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1.
Lancet ; 403(10443): 2489-2503, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38782004

ABSTRACT

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. Obesity exacerbates the reproductive complications of PCOS; however, the management of obesity in women with PCOS remains a large unmet clinical need. Observational studies have indicated that bariatric surgery could improve the rates of ovulatory cycles and prospects of fertility; however, the efficacy of surgery on ovulation rates has not yet been compared with behavioural modifications and medical therapy in a randomised trial. The aim of this study was to compare the safety and efficacy of bariatric surgery versus medical care on ovulation rates in women with PCOS, obesity, and oligomenorrhoea or amenorrhoea. METHODS: In this multicentre, open-label, randomised controlled trial, 80 women older than 18 years, with a diagnosis of PCOS based on the 2018 international evidence-based guidelines for assessing and managing PCOS, and a BMI of 35 kg/m2 or higher, were recruited from two specialist obesity management centres and via social media. Participants were randomly assigned at a 1:1 ratio to either vertical sleeve gastrectomy or behavioural interventions and medical therapy using a computer-generated random sequence (PLAN procedure in SAS) by an independent researcher not involved with any other aspect of the clinical trial. The median age of the entire cohort was 31 years and 79% of participants were White. The primary outcome was the number of biochemically confirmed ovulatory events over 52 weeks, and was assessed using weekly serum progesterone measurements. The primary endpoint included the intention-to-treat population and safety analyses were per-protocol population. This study is registered with the ISRCTN registry (ISRCTN16668711). FINDINGS: Participants were recruited from Feb 20, 2020 to Feb 1, 2021. 40 participants were assigned to each group and there were seven dropouts in the medical group and ten dropouts in the surgical group. The median number of ovulations was 6 (IQR 3·5-10·0) in the surgical group and 2 (0·0-4·0) in the medical group. Women in the surgical group had 2.5 times more spontaneous ovulations compared with the medical group (incidence rate ratio 2·5 [95% CI 1·5-4·2], p<0·0007). There were more complications in the surgical group than the medical group, although without long-term sequelae. There were 24 (66·7%) adverse events in the surgical group and 12 (30·0%) in the medical group. There were no treatment-related deaths. INTERPRETATION: Bariatric surgery was more effective than medical care for the induction of spontaneous ovulation in women with PCOS, obesity, and oligomenorrhoea or amenorrhoea. Bariatric surgery could, therefore, enhance the prospects of spontaneous fertility in this group of women. FUNDING: The Jon Moulton Charity Trust.


Subject(s)
Bariatric Surgery , Obesity , Ovulation , Polycystic Ovary Syndrome , Humans , Polycystic Ovary Syndrome/complications , Polycystic Ovary Syndrome/surgery , Female , Adult , Bariatric Surgery/adverse effects , Bariatric Surgery/methods , Obesity/complications , Obesity/surgery , Oligomenorrhea , Treatment Outcome , Amenorrhea/etiology , Young Adult , Gastrectomy/methods , Gastrectomy/adverse effects , Infertility, Female/etiology
2.
Int J Mol Sci ; 25(4)2024 Feb 17.
Article in English | MEDLINE | ID: mdl-38397043

ABSTRACT

Inflammasomes are multimeric protein complexes, sensors of intracellular danger signals, and crucial components of the innate immune system, with the NLRP3 inflammasome being the best characterized among them. The increasing scientific interest in the mechanisms interconnecting inflammation and tumorigenesis has led to the study of the NLRP3 inflammasome in the setting of various neoplasms. Despite a plethora of data regarding solid tumors, NLRP3 inflammasome's implication in the pathogenesis of hematological malignancies only recently gained attention. In this review, we investigate its role in normal lymphopoiesis and lymphomagenesis. Considering that lymphomas comprise a heterogeneous group of hematologic neoplasms, both tumor-promoting and tumor-suppressing properties were attributed to the NLRP3 inflammasome, affecting neoplastic cells and immune cells in the tumor microenvironment. NLRP3 inflammasome-related proteins were associated with disease characteristics, response to treatment, and prognosis. Few studies assess the efficacy of NLRP3 inflammasome therapeutic targeting with encouraging results, though most are still at the preclinical level. Further understanding of the mechanisms regulating NLRP3 inflammasome activation during lymphoma development and progression can contribute to the investigation of novel treatment approaches to cover unmet needs in lymphoma therapeutics.


