Combining radiotherapy with AZD2171, a potent inhibitor of vascular endothelial growth factor signaling: pathophysiologic effects and therapeutic benefit

AZD2171 is a highly potent, orally active inhibitor of vascular endothelial growth factor receptor signaling. The potential for AZD2171 to enhance the antitumor effects of radiotherapy was investigated in lung (Calu-6) and colon (LoVo) human tumor xenograft models. Combined treatment resulted in a significantly enhanced growth delay compared with either modality alone. The enhancement was independent of whether chronic once daily AZD2171 treatment was given 2 h prior to each radiation fraction (2 Gy daily for 3 or 5 consecutive days), and daily thereafter, or commenced immediately following the course of radiotherapy. Histologic assessments revealed that 5 days of radiation (2 Gy) or AZD2171 (3 or 6 mg/kg/d) reduced vessel density and perfusion. Concomitant AZD2171 and radiation enhanced this effect and produced a significant increase in tumor hypoxia. Concomitant AZD2171 (6 mg/kg/d) was also found to reduce tumor growth significantly during the course of radiotherapy (5 x 2 Gy). However, the extent and duration of tumor regression observed postradiotherapy was similar to sequentially treated tumors, suggesting that preirradiated tumors were sensitized to AZD2171 treatment. An enhanced antivascular effect of administering AZD2171 postradiotherapy was observed in real-time in Calu-6 tumors grown in dorsal window chambers. Collectively, these data support the clinical development of AZD2171 in combination with radiotherapy.     

Psychological trauma in a relief worker--a case report from earthquake-struck areas of north Pakistan

Vicarious traumatization is now a well-known entity and may have negative influences on those that are involved in rescue efforts in any disaster or traumatic events. Healthcare workers work with trauma survivors and witness an immense array of gruesome and ghastly images. This work has the potential to cause those engaged in rescue efforts to become affected subconsciously. Job-related stress may cause psychological symptoms in care providers who provide support and listen to the survivors' account of trauma. A therapist working in disaster situations may become a victim of psychological anguish--undermining their physical and mental well-being as well as their profession, adversely affecting their traumatized patients, and leading to a counter-productive therapist-survivor relationship. This significant theme of secondary trauma must be recognized in relief workers at early stages and must be addressed at an individual as well as organizational level. The key may lie in turning to social supports, adapting positive coping mechanisms, and subsequently seeking mental health consultation. Further research is required in this area to determine the best resolution.     

Association between ACE inhibitors and acute pancreatitis in the elderly

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitor-induced acute pancreatitis has been described in various case reports and drug surveillance databases. At present, no epidemiologic studies examining the potential association between ACE inhibitors and acute pancreatitis have been identified. OBJECTIVE: To determine whether there is an association between ACE inhibitor use and pancreatic events (acute pancreatitis, pancreatic surgery). METHODS: A retrospective cohort of Ontario residents aged >/=66 years was created using population-based administrative databases from January 1, 1994, through March 31, 2000. We compared the incidence of pancreatic events among new users of ACE inhibitors (study group), warfarin (null baseline group), and dihydropyridine calcium-channel antagonists (DCCAs; disease control group) using multivariate Cox proportional hazard models. OUTCOME MEASURES: The primary outcome measure was hospitalization with acute pancreatitis; the secondary outcome measure was incidence of pancreatic surgery. RESULTS: For acute pancreatitis, the crude incidence rates per 10,000 person-years were 9.0 for the ACE inhibitor group (n = 174,824); 7.1 for the DCCA group (n = 73,719), and 7.6 for the warfarin group (n = 40 057). Relative to warfarin users, neither ACE inhibitor users (adjusted rate ratio [aRR] = 1.35; 95% CI 0.94 to 1.93) nor DCCA users (aRR = 1.09; 95% CI 0.72 to 1.62) were at significantly higher risk of hospitalization for acute pancreatitis. For pancreatic surgery in the same population, the crude incidence rates per 10,000 person-years were 10.5 for the ACE inhibitor group, 10.6 for the DCCA group, and 10.7 for the warfarin group. Relative to subjects taking warfarin, neither ACE inhibitor users (aRR = 1.09; 95% CI 0.80 to 4.49) nor DCCA users (aRR = 1.11; 95% CI 0.79 to 1.56) were at significantly higher risk for pancreatic surgery. CONCLUSIONS: The use of ACE inhibitors does not appear to be associated with significant risk of acute pancreatitis among the elderly.     

