BACKGROUND:

A frequent complication in patients with subarachnoid hemorrhage (SAH) is recurrent bleeding from the aneurysm. The risk is highest within the first 6 hours after the initial hemorrhage. Securing the aneurysm within this timeframe is difficult owing to logistical delays. The rate of recurrent bleeding can also be reduced by ultra-early administration of antifibrinolytics, which probably improves functional outcome. The aim of this study is to investigate whether ultra-early and short-term administration of the antifibrinolytic agent tranexamic acid (TXA), as add-on to standard SAH management, leads to better functional outcome.

METHODS:

This is a multicenter, prospective, randomized, open-label trial with blinded endpoint (PROBE) assessment. Adult patients with the diagnosis of non-traumatic SAH, as proven by computed tomography (CT) within 24 hours after the onset of headache, will be randomly assigned to the treatment group or the control group. Patients in the treatment group will receive standard treatment with the addition of a bolus of TXA (1 g intravenously) immediately after randomization, followed by continuous infusion of 1 g per 8 hours until the start of aneurysm treatment, or a maximum of 24 hours after the start of medication. Patients in the control group will receive standard treatment without TXA. The primary outcome measure is favorable functional outcome, defined as a score of 0 to 3 on the modified Rankin Scale (mRS), at 6 months after SAH. Primary outcome will be determined by a trial nurse blinded for treatment allocation. We aim to include 950 patients in 3 years.

DISCUSSION:

The strengths of this study are: 1. the ultra-early and short-term administration of TXA, resulting in a lower dose as compared to previous studies, which should reduce the risk for delayed cerebral ischemia (DCI), an important risk factor in the long-term treatment with antifibrinolytics; 2. the power calculation is based on functional outcome and calculated with use of recent study results of our own population, supported by data from prominent studies; and 3. the participation of several specialized SAH centers, and their referring hospitals, in the Netherlands with comparative treatment protocols.Trial registration: Nederlands Trial Register (Dutch Trial Registry) number NTR3272.

Prostate cancer is the most common malignancy in men worldwide. The rate of patients presenting with locally advanced prostate cancer has declined in recent decades, mainly due to prostate-specific antigen screening, but the management of these patients still remains controversial. Current literature suggests that the standard of care for these patients is a combination approach with radiation therapy and androgen deprivation therapy. However, there remain many unresolved issues, including the role of dose-escalated radiation therapy, the additional benefit of surgery and the role of systemic therapy, both standard chemotherapeutic agents and novel agents. Furthermore, in the era of personalised medicine, additional research is needed to evaluate the role of biomarkers to better predict the risk of local and systemic relapse in this population.

The aim of this study was to explore the factors associated with the occurrence, subsequent prognoses and need for additional medications following cutaneous adverse drug reactions (ADRs) among inpatients.This is a case-control study, nested in a large cohort study of 473,446 inpatients hospitalised from 2005 to 2008, examined cutaneous ADRs. A 1 : 5 strategy of individually matching age and principal diagnosis was applied to the data of cases (n = 700) and corresponding controls (n = 3365).The severity of ADRs was evaluated using Naranjo algorithms by senior pharmacists in the medical centre. Medical chart reviews and claim data analyses were analysed to explore risk factors associated with the occurrence and impact of cutaneous ADRs. Economic impacts in terms of length of stay and medical expenses were also analysed.The number of drug prescriptions and secondary diagnoses, and the department to which the patient was admitted, significantly contributed to the risk of cutaneous ADRs and subsequent prognosis. In addition to physician's seniority, the Naranjo score was also positively associated with patients' prognosis. Medical expenses associated with cutaneous ADRs patients ($US 916) were more than 2.5-fold higher than those patients who were not afflicted ($US 318).The study identified risk factors for cutaneous ADRs in terms of both patient characteristics and drug complexity. The present analyses indicate characteristics and mechanisms of cutaneous ADRs among inpatients, which provide clues for future intervention strategies and management issues in healthcare settings.

