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Sanne Klaphake,1,2 Kevin de Leur,1 Paul GH Mulder,1,3 Gwan H Ho,1 Hans G de Groot,1 Eelco J Veen,1 Hence JM Verhagen,2 Lijckle van der Laan1 1Department of Surgery, Amphia Hospital, Breda, 2Department of Vascular Surgery, Erasmus University Medical Center, Rotterdam, 3Amphia Academy, Amphia Hospital, Breda, the Netherlands Background: Owing to the aging population, the number of elderly patients with critical limb ischemia (CLI) has increased. The consequence of amputation is immense. However, at the moment, information about the mortality after amputation in the elderly vascular patients is unknown. For this reason, this study evaluated mortality rates and patient-related factors associated with mortality after a major amputation in elderly patients with CLI.Methods: From 2006 to 2013, we included patients aged >70years who were treated for chronic CLI by primary or secondary major amputation within or after 3months of initial therapy (revascularization or conservative management). Outcome measurements were mortality after major amputation and factors associated with mortality (age, comorbidity and timing of amputation).Results: In total, 168/651 patients (178 legs; 26%) underwent a major amputation. Patients were stratified by age: 70–80years (n=86) and >80years (n=82). Overall mortality after major amputation was 44%, 66% and 85% after 1, 3 and 5years, respectively. The 6-month and 1-year mortality in patients aged 80years or older was, respectively, 59% or 63% after a secondary amputation 3months. Per year of age, the mortality rate increased by 4% (P=0.005). No significant difference in mortality after major amputation was found in the presence of comorbidity or according to Rutherford classification.Conclusion: Despite developments in the treatment of CLI by revascularization, amputation rates remain high and are associated with tremendous mortality rates. Secondary amputation after a failed attempt of revascularization causes a higher mortality. Further research concerning timing of amputation and patient-related outcome is needed to evaluate if selected patients might benefit from primary amputation. Keywords: peripheral arterial disease, aged, limb ischemia, primary amputation, octogenarians, patient selection

Willem A van Eijsden,1 Jelle W Raats,1 Paul GH Mulder,2 Lijckle van der Laan1 1Department of Surgery, 2Amphia Academy, Amphia Hospital, Breda, the Netherlands Objective: The primary objective was to identify possible risk factors for delirium in patients with critical limb ischemia undergoing surgery. The secondary objective was to study the effect of delirium on complications, the length of hospital stay, health care costs, and mortality. Methods: All patients 65years or older with critical limb ischemia undergoing surgery from February 2013 to July 2014 at Amphia Hospital, were included and followed up until December31, 2014. Delirium was scored using the Delirium Observation Screening Scale (DOSS). Perioperative risk factors (age, comorbidity, factors of frailty, operation type, hemoglobulin, and transfusion) were collected and analyzed using logistic regression. Secondary outcomes were the number of complications, total hospital stay, extra health care costs per delirium, and mortality within 3months and 6months of surgery Results: We included 92 patients with critical limb ischemia undergoing surgery. Twenty-nine (32%) patients developed a delirium during admission, of whom 17 (59%) developed delirium preoperatively. After multivariable analysis, only diabetes mellitus (odds ratio [OR] =6.23; 95% confidence interval [CI]: 1.11–52.2; P=0.035) and Short Nutritional Assessment Questionnaire for Residential Care (SNAQ-RC) ≥3 (OR =5.55; 95% CI: 1.07–42.0; P=0.039) was significantly associated with the onset of delirium. Delirium was associated with longer hospital stay (P=0.001), increased health care costs, and higher mortality after 6months (P

Objective: In two previous manuscripts, we described the efficacy of lamotrigine versus placebo as add-on to lithium (followed by the addition of paroxetine in nonresponders) in the short-term treatment of bipolar depression. In this paper we describe the long-term (68 weeks) outcome of that study. Methods: A total of 124 bipolar depressed patients receiving lithium were randomized to addition of lamotrigine or placebo. After eight weeks, paroxetine was added to nonresponders for another eight weeks. Responders continued medication and were followed for up to 68 weeks or until a relapse or recurrence of a depressive or manic episode. Results: After eight weeks, the addition of lamotrigine to lithium was significantly more efficacious than addition of placebo, while after addition of paroxetine in nonresponders both groups further improved with no significant difference between groups at week 16. During follow-up the efficacy of lamotrigine was maintained: time to relapse or recurrence was longer for the lamotrigine group [median time 10.0 months (confidence interval: 1.1-18.8)] versus the placebo group [3.5 months (confidence interval: 0.7-7.0)]. Conclusion: In patients with bipolar depression, despite continued use of lithium, addition of lamotrigine revealed a continued benefit compared to placebo throughout the entire study.

