Silent onset of postmenopausal endometriosis in a woman with renal failure in hormone replacement therapy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Postmenopausal endometriosis is a rare form of a common disease, since the absence of estrogenic hormone production should halt disease progression.</p> <p>Case presentation</p> <p>We present the case of a 54-year-old Italian Caucasian woman in surgical menopause with a history of ovarian endometriosis, who underwent voluntary hormone replacement therapy for seven years. She developed postrenal renal failure due to bilateral compression of the pelvic ureteral tract caused by two large, deeply infiltrating endometriotic nodules with no pelvic pain. She underwent operative laparoscopy with adhesiolysis of enteroenteric adhesions and excision of the endometriotic nodules encompassing the juxtavesical tract of the ureters, without obtaining improvement of renal failure.</p> <p>Conclusion</p> <p>Postmenopausal endometriosis can manifest itself in an unpredictable and potentially very serious manner. It is therefore important to carefully evaluate the risks and benefits of administering hormone replacement therapy to patients with previous endometriosis.</p

Synthesis, antitubercular activity and mechanism of resistance of highly effective thiacetazone analogues

Defining the pharmacological target(s) of currently used drugs and developing new analogues with greater potency are both important aspects of the search for agents that are effective against drug-sensitive and drug-resistant Mycobacterium tuberculosis. Thiacetazone (TAC) is an anti-tubercular drug that was formerly used in conjunction with isoniazid, but removed from the antitubercular chemotherapeutic arsenal due to toxic side effects. However, several recent studies have linked the mechanisms of action of TAC to mycolic acid metabolism and TAC-derived analogues have shown increased potency against M. tuberculosis. To obtain new insights into the molecular mechanisms of TAC resistance, we isolated and analyzed 10 mutants of M. tuberculosis that were highly resistant to TAC. One strain was found to be mutated in the methyltransferase MmaA4 at Gly101, consistent with its lack of oxygenated mycolic acids. All remaining strains harbored missense mutations in either HadA (at Cys61) or HadC (at Val85, Lys157 or Thr123), which are components of the bhydroxyacyl-ACP dehydratase complex that participates in the mycolic acid elongation step. Separately, a library of 31 new TAC analogues was synthesized and evaluated against M. tuberculosis. Two of these compounds, 15 and 16, exhibited minimal inhibitory concentrations 10-fold lower than the parental molecule, and inhibited mycolic acid biosynthesis in a dose-dependent manner. Moreover, overexpression of HadAB HadBC or HadABC in M. tuberculosis led to high level resistance to these compounds, demonstrating that their mode of action is similar to that of TAC. In summary, this study uncovered new mutations associated with TAC resistance and also demonstrated that simple structural optimization of the TAC scaffold was possible and may lead to a new generation of TAC-derived drug candidates for the potential treatment of tuberculosis as mycolic acid inhibitors

Approaches to interim analysis of cancer randomised clinical trials with time to event endpoints: A survey from the Italian National Monitoring Centre for Clinical Trials

<p>Abstract</p> <p>Background</p> <p>Although interim analysis approaches in clinical trials are widely known, information on current practice of planned monitoring is still scarce. Reports of studies rarely include details on the strategies for both data monitoring and interim analysis. The aim of this project is to investigate the forms of monitoring used in cancer clinical trials and in particular to gather information on the role of interim analyses in the data monitoring process of a clinical trial. This study focused on the prevalence of different types of interim analyses and data monitoring in cancer clinical trials.</p> <p>Methods</p> <p>Source of investigation were the protocols of cancer clinical trials included in the Italian registry of clinical trials from 2000 to 2005. Evaluation was restricted to protocols of randomised studies with a time to event endpoint, such as overall survival (OS) or progression free survival (PFS). A template data extraction form was developed and tested in a pilot phase. Selection of relevant protocols and data extraction were performed independently by two evaluators, with differences in the data assessment resolved by consensus with a third reviewer, referring back to the original protocol. Information was obtained on a) general characteristics of the protocol b) disease localization and patient setting; c) study design d) interim analyses; e) DSMC.</p> <p>Results</p> <p>The analysis of the collected protocols reveals that 70.7% of the protocols incorporate statistical interim analysis plans, but only 56% have also a DSMC and be considered adequately planned. The most concerning cases are related to lack of any form of monitoring (20.0% of the protocols), and the planning of interim analysis, without DSMC (14.7%).</p> <p>Conclusion</p> <p>The results indicate that there is still insufficient attention paid to the implementation of interim analysis.</p

