A pilot study of nimotuzumab plus single agent chemotherapy as second- or third-line treatment or more in patients with recurrent,persistent or metastatic cervical cancer

Nimotuzumab is a humanized IgG1 monoclonal antibody against the EGFR extracellular domain that has been evaluated in solid tumors as a single agent or in combination with chemotherapy and radiation. Cervical cancer patients who are refractory or progressive to first-line chemotherapy have a dismal prognosis, and no second- or third-line chemotherapy is considered standard. This pilot trial aimed to evaluate the efficacy and safety of nimotuzumab in 17 patients with pre-treated advanced refractory or progressive cervical cancer. Nimotuzumab was administered weekly at 200 mg/m² as single agent for 4 weeks (induction phase), then concurrent with 6 21-day cycles of gemcitabine (800 mg/m²) or cisplatin (50 mg/m²) for 18 weeks (concurrent phase) and then once every 2 weeks (maintenance phase). Nimotuzumab could be continued beyond disease progression. Seventeen patients were accrued and evaluated for safety and efficacy. The median number of nimotuzumab applications was 20 (5–96). The median number of chemotherapy cycles administered was 6 (1-6). No toxicity occurred during induction and maintenance phases (single agent nimotuzumab). In the concurrent phase, grade 3 toxicity events observed were leucopenia, anemia and diarrhea in 11.7%, 5.8% and 11.7% respectively. No complete or partial responses were observed. The stable disease (SD) rate was 35%. The median PFS and OS rates were163 days (95% CI, 104 to 222), and 299 days (95% IC, 177 to 421) respectively. Nimotuzumab is well tolerated and may have a role in the treatment of advanced cervical cancer.     

Polymorphisms of the farnesyl diphosphate synthase gene modulate bone changes in response to atorvastatin

Although their primary therapeutic indications are different, aminobisphosphonates and statins target enzymes in the mevalonate pathway, which is critical for bone homeostasis. Previous studies have shown that some polymorphisms of the gene encoding farnesyl diphosphate synthase (FDPS), the main target of aminobisphosphonates, modulate the response to these drugs. In this study, we explored whether those single nucleotide polymorphisms (SNPs) also influence the changes in bone mineral density (BMD) following therapy with statins. Sixty-six patients with coronary heart disease were studied at baseline and after 1-year therapy with atorvastatin. BMD was measured by DXA. Three SNPs of the FDPS gene (rs2297480, rs11264359 and rs17367421) were analyzed by using Taqman assays. The results showed that there was no association between the SNPs and basal BMD. However, rs2297480 and rs11264359 alleles, which are in linkage disequilibrium, were associated with changes in hip BMD following atorvastatin therapy. Thus, patients with AA genotype at the rs2297480 locus had a 0.8 ± 0.8 % increase in BMD at the femoral neck, whereas in patients with AC/CC genotypes, BMD showed a 2.3 ± 0.8 % decrease (p = 0.02). Similar results were obtained regarding changes of BMD at the femoral trochanter and when alleles at the rs11264359 locus were analyzed. However, there was no association between BMD and rs17367421 alleles. In conclusion, these results suggest that polymorphisms of the FDPS gene may influence the bone response to various drugs targeting the mevalonate pathway, including not only aminobisphosphonates but also statins.     

Prevalence of obesity in Denmark

There has been a pronounced, distinctive increase of the prevalence of obesity within almost all age groups of the Danish population, during the last 25-30 years. The largest increase has been documented in studies based on objective data from total populations and the latest data show the increase will continue. The Danish studies show heterogeneity in the development of the obesity epidemic. A close association with birth cohorts indicates a need for further aetiological research, not only into behavioural factors, but also into early life factors that may explain some of this developmental pattern.     

Therapy-related myelodysplastic syndrome

Introduction: Myelodysplastic syndrome (MDS) is a heterogeneous clonal disorder characterized by deregulation of apoptosis, dysplastic features in hematopoietic precursors, peripheral blood cytopenias and an increased risk for transformation to acute leukemia. Roughly 20% of MDS are therapy related (t-MDS), and this is considered an independent adverse prognostic factor.

