Craving as a predictor of treatment outcomes in heavy drinkers with comorbid depressed mood

Alcohol and depression comorbidity is high and is associated with poorer outcomes following treatment. The ability to predict likely treatment response would be advantageous for treatment planning. Craving has been widely studied as a potential predictor, but has performed inconsistently. The effect of comorbid depression on craving's predictive performance however, has been largely neglected, despite demonstrated associations between negative affect and craving. The current study examined the performance of craving, measured pretreatment using the Obsessive subscale of the Obsessive Compulsive Drinking Scale, in predicting 18-week and 12-month post-treatment alcohol use outcomes in a sample of depressed drinkers. Data for the current study were collected during a randomized controlled trial (Baker, Kavanagh, Kay-Lambkin, Hunt, Lewin, Carr, & Connolly, 2010) comparing treatments for comorbid alcohol and depression. A subset of 260 participants from that trial with a Timeline Followback measure of alcohol consumption was analyzed. Pre-treatment craving was a significant predictor of average weekly alcohol consumption at 18 weeks and of frequency of alcohol binges at 18 weeks and 12months, but pre-treatment depressive mood was not predictive, and effects of Baseline craving were independent of depressive mood. Results suggest a greater ongoing risk from craving than from depressive mood at Baseline.

Comparison of treatment effect sizes associated with surrogate and final patient relevant outcomes in randomised controlled trials: meta-epidemiological study

Objective To quantify and compare the treatment effect and risk of bias of trials reporting biomarkers or intermediate outcomes (surrogate outcomes) versus trials using final patient relevant primary outcomes. Design Meta-epidemiological study. Data sources All randomised clinical trials published in 2005 and 2006 in six high impact medical journals: Annals of Internal Medicine, BMJ, Journal of the American Medical Association, Lancet, New England Journal of Medicine, and PLoS Medicine. Study selection Two independent reviewers selected trials. Data extraction Trial characteristics, risk of bias, and outcomes were recorded according to a predefined form. Two reviewers independently checked data extraction. The ratio of odds ratios was used to quantify the degree of difference in treatment effects between the trials using surrogate outcomes and those using patient relevant outcomes, also adjusted for trial characteristics. A ratio of odds ratios >1.0 implies that trials with surrogate outcomes report larger intervention effects than trials with patient relevant outcomes. Results 84 trials using surrogate outcomes and 101 using patient relevant outcomes were considered for analyses. Study characteristics of trials using surrogate outcomes and those using patient relevant outcomes were well balanced, except for median sample size (371 v 741) and single centre status (23% v 9%). Their risk of bias did not differ. Primary analysis showed trials reporting surrogate endpoints to have larger treatment effects (odds ratio 0.51, 95% confidence interval 0.42 to 0.60) than trials reporting patient relevant outcomes (0.76, 0.70 to 0.82), with an unadjusted ratio of odds ratios of 1.47 (1.07 to 2.01) and adjusted ratio of odds ratios of 1.46 (1.05 to 2.04). This result was consistent across sensitivity and secondary analyses. Conclusions Trials reporting surrogate primary outcomes are more likely to report larger treatment effects than trials reporting final patient relevant primary outcomes. This finding was not explained by differences in the risk of bias or characteristics of the two groups of trials.

Long-term occlusal and soft-tissue profile outcomes after treatment of Class II Division 1 malocclusion with fixed appliances

Introduction: Our objective was to determine which factors were predictive of good long-term outcomes after fixed appliance treatment of Class II Division 1 malocclusion. Methods: Two hundred seven patients with Class II Division 1 malocclusion were examined in early adulthood at a mean of 4.6 years after treatment with fixed appliances. The peer assessment rating index was used to evaluate dental alignment and occlusal relationships. The soft-tissue profile was assessed with the Holdaway angle. Results: Logistic regression identified 3 pretreatment variables that were predictive of a good facial profile (Holdaway angle) at recall: the lower lip to E-plane distance (P

A study of initial therapy for glaucoma in southern India: India Glaucoma Outcomes and Treatment (INGOT) Study.

