Results of A trial with topotecan dose escalation and concurrent thoracic radiation therapy for locally advanced, inoperable nonsmall cell lung cancer

: To conduct a dose escalation clinical study with topotecan and concurrent standard dose thoracic irradiation to assess its feasibility and toxicity in the treatment of patients with locally advanced, inoperable nonsmall cell lung cancer (NSCLCA).

: Between April 1993 and August 1994, 12 patients with inoperable, loco-regionally advanced NSCLCA were entered in a prospective dose escalation trial and assigned to receive concurrent thoracic radiotherapy and topotecan. Patients received thoracic irradiation to a total tumor dose of 60 Gy in 30 fractions. Initial fields were to encompass the gross disease plus the mediastinum. Topotecan was delivered by bolus injection days 1 through 5, and days 22 through 26, beginning on the same day as the radiation therapy. The initial dose level was 0.5 mg/m². Two additional dose levels of 0.75 mg/m² and 1.0 mg/m² were tested.

: Six patients were accessioned to the 0.5 mg/m² dose level, three patients to the 0.75 mg/m² dose level, and three patients to the 1.0 mg/m² dose level. At the 0.5 mg/m² dose level, zero of six patients had ≥Grade 4 hematologic toxicity. One of the six had Grade 3 esophagitis. At the 0.75 mg/m² dose level, two of three patients had ≥Grade 3 nonhematologic toxicity including anorexia, fatigue, nausea, vomiting, and weakness; zero patients experienced ≥Grade 4 hematologic toxicity. At the 1.0 mg/m² dose level one of three patients had ≥Grade 3 esophagitis, and two of three patients experienced Grade 4 neutropenia. With a follow-up of 12 to 24 months, two patients are alive and free of disease, three patients are alive with disease (two with distant metastasis, one with local disease and distant metastasis), and the remaining seven patients are dead of disease.

: The combination of topotecan and thoracic radiotherapy for nonsmall lung cancer, in the manner given by this protocol, could be safely given at a dose level of only 0.5 mg/m² days 1 to 5 and 22 to 26 with 60 Gy of external beam radiotherapy. Higher doses of topotecan were associated with high hematologic and gastrointestinal toxicity. Distant metastasis was the primary pattern of failure.     

Effect of pulsed electromagnetic fields on maturation of regenerate bone in a rabbit limb lengthening model

To study the effect of applying pulsed electromagnetic fields (PEMF) during the consolidation phase of limb lengthening, a mid‐tibial osteotomy was performed in 18 adult New Zealand White rabbits and an external fixator was applied anteromedially. Animals were randomly assigned to treatment and control groups. After a 7‐day latency period, the tibiae were distracted 0.5 mm every 12 h for 10 days. The treatment group received a 20‐day course of PEMF for 60 min daily, coinciding with initiation of the consolidation phase. The control group received sham PEMF. Radiographs were performed weekly after distraction. Animals were euthanized 3 weeks after the end of distraction. Radiographic analysis revealed no significant difference in regenerate callus area between treatment and control tibiae immediately after distraction, at 1 week, 2 weeks, or 3 weeks after distraction ( p = 0.71, 0.22, 0.44, and 0.50, respectively). There was also no significant difference in percent callus mineralization ( p = 0.96, 0.69, 0.99, and 0.99, respectively). There was no significant difference between groups with respect to structural stiffness ( p = 0.80) or maximal torque to failure ( p = 0.62). However, there was a significant positive difference in mineral apposition rate between groups during the interval 1–2 weeks post‐distraction ( p < 0.05). This difference was no longer evident by the interval 2–3 weeks post‐distraction. While PEMF applied during the consolidation phase of limb lengthening did not appear to have a positive effect on bone regenerate, it increased osteoblastic activity in the cortical bone adjacent to the distraction site. Since the same PEMF signal was reported to be beneficial in the rabbit distraction osteogenesis when applied during distraction phase and consolidation phase, application of PEMF in the early phase may be more effective. Further work is necessary to determine optimal timing of the PEMF stimulation during distraction osteogenesis. © 2005 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res     

