Evidence‐based treatment strategies for treatment‐resistant bipolar depression: a systematic review

Sienaert P, Lambrichts L, Dols A, De Fruyt J.
Evidence‐based treatment strategies for treatment‐resistant bipolar depression: a systematic review.
Bipolar Disord 2012: 00: 000–000. © 2012 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd. Objectives: Treatment resistance in bipolar depression is a common clinical problem that constitutes a major challenge for the treating clinician as there is a paucity of treatment options. The objective of this paper was to review the evidence for treatment options in treatment‐resistant bipolar depression, as found in randomized controlled trials and with special attention to the definition and assessment of treatment resistance. Methods: A Medline search (from database inception to May 2012) was performed using the search terms treatment resistance or treatment refractory, and bipolar depression or bipolar disorder, supplemented with 43 separate searches using the various pharmacologic agents or technical interventions as search terms. Results: Only seven studies met our inclusion criteria. These studies examined the effects of ketamine (n = 1), (ar)modafinil (n = 2), pramipexole (n = 1), lamotrigine (n = 1), inositol (n = 1), risperidone (n = 1), and electroconvulsive therapy (ECT) (n = 2). Conclusions: The available level I evidence for treatment strategies in resistant bipolar depression is extremely scarce, and although the response rates reported are reassuring, most of the strategies remain experimental. There is an urgent need for further study in homogeneous patient samples using a clear concept of treatment resistance.     

Urinary detection of conjugated and unconjugated anabolic steroids by dilute‐and‐shoot liquid chromatography‐high resolution mass spectrometry

Anabolic androgenic steroids (AAS) are an important class of doping agents. The metabolism of these substances is generally very extensive and includes phase‐I and phase‐II pathways. In this work, a comprehensive detection of these metabolites is described using a 2‐fold dilution of urine and subsequent analysis by liquid chromatography‐high resolution mass spectrometry (LC‐HRMS). The method was applied to study 32 different metabolites, excreted free or conjugated (glucuronide or sulfate), which permit the detection of misuse of at least 21 anabolic steroids. The method has been fully validated for 21 target compounds (8 glucuronide, 1 sulfate and 12 free steroids) and 18 out of 21 compounds had detection limits in the range of 1–10 ng mL^?1 in urine. For the conjugated compounds, for which no reference standards are available, metabolites were synthesized in vitro or excretion studies were investigated. The detection limits for these compounds ranged between 0.5 and 18 ng mL^?1 in urine. The simple and straightforward methodology complements the traditional methods based on hydrolysis, liquid‐liquid extraction, derivatization and analysis by gas chromatography–mass spectrometry (GC‐MS) and liquid chromatography‐mass spectrometry (LC‐MS). Copyright © 2014 John Wiley & Sons, Ltd.     

Malignant pheochromocytomas. Apropos of a case with multiple metastatic localizations

We are reporting a case of malignant pheochromocytoma surgically treated initially for an isolated left pararenal localization, and which recurred several years later accompanied with numerous metastases. Despite of a treatment with Iodine 131 MIBG, the evolution was rapidly fatal with a picture of cardiac failure. This cardiac involvement would be linked to a myocarditis directly secondary to the catecholamines and causing a marked increase of the free fatty acids concentration in the heart tissue. In reference to this case, all the data which may tend to suspect the malignant nature of a pheochromocytoma, present in 10 p. cent of the cases, are successively reviewed. There is no clinical specificity. The presence of a mixed secretion with marked urinary dopamine secretion, would not present, for all authors, the same criteria of specificity. Thoraco-abdominal scan and scintigraphy with iodine 131 MIBG are the two tests permitting to demonstrate, with a great sensitivity and specificity, an extra-adrenal localization, which is the best argument in favor of a malignancy since 30 to 40 p. cent of extra-adrenal pheochromocytomas are malignant, more especially as the metastases are located in areas where there are no embryonic remnants of tissues containing chromaffin cells. This permits to appreciate the difference between a non-malignant multicentric pheochromocytoma and a malignant pheochromocytoma. The ideal treatment of a malignant pheochromocytoma rests on surgery under the condition that there are ony one or two metastases. This procedure is preceded by a sodium nitroprusside preparation and followed with an alpha-blockers treatment. In case of multiple metastases, the therapeutic use of iodine 131 MIBG seems to be a tempting alternative.     

Risk Selection into Consumer‐Directed Health Plans: An Analysis of Family Choices within Large Employers

Objective

To identify the degree of selection into consumer-directed health plans (CDHPs) versus traditional plans over time, and factors that influence choice and temper risk selection.

