Insulin related lipodystrophic lesions and hypoglycemia: Double standards?

Lipohypertophy (LH) is the most common skin complication of incorrect injection technique which does not only represent an aesthetic defect but also severely disrupts insulin pharmacokinetics/pharmacodynamics. As a consequence of that, hormone release is delayed and unexplained/unpredictable hypoglycemia occurs, both deteriorating metabolic control while negatively affecting adherence to treatment and quality of life. The economic burden due to unwanted intra-LH injections is accounted for by inappropriately high insulin requirements, increased emergency-related hospitalizations, and loss of work days. Greater attention has to be paid by diabetes care teams to education programs with periodic refreshers to achieve better metabolic control and reduce the economic burden of diabetes.     

Copula selection models for non-Gaussian outcomes that are missing not at random

Missing not at random (MNAR) data pose key challenges for statistical inference because the substantive model of interest is typically not identifiable without imposing further (eg, distributional) assumptions. Selection models have been routinely used for handling MNAR by jointly modeling the outcome and selection variables and typically assuming that these follow a bivariate normal distribution. Recent studies have advocated parametric selection approaches, for example, estimated by multiple imputation and maximum likelihood, that are more robust to departures from the normality assumption compared with those assuming that nonresponse and outcome are jointly normally distributed. However, the proposed methods have been mostly restricted to a specific joint distribution (eg, bivariate t-distribution). This paper discusses a flexible copula-based selection approach (which accommodates a wide range of non-Gaussian outcome distributions and offers great flexibility in the choice of functional form specifications for both the outcome and selection equations) and proposes a flexible imputation procedure that generates plausible imputed values from the copula selection model. A simulation study characterizes the relative performance of the copula model compared with the most commonly used selection models for estimating average treatment effects with MNAR data. We illustrate the methods in the REFLUX study, which evaluates the effect of laparoscopic surgery on long-term quality of life in patients with reflux disease. We provide software code for implementing the proposed copula framework using the R package GJRM .     

Multicenter phase II study of chemo-immunotherapy in the treatment of metastatic renal cell carcinoma

The purpose of this study was to evaluate the potential efficacy of a chemo-immunotherapy regimen for the treatment of metastatic renal cell carcinoma (MRCC). Forty-one patients with progressing MRCC and with a median age of 63 years were recruited. Planned treatment consisted of 6 courses of capecitabine 1000 mg/m twice daily on days 1 to 14 every 4 weeks, pegylated alpha-interferon 2b 50 microg every week, interleukin-2 1.8 M IU subcutaneously, and oral 13-cis-retinoic acid 0.5 mg/kg, all given 5 days/wk, 3 weeks of each month. After 6 courses of concomitant biochemotherapy, biotherapy was continued in patients who had a clinical benefit. The primary end point was response; secondary end points were the evaluation of the immunologic parameters, toxicity, progression-free, and overall survival. The treatment was well-tolerated. Grade 3 and 4 neutropenia and thrombocytopenia occurred in 5% and 7% of patients, respectively. The overall response rate in the 41 evaluable patients was 53.6% (95% confidence interval 37%-69%). Median progression-free and overall survivals were 14.7 and 27.8 months, respectively. A sustained improvement in all evaluated immunologic parameters was observed in the 36 patients treated with maintenance biotherapy. Six cycles of biochemotherapy, being followed by maintenance immunotherapy is well-tolerated and shows significant activity in patients with MRCC.     

Triptorelin depot for the treatment of children 2 years and older with central precocious puberty

Introduction: Triptorelin depot is largely used to treat central precocious puberty (CPP) in children.

Areas covered: This review updates triptorelin depot treatment of CPP, focusing on trials that compared 3.75 mg/28 day treated and untreated children till the adult height (AH). Efficacy of the new 11.25 mg/90 days or 22.5 mg/6 month formulations in suppressing pituitary–gonadal axis in short-term trials is also addressed. Short- and long-term safety was summarized.

Expert commentary: Long experience on triptorelin depot use in children with CPP is available. Outcome differences on AH are reported; they may be due to heterogenicity of treated patients; some items remain to be optimized. No long term-adverse events on reproductive function are reported; additional studies would clarify if CPP per sè or triptorelin depot administration may increase hyperandrogenism and/or polycystic ovary syndrome risk in adulthood. The quarterly formulation seems to be able to suppress pituitary–gonadal axis and pubertal development and to determine similar end-results as monthly formulation, but additional trials are needed. Few data are available for the 22.5 mg/6 month formulation. Triptorelin depot treatment of CPP should be restricted to tertiary pediatric endocrinology centers, considering that some uncertainties still exist and that rare but serious adverse events may occur.     

A new technique for bone augmentation and papilla reconstruction with autogenous free gingival-bone grafts

Autogenous grafting of gingival or bone tissue is often indicated to obtain optimal esthetics and function in periodontal and implant therapy. In the present study, 32 maxillary teeth were extracted, and the postextraction defects were treated with 32 autogenous cylindric free gingival-bone grafts retrieved with trephine burs from intraoral donor sites. Free gingival-bone grafts were also used to obtain root coverage and papilla reconstruction in three patients who required esthetic enhancement. Twelve to 16 weeks after the graft procedure, biopsies were retrieved and processed for histologic evaluation to verify integration of the grafts. The implants placed in the treated sites healed without complications and were functionally loaded after healing. The clinical and histologic results of this study suggest that the free gingival-bone graft technique may favor hard and soft tissue reconstruction of the sites treated, with esthetic and functional advantages.     

Gabapentin in the treatment of severe sweating experienced by advanced cancer patients

Nine patients with advanced cancer suffering from idiopathic severe sweating were treated with gabapentin (600–1,800 mg/day). All patients responded to the treatment; five patients experienced transient drowsiness. Gabapentin seems to be a safe and effective treatment for idiopathic sweating in advanced cancer patients. Further studies are warranted to confirm or refute these results.