHFS ≥ 5 were enrolled into this multicentre observer-blinded randomised control trial. Patients were allocated to either standard care or a combination of fluid optimisation and blood pressure control using a non-invasive system. The primary outcome was the number of patients with one or more complications in each group. Secondary outcomes included hospital length of stay (LOS), incidence of hypotension and fluid and vasopressor usage. RESULTS: Forty-six percent of patients in the intervention group suffered one or more complications compared to the 51% in the control group (OR 0.82 (95% CI 0.49-1.36)). Per-protocol analysis improved the OR to 0.73 (95% CI 0.43-1.24). Median LOS was the same between both groups; however, the mean LOS on a per-protocol analysis was longer in the control group compared to the intervention group (23.2 (18.0) days vs. 18.5 (16.5), p = 0.047). CONCLUSIONS: Haemodynamic optimisation including blood pressure management in high-risk patients undergoing repair of a hip fracture did not result in a statistically significant reduction in complications; however, a potential reduction in length of stay was seen. TRIAL REGISTRATION: A randomised trial of non-invasive cardiac output monitoring to guide haemodynamic optimisation in high risk patients undergoing urgent surgical repair of proximal femoral fractures (ClearNOF trial NCT02382185).

10.
Strategies Trauma Limb Reconstr ; 13(3): 171-177, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30443789

ABSTRACT

The aim of the study was to develop a simple and reliable clinical scoring system for delayed presenting clubfeet and assess how this score predicts the response to Ponseti casting. We measured all elements of the Diméglio and the Pirani scoring systems. To determine which aspects were useful in assessing children with delayed presenting clubfeet, 4 assessors examined 42 feet (28 patients) between the ages of 2-10 years. Selected variables demonstrating good agreement were combined to make a novel score and were assessed prospectively on a separate consecutive cohort of children with clubfeet aged 2-10, comprising 100 clubfeet (64 patients). Inter-observer and intra-observer agreement was found to be greatest using the following clinically measured angles of the deformities. These were plantaris, adductus, varus, equinus of the ankle and rotation around the talar head in the frontal plane (PAVER). Measured angles of 1-20, 21-45 and > 45 degrees scored 1, 2 and 3 points, respectively. The PAVER score was derived from both the sum of points derived from measured angles and a multiplier according to age. The sum of the points was multiplied with 1, 1.5 or 2 for ages 2-4, 5-7 and 8-10, respectively. This demonstrated a good association with the total number of casts to achieve a full correction (tau = 0.71). A score greater than 18 out of 30 indicated a cast-resistant clubfoot. The score could be used clinically for prognosis and treatment, and for research purposes to compare the severity of clubfoot deformities.

11.
J Laryngol Otol ; 131(8): 736-739, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28589872

ABSTRACT

BACKGROUND: A public health campaign on laryngeal cancer was conducted in 2011 in the Humber and Yorkshire Coast Cancer Network. This study evaluated its subsequent impact (if any) upon the stage of laryngeal cancer at presentation. METHODS: Cases of laryngeal cancer diagnosed in the Humber and Yorkshire Coast Cancer Network from January 2009 to July 2014 were identified from cancer registries and were dichotomised into early (tumour stage T1-2) and late (T3-4) disease. Statistical analysis using segmented regression analysis of interrupted time series data was performed. RESULTS: There were no statistically significant changes in laryngeal cancer cases immediately after the intervention for both early (p = 0.191) and late (p = 0.680) stage disease. There were also no significant changes to monthly detection rates in both groups on follow up. CONCLUSION: Findings of the first public health campaign on laryngeal cancer in the UK are described. Such processes are complex; the implications for future study are discussed.


Subject(s)
Early Detection of Cancer/statistics & numerical data , Health Promotion/statistics & numerical data , Laryngeal Neoplasms/diagnosis , Mass Screening/statistics & numerical data , Program Evaluation/statistics & numerical data , Aged , Early Detection of Cancer/methods , Female , Health Promotion/methods , Humans , Laryngeal Neoplasms/pathology , Male , Mass Screening/methods , Middle Aged , Neoplasm Staging , Registries , Regression Analysis , Retrospective Studies , Time Factors , United Kingdom , Voice
13.
Eur J Orthop Surg Traumatol ; 26(5): 483-92, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27193753

