Medical versus surgical management for gastro-oesophageal reflux disease (GORD) in adults.

BACKGROUND: Gastro-oesophageal reflux disease (GORD) is a common condition with up to 20% of patients from Westernised countries experiencing heartburn, reflux or both intermittently. It is unclear whether medical or surgical (laparoscopic fundoplication) management is the most clinically and cost-effective treatment for controlling GORD. OBJECTIVES: To compare the effects of medical management versus laparoscopic fundoplication surgery on health-related and GORD-specific quality of life (QOL) in adults with GORD. SEARCH STRATEGY: We searched CENTRAL (Issue 2, 2009), MEDLINE (1966 to May 2009) and EMBASE (1980 to May 2009). We handsearched conference abstracts and reference lists from published trials to identify further trials. We contacted experts in the field for relevant unpublished material. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing medical management with laparoscopic fundoplication surgery. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data from articles identified for inclusion and assessed the methodological quality of eligible trials. Primary outcomes were: health-related and GORD-specific QOL, heartburn, regurgitation and dysphagia. MAIN RESULTS: Four trials were included with a total of 1232 randomised participants. Health-related QOL was reported by four studies although data were combined using fixed-effect models for two studies (Anvari 2006; REFLUX Trial 2008). There were statistically significant improvements in health-related QOL at three months and one year after surgery compared to medical therapy (mean difference (MD) SF36 general health score -5.23, 95% CI -6.83 to -3.62; I(2) = 0%). All four studies reported significant improvements in GORD-specific QOL after surgery compared to medical therapy although data were not combined. There is evidence to suggest that symptoms of heartburn, reflux and bloating are improved after surgery compared to medical therapy, but a small proportion of participants have persistent postoperative dysphagia. Overall rates of postoperative complications were low but surgery is not without risk and postoperative adverse events occurred although they were uncommon. The costs of surgery are considerably higher than the cost of medical management although data are based on the first year of treatment therefore the cost and side effects associated with long-term treatment of chronic GORD need to be considered. AUTHORS' CONCLUSIONS: There is evidence that laparoscopic fundoplication surgery is more effective than medical management for the treatment of GORD at least in the short to medium term. Surgery does carry some risk and whether the benefits of surgery are sustained in the long term remains uncertain. Treatment decisions for GORD should be based on patient and surgeon preference.

Beliefs about surgery: Development and validation of an instrument to assess cognitive representations about surgery, in the context of a chronic illness.

OBJECTIVES: Within a trial of medical and surgical treatments for gastro-esophageal reflux disease (GORD), involving randomised arms and preference arms, we tested the applicability of the Beliefs about Medicines Questionnaire (BMQ) and developed and tested the validity of a new Beliefs about Surgery Questionnaire (BSQ). METHODS: Patients with GORD (N = 43) were interviewed to elicit their beliefs about medical and surgical treatments. These contributed to the development of BSQ items. The BMQ and BSQ were completed by trial participants at baseline (randomised trial: N = 325; preference trial: N = 414). Factor analysis and discriminant function analysis were used to assess validity. RESULTS: Principal components analysis (PCA) largely replicated the four-factor BMQ structure. PCA of the combined BMQ/BSQ yielded six factors explaining 54.5% variance. BSQ items loaded onto distinct factors, demonstrating divergence from BMQ. As predicted, BMQ/BSQ scores enabled correct classification of 78.5% of participants to medication and surgery groups in the preference trial (chi(2)(6) = 205.9, p < 0.001) but only 54.5% (no better than chance) in the randomised trial (chi(2)(6) = 9.4, p = 0.154). CONCLUSIONS: The BSQ is a valid measure of perceptions about surgical treatments for GORD. With the BMQ, it provides information that may guide patients' choices about treatment. This measure may be applicable to other conditions.

Minimal access surgery compared with medical management for chronic gastro-oesophageal reflux disease: UK collaborative randomised trial.

OBJECTIVE: To determine the relative benefits and risks of laparoscopic fundoplication surgery as an alternative to long term drug treatment for chronic gastro-oesophageal reflux disease (GORD). DESIGN: Multicentre, pragmatic randomised trial (with parallel preference groups). SETTING: 21 hospitals in the United Kingdom. PARTICIPANTS: 357 randomised participants (178 surgical, 179 medical) and 453 preference participants (261, 192); mean age 46; 66% men. All participants had documented evidence of GORD and symptoms for >12 months. INTERVENTION: The type of laparoscopic fundoplication used was left to the discretion of the surgeon. Those allocated to medical treatment had their treatment reviewed and adjusted as necessary by a local gastroenterologist, and subsequent clinical management was at the discretion of the clinician responsible for care. MAIN OUTCOME MEASURES: The disease specific REFLUX quality of life score (primary outcome), SF-36, EQ-5D, and medication use, measured at time points equivalent to three and 12 months after surgery, and surgical complications. MAIN RESULTS: Randomised participants had received drugs for GORD for median of 32 months before trial entry. Baseline REFLUX scores were 63.6 (SD 24.1) and 66.8 (SD 24.5) in the surgical and medical randomised groups, respectively. Of those randomised to surgery, 111 (62%) actually had total or partial fundoplication. Surgical complications were uncommon with a conversion rate of 0.6% and no mortality. By 12 months, 38% (59/154) randomised to surgery (14% (14/104) among those who had fundoplication) were taking reflux medication versus 90% (147/164) randomised medical management. The REFLUX score favoured the randomised surgical group (14.0, 95% confidence interval 9.6 to 18.4; P<0.001). Differences of a third to half of 1 SD in other health status measures also favoured the randomised surgical group. Baseline scores in the preference for surgery group were the worst; by 12 months these were better than in the preference for medical treatment group. CONCLUSION: At least up to 12 months after surgery, laparoscopic fundoplication significantly increased measures of health status in patients with GORD. TRIAL REGISTRATION: ISRCTN15517081.