Areas covered: This review based on a comprehensive literature search provides an overview on the main features of t-MDS, including its epidemiology, risk factors, molecular pathogenesis, prognostic classifications and therapy.

Expert opinion: Increasing evidence points out that the most important event in t-MDS is genetic alterations in hematopoietic stem precursor cells, however, ineffective hematopoiesis may also result from abnormalities in the bone marrow microenvironment. Thus, novel views onto the processes of t-MDS are needed such as the osteohematology concept. On the other hand, the number of people living with and beyond cancer is increasing worldwide; thus, most emphasis should be placed on preventing secondary malignancies such as t-MDS. From this review, it becomes clear that we are in urgent need not only to deepen our understanding of the leukemogenesis mechanisms induced by exposure to chemotherapy and radiation but also to translate this knowledge into clinical strategies aimed at risk reduction.     

Applying Andersen’s Model to Explain Service Use and Quality of Life Among Australian Caregivers of Children with Autism Spectrum Disorder

Access to necessary supports and services is extremely important for the wellbeing and, ultimately, quality of life (QOL) of family caregivers. By understanding patterns of health service utilization, we can better tailor current services to meet caregivers’ needs. Framed by Andersen’s Behavioral Model, predisposing, enabling and need factors associated with service utilization, and their relation to QOL, were examined in a cross-sectional sample of 156 Australian caregivers of children and adolescents with autism spectrum disorder (ASD). Participants completed an online survey to assess services accessed, QOL (Quality of Life in Autism - Part A), health beliefs (Health Opinions Questionnaire), ASD symptom severity (Quality of Life in Autism - Part B), and caregiver distress (Depression Anxiety Stress Scales – 21 item). Multivariate regression analyses confirmed the role of predisposing (i.e. higher education), and enabling (i.e. higher income) variables, although family structure (i.e. having more than one children with ASD; OR?=?7.22, CI: 1.77–29.54, p?<?.01) and caregiver distress (OR?=?1.04, CI: 1.0–1.07, p?<?.05) were identified as the strongest predictors of service access. Both of these variables also helped to explain a sizeable portion of the variance in QOL scores (R²?=?.32, adj. R²?=?.24, p?<?.001). Personal barriers to health care utilization exist for parents of children with ASD which impact their decision to access help. There is, however, a need for further research to expand Andersen’s model by examining subjective and objective QOL indicators applicable to the caregiver cohort.     

Postprandial coagulation activation in overweight individuals after weight loss: Acute and long-term effects of a high-monounsaturated fat diet and a low-fat diet

Diet is important in the prevention of cardiovascular disease, and it has been suggested that a high-MUFA diet is more cardioprotective than a low-fat diet. We hypothesised that the postprandial thrombotic risk profile is improved most favourably by a high-MUFA diet compared with a low-fat diet. This was tested in a parallel intervention trial on overweight individuals (aged 28.4 (SD 4.7) years) randomly assigned to a MUFA-diet (35-45% of energy as fat; > 20% as MUFA, n = 21) or a low-fat (LF) diet (20-30% of energy as fat, n = 22) for 6 months after a weight loss of ~ 10%. All foods were provided free of charge from a purpose-built supermarket. Meal tests designed after the same principles were performed before and after the dietary intervention, and blood samples were collected at 8.00 h (fasting), 12.00 h, and 18.00 h and analysed for factor VII coagulant activity (FVII:C), activated FVII, fibrinogen, prothrombin fragment 1 + 2 (F1 + 2), D-dimer, plasminogen activator inhibitor (PAI:Ag), and thrombin activatable fibrinolysis inhibitor. There were significant postprandial increases in F1 + 2 and D-dimer before and after dietary intervention, with significantly lower values after 6 months. No significant differences were observed between the postprandial changes induced by the two diets. The postprandial decrease in FVII:C and PAI:Ag did not differ before and after intervention, irrespective of the diets. Our findings suggest postprandial coagulation activation in overweight subjects with more pronounced acute than long-term effects. We observed similar effects of the MUFA diet and the LF diet on the postprandial prothrombotic risk profile.     