Data Sources/Study Setting

Sixteen large employers offering both CDHP and traditional plans during the 2004–2007 period, more than 200,000 families.

Study Design

We model CDHP choice with logistic regression; predictors include risk scores, in addition to family, choice setting, and plan characteristics. Additional models stratify by account type or single enrollee versus family.

Data Collection/Extraction Methods

Risk scores, family characteristics, and enrollment decisions are derived from medical claims and enrollment files. Interviews with human resources executives provide additional data.

Principal Findings

CDHP risk scores were 74 percent of traditional plan scores in the first year, and this difference declined over time. Employer contributions to accounts and employee premium savings fostered CDHP enrollment and reduced risk selection. Having to make an active choice of plan increased CDHP enrollment but also increased risk selection. Risk selection was greater for singles than families and did not differ between HRA and HSA-based CDHPs.

Conclusions

Risk selection was not severe and it was well managed. Employers have effective methods to encourage CDHP enrollment and temper selection against traditional plans.     

Bone Response to High-Intensity Interval Training versus Moderate-Intensity Continuous Training in Adolescents with Obesity

IntroductionSince adolescents with obesity are prone to bone fragility during weight loss, the aim was to compare the impact of high-intensity interval training (HIIT) versus moderate-intensity continuous training (MICT) on bone density, geometry, and strength.MethodsSixty-one adolescents were randomly assigned to 2 cycling trainings (HIIT and MICT) and a control (CTR, without training) group. Anthropometry, dual-energy X-ray absorptiometry with hip structural analysis and the trabecular bone score (TBS) were assessed before and after the 16-week intervention.ResultsBody mass index (BMI) and fat mass (FM) percentage decreased at T1 versus T0 in both training groups (p < 0.001 for HIIT, p = 0.01 for MICT), though to a larger extent in HIIT (p < 0.05). Total body bone mineral density (BMD) and bone mineral content (BMC) increased in both training groups (p < 0.001), but to a greater extent in HIIT for BMC (p < 0.05). Lumbar spine BMD and BMC increased in both training groups (p < 0.001 for HIIT, p < 0.01 for MICT), with a time × group interaction between HIIT and CTR (p < 0.05) only. TBS increased in both training groups (p < 0.01 for HIIT, p < 0.05 for MICT). Hip BMD and BMC increased in both HIIT (p < 0.001 and p < 0.01) and MICT (p < 0.01 and p < 0.05). At the narrow neck (NN), endocortical diameter, width (p < 0.01), cross-sectional moment of inertia, and section modulus (Z) (p < 0.05) increased only in the HIIT group, such as BMD and Z (p < 0.05) at the intertrochanteric region (IT) and average cortical thickness (p < 0.001) and width (p < 0.05) at the femoral shaft. At the NN and IT, the buckling ratio decreased only in the HIIT group (p < 0.05), predicting higher resistance to fracture.ConclusionsIn addition to inducing greater BMI and FM percentage decreases in comparison to MICT, HIIT improves multisite bone density, geometry, and strength, which heighten the justification for HIIT as part of weight loss interventions in adolescents with obesity.     

Chediak-Higashi disease: a new case treated by bone marrow allograft

We report a new case of Chediak-Higashi disease successfully treated by the transplantation of allogeneic bone marrow. Recurrent infections led to the diagnosis of the disease at the age of 15 months. At two and a half years of age, during a phase of accelerated disease activity, the patient received a bone marrow transplant donated by an HLA-identical brother. The patient was conditioned by chemotherapy alone; T-cells were removed from the graft and cyclosporin A was given to prevent graft-versus-host disease. Evidence of acceptance of the transplant was apparent 14 days after the procedure. Two months after the transplant, the blood count was normal, NK activity was satisfactory and no evidence of GVH disease was present. Incomplete hematopoietic chimerism was found (with two erythrocyte and lymphocyte populations). After four years follow-up, the patient is doing well and has no infections or evidence of active disease.     

Preoperative chemotherapy for hypopharyngeal carcinoma

Twenty patients with advanced squamous cell carcinoma of the hypopharynx received two courses of chemotherapy with cisplatinum, vincristine and bleomycin before undergoing surgery. The chemotherapy was well tolerated, with minimal toxicity and no intra or postoperative complications attributable to it. The response to the chemotherapy was dramatic with all but 2 patients exhibiting a greater than 50% tumor shrinkage. Only 3 patients, all with positive surgical margins, received postoperative radiation therapy. Surgical salvage of recurrent lesions was performed on 2 patients who are now free of disease. With a median follow-up of 20 months, 1 patient has died of recurrent disease, 3 have died of other causes, all others remain free of disease.