Severe skin reaction secondary to concomitant radiotherapy plus cetuximab

The therapeutic use of monoclonal antibodies against the epidermal growth factor receptor (EGFR) is specifically associated with dermatologic reactions of variable severity. Recent evidence suggests superiority of the EGFR inhibitor (EGFRI) cetuximab plus radiotherapy compared to radiotherapy alone in patients with squamous cell carcinoma of the head and neck. Although not documented in a study population, several reports indicate a possible overlap between radiation dermatitis and the EGFRI-induced skin rash. We here present a case of severe skin reaction secondary to the addition of cetuximab to radiotherapy

A decade of inequality in maternity care: antenatal care, professional attendance at delivery, and caesarean section in Bangladesh (1991–2004)

<p>Abstract</p> <p>Background</p> <p>Bangladesh is committed to the fifth Millennium Development Goal (MDG-5) target of reducing its maternal mortality ratio by three-quarters between 1990 and 2015. Since the early 1990s, Bangladesh has followed a strategy of improving access to facilities equipped and staffed to provide emergency obstetric care (EmOC).</p> <p>Methods</p> <p>We used data from four Demographic and Health Surveys conducted between 1993 and 2004 to examine trends in the proportions of live births preceded by antenatal consultation, attended by a health professional, and delivered by caesarean section, according to key socio-demographic characteristics.</p> <p>Results</p> <p>Utilization of antenatal care increased substantially, from 24% in 1991 to 60% in 2004. Despite a relatively greater increase in rural than urban areas, utilization remained much lower among the poorest rural women without formal education (18%) compared with the richest urban women with secondary or higher education (99%). Professional attendance at delivery increased by 50% (from 9% to 14%, more rapidly in rural than urban areas), and caesarean sections trebled (from 2% to 6%), but these indicators remained low even by developing country standards. Within these trends there were huge inequalities; 86% of live births among the richest urban women with secondary or higher education were attended by a health professional, and 35% were delivered by caesarean section, compared with 2% and 0.1% respectively of live births among the poorest rural women without formal education. The trend in professional attendance was entirely confounded by socioeconomic and demographic changes, but education of the woman and her husband remained important determinants of utilization of obstetric services.</p> <p>Conclusion</p> <p>Despite commendable progress in improving uptake of antenatal care, and in equipping health facilities to provide emergency obstetric care, the very low utilization of these facilities, especially by poor women, is a major impediment to meeting MDG-5 in Bangladesh.</p

Lack of Cetuximab induced skin toxicity in a previously irradiated field: case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Mutation, amplification or dysregulation of the EGFR family leads to uncontrolled division and predisposes to cancer. Inhibiting the EGFR represents a form of targeted cancer therapy.</p> <p>Case report</p> <p>We report the case of 79 year old gentlemen with a history of skin cancer involving the left ear who had radiation and surgical excision. He had presented with recurrent lymph node in the left upper neck. We treated him with radiation therapy concurrently with Cetuximab. He developed a skin rash over the face and neck area two weeks after starting Cetuximab, which however spared the previously irradiated area.</p> <p>Conclusion</p> <p>The etiology underlying the sparing of the previously irradiated skin maybe due to either decrease in the population of EGFR expressing cells or decrease in the EGFR expression.</p> <p>We raised the question that "Is it justifiable to use EGFR inhibitors for patients having recurrence in the previously irradiated field?" We may need further research to answer this question which may guide the physicians in choosing appropriate drug in this scenario.</p

Systemic antifungal treatment after posaconazole prophylaxis: results from the SEIFEM 2010-C survey.

OBJECTIVES: To investigate the incidence, treatment and outcome of breakthrough invasive fungal infections (IFIs) in adult acute myeloid leukaemia (AML) patients after posaconazole prophylaxis. METHODS: From January 2010 to April 2012, all consecutive patients with newly diagnosed AML were prospectively registered at 33 participating Italian centres. All cases of IFIs occurring within 30 days after the end of the first induction chemotherapy were recorded. The strategy of antifungal treatment (empirical, pre-emptive or targeted) and the drugs used were analysed. ClinicalTrials.gov code: NCT01315925. RESULTS: In total, 1192 patients with newly diagnosed AML were enrolled in the study, of whom 510 received posaconazole prophylaxis and were included in the present analysis. Of these patients, 140 (27%) needed systemic antifungal treatment. Among the 127 evaluable cases, an empirical approach was utilized in 102 patients (80%), a pre-emptive approach in 19 patients (15%) and targeted therapy in 6 patients (5%). Only five patients died of IFIs (three in the empirical group and two in the targeted group; 4%). A critical review of IFI diagnoses at 30 days demonstrated that among the patients treated empirically, ∼30% were not affected by IFIs but rather only by fever of unidentified origin. A comparison between the empirical and the pre-emptive groups showed no significant differences regarding the attributable and overall mortalities. CONCLUSIONS: This study confirms that posaconazole prophylaxis reduces the incidence of breakthrough IFIs and does not modify the efficacy of subsequent systemic antifungal treatment, regardless of the approach (empirical or pre-emptive) or the antifungal drug used

