Acute onset of pancreatitis with concomitant use of tenofovir and didanosine

OBJECTIVE: To report a case of pancreatitis associated with the combined use of didanosine and tenofovir. CASE SUMMARY: A 51-year-old white man with HIV was initiated on antiretroviral therapy with didanosine 250 mg/day, tenofovir 300 mg/day, lamivudine 300 mg/day, stavudine 60 mg/day, and efavirenz 600 mg/day. Didanosine was prescribed at a reduced dosage due to the known interaction with tenofovir. Despite this dosage adjustment, the patient developed acute pancreatitis 10 weeks after antiretrovirals were initiated. Pancreatitis resolved spontaneously after antiretroviral discontinuation. DISCUSSION: Our report of didanosine-induced pancreatitis secondary to concurrent use with tenofovir is the third reported case that utilized a reduced didanosine dosage. Five previous pancreatitis reports have been described using full-strength didanosine with tenofovir. The exact mechanism of action for this interaction is unknown. Utilizing the Naranjo probability scale to assess causality, a possible adverse drug reaction was determined. CONCLUSIONS: Tenofovir and didanosine may be used cautiously in antiretroviral combination therapy. Reduced didanosine dosage (250 mg) should be used to reduce serum didanosine concentrations and subsequent toxicities. Practitioners should be aware that a significant drug interaction with resulting pancreatitis may occur even when a reduced dosage is prescribed.     

Computer-assisted instruction for novice nurses in critical care

The current worldwide nursing shortage is having the greatest effect on the critical care areas as novice nurses enter these specialty areas in unprecedented numbers. Massive healthcare restructuring, a rapidly aging nursing work force, and high nursing turnover and absenteeism rates have all contributed to a healthcare environment that is struggling to care for critically ill patients. Computer-assisted instruction in the form of interactive computer programs may be used as an adjunct educational resource for these novice practitioners. These programs have the potential to bridge the gap between theory and practice, which may assist the novice nurse in achieving safe, competent clinical practice.     

The ECG in the differential diagnosis between takotsubo cardiomyopathy and acute coronary syndrome

Introduction: Takotsubo cardiomyopathy (TC) is an acquired cardiomyopathy affecting mostly postmenopausal women mimicking an acute coronary syndrome (ACS). TC clinical presentation involves chest pain, elevated cardiac enzymes, wall motion abnormalities and electrocardiographic changes, all of which share striking similarities to ACS.

Areas covered: Differential diagnosis between TC and ACS can be complex since there are no reliable and widely-accepted electrocardiographic criteria and, at the moment, only coronary angiography can rule out one of the two diagnoses with good certainty.

The present review will discuss the pros and cons of the ECG in TC, focusing on how the signal changes through the acute phase, the hospitalization, and after discharge. Specific information will be provided for each component of the ECG trace, and potential pitfalls will be highlighted, in order get to the core of this important unmet clinical issue.

Expert commentary: There are at least several reasons why the ECG is still not considered a useful tool in differential diagnosis between TC and ACS. These include recent awareness of the syndrome, lack of evidence-based therapy, and, more importantly, a wide range of ECG features according to race, patient characteristics, wall motion abnormalities, triggers, and time from symptoms onset.     

Hepatitis B virus DNA-positive, hepatitis B surface antigen-negative blood donations intercepted by anti-hepatitis B core antigen testing: the Canadian Blood Services experience

BACKGROUND: The benefit of introducing anti-hepatitis B core antigen (HBc) screening for intercepting potentially infectious donations missed by hepatitis B surface antigen (HBsAg) screening in Canada was studied. STUDY DESIGN AND METHODS: Anti-HBc testing of all donations was implemented in April 2005, along with antibody to hepatitis B surface antigen (anti-HBs) and hepatitis B virus (HBV) DNA supplemental testing of anti-HBc repeat-reactive, HBsAg-negative donations. The proportion of potentially infectious donations intercepted by anti-HBc over the initial 18 months of testing was calculated based on three assumptions relating infectivity of HBV DNA-positive units to anti-HBs levels. Lookback was conducted for all DNA-positive donations. RESULTS: Of 493,344 donors, 5,585 (1.13%) were repeat-reactive for the presence of anti-HBc, with 29 (0.52%) being HBV DNA-positive and HBsAg-negative. The proportion of potentially infectious donations intercepted by anti-HBc screening was 1 in 17,800 if all HBV DNA-positive donations were infectious, 1 in 26,900 if infectivity was limited to donations with an anti-HBs level of not more than 100 mIU per mL, and 1 in 69,300 if only donations with undetectable anti-HBs were infectious. For 279 components in the lookback study, no traced recipients were HBsAg-positive and 7 recipients were anti-HBc-reactive in association with 4 donors, 3 of whom had an anti-HBs level of more than 100 mIU per mL and 1 of whom had a level of 61 mIU per mL. CONCLUSION: Implementation of anti-HBc screening reduced the risk of transfusing potentially infectious units by at least as much as had been expected based on the literature. The lookback did not provide proof of transfusion transmission of HBV from HBV DNA-positive, anti-HBc-reactive, HBsAg-negative donors but it did not establish lack of transmission either.     

