Current and emerging osteoporosis pharmacotherapy for women: state of the art therapies for preventing bone loss

Introduction: Pharmacological options to address the imbalance between bone resorption and accrual in osteoporosis include anti-resorptive and osteoanabolic agents. Unique biologic pathways such as the Wnt/β-catenin pathway have been targeted in the quest for new emerging therapeutic strategies.

Areas covered: This review provides an overview of existing pharmacotherapy for osteoporosis in women and explore state-of–the-art and emerging therapies to prevent bone loss, with an emphasis on the mechanism of action, indications and side effects.

Expert opinion: Bisphosphonates appear to be a reliable and cost-effective option, whereas denosumab has introduced a simpler dosing regimen and may achieve a linear increase in bone mineral density (BMD) with no plateau being observed, along with continuous anti-fracture efficacy. Abaloparatide, a parathyroid-hormone-related peptide (PTHrP)-analogue, approved by the FDA in April 2017, constitutes the first new anabolic osteoporosis drug in the US for nearly 15 years and has also proven its anti-fracture efficacy. Romosozumab, a sclerostin inhibitor, which induces bone formation and suppresses bone resorption, has also been developed and shown a significant reduction in fracture incidence; however, concerns have arisen with regard to increased cardiovascular risk.     

Genetic variability of human metapneumo‐ and bocaviruses in children with respiratory tract infections

Objectives

The genotypic analysis of human metapneumo-(HMPV) and boca-(HBoV) viruses circulating in Greece and their comparison to reference and other clinical strains.

Design

Genetic analysis of representative strains over three consecutive winter seasons of the years 2005–2008.

Setting

Representative positive specimens for HMPV and HBoV from paediatric patients of healthcare units and hospitals in Southern Greece with influenza-like illness or other respiratory tract infections.

Sample

Seven to ten positive specimens for either HMPV or HBoV from each winter period. In total, 24 specimens positive for HMPV and 26 for HBoV, respectively.

Main outcome measures

Sequence diversity of HMPV and HBoV strains by sequencing the complete G and VP1/VP2 genes, respectively.

Results

In total, 24 HMPV strains were found to have a 92–100% nucleotide and a 85.9–100% amino acid identity. Phylogenetic analysis based on the number of amino acid differences, revealed circulation of 4 different subclusters belonging to genetic lineage B2. Similarly, analysis of 26 HBoV strains indicated that 22 clustered within genotype St2, 2 into genotype St1 and the remaining 2 formed a third cluster derived from potential recombination between different St1 genotype strains. St2 HBoV genotype was observed throughout the whole observation period whereas St1 only during the second and the third winter period. Higher levels of heterogeneity were observed between HMPV compared to HBoV strains.

Conclusions

Phylogenetic analysis revealed circulation of one single lineage (B2) for HMPV viruses and predominance of St2 genotype for HBoV viruses. A possible recombination between St1 genotype strains of HBoV was observed.     

Education and age affect skill acquisition and retention in lay rescuers after a European Resuscitation Council CPR/AED course

Objectives

To examine whether education and age affect skill acquisition and retention in lay rescuers after a European Resuscitation Council (ERC) CPR/AED course.

Background

Because of the importance of bystander CPR/AED skills in the setting of cardiac arrest, acquisition and retention of resuscitation skills has gained a great amount of interest.

Methods

The ERC CPR/AED course format for written and practical evaluation was used. Eighty lay people were trained and evaluated at the end of the course, as well as at one, three, and six months.

Results

Retention of CPR/AED skills improved over time, recording the lowest practical scores at one month after initial training and the lowest written scores at initial training. In practical evaluation scores, when examined longitudinally, age presented a significant adverse effect and higher background education presented a non-significant positive effect. Moreover, regarding written evaluation scores, when examined longitudinally, education presented a significant positive effect while age did not significantly correlate with written scores.

Conclusions

Education and age affected retention of CPR/AED skills in lay rescuers. Also, our results suggest that the ERC CPR/AED course format may be poorly designed to discriminate between participants with different levels of practical and written resuscitation skills and merit a thorough investigation in future studies.     

Cardiopulmonary exercise testing in chronic obstructive pulmonary disease: An update on its clinical value and applications

Chronic obstructive pulmonary disease is a debilitating disorder, characterized by airflow limitation, exercise impairment, reduced functional capacity and significant systemic comorbidity, which complicates the course of the disease. The critical inspiratory constraint to tidal volume expansion during exercise (that may be further complicated by the presence of dynamic hyperinflation), abnormalities in oxygen transportation and gas exchange abnormalities are the major pathophysiological mechanisms of exercise intolerance in COPD patients, and thus, exercise testing has been traditionally used for the functional evaluation of these patients. Compared to various laboratory and field exercise tests, cardiopulmonary exercise testing (CPET) provides a thorough assessment of exercise physiology, involving the integrative respiratory, cardiovascular, muscle and metabolic responses to exercise. This review highlights the clinical utility of CPET in COPD patients, as it provides important information for the determination of the major factors that limit exercise among patients with several comorbidities, allows the assessment of the severity of dynamic hyperinflation, provides valuable prognostic information and can be used to evaluate the response to several therapeutic interventions.     

