Hypocapnia during hypoxic exercise and its impact on cerebral oxygenation,ventilation and maximal whole body O2 uptake

With hypoxic exposure ventilation is elevated through the hypoxic ventilatory response. We tested the hypothesis that the resulting hypocapnia reduces maximal exercise capacity by decreasing (i) cerebral blood flow and oxygenation and (ii) the ventilatory drive.     

Increased risk of pneumonia among ventilated patients with traumatic brain injury: every day counts!

Background

Patients with traumatic brain injury (TBI) frequently require mechanical ventilation (MV). The objective of this study was to examine the association between time spent on MV and the development of pneumonia among patients with TBI.

Materials and methods

Patients older than 18 y with head abbreviated injury scale (AIS) scores coded 1–6 requiring MV in the National Trauma Data Bank 2007–2010 data set were included. The study was limited to hospitals reporting pneumonia cases. AIS scores were calculated using ICDMAP-90 software. Patients with injuries in any other region with AIS score >3, significant burns, or a hospital length of stay >30 d were excluded. A generalized linear model was used to determine the approximate relative risk of developing all-cause pneumonia (aspiration pneumonia, ventilator-associated pneumonia [VAP], and infectious pneumonia identified by the International Classification of Disease, Ninth Revision, diagnosis code) for each day of MV, controlling for age, gender, Glasgow coma scale motor score, comorbidity (Charlson comorbidity index) score, insurance status, and injury type and severity.

Results

Among the 24,525 patients with TBI who required MV included in this study, 1593 (6.5%) developed all-cause pneumonia. After controlling for demographic and injury factors, each additional day on the ventilator was associated with a 7% increase in the risk of pneumonia (risk ratio 1.07, 95% confidence interval 1.07–1.08).

Conclusions

Patients who have sustained TBIs and require MV are at higher risk for VAP than individuals extubated earlier; therefore, shortening MV exposure will likely reduce the risk of VAP. As patients with TBI frequently require MV because of neurologic impairment, it is key to develop aggressive strategies to expedite ventilator independence.     

Which Antithrombin for Whom? Identifying the Patient Population that Benefits Most from Novel Antithrombin Agents

Anticoagulation has proven to be a key component in the management of acute coronary syndromes (ACS). Pharmacological agents with various modes of action are utilized to reduce thrombus development by impairing thrombin formation, platelet activation, and platelet aggregation. The optimal management of these patients is to achieve maximal anti-ischemic benefit while avoiding bleeding complications. Synthetic "novel" agents have been developed to specifically target factor Xa or thrombin to achieve this goal. A growing amount of data show that these agents provide a net clinical benefit in the setting of stable ischemic heart disease, unstable angina, non-ST-elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI).     

Promising performance of chemically exfoliated Zr-doped MoS2 nanosheets for catalytic and antibacterial applications

Nanostructured materials incorporated with biological reducing agents have shown significant potential for use in bactericidal applications. Such materials have also demonstrated considerable efficacy to counter effects of chemical toxicity. In this study, nanostructured molybdenum disulfide (MoS₂) was doped with various concentrations (2.5, 5, 7.5, 10 wt%) of zirconium (Zr) using a hydrothermal route in order to assess its antimicrobial and catalytic potential. Doped and control samples were characterized with various techniques. X-ray diffraction (XRD) analysis confirmed the presence of the hexagonal phase of MoS₂ and identification of various functional groups and characteristic peaks (Mo bonding) was carried out using FTIR spectra. Micrographs obtained from FESEM and HR-TEM showed a sheet-like surface morphology, while agglomeration of nanosheets was observed upon doping with nanoparticles. To seek further clarity regarding the layered features of S–Mo–S planes, the defect densities and electronic band structure of pure MoS₂ and doped MoS₂ samples were investigated through Raman analysis. Optical properties of Zr-doped MoS₂ nanosheets were assessed using a UV-vis spectrophotometer and the results indicated a red-shift, i.e., movement of peaks towards longer wavelengths, of the material. Dynamics of migration and recombination of excited electron–hole pairs were investigated using PL spectroscopy, which was also used to confirm the presence of exfoliated nanosheets. In addition, the synthetic dye degradation potential of pure and doped samples was investigated in the presence of a reducing agent (NaBH₄). It was noted that doped MoS₂ showed superior catalytic activity compared to undoped MoS₂. The nanocatalyst synthesized in this study exhibited enhanced antibacterial activity against E. coli and S. aureus at high concentrations (0.5, 1.0 mg/50 μl). The present study suggests a cost-effective and environmentally friendly material that can be used to remove toxins such as synthetic dyes and tannery pollutants from industrial wastewater.