PURPOSE: To compare initial glaucoma therapy with medications and trabeculectomy in southern India. METHODS: Patients aged ≥ 30 years newly diagnosed with glaucoma were randomized to trabeculectomy with 5-fluorouracil or medical therapy. Subjects with best-corrected vision <6/18 due to cataract underwent phacoemulsification (phaco/intraocular lens, IOL). Intraocular pressure (IOP), vision and visual function were assessed at 12 months. RESULTS: Patients assigned to medications and surgery received the expected therapy in 86% (172/199) and 64% (126/199) of cases, respectively. Forty patients (20%) assigned to surgery refused any treatment and 33 (17%) received medications. Among 199 patients randomized to medications, 52 (26.1%) underwent phaco/IOL, as did 89/199 (43.7%) of patients randomized to trabeculectomy. Baseline parameters of the two groups did not differ, nor did 1-year follow-up rates (medication 65%, trabeculectomy 58%, P = 0.15). Final IOP was lower with randomization to trabeculectomy (16.3 ± 5.1 mmHg) than medication (18.8 ± 6.7 mmHg, P < 0.0001). In regression models, randomization to trabeculectomy (P < 0.0001) was associated with lower IOP, and simultaneous trabeculectomy and cataract surgery was associated with higher IOP (P = 0.008) than trabeculectomy alone. Subjects receiving Phaco/IOL had significantly better final acuity (P < 0.0001) and visual function (P = 0.035), despite concurrent glaucoma treatment. Final visual acuity was worse in those receiving trabeculectomy in addition to cataract surgery, but this was of borderline significance (P = 0.06). CONCLUSIONS: Trabeculectomy lowered IOP significantly more than medical treatment, but with slightly greater loss of visual acuity. Combined phaco/IOL and trabeculectomy improved visual acuity with substantial IOP lowering.

Cumulative long-term safety, efficacy and patient-reported outcomes in children with juvenile idiopathic arthritis treated with intravenous abatacept: up to 7 years of treatment

The long-term efficacy and safety of intravenous abatacept in patients (pts) with juvenile idiopathic arthritis (JIA) have been reported previously from the Phase III AWAKEN trial ([1, 2]). Here, we report efficacy, safety and pt-reported outcomes from the open-label, long-term extension (LTE) of AWAKEN, with up to 7 years of follow-up. Pts entered the LTE if they were JIA ACR 30 non-responders (NR) at the end of the 4-month lead-in period (abatacept only), or if they received abatacept or placebo (pbo) in the 6-month double-blind (DB) period. The Child Health Questionnaire was used to evaluate health-related quality of life (HRQoL); physical (PhS) and psychosocial (PsS) summary and pain scores were analyzed. Pain was assessed by parent global assessment using a 100 mm visual analog scale. Efficacy and HRQoL evaluations are reported up to Day 1765 (~ Year 5.5). Safety is presented for the cumulative period (lead-in, DB and LTE), for all pts who received abatacept during the LTE. Of the 153 pts entering the LTE (58 from DB abatacept group, 59 from DB pbo group, 36 NR), 69 completed the trial (29 abatacept, 27 pbo, 13 NR). For pts treated in the LTE, mean (range) exposure to abatacept was 53.6 (5.6–85.6) months. During the LTE, incidence rates of AEs and serious AEs per 100 pt-years were 209.1 and 5.6. Thirty pts (19.6%) had serious AEs; most were unrelated and were musculoskeletal (8.5%) or infectious events (6.5%). No malignancy was reported. There was one death (accidental; unrelated). At Day 169, JIA ACR 50 and 70 response rates were 79.3% and 55.2% in the abatacept group, and 52.5% and 30.5% in the pbo group; 31.0% and 10.2% of pts in the abatacept and pbo groups, respectively, had inactive disease. By Day 1765, JIA ACR 50 and 70 response rates were 93.9% and 78.8% in the abatacept group, and 80.0% and 63.3% in the pbo group; 51.5% and 33.3% had inactive disease. In the NR group, 69.2% and 53.8% of pts achieved JIA ACR 50 and 70 responses at Day 1765, and 30.8% had inactive disease. In pts who entered the LTE, mean baseline PhS scores were below the range for healthy children (abatacept 30.2, pbo 31.0, NR 29.5). At Day 169, 38.3% of pts had reached a PhS score >50 ((1). By the end of the LTE, 43.5% of pts had reached a PhS score >50. At baseline, mean PsS scores for those who entered the LTE were slightly lower than the mean for healthy children (abatacept 43.5, pbo 44.2, NR 47.0). At Day 169, 54.9% of pts had a PsS score >50 (1). By Day 1765, 58.1% of pts had reached a PsS score >50. At baseline, the mean pain score was 42.9. By Day 169, 13.9% of pts were considered pain free (pain score = 0); this was maintained over the LTE (1).