Subject(s)
Inflammasomes , Lymphoma , Humans , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Inflammation/metabolism , Lymphoma/etiology , Lymphoma/therapy , Tumor Microenvironment
3.
Surg Endosc ; 34(5): 2076-2081, 2020 05.
Article in English | MEDLINE | ID: mdl-31392513

ABSTRACT

BACKGROUND: An excessively long-blind end of the alimentary limb following a Roux-en-Y gastric bypass (RYGB), known as a 'candy cane' (CC), may cause symptoms including abdominal pain, regurgitation and vomiting. Very few studies have examined the efficacy of surgical resection of the CC. OBJECTIVES: The aim of this study was to assess sensitivity of preoperative diagnostic tools for CC, as well as perioperative outcomes and symptom resolution after CC revision surgery. SETTING: High volume bariatric centre of excellence, United Kingdom. METHODS: Observational study of CC revisions from 2010 to 2017. RESULTS: Twenty-eight CC revision cases were identified (mean age 45 ± 9 years, female preponderance 9:1). Presenting symptoms were abdominal pain (86%), regurgitation/vomiting (43%), suboptimal weight loss (36%) and acid reflux (21%). Preoperative tests provided correct diagnosis in 63% of barium contrast swallows, 50% of upper gastrointestinal endoscopies and 29% computed tomographies. Patients presenting with pain had significantly higher CC size as compared with pain-free group (4.2 vs. 2 cm, p = 0.001). Perioperative complications occurred in 25% of cases. Complete or partial symptom resolution was documented in 73% of patients undergoing CC revision. Highest success rates were recorded in the regurgitation/vomiting group (67%). CONCLUSION: Surgical revision of CC is associated with good symptom resolution in the majority of patients, especially those presenting with regurgitation/vomiting. However, it carries certain risk of complications. CC diagnosis may frequently be missed; hence more than one diagnostic tool should be considered when investigating symptomatic patients after RYGB.


Subject(s)
Gastric Bypass/methods , Obesity, Morbid/surgery , Female , Humans , Male , Middle Aged
4.
J Neural Transm (Vienna) ; 125(9): 1341-1349, 2018 09.
Article in English | MEDLINE | ID: mdl-29352351

ABSTRACT

We investigated whether there is a linear relationship between levodopa (LD) dose and treatment duration, and the development of levodopa-induced dyskinesia (LID) among patients with early untreated Parkinson's disease (PD). We performed a meta-analysis of randomized-controlled trials (RCTs) comparing LD monotherapy to any other antiparkinsonian treatment in early PD patients. Meta-regressions were conducted including as covariates the effects of LD dose, treatment duration, and age. We further proceeded in subgroup analyses based on the type of medications in the non-LD monotherapy (control) group and on whether patients in the control group received additional levodopa or not. Thirteen eligible RCTs were included, which revealed a significantly higher risk for dyskinesia in patients initially treated with LD monotherapy compared to any other treatment (OR = 2.82). None of the subsequent meta-regressions revealed any significant relationship with dose, treatment duration or age. Patients treated on LD monotherapy or MAOΙ plus LD were at a greater risk to develop LID than patients who received DA only or DA plus supplemental LD. The increased heterogeneity compromised the robustness of the results. The alleged correlation between LID and LD dose and treatment duration cannot be verified based on the data available so far. Well-designed, large-scale, long-term, RCTs on drug-naïve PD patients could allow the better comprehension of the pattern of the association between LID and LD treatment parameters.


Subject(s)
Antiparkinson Agents/adverse effects , Dyskinesia, Drug-Induced/etiology , Levodopa/adverse effects , Parkinson Disease/drug therapy , Antiparkinson Agents/administration & dosage , Antiparkinson Agents/therapeutic use , Causality , Dose-Response Relationship, Drug , Humans , Levodopa/administration & dosage , Levodopa/therapeutic use , Parkinson Disease/physiopathology , Randomized Controlled Trials as Topic , Regression Analysis
5.
Cancer Causes Control ; 27(7): 919-27, 2016 07.
Article in English | MEDLINE | ID: mdl-27294726