Persistent 7-tesla phase rim predicts poor outcome in new multiple sclerosis patient lesions

BACKGROUND. In some active multiple sclerosis (MS) lesions, a strong immune reaction at the lesion edge may contain growth and thereby isolate the lesion from the surrounding parenchyma. Our previous studies suggest that this process involves opening of the blood-brain barrier in capillaries at the lesion edge, seen on MRI as centripetal contrast enhancement and a colocalized phase rim. We hypothesized that using these features to characterize early lesion evolution will allow in vivo tracking of tissue degeneration and/or repair, thus improving the evaluation of potential therapies for chronic active lesions.METHODS. Centripetally and centrifugally enhancing lesions were studied in 17 patients with MS using 7-tesla MRI. High-resolution, susceptibility-weighted, T1-weighted (before/after gadolinium), and dynamic contrast–enhanced scans were acquired at baseline and months 1, 3, 6, and 12. For each lesion, time evolution of the phase rim, lesion volume, and T1 hypointensity were assessed. In autopsies of 3 progressive MS cases, the histopathology of the phase rim was determined.RESULTS. In centripetal lesions, a phase rim colocalized with initial contrast enhancement. In 12 of 22, this phase rim persisted after enhancement resolved. Compared with centripetal lesions with transient rim, those with persistent rim had less volume shrinkage and became more T1 hypointense between months 3 and 12. No centrifugal lesions developed phase rims at any time point. Pathologically, persistent rims corresponded to an iron-laden inflammatory myeloid cell population at the edge of chronic demyelinated lesions.CONCLUSION. In early lesion evolution, a persistent phase rim in lesions that shrink least and become more T1 hypointense over time suggests that the rim might mark failure of early lesion repair and/or irreversible tissue damage. In later stages of MS, phase rim lesions continue to smolder, exerting detrimental effects on affected brain tissue.TRIAL REGISTRATION. {"type":"clinical-trial","attrs":{"text":"NCT00001248","term_id":"NCT00001248"}}NCT00001248.FUNDING. The Intramural Research Program of NINDS supported this study.     

Measuring activity limitations in walking: development of a hierarchical scale for patients with lower-extremity disorders who live at home

OBJECTIVE: To develop a hierarchical scale that measures activity limitations in walking in patients with lower-extremity disorders who live at home. DESIGN: Cross-sectional study. SETTING: Orthopedic workshops and outpatient clinics of secondary and tertiary care centers. PARTICIPANTS: Patients (N=981; mean age +/- standard deviation, 58.6+/-15.4 y; 46% men) living at home, with different lower-extremity disorders: stroke, poliomyelitis, osteoarthritis, amputation, complex regional pain syndrome type I, and diabetic and degenerative foot disorders. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: (1) Fit of the monotone homogeneity model, indicating whether items can be used for measuring patients; (2) fit of the double monotonicity model, indicating invariant (hierarchical) item ordering; (3) intratest reliability, indicating repeatability of the sum score; (4) robustness, addressing the clinimetric properties within subgroups of patients; and (5) differential item functioning, addressing the validity of comparisons between subgroups of patients. RESULTS: Thirty-five of 41 dichotomous items had (1) good fit of the monotone homogeneity model (coefficient H=.50), (2) good fit of the double monotonicity model (coefficient H(T)=.33), (3) good intratest reliability (coefficient rho=.95), (4) satisfactory robustness (within subgroups of patients defined by age, sex, and diagnosis), and (5) some differential item functioning (6 items in amputees compared with nonamputees). CONCLUSIONS: A hierarchical scale, with excellent scaling characteristics, was developed to measure activity limitations in walking in patients with lower-extremity disorders who live at home. The measurements should be interpreted cautiously when making comparisons between amputees and nonamputees.     

Study protocol: The DOse REsponse Multicentre International collaborative initiative (DO-RE-MI)

Introduction

Current practices for renal replacement therapy in intensive care units (ICUs) remain poorly defined. The DOse REsponse Multicentre International collaborative initiative (DO-RE-MI) will address the issue of how the different modes of renal replacement therapy are currently chosen and performed. Here, we describe the study protocol, which was approved by the Scientific and Steering Committees.

Methods

DO-RE-MI is an observational, multicentre study conducted in ICUs. The primary end-point will be the delivered dose of dialysis, which will be compared with ICU mortality, 28-day mortality, hospital mortality, ICU length of stay and number of days of mechanical ventilation. The secondary end-point will be the haemodynamic response to renal replacement therapy, expressed as percentage reduction in noradrenaline (norepinephrine) requirement. Based on the the sample analysis calculation, at least 162 patients must be recruited. Anonymized patient data will be entered online in electronic case report forms and uploaded to an internet website. Each participating centre will have 2 months to become acquainted with the electronic case report forms. After this period official recruitment will begin. Patient data belong to the respective centre, which may use the database for its own needs. However, all centres have agreed to participate in a joint effort to achieve the sample size needed for statistical analysis.

Conclusion

The study will hopefully help to collect useful information on the current practice of renal replacement therapy in ICUs. It will also provide a centre-based collection of data that will be useful for monitoring all aspects of extracorporeal support, such as incidence, frequency, and duration.