Clinicopathological differences and correlations between right and left colon cancer

BACKGROUND The differences in histopathology and molecular biology between right colon cancer(RCC)and left colon cancer(LCC)were first reported in the literature by Bufill in 1990.Since then,a large number of studies have confirmed their differences in epidemiology,clinical presentation,comorbidities and biological behaviours,which may be related to the difference in prognosis and overall survival(OS)between the two groups.AIM To investigate statistically significant differences between Greek patients with LCC and RCC.METHODS The present observational study included 144 patients diagnosed with colon cancer of any stage who received chemotherapy in a Greek tertiary oncology hospital during a 2.5-year period.Clinical information,comorbidities,histopathologic characteristics and molecular biomarkers were collected from the patients’medical records retrospectively,while administered chemotherapy regimens,targeted agents,progression-free survival(PFS)periods with first-and second-line chemotherapy and OS were recorded retroactively and prospectively.Data analysis was performed with the SPSS statistical package.RESULTS Eighty-six males and 58 females participated in the study.One hundred(69.4%)patients had a primary lesion in the left colon,and 44(30.6%)patients had a primary lesion in the right colon.Patients with RCC were more likely to display anaemia than patients with LCC[odds ratio(OR)=3.09],while LCC patients were more likely to develop rectal bleeding(OR=3.37)and a feeling of incomplete evacuation(OR=2.78)than RCC patients.Considering comorbidities,RCC patients were more likely to suffer from diabetes(OR=3.31)and coronary artery disease(P=0.056)than LCC patients.The mucinous differentiation rate was higher in the right-sided group than in the left-sided group(OR=4.49),as was the number of infiltrated lymph nodes(P=0.039),while the percentage of high-grade differentiation was higher in the group of patients with left-sided colon cancer than in RCC patients(OR=2.78).RAS wild-type patients who received anti-epidermal growth factor receptor(EGFR):Treatment experienced greater benefit(PFS:16.5 mo)than those who received anti-vascular endothelial growth factor treatment(PFS:13.7 mo)(P=0.05),while among RAS wild-type patients who received anti-EGFR treatment,LCC patients experienced greater benefit(PFS:15.8 mo)than the RCC subgroup(PFS:5.5 mo)in the first-line chemotherapy setting(P=0.034).BRAF-mutant patients had shorter PFS(9.3 mo)than BRAF wild-type patients(14.5 mo)(P=0.033).RCC patients showed a shorter tumour recurrence period(7.7 mo)than those with LCC(14.5 mo)(P<0.001),as well as shorter(OS)(58.4 mo for RCC patients;82.4 mo for LCC patients)(P=0.018).CONCLUSION RCC patients present more comorbidities,worse histological and molecular characteristics and a consequently higher probability of tumour recurrence,poor response to targeted therapy and shorter OS than LCC patients.     

Aberrant p16 promoter methylation among Greek lung cancer patients and smokers: correlation with smoking.

Genetic and environmental factors (dietary and smoking) influence lung cancer epidemiology and induce epigenetic modifications that should be assessed in individual populations. We analyzed p16 methylation among Greek non-small cell lung carcinoma patients and smokers using two-stage methylation-specific polymerase chain reaction. One hundred and fifty specimens from cancerous and adjacent non-cancerous tissue, bronchial washings and sputum from patients and 48 specimens, mostly sputum, from disease-free smokers were included. p16 methylation was very frequent in biopsies (82.85%) and bronchial washings (non-small cell lung carcinoma, 80.35%; small cell lung carcinoma, 16.66%) from patients, but also in adjacent non-cancerous tissue (45.71%). Concordance of p16 methylation and positivity by cytological examination was 51.78%. Methylation was also observed in sputum from asymptomatic cytology-negative smokers (22.5%) and chronic obstructive pulmonary disease patients (three of eight). Among disease-free individuals, methylation correlated only with heavy smoking (>50 pack-years, P<0.001) and differed among male and female disease-free smokers. In summary, p16 methylation is very frequent among non-small cell lung carcinoma patients, and correlates with heavy cigarette consumption only in disease-free smokers.     

Intramuscular Administration of Very High Dose of a-Tocopherol Protects Liver from Severe Ischemia/Reperfusion Injury

The effect of intramuscular administration of high (30 mg/kg body weight for 3 days) or very high (300 mg/kg body weight for 3 days) doses of a-tocopherol to Wistar rats subjected to total severe warm hepatic ischemia and reperfusion was investigated. After a 60-minute period of total hepatic ischemia and 120 minutes of reperfusion, animals were killed, and liver samples were taken for determination of malondialdehyde (MDA) and histological examinations. Blood samples were also taken for assay of serum a-tocopherol, alanine transaminase (ALT), aspartate transaminase (AST), and lactic dehydrogenase (LDH). Additional animals were followed for a 7-day survival rate determination. Results showed that ischemia and reperfusion decreased the survival rate to 10%, whereas the levels of AST, ALT, and LDH in serum were increased compared with levels in animals that were sham operated. The MDA concentrations in liver were also increased, from 1.142 to 1.567 nmoles/g, whereas the levels of a-tocopherol in serum were decreased from 10.20 to 1.80 mmol/L. Pretreatment with a-tocopherol increased the viability to 50% and 70%, for the high and very high doses, respectively, and decreased the levels of AST, ALT, and LDH in serum. It also decreased the MDA concentrations in liver to 0.975 and 0.774 nmoles/g for the high and very high doses of a-tocopherol, respectively, whereas it increased the level of a-tocopherol in serum to 11.25 and 13.02 mmol/L for the high and very high doses, respectively. Histological examinations showed protection of the liver parenchyma in the animals treated with a-tocopherol.