Surgical Treatment of Type 2 Diabetes in Patients with BMI Below 35: Mid-term Outcomes of the Laparoscopic Ileal Interposition Associated with a Sleeve Gastrectomy in 202 Consecutive Cases

The objective of this study was to evaluate the mid-term outcomes of the laparoscopic ileal interposition into the jejunum (JII-SG) or into the duodenum (DII-SG) associated with sleeve gastrectomy for type 2 diabetes mellitus (T2DM) patients with BMI below 35. The procedures were performed on 202 consecutive patients. Mean age was 52.2 +/- 7.5. Mean duration of T2DM was 9.8 +/- 5.2 years. Insulin therapy was used by 41.1%. Dyslipidemia was observed in 78.2%, hypertension in 67.3%, nephropathy in 49.5%, retinopathy in 31.2%, coronary heart disease in 11.9%, and other cardiovascular events in 12.9%. Mean follow-up was 39.1 months (range, 25-61). Early and late mortality was 0.99% and 1.0%, respectively. Early reoperation was performed in 2.5%. Early and late major complications were 8.4% and 3.5%. Early most frequent complications were pneumonia and ileus. Intestinal obstruction was diagnosed in 1.5%. Mean BMI decreased from 29.7 to 23.5 kg/m(2), mean fasting glucose from 202.1 to 112.2 mg/dl, and mean postprandial glucose from 263.3 to 130 mg/dl. Triglycerides diminished from a mean of 273.4 to 110.3 mg/dl and cholesterol from a mean of 204.7 to 160.1 mg/dl. Hypertension was resolved in 87.5%. Mean hemoglobin A(1c) (HbA(1c)) decreased from 8.7 to 6.2% after the JII-SG and to 5.9% following the DII-SG. HbA(1c) below 7% was seen in 89.9% of the patients and below 6.5% in 78.3%. Overall, 86.4% of patients were off antidiabetic medications. Both JII-SG and DII-SG demonstrated to be safe, effective, and long-lasting alternatives for the treatment of T2DM patients with BMI < 35. Beyond glycemic control, other benefits were achieved.

Growth hormone pharmacogenetics: the interactive effect of a microsatellite in the IGF1 promoter region with the GHR-exon 3 and-202 A/C IGFBP3 variants on treatment outcomes of children with severe GH deficiency