ABSTRACT

Antibiotic prophylaxis with cefuroxime can reduce the incidence of deep wound infection (DWI) in hip-fracture surgery, but may increase the risk of C. difficile infection (CDI). An alternative is gentamicin with beta-lactam for which a question exists around clinical effectiveness and safety, given the gentamicin-associated nephrotoxicity particularly in the elderly and narrower sensitivity spectrum. We compared 744 consecutive patients (group I-cefuroxime) with 756 in group II (gentamicin + flucloxacillin) who were well matched. There were 4 cases of CDI in the cefuroxime prophylaxis, whereas none in flucloxacillin plus gentamicin (group II). There was a statistically significant (p = 0.036) increased DWI rate in group II (2.5 %) as compared to group I (1.1 %). However, after controlling for age, gender, ASA grade, surgeon grade, implant type and type of anaesthesia, there was no statistically significant difference between the two groups (p = 0.146). 8.5 % of group I and 16.5 % of group II developed AKI post-operatively (p = 0.023); however, 79 % of group I and 80 % of in group II had complete resolution of AKI prior to their discharge. Further, a significant increase in inpatient deaths (p = 0.057) in group II was observed, but not at 30 days (p = 0.378).


Subject(s)
Cefuroxime , Floxacillin , Gentamicins , Hip Fractures/surgery , Orthopedic Procedures/adverse effects , Surgical Wound Infection , Aged, 80 and over , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Antibiotic Prophylaxis/adverse effects , Antibiotic Prophylaxis/methods , Cefuroxime/administration & dosage , Cefuroxime/adverse effects , Drug Therapy, Combination/methods , Drug-Related Side Effects and Adverse Reactions/diagnosis , Drug-Related Side Effects and Adverse Reactions/etiology , Drug-Related Side Effects and Adverse Reactions/prevention & control , Female , Floxacillin/administration & dosage , Floxacillin/adverse effects , Gentamicins/administration & dosage , Gentamicins/adverse effects , Gentamicins/therapeutic use , Humans , Male , Orthopedic Procedures/methods , Retrospective Studies , Surgical Wound Infection/etiology , Surgical Wound Infection/prevention & control , United Kingdom
14.
Injury ; 46(6): 1108-11, 2015.
Article in English | MEDLINE | ID: mdl-25910819

ABSTRACT

INTRODUCTION: Venous thromboembolism (VTE) is a significant cause of morbidity and mortality following tibial fractures. The risk is as high as 77% without prophylaxis and around 10% with prophylaxis. Within the current literature there are no figures reported specifically for those individuals treated with circular frames. Our aim was to evaluate the VTE incidence within a single surgeon series and to evaluate potential risk factors. METHODS: We retrospectively reviewed our consecutive single surgeon series of 177 patients admitted to a major trauma unit with tibial fractures. All patients received standardised care, including chemical thromboprophylaxis within 24h of injury until independent mobility was achieved. We comprehensively reviewed our prospective database and medical records looking at demographics and potential risk factors. RESULTS: Seven patients (4.0% ± 2.87%) developed symptomatic VTE during the course of frame treatment; three deep vein thrombosis (DVTs) and four pulmonary embolisms (PEs). Those with a VTE event had significantly increased body mass index (BMI) (p = 0.01) when compared to those without symptomatic VTE. No differences (p > 0.05) were observed between the groups in age, gender, smoking status, fracture type (anatomical allocation or open/closed), delay to frame treatment, weight bearing status post-frame, inpatient stay or total duration of frame treatment. CONCLUSION: This study suggests that increased BMI is a statistically significant risk factor for VTE, as reported in current literature. In addition, we calculated the true risk of VTE following circular frame treatment for tibial fracture in our series is from 1.13% to 6.87%, which is at least comparable to other forms of treatment.


