Conversion from Cyclosporine to Tacrolimus Improves Quality-of-Life Indices, Renal Graft Function and Cardiovascular Risk Profile

Long-term use of cyclosporine after renal transplantation results in nephrotoxicity and an increased cardiovascular risk profile. Tacrolimus may be more favorable in this respect. In this randomized controlled study in 124 renal transplant patients, the effects of conversion from cyclosporine to tacrolimus on renal function, cardiovascular risk factors, and perceived side-effects were investigated after a follow-up of 2 years. After conversion from cyclosporine to tacrolimus renal function remained stable, whereas continuation of cyclosporine was accompanied by a rise in serum creatinine from 142 +/- 48 micromol/L to 157 +/- 62 micromol/L (p < 0.05 comparing both groups). Conversion to tacrolimus resulted in a sustained reduction in systolic and diastolic blood pressure, and a sustained improvement in the serum lipid profile, leading to a reduction in the Framingham risk score from 5.7 +/- 4.3 to 4.8 +/- 5.3 (p < 0.05). Finally, conversion to tacrolimus resulted in decreased scores for occurrence of and distress due to side-effects. In conclusion, conversion from cyclosporine to tacrolimus in stable renal transplant patients is beneficial with respect to renal function, cardiovascular risk profile, and side-effects. Therefore, for most renal transplant patients tacrolimus will be the drug of choice when long-term treatment with a calcineurin inhibitor is indicated.     

Graft intolerance syndrome requiring graft nephrectomy after late kidney graft failure: can it be predicted? A retrospective cohort study

Graft nephrectomy is recommended in case of early graft failure. When the graft fails more than 3–6 months after transplantation, it is current practice to follow a wait‐and‐see policy. A common indication for graft removal is the graft intolerance syndrome. We aimed to create a risk prediction model for the occurrence of graft intolerance resulting in graft nephrectomy. We collected data of kidney transplantations performed in our center between 1980 and 2010 that failed at least 6 months after transplantation. We evaluated the association between baseline characteristics and the occurrence of graft nephrectomy because of graft intolerance using a competing risk regression model. Prognostic factors were included in a multivariate prediction model. In‐ and exclusion criteria were met in 288 cases. In 48 patients, the graft was removed because of graft intolerance. Donor age, the number of rejections, and shorter graft survival were predictive factors for graft nephrectomy because of the graft intolerance syndrome. These factors were included in a prediction rule. Using donor age, graft survival, and the number of rejections, clinicians can predict the need for graft nephrectomy with a reasonable accuracy.     

A new method to evaluate the effects of shear on the skin

Currently, pressure ulcer preventive strategies focus mainly on pressure redistribution. Little attention is paid to reduce the harmful effects of shear‐force, because little is known about pathophysiological aspects of shear‐force. Even today, no method to measure the effects of shear‐force on the skin is available. Therefore, the aim of this study was to investigate the response to shear‐forces in terms of analyzing a noninvasive biomarker and reactive hyperemic parameter measured at the skin of healthy participants. A physical model was developed to produce a combination of pressure and shear or pressure alone on the skin. Ten healthy male participants were included and pressure (3.9 kPa) and a combined loading of pressure and shear (2.4 kPa + 14.5 N) was applied at the volar aspect of the forearms for 15 and 30 minutes. A Sebutape sample was used to collect IL‐1α and total protein (TP) noninvasively. The reactive hyperemic parameter was derived from a laser Doppler flowmeter. The increase in IL‐1α/TP‐ratio after a combined loading of pressure and shear for 30 minutes of 6.2 ± 2.5 was significantly higher compared with all other test conditions (p < 0.05). The increase in cutaneous blood cell flux was already significantly higher when a combined loading of pressure and shear was applied for 15 minutes compared with pressure alone. These results shows that the IL‐1α/TP‐ratio and cutaneous blood cell flux can be used as robust measures of the effect of shear‐force on skin in humans. Therefore, this model can be used to evaluate materials aimed at the reduction of shear.     

Comparing dual energy CT and subtraction CT on a phantom: which one provides the best contrast in iodine maps for sub-centimetre details?

Objectives

To compare contrast-to-noise ratios (CNRs) and iodine discrimination thresholds on iodine maps derived from dual energy CT (DECT) and subtraction CT (SCT).

