Direct effect on validity of response run-in selection in clinical trials

A run-in is a period prior to randomization during which potential participants who have met all entry criteria for a randomized clinical trial are assigned the same regimen, either the control (possibly placebo) or the experimental treatment. Typically, the intention is to exclude from the subsequent study (i.e., randomization) some segment of this cohort, based on their experiences during the run-in period. Selecting patients based on the run-in thereby forces differential representation of certain subpopulations relative to others. Previous studies have addressed the potential for a run-in to jeopardize validity through unintended mechanisms. While these concerns are valid, they leave open the possibility that modifications to the design of the run-in might be able to preserve validity, even if patient selection is based on the results of the run-in. As such, we address the potential for selecting patients based on response during a run-in period to jeopardize validity directly, through its intended effect of overrepresenting (relative to the screened population) some segments in the randomized portion of the trial and underrepresenting others.     

Empirical treatment of lower urinary tract infections in the face of spreading multidrug resistance: in vitro study on the effectiveness of nitroxoline

The spread of antimicrobial resistance challenges the empirical treatment of urinary tract infections (UTIs). Among others, nitrofurantoin is recommended for first-line treatment, but acceptance among clinicians is limited due to chronic nitrofurantoin-induced lung toxicity and insufficient coverage of Enterobacteriaceae other than Escherichia coli. Nitroxoline appears to be an alternative to nitrofurantoin owing to its favourable safety profile, however data on its current in vitro susceptibility are sparse. In this study, susceptibility to nitroxoline was tested against 3012 urinary clinical isolates (including multidrug-resistant bacteria and Candida spp.) by disk diffusion test and/or broth microdilution. At least 91% of all Gram-negatives (n?=?2000), Gram-positives (n?=?403) and yeasts (n?=?132) had inhibition zone diameters for nitroxoline ≥18?mm. Except for Pseudomonas aeruginosa, nitroxoline MIC₉₀ values were ≤16?mg/L and were 2- to >16-fold lower compared with nitrofurantoin. In extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and methicillin-resistant Staphylococcus aureus (MRSA), MIC₉₀ values of nitroxoline were two-fold higher compared with non-ESBL-producing enterobacteria and methicillin-susceptible S. aureus (MSSA). The in vitro efficacies of nitroxoline and nitrofurantoin against ATCC strains of E. coli, Enterococcus faecalis and Proteus mirabilis were compared by time–kill curves in Mueller–Hinton broth and artificial urine. Nitroxoline was non-inferior against E. coli, P. mirabilis and E. faecalis in artificial urine. In conclusion, nitroxoline showed a broad antimicrobial spectrum, with inhibition zone diameters and MICs of nitroxoline well below the EUCAST breakpoint for E. coli for most organisms, and thus may also be a target for therapy of uncomplicated UTIs.     

Apoptosis in Primary Hyperparathyroidism

Primary hyperparathyroidism (PHPT) is defined by inappropriate elevation of parathormone, caused by parathyroid hyperplasia, also known as multi-gland disease (MGD), parathyroid adenoma (PA), or parathyroid carcinoma (PC). Although several studies have already been conducted, there is a lack of a definite diagnostic marker, which could unambiguously distinguish MGD from PA or PC. The accurate and prompt diagnosis has the key meaning for effective treatment and follow-up. This review paper presents the role of apoptosis in PHPT. The comparison of the expression of Fas, TRAIL, BCL-2 family members, p53 in MGD, PA, and PC, among others, was described. The expression of described factors varies among proliferative lesions of parathyroid gland; therefore, these could serve as additional markers to assist in the diagnosis.     

Accessory spleens--diagnostic and therapeutic problem of the laparoscopic splenectomy in idiopathic thrombocytopenic purpura patients

The preoperative detection of accessory spleens (AS) is essential in ITP patients. The aim of this study was to evaluate the reasons of failure and long-term results of laparoscopic splenectomy (LS) in patients with idiopathic thrombocytopenic purpura (ITP). Thirty-four ITP patients (27 females and 7 males) underwent LS between June 1998 and January 2001. Computed Tomography (CT) and sonography (US) were performed preoperatively to evaluate the size of the spleen and to detect the presence of possible accessory spleens which were found in two cases. AS were seen during laparoscopy in three cases. During follow-up (median time = 23 months), in three patients a low platelet count was seen after 5 months, 1.5 and 1.8 years pop. In all these cases scintigraphy was performed, which revealed in one case the residual accessory spleen. In the two other patients, inspite of thrombocytopenia no residual spleens were found. The authors conclude that laparoscopic splenectomy is a safe and effective procedure in patients with ITP. The problem of accessory spleens can be managed by careful videoscopic examination of the abdominal cavity during splenectomy. The use of the preoperative imaging techniques for detection of accessory spleens is limited by the insufficient sensitivity of the examination.     