ABSTRACT

BACKGROUND: The etiology of small intestinal cancer (SIC) is largely unknown, and there are very few epidemiological studies published to date. No studies have investigated abdominal adiposity in relation to SIC. METHODS: We investigated overall obesity and abdominal adiposity in relation to SIC in the European Prospective Investigation into Cancer and Nutrition (EPIC), a large prospective cohort of approximately half a million men and women from ten European countries. Overall obesity and abdominal obesity were assessed by body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR). Multivariate Cox proportional hazards regression modeling was performed to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs). Stratified analyses were conducted by sex, BMI, and smoking status. RESULTS: During an average of 13.9 years of follow-up, 131 incident cases of SIC (including 41 adenocarcinomas, 44 malignant carcinoid tumors, 15 sarcomas and 10 lymphomas, and 21 unknown histology) were identified. WC was positively associated with SIC in a crude model that also included BMI (HR per 5-cm increase = 1.20, 95 % CI 1.04, 1.39), but this association attenuated in the multivariable model (HR 1.18, 95 % CI 0.98, 1.42). However, the association between WC and SIC was strengthened when the analysis was restricted to adenocarcinoma of the small intestine (multivariable HR adjusted for BMI = 1.56, 95 % CI 1.11, 2.17). There were no other significant associations. CONCLUSION: WC, rather than BMI, may be positively associated with adenocarcinomas but not carcinoid tumors of the small intestine. IMPACT: Abdominal obesity is a potential risk factor for adenocarcinoma in the small intestine.


Subject(s)
Adenocarcinoma/epidemiology , Adiposity , Intestinal Neoplasms/epidemiology , Obesity/complications , Adult , Aged , Body Height , Body Mass Index , Europe/epidemiology , Female , Humans , Male , Middle Aged , Obesity/epidemiology , Proportional Hazards Models , Prospective Studies , Risk Factors , Waist Circumference , Waist-Hip Ratio , White People
6.
Br J Cancer ; 113(5): 840-7, 2015 Sep 01.
Article in English | MEDLINE | ID: mdl-26313664

ABSTRACT

BACKGROUND: Results from several cohort and case-control studies suggest a protective association between current alcohol intake and risk of thyroid carcinoma, but the epidemiological evidence is not completely consistent and several questions remain unanswered. METHODS: The association between alcohol consumption at recruitment and over the lifetime and risk of differentiated thyroid carcinoma was examined in the European Prospective Investigation into Cancer and Nutrition. Among 477 263 eligible participants (70% women), 556 (90% women) were diagnosed with differentiated thyroid carcinoma over a mean follow-up of 11 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards models. RESULTS: Compared with participants consuming 0.1-4.9 g of alcohol per day at recruitment, participants consuming 15 or more grams (approximately 1-1.5 drinks) had a 23% lower risk of differentiated thyroid carcinoma (HR=0.77; 95% CI=0.60-0.98). These findings did not differ greatly when analyses were conducted for lifetime alcohol consumption, although the risk estimates were attenuated and not statistically significant anymore. Similar results were observed by type of alcoholic beverage, by differentiated thyroid carcinoma histology or according to age, sex, smoking status, body mass index and diabetes. CONCLUSIONS: Our study provides some support to the hypothesis that moderate alcohol consumption may be associated with a lower risk of papillary and follicular thyroid carcinomas.


Subject(s)
Alcohol Drinking/adverse effects , Thyroid Neoplasms/etiology , Adult , Female , Humans , Male , Middle Aged , Proportional Hazards Models , Risk Factors , Sex Distribution , Thyroid Neoplasms/epidemiology
7.
BMC Med ; 13: 107, 2015 May 07.
Article in English | MEDLINE | ID: mdl-25948112