Nanostructured materials incorporated with biological reducing agents have shown significant potential for use in bactericidal applications.     

A Randomized,Double-Blind,Dose-Finding,Multicenter, Phase 2 Study of Radium Chloride (Ra 223) in Patients with Bone Metastases and Castration-Resistant Prostate Cancer

Background

Patients with castration-resistant prostate cancer (CRPC) and bone metastases have an unmet clinical need for effective treatments that improve quality of life and survival with a favorable safety profile.

Objective

To prospectively evaluate the efficacy and safety of three different doses of radium chloride (Ra 223) in patients with CRPC and bone metastases.

Design, setting, and participants

In this phase 2 double-blind multicenter study, 122 patients were randomized to receive three injections of Ra 223 at 6-wk intervals, at doses of 25 kBq/kg (n = 41), 50 kBq/kg (n = 39), or 80 kBq/kg (n = 42). The study compared the proportion of patients in each dose group who had a confirmed decrease of ≥50% in baseline prostate-specific antigen (PSA) levels.

Outcome measurements and statistical analysis

Efficacy was evaluated using blood samples to measure PSA and other tumor markers, recorded skeletal-related events, and pain assessments. Safety was evaluated using adverse events (AEs), physical examination, and clinical laboratory tests. The Jonckheere-Terpstra test assessed trends between groups.

Results and limitations

The study met its primary end point with a statistically significant dose–response relationship in confirmed ≥50% PSA declines for no patients (0%) in the 25-kBq/kg dose group, two patients (6%) in the 50-kBq/kg dose group, and five patients (13%) in the 80-kBq/kg dose group (p = 0.0297). A ≥50% decrease in bone alkaline phosphatase levels was identified in six patients (16%), 24 patients (67%), and 25 patients (66%) in the 25-, 50-, and 80-kBq/kg dose groups, respectively (p < 0.0001). The most common treatment-related AEs (≥10%) occurring up to week 24 across all dose groups were diarrhea (21%), nausea (16%), and anemia (14%). No difference in incidence of hematologic events was seen among dose groups. Potential limitations include small patient numbers and differences among dose groups at baseline.

Conclusions

Ra 223 had a dose-dependent effect on serum markers of CRPC activity, suggesting that control of bone disease with Ra 223 may affect cancer-related outcomes. Ra 223 was well tolerated at all doses.

Trial registration

ClinicalTrials.gov: NCT00337155.     

Qualität in der klinischen Forschung

Clinical research—characteristics

Clinical research is a key component of developed health care systems, a major driving force of medical innovation, and, of course, an integral part of the German Federal Statutory Accident Insurance System. Specific institutions and well-trained experts are needed to cope with the rapidly emerging methodological, ethical, and administrative mandates of clinical research.

Quality assurance and independence

Similar to other areas of health care, clinical research must demonstrate and maintain a high degree of structural and process quality. Yet, it can be shown that this increases the internal and external validity of research findings, as well as their likelihood of publication in renowned scientific journals. Apart from content validity, the relationship between individual investigators, their institutions, as well as public and commercial sponsors must be disclosed to maintain the integrity of research.     

Health and wellbeing of Victorian adults with intellectual disability compared to the general Victorian population

Multiple measures of health and wellbeing of people with intellectual disability (ID) and the general Victorian population were compared using representative population level data. The sample consisted of adults with ID (N = 897) and the general Victorian population (N = 34,168) living in the state of Victoria in Australia. Proxy respondents were interviewed on behalf of people with ID, while respondents from the general Victorian population were interviewed directly. The data were weighted to reflect the age/sex/geographic distribution of the population. Results revealed that adults with ID reported higher prevalence of poor social determinants of health, behavioural risk factors, depression, diabetes, poor or fair health. A higher proportion of people with ID reported blood pressure and blood glucose checks, while a lower proportion reported cervical and breast cancer screening, compared with the general Victorian population. The survey identified areas where targeted approaches may be undertaken to improve the health outcomes of people with ID and provide an important understanding of the health and wellbeing of these Victorians.