Psychiatric disorders and left-handedness in children living in an urban environment

The objective of this study was to conduct an analysis of left-handed children treated in an urban mental health clinic to investigate the frequency and severity of psychiatric disorders compared to right-handed peers. Data on handedness, diagnoses, hospitalizations and severity of mental disorders were collected on 692 consecutive children, 4–18 years old (M = 10.1, SD = 3.2), referred for psychiatric evaluation. Left-handed children were 18.2% of patients in the study, a rate significantly higher than left-hand dominance in the USA (p < .05). Compared to children with right-handedness, logistic regression analysis yielded 31% [odds ratio (OR) = 1.31, 95% confidence interval (CI): 1.15–1.50] higher odds of having more psychiatric diagnosis, 70% (OR = 1.70, 95% CI: 1.10–2.62) increased odds of anxiety, 53% (OR = 1.53, 95% CI: 1.03–2.27) increased odds of depression and 78% (OR = 1.78, 95% CI: 1.21–2.62) increased odds of oppositional defiant disorder for children who were left-handed. Left-handed children had increased odds of being prescribed antipsychotic and anxiolytic medication uses, 53% and 86% increased odds, respectively, and 66% (OR = 1.66, 95% CI: 1.08–2.55) increased odds of psychiatric hospitalizations. Left-handedness was a phenotypic risk factor for psychiatric disorders and increased severity of psychiatric disorders.     

Use of antidepressants in the treatment of depression in Asia: Guidelines,clinical evidence,and experience revisited

Major depressive disorder is prevalent worldwide, and only about half of those affected will experience no further episodes or symptoms. Additionally, depressive symptoms can be challenging to identify, with many patients going undiagnosed despite a wide variety of available treatment options. Antidepressants are the cornerstone of depression treatment; however, a large number of factors must be considered in selecting the treatment best suited to the individual. To help support physicians in this process, international and national treatment guidelines have been developed. This review evaluates the current use of antidepressant treatment for major depressive disorder in six Asian countries (China, Korea, Malaysia, Philippines, Taiwan, and Thailand). No remarkable differences were noted between Asian and international treatment guidelines or among those from within Asia as these are adapted from western guidelines, although there were some local variations. Importantly, a shortage of evidence‐based information at a country level is the primary problem in developing guidelines appropriate for Asia, so most of the guidelines are consensus opinions derived from western research data utilized in western guidelines. Treatment guidelines need to evolve from being consensus based to evidence based when evidence is available, taking into consideration cost/effectiveness or cost/benefit with an evidence‐based approach that more accurately reflects clinical experience as well as the attributes of each antidepressant. In everyday practice, physicians must tailor their treatment to the patient's clinical needs while considering associated external factors; better tools are needed to help them reach the best possible prescribing decisions which are of maximum benefit to patients.     

Lifestyle advice with or without pelvic floor muscle training for pelvic organ prolapse: a randomized controlled trial

Introduction and hypothesis

We evaluated the effect of adding pelvic floor muscle training (PFMT) to a structured lifestyle advice program.

Methods

This was a single-blinded randomized trial of women with symptomatic pelvic organ prolapse (POP) stage?≥?II. Participants were randomized to a structured lifestyle advice program with or without PFMT. Both groups received similar lifestyle advice in six separate group sessions. The combined group performed group PFMT after an individual assessment. Primary outcome was a global improvement scale at six-month follow-up. Secondary outcomes were the global scale and objective POP at three-month follow-up, symptoms and quality of life including sexuality, at three and six-month follow-up. A clinically relevant change of symptoms was defined as ≥15 %.

Results

We included 109 women. Eighty-nine women (82 %) completed three months follow-up; 85 (78 %) completed six-month follow-up. At both follow-ups, significantly more women in the combined group reported improvement in the global scale. At the three-month follow-up, the combined group only had significant improvement of POP symptoms while only the lifestyle advice group had significant improvement of quality of life. Change in objective POP and sexuality was nonsignificant. The symptom score improved 17 % in the combined group and 14 % in the lifestyle advice group (P?=?0.57). Significantly more women in the lifestyle advice group had sought further treatment at the six-month follow-up.

Conclusion

Adding PFMT to a structured lifestyle advice program gave superior results in a global scale and for POP symptoms. Overall effect of either intervention barely reached clinical relevance.