Childhood intussusception in Uzbekistan: Analysis of retrospective surveillance data

<p>Abstract</p> <p>Background</p> <p>Estimates of baseline incidence of childhood intussusception could help safety monitoring after the introduction of rotavirus vaccines. We studied the incidence of intussusception in Uzbekistan, a GAVI-fund eligible state in Central Asia.</p> <p>Methods</p> <p>We retrospectively reviewed intussusception cases in children <2 years of age treated during 2004-2008 at 15 hospitals in the Bukhara region of Uzbekistan. Demographic and clinical data as well as information on diagnostic and treatment practices were obtained from hospital records. We categorized cases using the Brighton collaboration clinical case definition and calculated the national incidence rate.</p> <p>Results</p> <p>Over a 5-year study period, 67 confirmed cases were identified, of which 67% were boys. The median age was 12 months, and no seasonal trend in the distribution of cases was observed. The diagnostic methods used included abdominal radiography (87%) and ultrasonography (57%). Intussusception reduction by air enema was successful in 33 (49%) patients and 34 (50%) cases underwent surgery. A total of 4 deaths occurred, including 3 deaths in infants aged 0-6 months. The median length of hospital stay was 7.3 (range 0-37) days. The incidence of intussusception is estimated at 23 (95% CI 13.6-32.4) cases per 100,000 child-years, corresponding to approximately 237 cases annually.</p> <p>Conclusions</p> <p>This is the first study to estimate the incidence of childhood intussusception prior to the introduction of the rotavirus vaccination in Uzbekistan. A prospective surveillance system using a standardized case definition is needed in order to better examine the occurrence of intussusception in developing countries.</p

Cardiac safety of dual anti-HER2 blockade with pertuzumab plus trastuzumab in early HER2-positive breast cancer in the APHINITY trial.

BACKGROUND Trastuzumab increases the incidence of cardiac events (CEs) in patients with breast cancer (BC). Dual blockade with pertuzumab (P) and trastuzumab (T) improves BC outcomes and is the standard of care for high-risk human epidermal growth factor receptor 2 (HER2)-positive early BC patients. We analyzed the cardiac safety of P and T in the phase III APHINITY trial. PATIENTS AND METHODS Left ventricular ejection fraction (LVEF) ≥ 55% was required at study entry. LVEF assessment was carried out every 3 months during treatment, every 6 months up to month 36, and yearly up to 10 years. Primary CE was defined as heart failure class III/IV and a significant decrease in LVEF (defined as ≥10% from baseline and to <50%), or cardiac death. Secondary CE was defined as a confirmed significant decrease in LVEF, or CEs confirmed by the cardiac advisory board. RESULTS The safety analysis population consisted of 4769 patients. With 74 months of median follow-up, CEs were observed in 159 patients (3.3%): 83 (3.5%) in P + T and 76 (3.2%) in T arms, respectively. Most CEs occurred during anti-HER2 therapy (123; 77.4%) and were asymptomatic or mildly symptomatic decreases in LVEF (133; 83.6%). There were two cardiac deaths in each arm (0.1%). Cardiac risk factors indicated were age > 65 years, body mass index ≥ 25 kg/m2, baseline LVEF between 55% and <60%, and use of an anthracycline-containing chemotherapy regimen. Acute recovery from a CE based on subsequent LVEF values was observed in 127/155 patients (81.9%). CONCLUSIONS Dual blockade with P + T does not increase the risk of CEs compared with T alone. The use of anthracycline-based chemotherapy increases the risk of a CE; hence, non-anthracycline chemotherapy may be considered, particularly in patients with cardiovascular risk factors

Quality of life and sexual function after high-dose or conventional chemotherapy for high-risk breast cancer