ABSTRACT

BACKGROUND: Cancer survivors are advised to follow lifestyle recommendations on diet, physical activity, and body fatness proposed by the World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) for cancer prevention. Previous studies have demonstrated that higher concordance with these recommendations measured using an index score (the WCRF/AICR score) was associated with lower cancer incidence and mortality. The aim of this study was to evaluate the association between pre-diagnostic concordance with WCRF/AICR recommendations and mortality in colorectal cancer (CRC) patients. METHODS: The association between the WCRF/AICR score (score range 0-6 in men and 0-7 in women; higher scores indicate greater concordance) assessed on average 6.4 years before diagnosis and CRC-specific (n = 872) and overall mortality (n = 1,113) was prospectively examined among 3,292 participants diagnosed with CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (mean follow-up time after diagnosis 4.2 years). Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. RESULTS: The HRs (95% CIs) for CRC-specific mortality among participants in the second (score range in men/women: 2.25-2.75/3.25-3.75), third (3-3.75/4-4.75), and fourth (4-6/5-7) categories of the score were 0.87 (0.72-1.06), 0.74 (0.61-0.90), and 0.70 (0.56-0.89), respectively (P for trend <0.0001), compared to participants with the lowest concordance with the recommendations (category 1 of the score: 0-2/0-3). Similar HRs for overall mortality were observed (P for trend 0.004). Meeting the recommendations on body fatness and plant food consumption were associated with improved survival among CRC cases in mutually adjusted models. CONCLUSIONS: Greater concordance with the WCRF/AICR recommendations on diet, physical activity, and body fatness prior to CRC diagnosis is associated with improved survival among CRC patients.


Subject(s)
Colorectal Neoplasms/mortality , Life Style , Patient Compliance/statistics & numerical data , Adult , Aged , Aged, 80 and over , Cohort Studies , Diet , Female , Humans , Incidence , Male , Middle Aged , Proportional Hazards Models , Prospective Studies , White People
8.
Obes Surg ; 34(5): 1748-1755, 2024 May.
Article in English | MEDLINE | ID: mdl-38575742

ABSTRACT

PURPOSE: Chronic abdominal pain after RYGB is a known issue. Identifying the potential patient-related and modifiable risk factors might contribute to diminish the risk for this undesirable outcome. METHODS: A single-center retrospective cohort study with prospective data collection was conducted with inclusion of all patients who underwent RYGB surgery between 2015 and 2021. Data from the NBSR and medical records were used. Patients with chronic abdominal pain were defined when pain lasting or recurring for more than 3 to 6 months. RESULTS: Six hundred sixty-four patients who underwent RYGB surgery were included with a median follow-up of 60.5 months. Forty-nine patients (7.3%) presented with chronic abdominal pain. Postoperative complications (OR 13.376, p = 0.020) and diagnosis of depression (OR 1.971, p = 0.037) were associated with developing abdominal pain. On the other hand, ex-smokers (OR 0.222, p = 0.040) and older age (0.959, p = 0.004) presented as protective factors. CONCLUSION: Postoperative complications and diagnosis of depression are risk factors for chronic pain after RYGB. The role of the bariatric MDT remains crucial to select these patients adequately beforehand.


Subject(s)
Gastric Bypass , Obesity, Morbid , Humans , Obesity, Morbid/surgery , Gastric Bypass/adverse effects , Retrospective Studies , Abdominal Pain/epidemiology , Abdominal Pain/etiology , Risk Factors , Postoperative Complications/epidemiology , Postoperative Complications/etiology
9.
BMJ Open Diabetes Res Care ; 12(1)2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38233077

ABSTRACT

INTRODUCTION: Bariatric surgery is associated with adverse pregnancy outcomes such as reduced birth weight and premature birth. One possible mechanism for this is increased glycemic variability (GV) which occurs after bariatric surgery. The objective of this study was to compare the effect of Roux-en-Y gastric bypass (RYGB) versus vertical sleeve gastrectomy (SG) on GV during pregnancy and to investigate the relationships of GV, type of bariatric surgery and maternal and neonatal outcomes. RESEARCH DESIGN AND METHODS: Fourteen pregnant women after RYGB and 14 after SG were investigated with continuous glucose monitoring in their second or third trimester in this observational study carried out as part of routine clinical care. RESULTS: Pregnant women with RYGB had similar mean interstitial glucose values but significantly increased indices of GV and a lower %time in range 3.9-7.8 mmol/L (70-140 mg/dL), compared with SG. CONCLUSIONS: Pregnant women who have undergone RYGB have greater GV during pregnancy compared with those who have undergone SG. Further research is needed to establish the relationship between GV and pregnancy outcomes to determine the preferred bariatric operation in women of reproductive age, and whether interventions to reduce GV might improve outcomes.