Subject(s)
Fracture Fixation/adverse effects , Obesity/complications , Tibial Fractures/complications , Venous Thromboembolism/etiology , Body Mass Index , Chemoprevention/methods , Humans , Incidence , Retrospective Studies , Risk Factors , Tibial Fractures/surgery , Treatment Outcome , United Kingdom/epidemiology , Venous Thromboembolism/prevention & control
16.
Eye (Lond) ; 28(10): 1218-22, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25081290

ABSTRACT

PURPOSE: To determine the effect of oral acetazolamide on lowering the peak and duration of intraocular pressure (IOP) rise in glaucoma and glaucoma suspect patients, following intravitreal injection of ranibizumab for neovascular age-related macular degeneration. METHODS: The study was an open-label, parallel, randomised, controlled trial (EudraCT Number: 2010-023037-35). Twenty-four glaucoma or glaucoma suspect patients received either 500 mg acetazolamide or no treatment 60-90 min before 0.5 mg ranibizumab. The primary outcome measure was the difference in IOP immediately after injection (T0) and 5, 10, and 30 min following injection. ANCOVA was used to compare groups, adjusting for baseline IOP. The study was powered to detect a 9-mm Hg difference at T0. RESULTS: The IOP at T0 was 2.3 mm Hg higher in the non-treated group (mean 44.5 mm Hg, range (19-86 mm Hg)) compared with the treated group (mean 42.2 mm Hg, range (25-58 mm Hg)), but was not statistically significant after adjusting for baseline IOP (P=0.440). At 30 min, IOP was 4.9 mm Hg higher in the non-treated group (mean 20.6 mm Hg, range (11-46 mm Hg)) compared with the treated group (mean 15.7 mm Hg, range (8-21 mm Hg)). This was statistically significant after adjusting for baseline IOP (P=0.013). CONCLUSIONS: Although the primary end points were not reached, 500 mg oral acetazolamide, 60-90 min before intravitreal injection, results in a statistically significant reduction in IOP at 3O min post injection. Prophylactic treatment may be considered as an option to minimise neuro-retinal rim damage in high-risk glaucoma patients who are most vulnerable to IOP spikes and undergoing repeated intravitreal injections of ranibizumab.


Subject(s)
Acetazolamide/administration & dosage , Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Carbonic Anhydrase Inhibitors/administration & dosage , Glaucoma/prevention & control , Intraocular Pressure/drug effects , Wet Macular Degeneration/drug therapy , Administration, Oral , Aged , Aged, 80 and over , Female , Humans , Intravitreal Injections , Male , Ocular Hypertension/prevention & control , Ophthalmic Solutions , Ranibizumab , Tonometry, Ocular , Vascular Endothelial Growth Factor A/antagonists & inhibitors
17.
Thromb Res ; 134(2): 479-87, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24929839

ABSTRACT

In this study, 52 patients were studied to elucidate the relative impact of resection of localized pancreaticobiliary adenocarcinoma (PBC) on circulating factors of tumour-associated angiogenesis e.g. tissue factor bearing microparticles (TFMP) and vascular endothelial growth factor (VEGF) and their clinicopathological significance to angiogenesis markers in cancer tissue from PBC patients. Angiogenesis array analysis on serum samples revealed that surgical resection of tumour lesion in PBC patients affects the levels of a panel of angiogenesis-related molecules, including VEGF that was verified by ELISA to significantly reduce (median & IQR: 1003(369-2000) vs. 457(159-834) pg/ml; p<0.05). Correspondingly, a significant decrease in the angiogenic activity (decreased capillary tube formation; p<0.05) of serum samples after the surgery was also found. Despite a decrease in number of circulating TFMP after surgery, this did not reach statistical significance; there was a significant reduction in pro-coagulant activity (prolonged prothrombin time, p<0.001) post-operatively. In addition, the activity of total microparticles (MP activity assay, p<0.05) was decreased significantly. Immunohistochemical staining of tumour tissue revealed a strong correlation between the microvessel density (MVD) and VEGF expression. Also, higher levels of circulating TFMP or TF related activity (prothrombin time) correlated significantly with TF expression and MVD on tumour tissues from PBC patients. These findings suggest that in pancreaticobiliary adenocarcinoma TF related angiogenesis drivers are equally significant to VEGF ones, raising the clinical question of whether the effectiveness of angiogenesis targeting studies could be improved through the 'dual' targeting of these pathways in PBC.