Besides short stature, gonadal dysgenesis leading to a lack of oestrogen is one of the main characteristics of Turner syndrome (TS). In most TS girls, puberty is induced with exogenous oestrogens. To describe the pubertal development and uterine dimensions achieved by low-dose 17 beta-oestradiol (17 beta-E2) orally started at an appropriate age. Additionally, to determine whether serum hormone levels aid evaluation of pubertal progression. In 56 TS girls, we prospectively studied pubertal stage, serum E2, LH, FSH, SHBG and oestrone (E1), starting oestrogen treatment with a low-dose 17 beta-E2 (5 mu g/kg/day) during GH treatment at mean (SD) age 12.7 (0.7) years. Hormone levels were measured at start, 3 months after start and after increasing 17 beta-E2 dosage. Uterine dimensions were measured in 39 TS women at age 19.9 (2.2) years. Although breast and pubic hair development were similar to that in normal Dutch girls up to Tanner stage B5 and P5, respectively, breast development was 2 years later. Before oestrogen therapy, E2 levels were comparable to those in prepubertal girls. With a 17 beta-E2 dose of 5 mu g/kg/day, these levels increased significantly, becoming comparable to normal late pubertal or adult concentrations, whereas SHBG levels were unchanged. At the adult 17 beta-E2 dose, SHBG had increased significantly. Uterus shape was juvenile in four (10.2%), cylindrical in four and mature-adult shaped in 31 (79.5%) of TS patients. During GH treatment in TS girls, normal breast development up to B5 can be mimicked, with just a 2-year delay. In a clinical setting, serum hormone levels provide no additional information for evaluating pubertal progression. After age-appropriate pubertal induction, uterine dimensions in women aged nearly 20 years were subnormal. It remains unclear whether this was related to E2 dosage, timing or duration, or factors related to TS.

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BACKGROUND To investigate in a group of short children born small for gestational age (SGA), the effects of 3 years of GH treatment vs. no treatment on bone age (BA), height and bone mineral density (BMD). Also, to evaluate the influence of the severity of growth retardation at start and the GH dose on the gain in height. PATIENTS AND METHODS The study design was an open-labelled, controlled multicentre GH study for 3 years. Non-GH-deficient (GHD) children (n = 87) were randomized to either a GH group (n = 61) or an untreated control group (n = 26). In addition, 12 SGA children had GHD (GHD group) and were treated in parallel. Both the GH and the GHD group were treated with a GH dose of 33 mug/kg/day. BMD was evaluated using dual energy X-ray absorptiometry (DEXA). In addition, data of our first GH trial in which short SGA children were treated with a GH dose of 66 mug/kg/day (n = 24) were used for comparison of height gain. RESULTS In contrast to the control group, the GH group showed a significant increase in height (P

Item does not contain fulltext OBJECTIVE: To determine the prophylactic effect of oral acyclovir on the recurrence rate of herpetic eye disease after penetrating keratoplasty. DESIGN: A randomized, double-masked, placebo-controlled multicenter trial. PARTICIPANTS: Sixty-eight consecutive patients (68 eyes) with corneal opacities due to herpetic eye disease who underwent penetrating keratoplasty. INTERVENTION: Oral acyclovir 400 mg twice daily or placebo tablets for 6 months. MAIN OUTCOME MEASURES: The recurrence rate of herpetic eye disease-related events and rejection episodes, proven by viral cell culture or polymerase chain reaction. RESULTS: During the 2-year follow-up period, there were 3 culture-proven herpetic eye disease recurrences in the acyclovir group and 9 in the placebo group. Lifetime survival analysis of the probability of remaining free from recurrence revealed a significantly reduced risk of recurrent herpetic disease in the acyclovir-treated group. CONCLUSION: This study suggests that oral acyclovir effectively prevents herpes-related recurrences after penetrating keratoplasty in herpetic eye disease.

Background. After successful kidney transplantation patients may suffer from the adverse effects due to the use of calcineurin inhibitors. Calcium channel blockers are effective in the treatment of hypertension and may ameliorate cyclosporine- (CsA) induced impairment of renal function after kidney transplantation. Calcium channel blockers may also modulate the immune-system which may result in reduction of acute rejection episodes. Patients and methods. From June 1995 till 1997 the effect of isradipine (Lomir) on renal function, incidence and severity of delayed graft function (DGF), and acute rejection after kidney transplantation, was studied in 210 renal transplant recipients, who were randomized to receive isradipine (n=98) or placebo (n=112) after renal transplantation in a double-blind fashion. Results. In the isradipine group renal function was significantly better at 3 and 12 months (P=0.002 and P=0.021) compared with the placebo group. DGF was present, in both groups: isradipine: (28+6)/98 (35%); placebo: (35+9)/112 (40%), P=0.57. Severity of DGF was comparable in both groups (isradipine: 9.1+/-8.7 vs. placebo: 9.3+/-8.1 days). No statistical difference was found in incidence or severity of biopsy-proven acute rejection [isradipine: (42+6)/98 (49%) versus placebo: (46+9)/112 (49%), P=1.00]. Renal vein thrombosis was observed in eight patients, This proved to be associated with the route of administration of the study medication [6/45 (13%) on i.v. medication versus 2/165 (1%) on oral medication, P