Kaposi's sarcoma (KS) is an important mucocutaneous neoplasm with four well-known clinicopathologic types. Involvement of the oral cavity may be seen in all variants but is most common with AIDS-KS. The latter may signal undiagnosed HIV infection. Its common association with disseminated disease has potentially important diagnostic and therapeutic implications. Oral KS (OKS) most often affects the hard and soft palate, gingiva, and dorsal tongue with plaques or tumors of coloration ranging from non-pigmented to brownish-red or violaceous. Its involvement ranges from an incidental finding to proliferative tumor formation that interferes with mastication. OKS needs to be distinguished clinically from other entities, including pyogenic granuloma, hemangioma, bacillary angiomatosis, and gingival enlargement caused by cyclosporine, a drug frequently used in recipients of organ transplantation. KS may flare as part of the immune reconstitution inflammatory syndrome in HIV patients or develop in the context of iatrogenic immunosuppression. Management, which may depend upon a variety of factors including the clinicopathologic type of KS and results of staging, ranges from no treatment to local measures such as intralesional vinblastine or systemic administration of cytotoxic chemotherapy for disseminated disease. Modification of immunosuppressive regimens often helps control post-transplant OKS but enhances the risk of graft rejection. Screening donors and recipients of organ transplants for HHV-8, with prophylactic treatment if infected as well as institution of sirolimus early after transplantation, are proposed strategies aimed at preventing post-transplant OKS.

Disaster management refers to the policies, administrative decisions, and operational activities carried out by different sectors of society in responding to disasters. The focus of this article is on disaster recovery and rebuilding. The preventive approach manages risks and engages in the process of risk avoidance and disaster preparedness. Such an approach frequently involves multiple layers of society working together. Social workers should be involved in social intervention and preparation as well as the prevention of disasters. Greater professionalization, integration, and coordination of emergency services are observed both within and between nations.

Vertical variations of polycyclic aromatic hydrocarbon (PAH) concentrations in PM10 were investigated in order to assess the factors controlling their behavior in the urban atmosphere of Bangkok City, Thailand. Air samples were collected every three hours for three days at three different levels at Bai-Yok Suit Hotel (site-1 and site-2) and Bai-Yok Sky Hotel (site-3) in February 18th-21st, 2008. The B[a]P concentration showed a value 0.54 fold, lower than the United Kingdom Expert Panel on Air Quality Standard (UK-EPAQS; i.e. 250 pg m-3) at the top level. In contrast, the B[a]P concentrations exhibited, at the ground and middle level, values 1.50 and 1.43 times higher than the UK-EPAQS standard respectively. PAHs displayed a diurnal variation with maximums at night time because of the traffic rush hour coupled with lower nocturnal mixing layer, and the decreased wind speed, which consequently stabilized nocturnal boundary layer and thus enhanced the PAH contents around midnight. By applying Nielsen's technique, the estimated traffic contributions at Site-3 were higher than those of Site-1: about 10% and 22% for Method 1 and Method 2 respectively. These results reflect the more complicated emission sources of PAHs at ground level in comparison with those of higher altitudes. The average values of incremental individual lifetime cancer risk (ILCR) for all sampling sites fell within the range of 10?7-10?6, being close to the acceptable risk level (10?6) but much lower than the priority risk level (10?4).

Background:

Colorectal cancer is a main leading cause of cancer death in western countries. Although many studies have been conducted on incidence trends all over the world in recent years, information regarding changes in incidence of colorectal cancer in Iran is insufficient. The present study of colorectal cancer in the west of Iran during recent years was therefore performed. Materials and

Methods:

The registered data for colorectal cancer cases in National Cancer Registry System were extracted from the Ministry of Health and Medical Education, Center for Disease Control and Management. The codes from 18-21 among cancers were selected for colon and rectum cancers. Incidence rates were standardized directly using WHO population. The significance of incidence rate trends during 2000-2005 was tested through Poisson regression.

Results:

762 cases of colorectal cancer were observed during 6 years in this region, with a gender ratio of men to women of 1.2. It increased from 65 cases in 2000 to 213 cases in 2005 or from 1.5 per100,000 per persons per year to 4.8. Significant increasing trends were evident in Kermanshah and Hamadan provinces; however, change did not reach significance in Ilam and Kurdistan provinces.

Conclusions:

Colorectal cancer has an increasing trend in the west of Iran. Although it seems that the increasing rate of colorectal cancer is due to increasing of cancer risk factors, some proportion may be related to the improvement of surveillance systems in Iran.

