Neo‐adjuvant Capecitabine Chemotherapy in Women with Newly Diagnosed Locally Advanced Breast Cancer in a Resource‐poor Setting (Nigeria): Efficacy and Safety in a Phase II Feasibility Study

The majority of clinical trials of neo‐adjuvant therapy for breast cancer have been conducted in resource‐rich countries. We chose Nigeria, a resource‐poor country, as the major site for a phase II feasibility open‐label multicenter clinical trial designed to evaluate the efficacy, safety, and tolerability of neo‐adjuvant capecitabine in locally advanced breast cancer (LABC). Planned treatment consisted of 24 weeks of capecitabine at a dose of 1,000 mg/m² twice daily (2,000 mg/m² total per day). The primary endpoints were overall, partial, complete clinical response rate (OCR, PCR, CCR) and complete pathologic response (cPR). A total of 16 patients were recruited from August 2007 to April 2010. The study was terminated early as a result of slow accrual. After the first three cycles of therapy, PCR were seen in five of 16 patients (31%; 95% CI 11–59%). Of the remaining 11 patients, eight had no response (NR) or stable disease (SD), and three had progressive disease (PD). Seven patients proceeded with further therapy of which had SD. OCR at the end of eight cycles was 44% (95% CI 20–70%). Clinical response and radiologic response by ultrasonomammography were highly concordant (spearman correlation 0.70). The most common adverse effect was Grade 1 hand–foot syndrome, which was seen in 75% of patients. Despite several limitations, we successfully carried out this phase II feasibility study of neo‐adjuvant capecitabine for LABC in Nigeria. Capecitabine monotherapy showed good overall response rates with minimal toxicity and further studies are warranted.     

Identifying febrile young infants with bacteremia: is the peripheral white blood cell count an accurate screen?

STUDY OBJECTIVE: We estimated the accuracy of the total peripheral WBC count as a screen for bacteremia in febrile young infants. METHODS: We evaluated, retrospectively, the performance characteristics of linear and nonlinear (U-shaped) logistic models for predicting bacteremia that are based on the total peripheral WBC count. Research subjects were consecutive 0- to 89-day-old infants who had a temperature in triage of greater than or equal to 38 degrees C (> or =100.4 degrees F) and were evaluated for infection at a pediatric emergency department (1993 to 1999). Infants with leukemia were excluded. Areas under the receiver operator characteristic curves (AUC), as well as sensitivity, specificity, interval likelihood ratios, and the corresponding odds of bacteremia predicted at various thresholds of the test, were calculated. RESULTS: The rate of bacteremia was 1% (38/3,810). The U-shaped model was more accurate (AUC 0.69 versus 0.56); however, no threshold of the total peripheral WBC count had both good sensitivity and specificity. Sensitivity and specificity values were 79% and 5%, respectively, at a peripheral WBC count cutoff of 5,000 cells/mm(3), and 45% and 78%, respectively, at a cutoff of 15,000 cells/mm(3). The odds of bacteremia were not decreased substantially at any cutoff and were increased only modestly at values outside published norms of the test. CONCLUSION: The total peripheral WBC count is an inaccurate screen for bacteremia in febrile young infants; thus, decisions to obtain blood cultures should not rely on this test.     