Methods

A contrast-detail phantom experiment was performed with 2 to 15 mm diameter tubes containing water or iodinated contrast concentrations ranging from 0.5 mg/mL to 20 mg/mL. DECT scans were acquired at 100 kVp and at 140 kVp+Sn filtration. SCT scans were acquired at 100 kVp. Iodine maps were created by material decomposition (DECT) or by subtraction of water scans from iodine scans (SCT). Matched exposure levels varied from 8 to 15 mGy. Iodine discrimination thresholds (C_r) and response times were determined by eight observers.

Results

The adjusted mean CNR was 1.9 times higher for SCT than for DECT. Exposure level had no effect on CNR. All observers discriminated all details ≥10 mm at 12 and 15 mGy. For sub-centimetre details, the lowest calculated C_r was ≤ 0.50 mg/mL for SCT and 0.64 mg/mL for DECT. The smallest detail was discriminated at ≥4.4 mg/mL with SCT and at ≥7.4 mg/mL with DECT. Response times were lower for SCT than DECT.

Conclusions

SCT results in higher CNR and reduced iodine discrimination thresholds compared to DECT for sub-centimetre details.

Key Points

? Subtraction CT iodine maps exhibit higher CNR than dual-energy iodine maps ? Lower iodine concentrations can be discriminated for sub-cm details with SCT ? Response times are lower using SCT compared to dual-energy CT

     

The 5-Year Course of Obsessive-Compulsive Symptoms and Obsessive-Compulsive Disorder in First-Episode Schizophrenia and Related Disorders

Objective: To determine the course of obsessive-compulsive symptoms (OCS) and obsessive-compulsive disorder (OCD) in first-episode schizophrenia and related disorders and their relationship with clinical characteristics. Methods: Consecutively, admitted patients with a first-episode of schizophrenia, schizophreniform disorder, or schizoaffective disorder were screened for OCS, and these were measured with the Yale-Brown Obsessive-Compulsive Scale. Positive and Negative Syndrome Scale and Montgomery Åsberg Depression Rating Scale were used to assess severity of other symptoms. The course of 3- and 5-year symptoms, psychotic relapse, substance use, remission, full recovery, suicide, and social functioning were assessed. Results: One hundred and eighty-six consecutively admitted and consenting patients were included. Five years after admission, OCS could be assessed in 172 patients. Ninety-one patients (48.9%) reported no OCS symptoms on any of the assessments. OCS restricted to the first assessments occured in 15.1%, 13.4% had persistent OCS, 7.0% had no OCS at first assessment but developed OCS subsequently, and 15.6% had intermittent OCS. The proportion of patients with comorbid OCD varied between 7.3% and 11.8% during follow-up. OCD was associated with more severe depressive symptoms and poorer premorbid functioning and social functioning at follow-up. Conclusions: The 5-year course of OCS/OCD in patients with first-episode schizophrenia or related disorders is variable. OCS/OCD comorbidity was not associated with a more severe course of psychotic symptoms and relapse. Comorbid OCD was associated with more severe depressive symptoms, social dysfunction and worse premorbid functioning. Specific treatment options for schizophrenia patients with comorbid OCD are needed.     

Psychiatric disorders in a representative sample of incarcerated boys in the Netherlands

OBJECTIVE: To determine the prevalence of psychiatric disorders among incarcerated male adolescents and to investigate the influence of psychopathology on allocation to either plain detention or detention with compulsory treatment. METHOD: A cross-sectional study of a representative sample (N = 204) of incarcerated boys aged 12 to 18, using the Diagnostic Interview Schedule for Children (DISC). Data were collected from December 1998 to December 1999. RESULTS: Of the eligible subjects, 79% agreed to participate. Ninety percent reported at least one psychiatric disorder: disruptive behavior disorder 75% (95% confidence interval [CI]: 68-81%), substance use disorder 55% (95% CI: 48-63%), psychotic symptoms 34% (95% CI: 27-41%), ADHD 8% (95% CI: 5-13%), anxiety disorder 9% (95% CI: 6-15%), and affective disorder 6% (95% CI: 3-10%). After controlling for a broad range of sociodemographic characteristics and former treatment parameters, the presence of a psychiatric disorder was not associated with allocation to compulsory treatment. CONCLUSIONS: Compared with North American studies, relatively low rates of anxiety and affective disorders were found, probably due to the better availability of mental health services to disadvantaged youths with internalizing problems in the Netherlands. It should be examined whether standardized psychiatric assessments can improve the efficiency of allocation to detention programs with or without psychiatric treatment options.     