Insulin-like growth factor type 1 (IGF1) is a mediator of growth hormone (GH) action, and therefore, IGF1 is a candidate gene for recombinant human GH (rhGH) pharmacogenetics. Lower serum IGF1 levels were found in adults homozygous for 19 cytosine-adenosine (CA) repeats in the IGF1 promoter. The aim of this study was to evaluate the influence of (CA)n IGF1 polymorphism, alone or in combination with GH receptor (GHR)-exon 3 and -202 A/C insulin-like growth factor binding protein-3 (IGFBP3) polymorphisms, on the growth response to rhGH therapy in GH-deficient (GHD) patients. Eighty-four severe GHD patients were genotyped for (CA) n IGF1, -202 A/C IGFBP3 and GHR-exon 3 polymorphisms. Multiple linear regressions were performed to estimate the effect of each genotype, after adjustment for other influential factors. We assessed the influence of genotypes on the first year growth velocity (1st y GV) (n = 84) and adult height standard deviation score (SDS) adjusted for target-height SDS (AH-TH SDS) after rhGH therapy (n = 37). Homozygosity for the IGF1 19CA repeat allele was negatively correlated with 1st y GV (P = 0.03) and AH-TH SDS (P = 0.002) in multiple linear regression analysis. In conjunction with clinical factors, IGF1 and IGFBP3 genotypes explain 29% of the 1st y GV variability, whereas IGF1 and GHR polymorphisms explain 59% of final height-target-height SDS variability. We conclude that homozygosity for IGF1 (CA) 19 allele is associated with less favorable short-and long-term growth outcomes after rhGH treatment in patients with severe GHD. Furthermore, this polymorphism exhibits a non-additive interaction with -202 A/C IGFBP3 genotype on the 1st y GV and with GHR-exon 3 genotype on adult height. The Pharmacogenomics Journal (2012) 12, 439-445; doi:10.1038/tpj.2011.13; published online 5 April 2011

Judet quadricepsplasty in the treatment of posttraumatic knee rigidity: Long-term outcomes of 45 cases

BACKGROUND: Posttraumatic knee stiffness is a very debilitating condition. Judet's quadricepsplasty technique has been used for more than 50 years. However, few reports of quadricepsplasty results exist in the literature. METHODS: We report the results of 45 cases of posttraumatic arthrofibrosis of the knee treated with Judet's quadricepsplasty. The results of the procedure were analyzed by measuring the degrees of flexion of the operated knees at different time points (before, immediately after, and late postoperatively). RESULTS: The degree of flexion increased from 33.6 degrees (range, 5-80 degrees) preoperatively to 105 degrees (range, 45-160 degrees) immediately after surgery, followed by a slight fall in the range of motion (ROM) in the late postoperative period, which reached an average of 84.8 degrees. There was no significant correlation between knee strength and the patient's gender, but there was a slight trend of lower strength with age. Although Judet's quadricepsplasty technique dates from more than 50 years ago, it still provides good outcomes in the treatment of rigid knees of various etiologies. In general, all cases showed the same pattern of a small decrease in the ROM in the late postoperative period. CONCLUSION: Judet's quadricepsplasty can increase the ROM of rigid knees. The ROM obtained with the surgery persists long term. (J Trauma. 2012; 72: E77-E80. Copyright (C) 2012 by Lippincott Williams & Wilkins)

Clinical Outcomes Following Treatment of Non-contained Intrabony Defects with Enamel Matrix Derivative (EMD) or Guided Tissue Regeneration (GTR). A 12-month Randomized Controlled Clinical trial

The purpose of this study is to compare the healing of deep, non-contained intrabony defects (i.e., with a ?80% 1-wall component and a residual 2- to 3-wall component in the most apical part) treated with either an enamel matrix derivative (EMD) or guided tissue regeneration (GTR) after 12 months.

The effects of a flexible visual acuity-driven ranibizumab treatment regimen in age-related macular degeneration: outcomes of a drug and disease model

Differences in treatment responses to ranibizumab injections observed within trials involving monthly (MARINA and ANCHOR studies) and quarterly (PIER study) treatment suggest that an individualized treatment regimen may be effective in neovascular age-related macular degeneration. In the present study, a drug and disease model was used to evaluate the impact of an individualized, flexible treatment regimen on disease progression.