Stabilisierung des dorsalen Beckenrings mit eingeschobener Platte

OBJECTIVE: Minimally invasive stabilization of the posterior pelvic ring in type C injuries. INDICATIONS: Unstable type C injuries of the pelvic ring, uni- or bilateral. - Transsymphyseal-transsacral instability. - Transpubic-transsacral instability. - Transsymphyseal-transsacroiliac instability. - Transpubic-transsacroiliac instability. CONTRAINDICATIONS: Fractures in childhood. Comminuted fractures of the ilium. Patients with skin and soft tissues in a poor condition and/or local infection. Sacral fractures with a neurologic deficit are not a contraindication because they can be decompressed by distraction and stabilized in a neutral position by plate fixation. SURGICAL TECHNIQUE: Nut-shaped osteotomy of the posterior superior iliac spine bilaterally through two short, vertical skin incisions. Tunneling through the muscles of the back to the opposite side. Length measurement for a 4.5-mm pelvic reconstruction plate. The plate is bent by about 70 degrees over the fourth lateral hole. Slide-insertion of the plate and bending of the free plate end for close fit. Cancellous bone screws are inserted into the plate holes. Refixation of the osteotomized bone fragments over the plate with small-fragment, cancellous bone screws. RESULTS: 34 patients with an average age of 42.6 years were treated according to the described method from 1998 to 2005; 18 were polytraumatized. The anterior pelvic ring was also stabilized by surgery in 28 patients for eleven of whom it was the first intervention in a two-stage procedure. 25 patients were available for clinical and radiologic follow-up at 17 months, on average. The plain radiographs after 1 year showed a very good outcome in 16 patients (maximal displacement of the posterior pelvic ring < 5 mm) and a good outcome in eight patients (displacement of 5-10 mm). In two patients there was loss of reduction in the 1st postoperative year despite a very good reduction result immediately postoperatively (dislocation < 5 mm), whereby the dislocation for one patient was < 10 mm on the final radiograph and 19 mm for the other. One patient presented with a late infection 11 weeks postoperatively that healed after implant removal and wound debridement. In two other patients, prominent screw heads, which were used for refixation of the osteotomized posterior superior iliac spine, had to be removed under local anesthesia in the 10th postoperative week. The further course for these two patients was uneventful. In one patient the implants were retrieved in the 5th postoperative month because the patient complained of internal hot and cold sensations although the soft tissue was not irritated. The plates were removed in six other cases after the fracture/instability had healed, i. e., after 9-12 months, on average; in all other cases the implants were left in situ.     

Comparison of blood concentrations of 1,3-butadiene and butadiene epoxides in mice and rats exposed to 1,3-butadiene by inhalation

1,3–Butadiene (BD), an important commodity chemical usedin the production of synthetic rubber, is carcinogenic in B6C3F1mice and Sprague-Dawley rats, raising concern for potentialcarcinogenicity in humans. Mice are more sensitive than ratsto the carcinogenic effects of BD. Metabolic activation of BDto form the putative DNAreactive metabolites, butadiene monoxide(BMO) and butadiene diepoxide (BDE), is mediated by cytochromeP450. Detoxication of the epoxides occurs by glutathione Stransferase-catalyzedconjugation with glutathione and hydrolysis by epoxide hydrolase.Species differences in metabolic activation and detoxicationmost likely contribute to the difference in carcinogenic potencyof BD by modulating the circulating blood levels of the epoxides.This study measured the in vivo concentrations of BD, BMO andBDE in the blood of male Sprague-Dawley rats and B6C3F1 miceduring and following 6 h nose-only exposure to inhaled BD at62.5, 625 or 1250 p.p.m. BD. Blood samples for BD and BMO (     

Survival after hip fracture

Although it is known that overall mortality is increased after hip fracture, the influence of hip fracture risk factors on the subsequent mortality and cause of death has not been well studied. The objective of this study was to establish the survival after hip fracture in women and to assess the impact of comorbidity on mortality. We identified a complete population-based set of 2,245 incident hip fracture cases and 4,035 randomly selected population-based controls among women 50–81 years old in Sweden and followed these subjects for an average of 5 years through the Swedish National Inpatient and Cause-of-Death Registers. Information on factors related to hip fracture was obtained through linkage to hospital discharge data and through a mailed questionnaire. We studied excess mortality of hip fracture patients compared to controls using survival curves and proportional hazard regression models. During follow-up, 896 hip fracture patients (40%) and 516 (13%) controls died. The relative risk (RR) of death, adjusted for age and previous hospitalization for serious disease, was 2.3 (95% CI 2.0–2.5). Although the highest mortality risks were in the 1st 6 months post-fracture, RRs for fractures versus controls were increased for at least 6 years. Increased mortality was apparent both in those with evidence of comorbidity and those without. Hip fracture patients have a substantially increased risk of death that persists for at least 6 years post-fracture. The relative excess mortality is independent of comorbidity and known hip fracture risk factors.The authors represent the Swedish Hip Fracture Study Group, whose members include Akke Alberts, John A. Baron, Thomas Dolk, Bahman Y. Farahmand, Olof Johnell, Lena Lindén, Sverker Ljunghall, Karl Michaëlsson, Gunnar Brobert, Karl-Göran Thorngren, Mats Thorslund, Carl Zetterberg and Lena Zidén.     