Subject(s)
Gastric Bypass , Infant, Newborn , Humans , Female , Pregnancy , Gastric Bypass/adverse effects , Pregnant Women , Blood Glucose Self-Monitoring , Blood Glucose , Pregnancy Outcome/epidemiology , Gastrectomy/adverse effects
10.
Autoimmun Rev ; 22(6): 103327, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36990134

ABSTRACT

The incidence and prevalence of Inflammatory Bowel Disease (IBD) has increased over the past decades, imposing a growing socioeconomic burden on healthcare systems globally. Most of the morbidity and mortality related to IBD is typically attributed to gut inflammation and its complications; yet the disease is characterized by various extraintestinal manifestations that can be severe. Glomerulonephritis (GN) is of particular interest since a significant proportion of patients evolve into end-stage kidney disease, requiring kidney replacement therapy and associated with high morbidity and mortality. Herein, we review the GN landscape in IBD and define the clinical and pathogenic associations reported to date in the literature. Underlying pathogenic mechanisms suggest either the initiation of antigen-specific immune responses in the inflamed gut that cross react with non-intestinal sites, such as the glomerulus, or that extraintestinal manifestations are gut-independent events that occur due to an interaction between common genetic and environmental risk factors. We present data associating GN with IBD either as a bona fide extraintestinal manifestation or reporting it as an extraneous co-existing entity, involving various histological subtypes, such as focal segmental glomerulosclerosis, proliferative GN, minimal change disease, crescentic GN, but most emphatically IgA nephropathy. Supporting the pathogenic interplay between gut inflammation and intrinsic glomerular processes, enteric targeting the intestinal mucosa with budesonide reduced IgA nephropathy-mediated proteinuria. Elucidating the mechanisms at play would provide insight not only into IBD pathogenesis but also into the gut's role in the development of extraintestinal diseases, such as glomerular diseases.


Subject(s)
Glomerulonephritis, IGA , Glomerulonephritis , Inflammatory Bowel Diseases , Humans , Glomerulonephritis/complications , Kidney Glomerulus , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/pathology , Inflammation/pathology
11.
Surg Obes Relat Dis ; 18(6): 704-713, 2022 06.
Article in English | MEDLINE | ID: mdl-35400625

ABSTRACT

BACKGROUND: Surgeon specific outcome reports (SSOR) in the UK can be accessed freely by the general public to promote transparency and informed decision-making. However, the views amongst bariatric patients concerning these data are unknown. OBJECTIVES: The aims of this study were to determine patient awareness, views and priorities for outcome reporting in bariatric surgery, and to provide recommendations for future surgeon-specific outcome reporting through the United Kingdom National Bariatric Surgery Registry. SETTING: Bariatric surgical unit in a UK university teaching hospital. METHODS: We adapted a previously validated questionnaire and surveyed the views of 150 patients in a single bariatric surgical unit. We collected data concerning awareness, views, and future priorities for outcome reporting. RESULTS: A full 73% of participants were unaware they could access SSOR. Of the participants that were unaware, 75% stated that they would have accessed SSOR had they been aware they could. Of the participants that had previously accessed SSOR, 86% stated they understood the data, although 61% indicated it did not influence their choice of surgeon. The majority of participants favored public release of outcome reports at the surgeon-level (75%) and hospital-level (83%). The 3 main priorities indicated by participants for future outcome reporting were complication rates (91%), patient reported outcome measures (90%), and reoperation rate (89%), all at the surgeon level. CONCLUSION: Patient awareness of outcome reporting is poor. Efforts must be made to increase awareness of SSOR. Patients should be incorporated as key stakeholders in determining future outcome reporting in bariatric surgery.


Subject(s)
Bariatric Surgery , Surgeons , Humans , Patient Reported Outcome Measures , Surveys and Questionnaires , United Kingdom/epidemiology
12.
BMC Infect Dis ; 11: 309, 2011 Nov 04.
Article in English | MEDLINE | ID: mdl-22050935