Clinical outcomes of patients with severe aortic stenosis at increased surgical risk according to treatment modality

Objectives The aim of this study was to assess the role of transcatheter aortic valve implantation (TAVI) compared with medical treatment (MT) and surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis (AS) at increased surgical risk. Background Elderly patients with comorbidities are at considerable risk for SAVR. Methods Since July 2007, 442 patients with severe AS (age: 81.7 ± 6.0 years, mean logistic European System for Cardiac Operative Risk Evaluation: 22.3 ± 14.6%) underwent treatment allocation to MT (n = 78), SAVR (n = 107), or TAVI (n = 257) on the basis of a comprehensive evaluation protocol as part of a prospective registry. Results Baseline clinical characteristics were similar among patients allocated to MT and TAVI, whereas patients allocated to SAVR were younger (p < 0.001) and had a lower predicted peri-operative risk (p < 0.001). Unadjusted rates of all-cause mortality at 30 months were lower for SAVR (22.4%) and TAVI (22.6%) compared with MT (61.5%, p < 0.001). Adjusted hazard ratios for death were 0.51 (95% confidence interval: 0.30 to 0.87) for SAVR compared with MT and 0.38 (95% confidence interval: 0.25 to 0.58) for TAVI compared with MT. Medical treatment (<0.001), older age (>80 years, p = 0.01), peripheral vascular disease (<0.001), and atrial fibrillation (p = 0.04) were significantly associated with all-cause mortality at 30 months in the multivariate analysis. At 1 year, more patients undergoing SAVR (92.3%) or TAVI (93.2%) had New York Heart Association functional class I/II as compared with patients with MT (70.8%, p = 0.003). Conclusions Among patients with severe AS with increased surgical risk, SAVR and TAVI improve survival and symptoms compared with MT. Clinical outcomes of TAVI and SAVR seem similar among carefully selected patients with severe symptomatic AS at increased risk.

Outcomes of antiretroviral treatment programs in rural Southern Africa

Data on outcomes of antiretroviral treatment (ART) programs in rural sub-Saharan African are scarce. We describe early losses and long-term outcomes in 6 rural programs in Southern Africa with limited access to viral load monitoring and second-line ART.

Outcomes of antiretroviral treatment in programmes with and without routine viral load monitoring in Southern Africa

Objectives: To compare outcomes of antiretroviral therapy (ART) in South Africa, where viral load monitoring is routine, with those in Malawi and Zambia, where monitoring is based on CD4 cell counts. Methods: We included 18 706 adult patients starting ART in South Africa and 80 937 patients in Zambia or Malawi. We examined CD4 responses in models for repeated measures and the probability of switching to second-line regimens, mortality and loss to follow-up in multistate models, measuring time from 6 months. Results: In South Africa, 9.8% [95% confidence interval (CI) 9.1–10.5] had switched at 3 years, 1.3% (95% CI 0.9–1.6) remained on failing first-line regimens, 9.2% (95% CI 8.5–9.8) were lost to follow-up and 4.3% (95% CI 3.9–4.8) had died. In Malawi and Zambia, more patients were on a failing first-line regimen [3.7% (95% CI 3.6–3.9], fewer patients had switched [2.1% (95% CI 2.0–2.3)] and more patients were lost to follow-up [15.3% (95% CI 15.0–15.6)] or had died [6.3% (95% CI 6.0–6.5)]. Median CD4 cell counts were lower in South Africa at the start of ART (93 vs. 132 cells/μl; P < 0.001) but higher after 3 years (425 vs. 383 cells/μl; P < 0.001). The hazard ratio comparing South Africa with Malawi and Zambia after adjusting for age, sex, first-line regimen and CD4 cell count was 0.58 (0.50–0.66) for death and 0.53 (0.48–0.58) for loss to follow-up. Conclusion: Over 3 years of ART mortality was lower in South Africa than in Malawi or Zambia. The more favourable outcome in South Africa might be explained by viral load monitoring leading to earlier detection of treatment failure, adherence counselling and timelier switching to second-line ART.