A retrospective analysis of 3954 patients in phase 2/3 trials of bortezomib for the treatment of multiple myeloma: towards providing a benchmark for the cardiac safety profile of proteasome inhibition in multiple myeloma.

This retrospective analysis aimed to establish the overall cardiac safety profile of bortezomib using patient-level data from one phase 2 and seven phase 3 studies in previously untreated and relapsed/refractory multiple myeloma (MM). Seven clinically relevant primary [congestive heart failure (CHF), arrhythmias, ischaemic heart disease (IHD), cardiac death] and secondary (hypertension, dyspnoea, oedema) cardiac endpoints were defined based on MedDRA v16.0 preferred terms. 2509 bortezomib-treated patients and 1445 patients in non-bortezomib-based control arms were included. The incidence of grade ≥3 CHF was 1·3-4·0% in studies in relapsed/refractory MM and 1·2-4·7% in previously untreated MM (2·0-7·6% all grades), with no significant differences between bortezomib- and non-bortezomib-based arms in comparative studies. Incidences of arrhythmias (1·3-5·9% grade ≥2; 0·6-4·1% grade ≥3), IHD (1·2-2·9% all grades; 0·4-2·7% grade ≥3) and cardiac death (0-1·4%) were low, with no differences between bortezomib-based and non-bortezomib-based arms. Higher rates of oedema (mostly grade 1/2) were seen in bortezomib-based versus non-bortezomib-based arms in one study and a pooled transplant study analysis. Logistic regression analyses of comparative studies showed no impact on cardiac risk with bortezomib-based versus non-bortezomib-based treatment. Bortezomib-based treatment was associated with low incidences of cardiac events.

Differentiation of tuberculous meningitis from acute bacterial meningitis using simple clinical and laboratory parameters.

Tuberculous meningitis (TBM) is still a major cause of serious illness in many parts of the world. The newer diagnostic tests and neuroimaging methods are unlikely to be available in many developing countries. We attempt to identify simple parameters for early diagnosis. A retrospective study was performed to compare the clinical and laboratory features of cultured-confirmed, TBM (134) and other bacterial meningitis (709). Features independently predictive of TBM were studied by multivariate logistic regression to develop a diagnostic rule. Six features were found predictive: length of clinical history >5 days, headache, total cerebrospinal fluid (CSF) white blood cell count of <1000/mm3, clear appearance of CSF, lymphocyte proportion of >30%, and protein content of >100 mg/dL. Application of 3 or more parameters revealed 93% sensitivity and 77% specificity. Applying this diagnostic rule can help in the early diagnosis of TBM, in both children and adults.

Knowledge, attitudes, and practices regarding epidemiology and management of travelers' diarrhea: a survey of front-line providers in Iraq and Afghanistan.

To evaluate the relationship between medical knowledge and clinical practice, a survey on travelers' diarrhea was administered to military health care providers attending a professional development and trauma management conference. The survey was administered at the beginning of the conference and 58 of the 76 attendees participated by completing a questionnaire. Respondents were aware of the standard definition of travelers' diarrhea; however, their knowledge about the epidemiology and management of travelers' diarrhea was low. Less than one-third correctly answered questions on etiology and more than two-thirds made incorrect management choices in treatment of mild to moderate watery diarrhea and dysentery. Important knowledge gaps about gastroenteritis were identified and should serve as a basis to develop military-specific clinical guidelines and training programs.

The epidemiology of self-reported diarrhea in operations Iraqi freedom and enduring freedom.

Diarrhea remains a potential cause of compromised military effectiveness. To assess diarrhea rates and mission impact in operations in Iraq and Afghanistan, a survey was administered to soldiers participating in the "Rest and Recuperation" program in Doha, Qatar. Between October and December 2003, 2,389 volunteers completed a questionnaire designed to assess the occurrence and impact of diarrhea. The median length of deployment was 7.2 months, 70% reported at least one episode, and 56% had multiple episodes of diarrhea. Overall, 43% reported decreased job performance for a median of 2 days, and 17% reported being on bed rest for a median of 2 days. While this survey showed high rates of diarrhea associated with decreased operational effectiveness, the results are consistent with prior military operations in this region. Further research is needed to develop better methods for illness prevention and its minimization on operational impact.