Dates of birth and seasonal changes in well-being among 4904 subjects completing the seasonal pattern assessment questionnaire.

BACKGROUND: Abnormal distributions of birthdates, suggesting intrauterine aetiological factors, have been found in several psychiatric disorders, including one study of out-patients with Seasonal Affective Disorder (S.A.D.). We investigated birthdate distribution in relation to seasonal changes in well-being among a cohort who had completed the Seasonal Pattern Assessment Questionnaire (SPAQ). METHOD: A sample of 4904 subjects, aged 16 to 64, completed the SPAQ. 476 were cases of S.A.D. on the SPAQ and 580 were cases of sub-syndromal S.A.D. (S-S.A.D.). 92 were interview confirmed cases of S.A.D. Months and dates of birth were compared between S.A.D. cases and all others, between S.A.D. and S-S.A.D. cases combined and all others, and between interview confirmed cases and all others. Seasonality, as measured through seasonal fluctuations in well-being on the Global Seasonality Scores (GSS) of the SPAQ, was compared for all subjects by month and season of birth. RESULTS: There was no evidence of an atypical pattern of birthdates for subjects fulfilling criteria for S.A.D., for the combined S.A.D./S-S.A.D. group or for interview confirmed cases. There was also no relationship between seasonality on the GSS and month or season of birth. LIMITATIONS: Diagnoses of S.A.D. made by SPAQ criteria are likely to be overinclusive. CONCLUSION: Our findings differ from studies of patients with more severe mood disorders, including psychiatric out-patients with S.A.D. The lack of association between seasonality and birthdates in our study adds credence to the view that the aetiology of S.A.D. relates to separable factors predisposing to affective disorders and to seasonality.

Role of L-citrulline transport in nitric oxide synthesis in rat aortic smooth muscle cells activated with LPS and interferon-gamma.

(1) l-citrulline, a coproduct of nitric oxide synthase (NOS)-catalysed metabolism of l-arginine to nitric oxide (NO), is an important intermediate of the urea cycle and a precursor for l-arginine biosynthesis in vascular cells. (2) In the present study, we have examined the characteristics of l-citrulline transport, regulation by lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) and the ability of l-citrulline to sustain NO synthesis in rat cultured aortic smooth muscle cells. (3) l-citrulline transport was saturable with an apparent Km=1.6+/-0.2 mm and Vmax=5.9+/-0.6 pmol microg-1 protein min-1. Transport was pH-insensitive, partially Na+-dependent and markedly inhibited by substrates selective for amino-acid transport systems L and N but not by l-arginine or substrates for systems A, ASC, xc- or XAG. Moreover, transport was not altered in cells treated with LPS (100 microg ml-1) and IFN-gamma (50 U ml-1) for 0-24 h. (4) Unlike l-arginine, l-citrulline could not sustain maximal NO production in cells expressing iNOS. (5) Our findings provide the first evidence in vascular smooth muscle cells that l-citrulline transport is mediated via a low-affinity carrier with characteristics resembling systems L and N. Moreover, in l-arginine-deprived rat aortic smooth muscle cells, l-citrulline cannot sustain maximal NO release via iNOS.

Seasonal affective disorder and social deprivation in Aberdeen.

BACKGROUND: Unlike non-seasonal depression, there is some evidence that seasonal affective disorder (SAD) is more common among more affluent socioeconomic groups. METHODS: In primary care settings in Aberdeen, 4557 subjects had previously completed a Seasonal Pattern Assessment Questionnaire (SPAQ). From the subjects' postcodes they were allocated a Carstairs score which placed them in one of seven categories of socioeconomic deprivation. These categories were compared with regard to seasonal pathology from the SPAQ ratings. RESULTS: Complete postcodes and Carstairs scores were established for 3772 (83%) of the 4557 subjects. No statistically significant relationship between socioeconomic deprivation and SPAQ ratings was detected. LIMITATIONS: The study population was an affluent one relative to Scotland as a whole which may have reduced the likelihood of a positive finding. The study was conducted 7 years after the census on which postcode deprivation scores were calculated, and changes therein may have occurred. CONCLUSIONS: SAD either has no relationship to social deprivation or is associated with affluence and this distinguishes it from non-seasonal depression.

Use of health care services in seasonal affective disorder.

BACKGROUND: Little is known about the presentation and management of seasonal affective disorder (SAD) in primary care. AIMS: To determine the use of health care services by people suffering from SAD. METHOD: Following a screening of patients consulting in primary care, 123 were identified as suffering from SAD. Each was age- and gender-matched with two primary care consulters with minimal seasonal morbidity, yielding 246 non-seasonal controls. From primary care records, health care usage over a 5-year period was established. RESULTS: Patients with SAD consulted in primary care significantly more often than controls and presented with a wider variety of symptoms. They received more prescriptions, underwent more investigations and had more referrals to secondary care. CONCLUSIONS: Patients with SAD are heavy users of health care services. This may reflect the condition itself, its comorbidity or factors related to the personality or help-seeking behaviour of sufferers.