Background:

To identify the risk factors and assess the role of survivin in predicting progessivity precancerous cervical lesions. Materials and

Methods:

This case-control study was conducted from October 2009 until May 2010. We obtained 74 samples, classified according to the degree of cervical intraepithelial neoplasia (CIN): 19 samples for CIN 1, 18 samples for CIN 2, 18 samples for CIN 3, and 19 samples as controls. Demographic profiles and risk factors assesment, histopathologic examination, HPV DNA tests, immunocytochemistry (ICC) and immunohistochemistry (IHC) staining for survivin expression were performed on all samples. Data was analyzed with bivariate and multivariate analysis.

Results:

Multivariate analysis revealed significant risk factors for developing precancerous cervical lesions are age <41 years, women with ≥2 sexual partners, course of education ≥13 years, use of oral contraceptives, positive high-risk HPV DNA, and high survivin expression by ICC or IHC staining. These factors were fit to a prediction model and we obtained a scoring system to predict the progressivity of CIN lesions.

Conclusions:

Determination of survivin expression by immunocytochemistry staining, along with other significant risk factors, can be used in a scoring system to predict the progressivity of CIN lesions. Application of this scoring system may be beneficial in determining the action of therapy towards the patient.

A determination of circulating tumor cell (CTC) effectiveness for prediction of progression-free survival (PFS) and overall survival (OS) was conducted as an adjunct to standard treatment of care in breast cancer management. Between November 2008 and March 2009, 22 metastatic and 12 early stage breast carcinoma patients, admitted to Ankara Oncology Training and Research Hospital, were included in this prospective trial. Patients' characteristics, treatment schedules and survival data were evaluated. CTC was detected twice by CellSearch method before and 9-12 weeks after the initiation of chemotherapy. A cut-off value equal or greater than 5 cells per 7.5 ml blood sample was considered positive. All patients were female. Median ages were 48.0 (range: 29-65) and 52.5 (range: 35-66) in early stage and metastatic subgroups, respectively. CTC was positive in 3 (13.6%) patients before chemotherapy and 6 (27.3%) patients during chemotherapy in the metastatic subgroup whereas positive in only one patient in the early stage subgroup before and during chemotherapy. The median follow-up was 22.0 (range: 21-23) and 19.0 (range: 5-23) months in the early stage and metastatic groups, respectively. In the metastatic group, both median PFS and OS were significantly shorter in any time CTC positive patients compared to CTC negative patients (PFS: 4.0 vs 14.0 months, Log-Rank p=0.013; and OS: 8.0 months vs. 20.5 months, Log-Rank p<0.001). OS was affected from multiple visceral metastatic sites (p=0.055) and higher grade (p=0.044) besides CTC positivity (log rank p<0.001). Radiological response of chemotherapy was also correlated with better survival (p<0.001). As a result, CTC positivity was confirmed as a prospective marker even in a small patient population, in this single center study. Measurement of CTC by CellSearch method in metastatic breast carcinoma cases may allow indications of early risk of relapse or death with even as few as two measurements during a chemotherapy program, but this finding should be confirmed with prospective trials in larger study populations.

A 10-month-old boy with congenital lamellar ichthyosis presented with a chronic Trichophyton rubrum infection. There was no history of atopy or immunosuppression, and examination revealed high total immunoglobulin E (IgE) with a positive specific IgE for T. rubrum. Multiple treatments with fluconazole were necessary to control the infection. T. rubrum is present worldwide and is responsible for the vast majority of chronic dermatophytosis. Lamellar ichthyosis is a risk factor for chronic dermatophytosis because of excessive keratin and the barrier defect. A delayed-type hypersensitivity reaction to T. rubrum is associated with cure, whereas immediate hypersensitivity and IgE are not protective and may lead to chronic infection. Atopy and the Th2 profile therefore seem to be associated with chronic dermatophytosis. The association between ichthyosis and atopy is well documented. T. rubrum also has an interesting ability to evade immunity, which helps explain the chronic infection. Finally, in ichthyosis, it is likely that fluconazole has difficulty penetrating the acanthotic stratum corneum, which explains treatment failure. We report this case to alert clinicians to the possible association between lamellar ichthyosis and chronic dermatophytosis and to report the difficulties of management.