Prevalence of gestational diabetes mellitus in Kashmiri women from the Indian subcontinent

This prospective study was carried out to determine the prevalence of gestational diabetes mellitus (GDM) in Kashmiri women and to assess the effect of various demographic factors. Two thousand pregnant women (divided into groups A and B, being the first and last 1000 consecutive women) attending various antenatal clinics in six districts of Kashmir valley were screened for GDM by 1 h 50 g oral glucose challenge test. Four hundred and fourteen (20.8%) women (216 from group A and 198 from group B) had an abnormal screening test and proceeded to oral glucose tolerance testing. Women from group A had a 3 h 100 gram oral glucose tolerance test (OGTT) and GDM was as classified by Carpenter and Coustan. A 2 h 75 g OGTT was performed on group B subjects and WHO criteria applied for diagnosis of GDM. The overall prevalence of GDM was 3.8% (3.1% in group A versus 4.4% in group B-P-value 0.071). GDM prevalence steadily increased with age (from 1.7% in women below 25 years to 18% in women 35 years or older). GDM occurred more frequently in women who were residing in urban areas, had borne three or more children, had history of abortion(s) or GDM during previous pregnancies, had given birth to a macrosomic baby, or had a family history of diabetes mellitus. Women with obesity, hypertension, osmotic symptoms, proteinuria or hydramnios had a higher prevalence of GDM.     

Developing a conceptual framework for patient safety culture in emergency department: A review of the literature

Patient safety culture is a critical component of modern health care. However, the high‐paced, unpredictable nature of the emergency department (ED) environment may impact adversely on it. The aim of this paper is to explore the concept of patient safety culture as it may apply to emergency health care, and to propose a conceptual framework that could form the basis for interventions designed to improve it. This is a systematic review of the literature. A search was undertaken of common electronic bibliographic databases using key words such as safety culture, safety climate, and Emergency Department. Articles were analysed for consistent themes with the aim to construct a conceptual framework. Ten articles met the inclusion criteria that specifically examined safety culture in the ED. Synthesis of the literature resulted in the emergence of three overarching themes of ED practice found to impact on safety culture in the ED. These were the dimensions of patient safety culture, the factors influencing it, and the interventions for improving it. A conceptual framework was constructed that identifies elements that significantly impact the patient safety culture in the ED. This framework may assist managers and researchers to take a comprehensive approach to build an effective safety culture in ED setting.     

Gold Nanoparticle Conjugation Enhances the Antiacanthamoebic Effects of Chlorhexidine

Acanthamoeba keratitis is a serious infection with blinding consequences and often associated with contact lens wear. Early diagnosis, followed by aggressive topical application of drugs, is a prerequisite in successful treatment, but even then prognosis remains poor. Several drugs have shown promise, including chlorhexidine gluconate; however, host cell toxicity at physiologically relevant concentrations remains a challenge. Nanoparticles, subcolloidal structures ranging in size from 10 to 100 nm, are effective drug carriers for enhancing drug potency. The overall aim of the present study was to determine whether conjugation with gold nanoparticles enhances the antiacanthamoebic potential of chlorhexidine. Gold-conjugated chlorhexidine nanoparticles were synthesized. Briefly, gold solution was mixed with chlorhexidine and reduced by adding sodium borohydride, resulting in an intense deep red color, indicative of colloidal gold-conjugated chlorhexidine nanoparticles. The synthesis was confirmed using UV-visible spectrophotometry that shows a plasmon resonance peak of 500 to 550 nm, indicative of gold nanoparticles. Further characterization using matrix-assisted laser desorption ionization-mass spectrometry showed a gold-conjugated chlorhexidine complex at m/z 699 ranging in size from 20 to 100 nm, as determined using atomic force microscopy. To determine the amoebicidal and amoebistatic effects, amoebae were incubated with gold-conjugated chlorhexidine nanoparticles. For controls, amoebae also were incubated with gold and silver nanoparticles alone, chlorhexidine alone, neomycin-conjugated nanoparticles, and neomycin alone. The findings showed that gold-conjugated chlorhexidine nanoparticles exhibited significant amoebicidal and amoebistatic effects at 5 μM. Amoebicidal effects were observed by parasite viability testing using a Trypan blue exclusion assay and flow-cytometric analysis using propidium iodide, while amoebistatic effects were observed using growth assays. In contrast, chlorhexidine alone, at a similar concentration, showed limited effects. Notably, neomycin alone or conjugated with nanoparticles did not show amoebicidal or amoebistatic effects. Pretreatment of A. castellanii with gold-conjugated chlorhexidine nanoparticles reduced amoeba-mediated host cell cytotoxicity from 90% to 40% at 5 μM. In contrast, chlorhexidine alone, at similar concentrations, had no protective effects for the host cells. Similarly, amoebae treated with neomycin alone or neomycin-conjugated nanoparticles showed no protective effects. Overall, these findings suggest that gold-conjugated chlorhexidine nanoparticles hold promise in the improved treatment of A. castellanii keratitis.     