ABSTRACT

BACKGROUND: Current knowledge on the exact ligand causing expression of TREM-1 on neutrophils and monocytes is limited. The present study aimed at the role of underlying infection and of the causative pathogen in the expression of TREM-1 in sepsis. METHODS: Peripheral venous blood was sampled from 125 patients with sepsis and 88 with severe sepsis/septic shock. The causative pathogen was isolated in 91 patients. Patients were suffering from acute pyelonephritis, community-acquired pneumonia (CAP), intra-abdominal infections (IAIs), primary bacteremia and ventilator-associated pneumonia or hospital-acquired pneumonia (VAP/HAP). Blood monocytes and neutrophils were isolated. Flow cytometry was used to estimate the TREM-1 expression from septic patients. RESULTS: Within patients bearing intrabdominal infections, expression of TREM-1 was significantly lower on neutrophils and on monocytes at severe sepsis/shock than at sepsis. That was also the case for severe sepsis/shock developed in the field of VAP/HAP. Among patients who suffered infections by Gram-negative community-acquired pathogens or among patients who suffered polymicrobial infections, expression of TREM-1 on monocytes was significantly lower at the stage of severe sepsis/shock than at the stage of sepsis. CONCLUSIONS: Decrease of the expression of TREM-1 on the membrane of monocytes and neutrophils upon transition from sepsis to severe sepsis/septic shock depends on the underlying type of infection and the causative pathogen.


Subject(s)
Membrane Glycoproteins/analysis , Monocytes/chemistry , Monocytes/immunology , Neutrophils/chemistry , Neutrophils/immunology , Receptors, Immunologic/analysis , Sepsis/pathology , Adult , Aged , Aged, 80 and over , Female , Flow Cytometry , Humans , Male , Middle Aged , Prospective Studies , Sepsis/etiology , Severity of Illness Index , Triggering Receptor Expressed on Myeloid Cells-1
13.
Diabetes Care ; 44(2): 614-617, 2021 02.
Article in English | MEDLINE | ID: mdl-33334806

ABSTRACT

OBJECTIVE: Roux-en-Y gastric bypass (RYGB) is an established treatment for type 2 diabetes and obesity. The study objective was to establish RYGB's effects on glycemic variability (GV) and hypoglycemia. RESEARCH DESIGN AND METHODS: This was a prospective observational study of 10 participants with obesity and prediabetes or type 2 diabetes who underwent RYGB. Patients were studied before RYGB (Pre) and 1 month, 1 year, and 2 years postsurgery with continuous glucose measurement (CGM). A mixed-meal test (MMT) was conducted at Pre, 1 month, and 1 year. RESULTS: After RYGB, mean CGM decreased (at 1 month, 1 year, and 2 years), and GV increased (at 1 year and 2 years). Five of the 10 participants had a percent time in range (%TIR) <3.0 mmol/L (54 mg/dL) greater than the international consensus target of 1% at 1 or 2 years. Peak glucagon-like peptide-1 (GLP-1) and glucagon area under the curve during MMT were positively and negatively associated, respectively, with contemporaneous %TIR <3.0 mmol/L. CONCLUSIONS: Patients undergoing RYGB are at risk for development of postbariatric hypoglycemia due to a combination of reduced mean glucose, increased GV, and increased GLP-1 response.


Subject(s)
Diabetes Mellitus, Type 2 , Gastric Bypass , Hypoglycemia , Obesity, Morbid , Prediabetic State , Blood Glucose , Diabetes Mellitus, Type 2/complications , Gastric Bypass/adverse effects , Humans , Hypoglycemia/etiology , Insulin , Obesity/complications , Obesity, Morbid/surgery , Prospective Studies
14.
Front Surg ; 7: 42, 2020.
Article in English | MEDLINE | ID: mdl-32793627

ABSTRACT

Gallstone disease accounts for the vast majority of acute surgical admissions in the UK, with a major treatment being cholecystectomy. Practice varies significantly as to whether surgery is performed during the acute symptomatic phase, or after a period of recovery. Differences in practice relate to operative factors, patient factors, surgeon factors and hospital and trust wide policies. In this review we summarize recent evidence on management of gallstone disease, particularly with respect to whether cholecystectomy should occur during index presentation or following recovery. We highlight morbidity and mortality studies, cost, and patient reported outcomes. We speculate on barriers to change in service delivery. Finally, we propose potential solutions to optimize care.