Comparison of two groups of patients with serous and mucinous types of borderline ovarian tumors

OBJECTIVE: The retrospective comparison of two groups of patients with the most common types of borderline ovarian tumors (BTO): serous and mucinous. METHODS: All patients were treated between 1978 and 2000 at the 2nd Department of Obstetrics and Gynecology Medical University of Gdańsk. The first group consisted of 58 patients with serous BTO. The second group consisted of 48 patients with mucinous BTO. These groups were compared according to such parameters: age at diagnosis, parity, clinical symptoms, localization of tumor, tumor size, type of operation, stage of disease, utilization of adjuvant therapy, presence of recurrence and 5-year survival. Statistical comparisons were made by the chi 2 test. The clinical life table analysis was performed to determine 5-year survival and comparisons were made by means of the Long Rank tests. RESULTS: The mean age of serous BTO was 53.1 +/- 12.8 and of mucinous BTO 43.3 +/- 17.9 (p = 0.0000). In the first group 15.5% and in the second 43.8% women were nullipara (p = 0.0602). The main symptom of serous BTO was pain--53.5% patients and that of mucinous BTO increasing girth--47.9% patients (p = 0.0456). The mean size of serous BTO was 13.7 +/- 6.9 cm and that of mucinous BTO was 20.3 +/- 9.5 cm (p = 0.004). 43 patients (89.6%) with mucinous and 28 patients (48.3%) with serous BTO were at I A stage and 9 patients (15.5%) with serous and only one (2.1%) with mucinous were at III stage (p = 0.0008). The mucinous BTO--affected were more frequently treated conservatively than serous BTO--ones which were rather treated radically with using adjuvant therapy (p = 0.003). Residual disease was observed mainly in patients with serous BTO. 5-years survival was better in patients with mucinous BTO, 87.7% and 85.2% respectively (p = 0.0001). CONCLUSIONS: 1. The mucinous BTO occurred more frequently than serous BTO in women of the childbearing age. 2. The extraovarian disease was observed more often with serous BTO than the mucinous BTO. 3. The mucinous BTO was usually bigger than serous BTO and mainly affected only one ovary. 4. The mucinous BTO was more frequently treated conservatively than serous BTO which were rather treated radically with use of adjuvant therapy. 5. The recurrence rate was higher and the 5-year survival was worse in patients with serous BTO.     

Pregnancy and delivery after conservative treatment of borderline ovarian tumor with FIGO stage III C--a case report

This study presents a case of pregnancy after conservative surgical treatment of borderline ovarian tumor with III C stage according to FIGO classification. The caesarean section in 37 week of pregnancy was performed and connected with very precise staging. In normal-appearing both ovaries the foci of borderline ovarian tumor were found. There were no foci of borderline ovarian tumor or foci of invasive carcinoma in tissues routinely sampled during the second look operation. All benefits and costs of conservative surgical approaches to very young, childless women with advanced borderline ovarian tumor were exactly estimated.     

Quality of Life Improvement after Videothoracoscopic Splanchnicectomy in Chronic Pancreatitis Patients: Case Control Study

The authors report on the effectiveness of videothoracoscopic splanchnicectomy (VSPL) as a method of pain treatment in patients with chronic pancreatitis (CP). A minimally invasive technique, VSPL is used in CP as an alternative method of pain treatment. The aim of the investigation was to evaluate by a prospective, semirandomized case-control study the influence of VSPL on the quality of life and the level of pain suffered by patients with CP. The study groups consisted of 32 patients who underwent VSPL between March 2000 and January 2001 and a control group of 32 CP patients who received conservative treatment. The effect of the therapy on subjective pain measures and multiparametric quality of life was measured before VSPL and throughout the first year thereafter. In the follow-up period there was a significant decrease in intensity of pain and an improvement in the quality of life of the patients—most significantly concerning emotional well-being and functioning in everyday life. We conclude that the VSPL is a safe, effective, and minimally invasive procedure and recommend that it be used in such cases.     

Nineteen year old patient with serous ovarian tumors of low malignant potential with non-invasive peritoneal implants: a case report

10-15% of ovarian epithelial tumors are the borderline ovarian tumors (BOT-s). The prognosis in those cases is excellent with 5-years survival rates in the range of 95% in Stage I. The most of women suffering from BOT-s are young and they have not got any children. The distinct biology of this illness makes possible to change previous treatment of ovarian cancers. We are able operate the young women planning maternity in conservative way (uni or bilateral cystectomy, adnexectomy). We present a case of young woman with BOT-s with non-invasive peritoneal implants. The bilateral cystectomy, omentectomy and staging was done. At present this woman is in 16 week pregnancy with good health. This confirms rightness of conservative treatment in BOT-s.     

The new IAEA-372 grass-certified reference material for (40)K and (137)Cs.

A new grass-certified reference material characterized for (137)Cs and (40)K has been issued by the International Atomic Energy Agency. Characterization of this material was conducted by a group of national metrological institutes and expert laboratories. The paper describes the process for assigning the certified reference value to the material.