Amifostine and rituximab in refractory immune thrombocytopaenia: A case series.

BACKGROUND AND OBJECTIVES: Management of refractory immune thrombocytopaenia (ITP) can be challenging. Amifostine, a thiophosphate prodrug, induces megakaryocyte maturation. In 2010, Fan et al. published results for 21 Chinese splenectomized patients, aged 13-92, with steroid-refractory ITP. Nineteen patients (15 patients aged >18 years) achieved remission 2 months post-amifostine. This is the first publication utilizing amifostine and rituximab in refractory ITP. MATERIALS AND METHODS: At the Cairns Hospital in Australia, we identified five patients treated with amifostine and rituximab for refractory ITP. Amifostine IV 400 mg once daily was administered 5 days/week for 5 weeks as tolerated. Rituximab was administered concurrently with/preceding amifostine based on clinician preference. Data were obtained through medical records and follow-up serology up to 5 years post-amifostine was available. RESULTS: Three cases demonstrated durable responses up to 5 years' follow-up. One patient initially achieved remission but relapsed 1-year post-amifostine. One patient who did not have a splenectomy prior to amifostine did not respond. CONCLUSION: Three out of five patients achieved durable responses with amifostine and rituximab. Although there is confounding by rituximab, given its established low durable response rate, it is likely that the excellent long-term responses achieved were a result of amifostine. Clinical trials with larger patient cohorts and further investigation are required to confirm the efficacy and mechanism of amifostine in ITP.

Fresh frozen plasma and platelet concentrate storage duration not associated with in hospital mortality risk.

BACKGROUND AND OBJECTIVES: To date, the effects of FFP and PC storage duration on mortality have only been studied in a few studies in limited patient subpopulations. The aim of the current study was to determine whether FFP and PC storage duration is associated with increased in hospital mortality risk across cardiac surgery, acute medicine, ICU and orthopaedic surgery patients. MATERIALS AND METHODS: Two-stage individual patient data meta-analyses were performed to determine the effects of FFP and PC storage duration on in hospital mortality. Preset random effects models were used to determine pooled unadjusted and adjusted (adjusted for age, gender and units of product transfused) effect estimates. RESULTS: The FFP storage duration analysis included 3625 patients across four studies. No significant association was observed between duration of storage and in hospital mortality in unadjusted analysis, but after adjusting for patient age, gender and units of product a small increased risk of in hospital mortality was observed for each additional month of storage (OR: 1·05, 95% CI: 1·01-1·08). This effect was no longer statistically significant when donor ABO blood group was incorporated into the random effects model on post hoc analyses. A total of 547 patients across five studies were incorporated in the PC storage duration analysis. No association was observed between PC storage duration and odds of in hospital morality (adjusted OR: 0·94, 95% CI: 0·79-1·11). CONCLUSIONS: There is insufficient evidence to support shortening FFP or PC shelf life based on in hospital mortality.

Chest radiographs for acute lower respiratory tract infections.

BACKGROUND: Acute lower respiratory tract infections (LRTIs) (e.g. pneumonia) are a major cause of morbidity and mortality and management focuses on early treatment. Chest radiographs (X-rays) are one of the commonly used strategies. Although radiological facilities are easily accessible in high-income countries, access can be limited in low-income countries. The efficacy of chest radiographs as a tool in the management of acute LRTIs has not been determined. Although chest radiographs are used for both diagnosis and management, our review focuses only on management. OBJECTIVES: To assess the effectiveness of chest radiographs in addition to clinical judgement, compared to clinical judgement alone, in the management of acute LRTIs in children and adults. SEARCH METHODS: We searched CENTRAL 2013, Issue 1; MEDLINE (1948 to January week 4, 2013); EMBASE (1974 to February 2013); CINAHL (1985 to February 2013) and LILACS (1985 to February 2013). We also searched NHS EED, DARE, ClinicalTrials.gov and WHO ICTRP (up to February 2013). SELECTION CRITERIA: Randomised controlled trials (RCTs) of chest radiographs versus no chest radiographs in acute LRTIs in children and adults. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the inclusion criteria, extracted data and assessed risk of bias. A third review author compiled the findings and any discrepancies were discussed among all review authors. We used the standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: Two RCTs involving 2024 patients (1502 adults and 522 children) were included in this review. Both RCTs excluded patients with suspected severe disease. It was not possible to pool the results due to incomplete data. Both included trials concluded that the use of chest radiographs did not result in a better clinical outcome (duration of illness and of symptoms) for patients with acute LRTIs. In the study involving children in South Africa, the median time to recovery was seven days (95% confidence interval (CI) six to eight days (radiograph group) and six to nine days (control group)), P value = 0.50, log-rank test) and the hazard ratio for recovery was 1.08 (95% CI 0.85 to 1.34). In the study with adult participants in the USA, the average duration of illness was 16.9 days versus 17.0 days (P value > 0.05) in the radiograph and no radiograph groups respectively. This result was not statistically significant and there were no significant differences in patient outcomes between the groups with or without chest radiograph.The study in adults also reports that chest radiographs did not affect the frequencies with which clinicians ordered return visits or antibiotics. However, there was a benefit of chest radiographs in a subgroup of the adult participants with an infiltrate on their radiograph, with a reduction in length of illness (16.2 days in the group allocated to chest radiographs and 22.6 in the non-chest radiograph group, P < 0.05), duration of cough (14.2 versus 21.3 days, P < 0.05) and duration of sputum production (8.5 versus 17.8 days, P < 0.05). The authors mention that this difference in outcome between the intervention and control group in this particular subgroup only was probably a result of "the higher proportion of patients treated with antibiotics when the radiograph was used in patient care".Hospitalisation rates were only reported in the study involving children and it was found that a higher proportion of patients in the radiograph group (4.7%) required hospitalisation compared to the control group (2.3%) with the result not being statistically significant (P = 0.14). None of the trials report the effect on mortality, complications of infection or adverse events from chest radiographs. Overall, the included studies had a low or unclear risk for blinding, attrition bias and reporting bias, but a high risk of selection bias. Both trials had strict exclusion criteria which is important but may limit the clinical practicability of the results as participants may not reflect those presenting in clinical practice. AUTHORS' CONCLUSIONS: Data from two trials suggest that routine chest radiography does not affect the clinical outcomes in adults and children presenting to a hospital with signs and symptoms suggestive of a LRTI. This conclusion may be weakened by the risk of bias of the studies and the lack of complete data available.

A Rare Case of Renal Impairment Caused by Primary Hypothyroidism.

An association between hypothyroidism and renal impairment has rarely been reported in the literature. We describe a case of hypothyroidism that was associated with otherwise unexplained acute kidney impairment, which was reversed with treatment. A 21-year-old female patient presented to her family physician with myalgia, and preliminary investigations revealed an elevated level of creatine kinase and poor renal function. Primary hypothyroidism was diagnosed and no other apparent etiology for renal failure could be identified despite extensive investigations by the Nephrology Department. Notably, the patient's renal impairment showed prompt resolution following thyroid hormone replacement.