Health-Related Anxiety and Hypochondriacal Concerns in Medical Students: A Cross-Sectional Study From Pakistan

Phenomenon: Transient health-related anxiety/hypochondriacal concerns in medical students are well documented. The literature suggests that after studying a particular disease, medical students are likely to consider any symptoms earlier regarded as normal to be signs of the disease they are studying. The aim of this study was to investigate the prevalence of these phenomena and their cognitive and distress aspects among medicals students in Karachi, Pakistan. Approach: This was an analytical, cross-sectional study. Self-administered questionnaires comprising demographic details, the Short Health Anxiety Inventory, Medical Students’ Disease (MSD) Perception Scale, and MSD Distress Scale were distributed to 1st- through 5th-year medical students. Findings: In total, 513 medical students (66% female) participated. Their mean age was 21 ± 1.6 years. Three hundred seventy-five students (73%) reported having visited a doctor at least once in the past 6 months. Fifty students (9.9%) admitted to having addictions. The overall prevalence of significant hypochondriacal concerns was 11.9% (61 students). The presence of addiction was associated with a greater likelihood of developing significant health-related anxiety (odds ratio = 3.82, p = .003), 95% confidence interval [1.51, 7.11]. Age, gender, medical school, year of medical school, and visits to the doctor in the previous 6 months were not associated with greater likelihood of developing significant health-related anxiety. Second-year medical students experienced a significantly greater degree of worry (MSD–Distress scale) than 5th-year students (M score = 12.6 ± 4.6 vs. 10.7 ± 4.4, p = .04). Insights: The prevalence of substantial hypochondriacal concerns in medical students in Pakistan was low in comparison to similar studies published in literature. Student health physicians should be aware of the true prevalence of hypochondriacal concerns and behavior and not dismiss legitimate complaints. Educational sessions to counteract this phenomenon can be incorporated into the curriculum of undergraduate medicine. By defining heightened awareness of symptoms as a normal process, different coping techniques can be discussed to help medical students reduce their level of stress.     

Racial and age-related disparities in obtaining screening mammography: results of a statewide database

BACKGROUND: This study compared mammography rates in Arkansas, based on race and age, to identify any disparities in obtaining mammography. METHODS: The Arkansas Mammography Data Collection Project contained data on 133,549 women, 87,680 of them aged 40 to 64 and 45,869 aged 65 years or older. Race data were available on 64,526 women. Mammography rates were compared by patient age and race. RESULTS: Women aged 65 years and older were less likely to obtain mammograms than younger women: 21.67% versus 23.30%. Mammograms were more likely to be classified as diagnostic in older women and as screening in younger women. Older African American women were less likely to obtain mammograms than younger women of the same race (7.23% vs 8.02%), while older white women were more likely to obtain mammograms than younger white women (11.64% vs 11.31%). African Americans were less likely to obtain mammograms in both age groups. CONCLUSIONS: Older African American women are less likely to obtain mammograms than white and younger women. The reasons for this disparity warrant further evaluation.