Randomized controlled trial comparing four strategies for delivering e-curriculum to health care professionals [ISRCTN88148532]

BACKGROUND: Internet education is increasingly provided to health professionals, but little is known about the most effective strategies for delivering the content. The purpose of this study is to compare four strategies for delivering an Internet-based (e-) curriculum on clinicians' knowledge (K), confidence (CONF), and communication (COMM) about herbs and other dietary supplements (HDS). METHODS: This national randomized 2 × 2 factorial trial included physicians, pharmacists, nurses, nutritionists and trainees in these fields. Participants were randomly assigned to one of four curriculum delivery strategies for 40 brief modules about HDS: a) delivering four (4) modules weekly over ten (10) weeks by email (drip-push); b) modules accessible on web site with 4 reminders weekly for 10 weeks (drip-pull); c) 40 modules delivered within 4 days by email (bolus-push); and d) 40 modules available on the Internet with one email informing participants of availability (bolus-pull). RESULTS: Of the 1,267 enrollees, 25% were male; the average age was 40 years. The completion rate was 62%, without significant differences between delivery groups. There were statistically significant improvements in K, CONF and COMM scores after the course (P<0.001 for all), although the difference in COMM was small. There were no significant differences in any of the three outcomes by delivery strategy, but outcomes were better for those who paid for continuing education credit. CONCLUSION: All delivery strategies tested similarly improved K, CONF, COMM scores about HDS. Educators can use the strategy that is most convenient without diminishing effectiveness. Additional curricula may be necessary to make substantial changes in clinicians' communication practices

Higher-Order Airy Scaling in Deformed Dyck Paths

21 pages, 8 figure

Strain-dependent host transcriptional responses to toxoplasma infection are largely conserved in mammalian and avian hosts

Toxoplasma gondii has a remarkable ability to infect an enormous variety of mammalian and avian species. Given this, it is surprising that three strains (Types I/II/III) account for the majority of isolates from Europe/North America. The selective pressures that have driven the emergence of these particular strains, however, remain enigmatic. We hypothesized that strain selection might be partially driven by adaptation of strains for mammalian versus avian hosts. To test this, we examine in vitro, strain-dependent host responses in fibroblasts of a representative avian host, the chicken (Gallus gallus). Using gene expression profiling of infected chicken embryonic fibroblasts and pathway analysis to assess host response, we show here that chicken cells respond with distinct transcriptional profiles upon infection with Type II versus III strains that are reminiscent of profiles observed in mammalian cells. To identify the parasite drivers of these differences, chicken fibroblasts were infected with individual F1 progeny of a Type II x III cross and host gene expression was assessed for each by microarray. QTL mapping of transcriptional differences suggested, and deletion strains confirmed, that, as in mammalian cells, the polymorphic rhoptry kinase ROP16 is the major driver of strain-specific responses. We originally hypothesized that comparing avian versus mammalian host response might reveal an inversion in parasite strain-dependent phenotypes; specifically, for polymorphic effectors like ROP16, we hypothesized that the allele with most activity in mammalian cells might be less active in avian cells. Instead, we found that activity of ROP16 alleles appears to be conserved across host species; moreover, additional parasite loci that were previously mapped for strain-specific effects on mammalian response showed similar strain-specific effects in chicken cells. These results indicate that if different hosts select for different parasite genotypes, the selection operates downstream of the signaling occurring during the beginning of the host's immune response. © 2011 Ong et al

The EX-FRAIL CKD trial: A study protocol for a pilot randomised controlled trial of a home-based EXercise programme for pre-frail and FRAIL, older adults with Chronic Kidney Disease