Three hundred and ninety women participated in the quality of life (QL) study of ACCOG1, a high-dose vs conventional adjuvant chemotherapy breast cancer trial, for patients with a high risk of relapse. Patients completed the European Organisation for Research and Treatment of Cancer QLQ-C30, questions on menopausal symptoms and the Sexual Activity Questionnaire. Pretreatment, 6,12, 24, 36, 48 and 60-month assessments were conducted. For the high dose group the median decrease in global QL at 6 months was significantly greater than in the conventional group. At 12 months, however, the median change had returned to 0 for both groups. Social functioning was also significantly lower in the high-dose group at 6 months, again returning to prebaseline levels for both groups after 12 months. The most persistent changes appear to be in the effect of treatment in both arms on sexual outcomes, reflected in problems with discomfort and pleasure. Both high-dose and conventional chemotherapy showed persisting negative effects on sexual health. This has not been previously reported as a long-term complication of high-dose chemotherapy. However, it did not have long-term affects on sexual habit, which appeared to return to pretreatment frequency and similar to that of conventional chemotherapy by about 12 months from treatment

Ovarian cysts in women receiving tamoxifen for breast cancer

Tamoxifen is a nonsteroidal anti-oestrogen with gynaecological side-effects. Only recently, ovarian cyst formation during tamoxifen treatment has been reported. The present study aimed to evaluate patient-related parameters that determine ovarian cyst formation in women using tamoxifen for breast cancer. A cross-sectional study was performed in 142 breast cancer patients using tamoxifen. Forty-five patients were also examined prior to tamoxifen treatment. Gynaecological assessment, transvaginal ultrasonography (TVU) and serum oestradiol (E2) and follicle stimulating hormone (FSH) analysis were performed. Follow-up assessments were performed twice a year. Uni- or bilateral ovarian cysts were detected by TVU in 24 tamoxifen-using patients and in one patient before tamoxifen treatment. Multiple regression analysis showed that cyst development is related (multiple R = 0.73) to high E2 (P < 0.001), younger age (P < 0.001) and absence of high-dose chemotherapy (P = 0.007). Patients with ovarian cysts had higher serum E2 levels compared to patients without cysts (1.95 vs 0.05 nmol l−1; P < 0.001). All patients after high-dose chemotherapy or older than 50 years had E2 < 0.10 nmol l−1 and/or amenorrhoea > 1 year and did not develop ovarian cysts. Patients still having a menstrual cycle during tamoxifen had a high chance (81%) of developing ovarian cysts. Breast cancer patients receiving tamoxifen only develop ovarian cysts if their ovaries are able to respond to FSH stimulation as shown by E2 production. © 1999 Cancer Research Campaig

Inclusive education in the academy: pedagogical and political imperatives in a master’s course

Many universities offer undergraduate and postgraduate courses in inclusive education. There has been much research into the impact of these courses, but little is written about their design. This article focuses on a master’s course in inclusive education in a South African university. The course positions inclusive education as a critical education project and is designed around the four propositions presented by Slee in The Irregular School (2011. Milton Park: Routledge). Using Bernsteinian ideas about pedagogising knowledge, this article accounts for the pedagogical choices made in content selection and course design. The focal questions in the course are described, together with an indication of the range of additional texts that students read. Given that Slee asserts that inclusive education is a political project, and that Allan (2010. “The Inclusive Teacher Educator: Spaces for Civic Engagement.” Discourse: Studies in the Cultural Politics of Education 31 (4): 411–422) urges inclusive teacher educators to reorientate themselves towards civic duty, I argue that producing a pedagogic discourse of inclusive education is a political task that should result in both the teacher educator and the students being oriented towards a critique of existing exclusionary arrangements and an activism that leads to change

Cisplatin and Doxorubicin Induce Distinct Mechanisms of Ovarian Follicle Loss; Imatinib Provides Selective Protection Only against Cisplatin