15.
Int J Antimicrob Agents ; 54(6): 750-756, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31479742

ABSTRACT

Although clinical definitions of acute bacterial skin and skin-structure infection (ABSSSI) are now well established, guidance of the prediction of likely pathogens based on evidence is missing. This was a large survey of the microbiology of ABSSSIs in Greece. During the period November 2014 to December 2016, all admissions for ABSSSI in 16 departments of internal medicine or surgery in Greece were screened to determine the likely bacterial aetiology. Samples were cultured on conventional media. Expression of the SA442, mecA/mecC and SCCmec-orfX junction genes was assessed. Following univariate and forward logistic regression analysis, clinical characteristics were used to develop scores to predict the likely pathogen with a target of 90% specificity. In total, 1027 patients were screened and 633 had positive microbiology. Monomicrobial infection by Gram-positive cocci occurred in 52.1% and by Gram-negative bacteria in 20.5%, and mixed infection by Gram-positive cocci and Gram-negative bacteria in 27.3%. The most common isolated pathogens were Staphylococcus aureus and coagulase-negative staphylococci. Resistance to methicillin was 57.3% (53.5-61.1%). Three predictive scores were developed: one for infection by methicillin-resistant S. aureus, incorporating recent hospitalisation, atrial fibrillation, residency in long-term care facility (LTCF) and stroke; one for mixed Gram-positive and Gram-negative infections, incorporating localisation of ABSSSI in lumbar area, fluoroquinolone intake in last 6 days, residency in LTCF and stroke; and another for Gram-negative infection, incorporating skin ulcer presentation, peptic ulcer and solid tumour malignancy. In conclusion, methicillin-resistant staphylococci are the main pathogens of ABSSSIs. The scores developed may help to predict the likely pathogen.


Subject(s)
Bacteria/classification , Skin Diseases, Bacterial/microbiology , Soft Tissue Infections/epidemiology , Soft Tissue Infections/microbiology , Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial , Female , Greece , Humans , Male , Skin Diseases, Bacterial/epidemiology
16.
Mov Disord ; 23(7): 950-957, 2008 May 15.
Article in English | MEDLINE | ID: mdl-18442128

ABSTRACT

The aim of the present study was to investigate the course of levodopa induced dyskinesia (LID) development in parkinsonian rats treated with several different levodopa dosing regiments. Administration of 6.25 mg/kg levodopa once daily did not induce any dyskinesia for the first 12.5 +/- 2.5 days. Then, LID gradually increased in intensity reaching an AIMs score on day 40 of 6.3 +/- 0.9. Treatment with 6.25 mg/kg of levodopa qid resulted in the rapid appearance of LID with a mean latency of 2 days and an AIMs score of 19.9 +/- 2.9 on day 10. Levodopa (25 mg/kg) once daily induced severe LID from the second day of treatment reaching an AIMs score of 35 +/- 3.2. In summary, the worst way for delivering levodopa was through intermittent administration of high doses. The daily cumulative dose of levodopa was found more important for LID induction than the total amount of levodopa received. In contrast, the best way to administer levodopa in respect to prevention/delay of LID was "low dopaminergic stimulation" with one low daily dose, instead of trying to achieve "continuous dopaminergic stimulation" using several levodopa doses throughout the day. The benefits of this strategy offered protection against severe dyskinesia even if subsequently subjects were switched to high dose levodopa.


Subject(s)
Dopamine Agonists/adverse effects , Dyskinesia, Drug-Induced/etiology , Levodopa/adverse effects , Parkinson Disease/drug therapy , Animals , Basal Ganglia/pathology , Dopamine Agonists/therapeutic use , Dose-Response Relationship, Drug , Drug Administration Schedule , Levodopa/therapeutic use , Parkinson Disease/pathology , Rats , Rats, Wistar
17.
Psychopharmacology (Berl) ; 185(3): 369-77, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16518645

ABSTRACT

RATIONALE: Tardive dyskinesia is a syndrome of abnormal, involuntary movements, which occurs as a complication of long-term neuroleptic therapy. The pathophysiology of this potentially irreversible syndrome is still an enigma. OBJECTIVE: The objective of the present study was to elucidate the role of N-methyl-D-aspartate (NMDA) receptor involvement in neuroleptic-induced orofacial dyskinesia in rats. METHODS: Animals chronically treated with haloperidol for a period of 40 weeks exhibited significantly more vacuous chewing movements (VCMs), as compared to vehicle-treated controls. In a series of acute experiments, rats received: amantadine (10, 20, and 40 mg/kg i.p.), a low-affinity, uncompetitive NMDA-receptor antagonist (open channel blocker); dextrorphan (5, 10, and 20 mg/kg i.p.), an NMDA receptor channel antagonist; ifenprodil (2.5, 5, and 10 mg/kg i.p.), a noncompetitive allosteric NMDA receptor antagonist acting at the polyamine site; and Ro 25-6981 (2.5, 5, and 10 mg/kg i.p.), a potent and selective blocker of NMDA receptors which contain the NR2B subunit. RESULTS: All the drugs tested, except dextrorphan, reduced VCMs and tongue protrusions with varying efficacies and side effects profiles. Ro 25-6981 was found significantly more potent than amantadine and ifenprodil in reducing VCMs and tongue protrusions at all doses tested, and at the higher dose, it completely eliminated orofacial dyskinesia (p<0.05). CONCLUSIONS: These results suggest that NMDA receptors may play a significant role in the pathophysiology of tardive dyskinesia. Furthermore, antagonists showing selectivity for NMDA receptors containing the NR2B subunit may be particularly efficacious as novel therapeutic agents for the treatment of tardive dyskinesia and deserve further testing.