Laser-induced collagen remodeling and deposition within the basilar membrane of the mouse cochlea

The cochlea is the mammalian organ of hearing. Its predominant vibratory element, the basilar membrane, is tonotopically tuned, based on the spatial variation of its mass and stiffness. The constituent collagen fibers of the basilar membrane affect its stiffness. Laser irradiation can induce collagen remodeling and deposition in various tissues. We tested whether similar effects could be induced within the basilar membrane. Trypan blue was perfused into the scala tympani of anesthetized mice to stain the basilar membrane. We then irradiated the cochleas with a 694-nm pulsed ruby laser at 15 or 180 Jcm(2). The mice were sacrificed 14 to 16 days later and collagen organization was studied. Polarization microscopy revealed that laser irradiation increased the birefringence within the basilar membrane in a dose-dependent manner. Electron microscopy demonstrated an increase in the density of collagen fibers and the deposition of new fibrils between collagen fibers after laser irradiation. As an assessment of hearing, auditory brainstem response (ABR) thresholds were found to increase moderately after 15 Jcm(2) and substantially after 180 Jcm(2). Our results demonstrate that collagen remodeling and new collagen deposition occurs within the basilar membrane after laser irradiation in a similar fashion to that found in other tissues.     

Prevalence of National Responsiveness to HBV Vaccine After 22 Years of Iranian Expanded Program on Immunization (EPI): A Systematic Review and Meta-Analysis Study

Context:

Hepatitis B Virus expanded program on immunization (EPI) started on 1993 in Iran. Most surveys have assessed the level of response to vaccine by measuring the titers of anti-HBs. This meta- analysis aimed to summarize the Iranian published data on the rate of vaccine-responders versus non-responders. Moreover, the impact of variables such as age, gender, type of vaccine, etc. on the levels of responsiveness was evaluated.

Evidence Acquisition:

All published papers on this topic in Iranian and international journals with affiliation of “Iran” were reviewed using standard keywords up to 2014. We included our study to healthy participants with no previous HBV infection and who had already received a complete course of HB vaccine. The estimated prevalence and 95% confidence intervals in 28 eligible articles for HBV vaccine responders (anti-HBs > 10 IU/mL) and non-responders (10 <) were analyzed by random effect method due to between-study heterogeneity.

Results:

The age of subjects was between 6 months and 15 years old. Overall, 5991 (51.5%) were male and 4571 (48.5%) females. Overall, 80% were responders to vaccine versus 20% nonresponders. With increase in age, the number of responders to vaccine decreased significantly (P = 0.001). There was no strong difference between responders versus nonresponders to vaccine for gender, types of vaccine, ethnicity and living area.

Conclusions:

The results arose from this meta-analysis highlighted the safety of vaccine and its effectiveness in stimulating immune response of vaccines, despite being different in generation, manufacturers and types. Moreover, there was no substantial difference between Iranian and other international investigations in the rate of nonresponsiveness to HBV vaccine.     

Health system drivers of hospital medicine in Canada: Systematic review

Objective

To identify the underlying systemic drivers of the development and ongoing expansion of hospitalist programs in Canada.

Data sources

MEDLINE and Google Scholar were searched using combinations of the terms hospitalist, hospital medicine, and Canada.

Study selection

All publications that addressed the study question, including review articles, original research, editorials, commentaries, and letters or news articles, were included in the review.

Synthesis

Constant comparative methodology was used to analyze and code the articles and to synthesize the identified codes into broader themes. Three broad categories were identified: physician-related drivers, health system–related drivers, and patient-related drivers. Within each category, we identified a number of drivers.

Conclusion

Many drivers have been cited in the literature as reasons behind the emergence and growth of the hospitalist model in the Canadian health care system. While their interplay makes simple cause-and-effect conclusions difficult, these drivers demonstrate that hospitalist programs in Canada have developed in response to a complex set of provider, system, and patient factors.