Chemotherapy treatment in premenopausal women has been linked to ovarian follicle loss and premature ovarian failure; the exact mechanism by which this occurs is uncertain. Here, two commonly used chemotherapeutic agents (cisplatin and doxorubicin) were added to a mouse ovary culture system, to compare the sequence of events that leads to germ cell loss. The ability of imatinib mesylate to protect the ovary against cisplatin or doxorubicin-induced ovarian damage was also examined.Newborn mouse ovaries were cultured for a total of six days, exposed to a chemotherapeutic agent on the second day: this allowed for the examination of the earliest stages of follicle development. Cleaved PARP and TUNEL were used to assess apoptosis following drug treatment. Imatinib was added to cultures with cisplatin and doxorubicin to determine any protective effect.Histological analysis of ovaries treated with cisplatin showed oocyte-specific damage; in comparison doxorubicin preferentially caused damage to the granulosa cells. Cleaved PARP expression significantly increased for cisplatin (16 fold, p<0.001) and doxorubicin (3 fold, p<0.01). TUNEL staining gave little evidence of primordial follicle damage with either drug. Imatinib had a significant protective effect against cisplatin-induced follicle damage (p<0.01) but not against doxorubicin treatment.Cisplatin and doxorubicin both induced ovarian damage, but in a markedly different pattern, with imatinib protecting the ovary against damage by cisplatin but not doxorubicin. Any treatment designed to block the effects of chemotherapeutic agents on the ovary may need to be specific to the drug(s) the patient is exposed to

The effects of long-term total parenteral nutrition on gut mucosal immunity in children with short bowel syndrome: a systematic review

BACKGROUND: Short bowel syndrome (SBS) is defined as the malabsorptive state that often follows massive resection of the small intestine. Most cases originate in the newborn period and result from congenital anomalies. It is associated with a high morbidity, is potentially lethal and often requires months, sometimes years, in the hospital and home on total parenteral nutrition (TPN). Long-term survival without parenteral nutrition depends upon establishing enteral nutrition and the process of intestinal adaptation through which the remaining small bowel gradually increases its absorptive capacity. The purpose of this article is to perform a descriptive systematic review of the published articles on the effects of TPN on the intestinal immune system investigating whether long-term TPN induces bacterial translocation, decreases secretory immunoglobulin A (S-IgA), impairs intestinal immunity, and changes mucosal architecture in children with SBS. METHODS: The databases of OVID, such as MEDLINE and CINAHL, Cochran Library, and Evidence-Based Medicine were searched for articles published from 1990 to 2001. Search terms were total parenteral nutrition, children, bacterial translocation, small bowel syndrome, short gut syndrome, intestinal immunity, gut permeability, sepsis, hyperglycemia, immunonutrition, glutamine, enteral tube feeding, and systematic reviews. The goal was to include all clinical studies conducted in children directly addressing the effects of TPN on gut immunity. RESULTS: A total of 13 studies were identified. These 13 studies included a total of 414 infants and children between the ages approximately 4 months to 17 years old, and 16 healthy adults as controls; and they varied in design and were conducted in several disciplines. The results were integrated into common themes. Five themes were identified: 1) sepsis, 2) impaired immune functions: In vitro studies, 3) mortality, 4) villous atrophy, 5) duration of dependency on TPN after bowel resection. CONCLUSION: Based on this exhaustive literature review, there is no direct evidence suggesting that TPN promotes bacterial overgrowth, impairs neutrophil functions, inhibits blood's bactericidal effect, causes villous atrophy, or causes to death in human model. The hypothesis relating negative effects of TPN on gut immunity remains attractive, but unproven. Enteral nutrition is cheaper, but no safer than TPN. Based on the current evidence, TPN seems to be safe and a life saving solution

Development of inclusive education in England: Impact on children with special educational needs and disabilities

This is an accepted manuscript of a book chapter published by Springer Routledge in the Handbook on Promoting Social Justice in Education, available online: https://doi.org/10.1007/978-3-319-74078-2_151-1 The accepted version of the publication may differ from the final published version. Please refer to the publisher's terms and conditions for re-use.This chapter considers a historical account of the development of inclusion in England and the changes made to the education of children with SEND since the 1940s. The chapter details the development of inclusive education, the complexity of defining inclusion, and what inclusion has come to mean in current practice. This historical account is considered alongside the development and dominance of the standards agenda. In considering inclusion in this manner, the original intentions of its agenda are questioned against the practical implementation of inclusive education in current practice. The chapter concludes by proposing that significant progress has not been made with inclusion because it has not been possible to accommodate it within the competing political agendas replete in England’s education system