Subject(s)
Antipsychotic Agents/adverse effects , Dyskinesia, Drug-Induced/drug therapy , Haloperidol/adverse effects , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Allosteric Regulation , Amantadine/therapeutic use , Animals , Dextrorphan/therapeutic use , Dose-Response Relationship, Drug , Dyskinesia, Drug-Induced/etiology , Male , Phenols/therapeutic use , Piperidines/therapeutic use , Rats , Rats, Wistar
18.
Behav Brain Res ; 170(2): 337-41, 2006 Jun 30.
Article in English | MEDLINE | ID: mdl-16621050

ABSTRACT

Chronic daily administration of 6.25mg/kg of levodopa in unilaterally 6-OHDA lesioned rats did not induce any observable behavioral effects for the first 12.5+/-2.5 days. Thereafter, levodopa administration induced abnormal involuntary movements (AIMs), involving the contralateral limb, head, neck and trunk, along with the development of contralateral rotations. AIMs and rotations followed a progressively worsening, highly correlated, parallel course. We suggest that rotational behavior does not represent a pure antiparkinsonian response, but along with levodopa-induced dyskinesia is part of the levodopa-induced motor response complications syndrome.


Subject(s)
Antiparkinson Agents/adverse effects , Dyskinesia, Drug-Induced/etiology , Dyskinesia, Drug-Induced/physiopathology , Levodopa/adverse effects , Parkinsonian Disorders/drug therapy , Rotation , Animals , Behavior, Animal , Disease Models, Animal , Male , Oxidopamine/toxicity , Parkinsonian Disorders/chemically induced , Rats , Rats, Wistar , Time Factors
19.
Annu Int Conf IEEE Eng Med Biol Soc ; 2016: 5364-5367, 2016 Aug.
Article in English | MEDLINE | ID: mdl-28269472

ABSTRACT

The ALZCARE project aims at assisting people at risk or already suffering of dementia, their family and health professionals in the dementia care pathway by providing an integrated ICT-enabled information System. The system consists of a mobile platform for screening people at risk, a Clinical Information System and a satellite-based patient tracking system. The system is currently on the evaluation phase focusing on addressing the needs of citizens of the cross-border areas of Greece and Albania.


Subject(s)
Dementia , Geographic Information Systems , Telemedicine/methods , Albania , Caregivers , Computer Systems , Dementia/diagnosis , Electronic Health Records , Greece , Humans , Quality of Life
20.
Annu Int Conf IEEE Eng Med Biol Soc ; 2016: 3642-3645, 2016 Aug.
Article in English | MEDLINE | ID: mdl-28269083

ABSTRACT

In this paper, a method for the assessment of the Unified Parkinson Disease Rating scale (UPDRS) related to tremor is presented. The method described consists of hand resting and posture state detection, tremor detection and tremor quantification based on accelerometer and gyroscope readings from a wrist worn sensor. The initial results on PD patient recordings on home environment indicate the feasibility of the proposed method in monitoring UPDRS tremor in patient home environment.


Subject(s)
Monitoring, Ambulatory/methods , Parkinson Disease/physiopathology , Tremor/diagnosis , Accelerometry/instrumentation , Accelerometry/methods , Activities of Daily Living , Hand/physiology , Hand/physiopathology , Humans , Monitoring, Ambulatory/instrumentation , Parkinson Disease/diagnosis , Posture/physiology , Rest , Tremor/physiopathology
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