Drug utilization and cost in a Medicaid population: A simulation study of community vs. mail order pharmacy

<p>Abstract</p> <p>Background</p> <p>Outpatient drugs are dispensed through both community and mail order pharmacies. There is no empirical evidence that substitution of community pharmacy with mail order reduces overall drug expenditures. The need for evaluating the potential effects on utilization and costs of the possible extension of mail order services in Medicaid provides the rationale for conducting this study. This study compares drug utilization and drug product cost in community vs. mail order pharmacy dispensing services in a Medicaid population.</p> <p>Methods</p> <p>This study is a retrospective cohort study comparing utilization and cost patterns in community vs. mail order pharmacy. A simulation model was employed to assess drug utilization and cost in mail order pharmacy using community pharmacy claim data. The model assumed that courses of drug therapy (CDT) in mail order pharmacy would have utilization patterns similar to those found in community pharmacy. A 95% confidence interval surrounding changes in average utilization and average cost were estimated using bootstrap analysis. A sensitivity analysis was performed by varying drug selection criteria and supply, fill point, and medication possession ratio (MPR). Sub-analyses were performed to address differences between mail order and community pharmacy related to therapeutic class and dual-eligible patients.</p> <p>Data for the study derived from pharmacy claims database of Ohio Medicaid State program for the period January 2000-September 2004. Drug claims were aggregated to obtain a set of CDTs representing unique patient IDs and unique drug products. Drug product cost estimates excluded dispensing fees and were used to estimate the cost reduction required in mail order to become cost neutral in comparison with community pharmacy.</p> <p>Results</p> <p>The baseline model revealed that the use of mail order vs. community pharmacy would result in a 5.5% increase in drug utilization and a 5.4% cost reduction required in mail order to become cost neutral. Results from Ohio Medicaid drugs for chronic use revealed a 5.1% increase in utilization and a 4.9% cost reduction required to become cost neutral in comparison with community pharmacy.</p> <p>Conclusion</p> <p>The results of the simulation model indicate that mail order pharmacy increases drug utilization and can also increase drug product cost if the cost per unit is not reduced accordingly. Prior consideration should be given to the patient population, day-supply, disease, therapy, and insurance characteristics to ensure the appropriate use of mail order pharmacy services.</p

Motor development of children with attention deficit hyperactivity disorder

Objective: To compare both global and specific domains of motor development of children with attention deficit hyperactivity disorder (ADHD) with that of typically developing children. Methods: Two hundred children (50 children with clinical diagnoses of ADHD, according to the DSM-IV-TR and 150 typically developing controls), aged 5 to 10 years, participated in this crosssectional study. The Motor Development Scale was used to assess fine and global motricity, balance, body schema, and spatial and temporal organization. Results: Between-group testing revealed statistically significant differences between the ADHD and control groups for all domains. The results also revealed a deficit of nearly two years in the motor development of children with ADHD compared with the normative sample. Conclusion: The current study shows that ADHD is associated with a delay in motor development when compared to typically developing children. The results also suggested difficulties in certain motor areas for those with ADHD. These results may point to plausible mechanisms underlying the relationship between ADHD and motor difficulties

Neck emergency due to parathyroid adenoma bleeding: a case report

<p>Abstract</p> <p>Introduction</p> <p>The spontaneous rupture of a parathyroid adenoma accompanied by extracapsular hemorrhage is a rare, potentially fatal, condition and is a cervicomediastinal surgical emergency.</p> <p>Case presentation</p> <p>This report describes an atypical two-step spontaneous rupture of an asymptomatic parathyroid adenoma in a 56-year-old Caucasian woman who presented with a painful mass in the right side of her neck.</p> <p>Conclusion</p> <p>Based on this case report and similar cases reported in the medical literature, a diagnosis of extracapsular parathyroid hemorrhage should be considered when a non-traumatic sudden neck swelling coexists with hypercalcemia and regional ecchymosis.</p