Withdrawal of cyclosporine or prednisone six months after kidney transplantation in patients on triple drug therapy: a randomized, prospective, multicenter study

Uncertainty exists regarding the necessity of continuing triple therapy consisting of mycophenolate mofetil (MMF), cyclosporine (CsA), and prednisone (Pred) after kidney transplantation (RTx). At 6 mo after RTx, 212 patients were randomized to stop CsA (n = 63), stop Pred (n = 76), or continue triple drug therapy (n = 73). The MMF dose was 1000 mg twice daily, target CsA trough levels were 150 ng/ml, and Pred dose was 0.10 mg/kg per d. Follow-up was until 24 mo after RTx. Biopsy-proven acute rejection occurred in 14 (22%) of 63 patients after CsA withdrawal compared with 3 (4%) of 76 in the Pred withdrawal group (P = 0.001) and 1 (1.4%) of 73 in the control group (P = 0.0001). Biopsy-proven chronic rejection was present in one patient in the control group, in nine patients after CsA withdrawal (P = 0.006 versus control group); and in four patients after discontinuation of Pred (NS). Graft loss occurred in two versus one patient after CsA or Pred withdrawal, respectively, and in two patients in the control group (NS). Patients who successfully withdrew CsA had a significantly lower serum creatinine during follow-up. Pred withdrawal resulted in a reduction in mean arterial pressure, and the total cholesterol/HDL ratio increased. In conclusion, rapid CsA withdrawal at 6 mo after RTx results in a significantly increased incidence of biopsy-proven acute and chronic rejection. Pred withdrawal was safe and resulted in a reduction in mean arterial pressure. However, patient and graft survival and renal function 2 yr after RTx were not different among groups.     

Endoscopic ultrasound added to mediastinoscopy for preoperative staging of patients with lung cancer

Context  Up to 40% of thoracotomies performed for non–small cell lung cancer are unnecessary, predominantly due to inaccurate preoperative detection of lymph node metastases and mediastinal tumor invasion (T4). Mediastinoscopy and the novel, minimally invasive technique of transesophageal ultrasound–guided fine-needle aspiration (EUS-FNA) target different mediastinal lymph node stations. In addition, EUS can identify tumor invasion in neighboring organs if tumors are located adjacent to the esophagus. Objective  To investigate the additional value of EUS-FNA to mediastinoscopy in the preoperative staging of patients with non–small cell lung cancer. Design, Setting, and Patients  Prospective, nonrandomized multicenter trial performed in 1 referral and 5 general hospitals in the Netherlands. During a 3-year period (2000-2003), 107 consecutive patients with potential resectable non–small cell lung cancer underwent preoperative staging by both EUS-FNA and mediastinoscopy. Patients underwent thoracotomy with tumor resection if mediastinoscopy was negative. Surgical-pathological staging was compared with preoperative findings and the added benefit of the combined strategy was assessed. Intervention  The EUS-FNA examination was performed as an additional staging test to mediastinoscopy in all patients. Main Outcome Measure  Detection of mediastinal tumor invasion (T4) and lymph node metastases (N2/N3) comparing the combined staging by both EUS-FNA and mediastinoscopy with staging by mediastinoscopy alone. Results  The combination of EUS-FNA and mediastinoscopy identified more patients with tumor invasion or lymph node metastases (36%; 95% confidence interval [CI], 27%-46%) compared with either mediastinoscopy alone (20%; 95% CI, 13%-29%) or EUS-FNA (28%; 95% CI, 19%-38%) alone. This indicated that 16% of thoracotomies could have been avoided by using EUS-FNA in addition to mediastinoscopy. However, 2% of the EUS-FNA findings were false-positive. Conclusion  These preliminary findings suggest that EUS-FNA, when added to mediastinoscopy, improves the preoperative staging of lung cancer due to the complementary reach of EUS-FNA in detecting mediastinal lymph node metastases and the ability to assess mediastinal tumor invasion.