Subject(s)
Adenocarcinoma/blood , Neovascularization, Pathologic/blood , Pancreas/pathology , Pancreatic Neoplasms/blood , Thromboplastin/analysis , Thrombosis/blood , Adenocarcinoma/complications , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Aged , Cell-Derived Microparticles/pathology , Female , Humans , Male , Middle Aged , Neovascularization, Pathologic/complications , Pancreas/blood supply , Pancreas/surgery , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery , Thrombosis/complications , Vascular Endothelial Growth Factor A/analysis , Vascular Endothelial Growth Factor A/blood
18.
Int J Clin Pract ; 68(8): 1041-7, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24797624

ABSTRACT

AIM: To systematically review evidence and perform a meta-analysis of the efficacy of intra-articular (IA) injections of Hylan G-F 20 for the treatment of painful osteoarthritis (OA) of the knee. METHODS: Systematic review of the Embase and PubMed databases up to July 2013 of randomised placebo-controlled trials studying the effect of Hylan G-F 20 in patients with painful knee OA, with a meta-analysis of trials reporting visual analogue scores (VAS) for weight-bearing pain in the knees of patients followed up for a minimum of 6 months. RESULTS: Six placebo-controlled randomised trials were identified on systematic review of which two studies met criteria for inclusion in the meta-analysis. Meta-analysis demonstrated that at 6-month follow up, there was no significant difference between Hylan G-F 20 and control in terms of reduction in VAS for weight bearing pain. (Mean Difference - 12.96 (95% CI: -35.48, 9.56). Z tests used to test for overall effect showed that the difference between the two groups was not significant (p = 0.26). DISCUSSION: A significant placebo effect exists for patients receiving IA injections for the treatment of painful knee OA. The withdrawal of fluid from the affected knee prior to any injectable therapy may itself have additional benefits which in isolation have not been studied. This may form the basis of future research. The authors' acknowledge that although limited conclusions can be drawn from the results of this study, the meta-analysis presented has not been performed previously and will further contribute to the knowledge on this subject. CONCLUSION: Although Hylan G-F 20 may produce improvement in VAS scores for weight-bearing pain at 6-month follow up in OA knees treated with it, patients should be informed that this may be equivalent to that seen with control treatments.


Subject(s)
Hyaluronic Acid/analogs & derivatives , Injections, Intra-Articular/statistics & numerical data , Osteoarthritis, Knee/drug therapy , Pain/drug therapy , Placebo Effect , Humans , Hyaluronic Acid/administration & dosage , Hyaluronic Acid/therapeutic use , Osteoarthritis, Knee/complications
20.
Postgrad Med J ; 88(1039): 249-54, 2012 May.
Article in English | MEDLINE | ID: mdl-22331918

ABSTRACT

BACKGROUND: There is a lack of evidence on whether graduates from different medical schools perform differently in postgraduate examinations. OBJECTIVE: To evaluate the variations in performance of UK medical graduates in Member of the Royal College of Obstetricians and Gynaecologists (MRCOG) examination. METHODS: A retrospective analysis of performance of 1335 doctors graduating in UK medical schools who entered the Part 1 MRCOG and 822 doctors taking the Part 2 MRCOG written examination for the first time between 1998 and 2008. The main outcome measures were to evaluate medical school effects, gender effects and academic performance effect. RESULTS: Graduates of UK medical schools performed differently in the Part 1 and Part 2 written MRCOG examination. The graduates of Oxford (pass rate 82.6%), Cambridge (75%), Bristol (59.3%) and Edinburgh (57.5%) performed significantly better and the graduates of Liverpool (26.8%), Southampton (21.8%) and Wales (18.2%) performed significantly worse than the remaining cohort in the Part 1 examination. The candidates of Newcastle (88.9%), Oxford (82.4%), Cambridge (81%) and Edinburgh (78.2%) performed significantly better and the graduates of Glasgow (49.2%) and Leicester (36.2%) have significantly underperformed compared with the remaining cohort in Part 2 written examination. There was no difference in the success rates of male (47.5%) and female (42.0%) candidates in the Part 1; however, female candidates had a significantly better success rate in the Part 2 written examination than male candidates (65.6% vs 52.9%). CONCLUSION: These results show that there is variation in performance among the graduates from different medical schools in the Part 1 and Part 2 MRCOG written examination.


Subject(s)
Education, Medical, Graduate/standards , Educational Measurement , Gynecology/education , Obstetrics/education , Schools, Medical , Aptitude Tests/statistics & numerical data , Educational Measurement/methods , Educational Measurement/statistics & numerical data , Educational Status , Female , Humans , Male , Retrospective Studies , Schools, Medical/standards , Schools, Medical/statistics & numerical data , Sex Factors , Teaching/standards , United Kingdom , Universities/standards , Universities/statistics & numerical data
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