Introduction Frailty is highly prevalent in adults with chronic kidney disease (CKD) and is associated with adverse health outcomes including falls, poorer health-related quality of life (HRQOL), hospitalisation and mortality. Low physical activity and muscle wasting are important contributors to physical frailty in adults with CKD. Exercise training may improve physical function and frailty status leading to associated improvements in health outcomes, including HRQOL. The EX-FRAIL CKD trial aims to inform the design of a definitive randomised controlled trial (RCT) that investigates the effectiveness of a progressive, multicomponent home-based exercise programme in prefrail and frail older adults with CKD. Methods and analysis The EX-FRAIL CKD trial is a two-arm parallel group pilot RCT. Participants categorised as prefrail or frail, following Frailty Phenotype (FP) assessment, will be randomised to receive exercise or usual care. Participants randomised to the intervention arm will receive a tailored 12-week exercise programme, which includes weekly telephone calls to advise on exercise progression. Primary feasibility outcome measures include rate of recruitment, intervention adherence, outcome measure completion and participant attrition. Semistructured interviews with a purposively selected group of participants will inform the feasibility of the randomisation procedures, outcome measures and intervention. Secondary outcome measures include physical function (walking speed and Short Physical Performance Battery), frailty status (FP), fall concern (Falls Efficacy Scale-International tool), activities of daily living (Barthel Index), symptom burden (Palliative care Outcome Scale-Symptoms RENAL) and HRQOL (Short Form-12v2). Ethics and dissemination Ethical approval was granted by a National Health Service (NHS) Regional Ethics Committee and the NHS Health Research Authority. The study team aims to publish findings in a peer-reviewed journal and presents the results at relevant national and international conferences. A summary of findings will be provided to participants, a local kidney patient charity and the funding body. Trial registration number ISRCTN87708989

Home-based exercise for people living with frailty and chronic kidney disease: A mixedmethods pilot randomised controlled trial

Background Frailty is associated with adverse health outcomes in people with chronic kidney disease (CKD). Evidence supporting targeted interventions is needed. This pilot randomised controlled trial (RCT) aimed to inform the design of a definitive RCT evaluating the effectiveness of a home-based exercise intervention for pre-frail and frail older adults with CKD. Methods Participants were recruited from nephrology outpatient clinics to this two-arm parallel group mixed-methods pilot RCT. Inclusion criteria were: ≥65 years old; CKD G3b-5; and Clinical Frailty Scale score ≥4. Participants categorised as pre-frail or frail using the Frailty Phenotype were randomised to a 12-week progressive multi-component home-based exercise programme or usual care. Primary outcome measures included eligibility, recruitment, adherence, outcome measure completion and participant attrition rate. Semi-structured interviews were conducted with participants to explore trial and intervention acceptability. Results Six hundred and sixty-five patients had an eligibility assessment with 217 (33%; 95% CI 29, 36) eligible. Thirty-five (16%; 95% CI 12, 22) participants were recruited. Six were categorised as robust and withdrawn prior to randomisation. Fifteen participants were randomised to exercise and 14 to usual care. Eleven (73%; 95% CI 45, 91) participants completed ≥2 exercise sessions/week. Retained participants completed all outcome measures (n = 21; 100%; 95% CI 81, 100). Eight (28%; 95% CI 13, 47) participants were withdrawn. Fifteen participated in interviews. Decision to participate/withdraw was influenced by perceived risk of exercise worsening symptoms. Participant perceived benefits included improved fitness, balance, strength, well-being, energy levels and confidence. Conclusions This pilot RCT demonstrates that progression to definitive RCT is possible provided recruitment and retention challenges are addressed. It has also provided preliminary evidence that home-based exercise may be beneficial for people living with frailty and CKD

Pneumocystis carinii pneumonia in patients with malignant haematological diseases: 10 years' experience of infection in GIMEMA centres.

A retrospective survey was conducted over a 10-year period (1990-99) among 52 haematology divisions in order to evaluate the clinical and laboratory characteristics and outcome of patients with proven Pneumocystis carinii pneumonia (PCP) complicating haematological diseases. The study included 55 patients (18 with non-Hodgkin's lymphoma, 10 with acute lymphoblastic leukaemia, eight with acute myeloid leukaemia, five with chronic myeloid leukaemia, four with chronic lymphocytic leukaemia, four with multiple myeloma, three with myelodys-plastic syndrome, two with myelofibrosis and one with thalassemia) who developed PCP. Among these, 18 (33%) underwent stem cell transplantation; only two received an oral prophylaxis with trimethroprim/sulphamethoxazole. Twelve patients (22%) developed PCP despite protective isolation in a laminar airflow room. The most frequent symptoms were: fever (86%), dyspnoea (78%), non-productive cough (71%), thoracic pain (14%) and chills (5%); a severe hypoxaemia was present in 39 patients (71%). Chest radiography or computerized tomography showed interstitial infiltrates in 34 patients (62%), alveolar infiltrates in 12 patients (22%), and alveolar-interstitial infiltrates in nine patients (16%). Bronchoalveolar lavage was diagnostic in 47/48 patients, induced sputum in 9/18 patients and lung biopsy in 3/8 patients. The diagnosis was made in two patients at autopsy. All patients except one started a specific treatment (52 patients trimethroprim/sulphamethoxazole, one pentamidine and one dapsone). Sixteen patients (29%) died of PCP within 30 d of diagnosis. Multivariate analysis showed that prolonged steroid treatment (P < 0.006) and a radiological picture of diffuse lung involvement (P < 0.003) were negative diagnostic factors