Dexmedetomidine hemodynamics in children after cardiac surgery

Background: Dexmedetomidine has opposing effects on the cardiovascular system. Action in the central nervous system produces sympatholysis and a reduction in blood pressure, while peripherally it causes vasoconstriction leading to an increase in blood pressure. The purpose of our study is to define the concentration–response profile for these hemodynamic effects in children after cardiac surgery. Methods: A simultaneous pharmacokinetic–pharmacodynamic analysis of data from 29 children given a single bolus of dexmedetomidine 1–4 mcg·kg^?1 following cardiac surgery was undertaken using mixed effects modeling. There were four dexmedetomidine concentrations available from each patient, and mean arterial blood pressure (MAP) was recorded electronically every 5 min for 5 h after drug administration. A composite Emax model was used to relate mean arterial pressure changes to plasma dexmedetomidine concentration. Results: Children had a mean age of 2.67 years (range 4 days–14 years) and a mean weight of 12.34 (range 3.4–48.4) kg. The peripheral vasopressor effect was directly related to plasma concentration with an Emax_pos of 50.3 (CV 44.50%) mmHg, EC_50pos 1.1 (48.27%) μg·l^?1 and a Hill_pos coefficient of 1.65. The delayed central sympatholytic response was described with an Emax_neg of ?12.30 (CV 37.01%) mmHg, EC_50neg 0.10 (104.40%) μg·l^?1 and a Hill_neg coefficient of 2.35. The equilibration half‐time (T_1/2keo) was 9.66 (165.23%) min. Conclusions: Dexmedetomidine administered as a single bolus dose following cardiac surgery produces a biphasic effect on MAP. A plasma dexmedetomidine concentration of above 1.0 μg·l^?1 was associated with a 20% increase in MAP in this specific cohort. A dosage regimen involving a small bolus dose (0.5 μg·kg^?1) followed by a continuous infusion should be used to avoid initial increases in MAP.     

Congenital Self-healing Reticulohistiocytosis: Report of a Case

A newborn male infant presented with a single crateriform nodule in the region of the right iliac fossa. No extracutaneous involvement was found and the lesion involuted spontaneously without scarring in one month. Histology showed histiocytelike cells of which 10% to 15% contained Birbeck granules. S100 protein could not be demonstrated. This case possibly represents a solitary variant of congenital self-healing reticulohistiocytosis.     

Elderly people from ethnic minorities in Liverpool: mental illness, unmet need and barriers to service use

The objective of the Health and Ethnicity Project was to identify unmet need and barriers to the use of psychogeriatric and welfare services by ethnic minority older people living in Liverpool's inner-city. The results presented here are the findings of Phase II of the project in which 71 ethnic minority older people aged 65 years and over were interviewed. These respondents had been diagnosed as suffering from dementia or depression earlier in Phase I. They include Black British, Afro Caribbean and Chinese older people. Findings show a low level of service use in spite of considerable unmet need. Only 8% were in institutions and 46% lived alone. For the 17% living alone in sheltered housing, there was evidence of violence towards wardens, wandering, neglect of rooms and occasional fires. Of the 27% living with a family nearly a half of cases also experienced physical disability. Those in institutions were finding language difficulties and problems in obtaining a suitable diet. Using Yeatts et al.'s typology (1992) ‘lack of knowledge’ barriers and ‘lack of intent’ barriers concerned the group as a whole most, i.e. they either did not know of services or perceived them as being culturally inappropriate. Implications for service providers are considerable: to ensure improved access it is necessary not only to invest more in general medical services but to work in partnership with ethnic minority groups to overcome barriers of mistrust and ensure cultural sensitivity in the services offered.     

Impact of diabetes and smoking epidemic in the Middle East on the presentation with acute coronary syndrome in very young patients

We describe the baseline characteristics, management, and outcomes of acute coronary syndrome (ACS) in patients of age ≤ 40 in the Gulf region of the Middle East. We studied 8176 hospitalized patients (≤ 40 years) with ACS. Ten percent (805) of the recruited patients were ≤ 40 years. The mean age was 37 years and 89% were males. The prevalence of smoking and diabetes in the young patients was high (58% and 21%, respectively). The most common ACS was ST elevation myocardial infarction. Younger patients were more aggressively treated with more frequent use of glycoprotein inhibitors, thrombolytics, and primary percutaneous coronary intervention. They had less in-hospital heart failure, left ventricular dysfunction, shock, stroke, and low rate of in-hospital mortality (1%). Measures to combat the rising prevalence of diabetes and smoking are needed.     

Covert dysphagia in the mentally handicapped: Two case reports and a review of published literature

Mentally handicapped patients with esophageal pathology may present a diagnostic challenge, as they may not complain of any specific symptoms or be able to give a clear history of either dysphagia or odynophagia. This paper reports 2 such patients who recently presented to the Royal Wolverhampton Hospitals. In the first case, upper gastrointestinal endoscopy under general anesthesia enabled both the identification and removal of a large esophageal foreign body. In the second case, repeated upper gastrointestinal endoscopy facilitated both the identification and nonsurgical management of a paraesophageal abscess.