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.     

Dentoskeletal treatment changes in Class II subdivision malocclusions in submentovertex and posteroanterior radiographs.

The objective of this study was to evaluate the dentoskeletal changes consequent to orthodontic treatment in subjects with Class II subdivision malocclusions, treated with asymmetric extractions, compared with a normal-occlusion control group. The sample consisted of 3 groups, with 30 subjects in each: normal-occlusion subjects (group 1), untreated Class II subdivision subjects (group 2), and Class II subdivision patients treated with asymmetric extractions (group 3). All subjects had a full complement of permanent teeth at the beginning of treatment. The average ages of the subjects were 22.42, 15.76, and 18.57 years, respectively, in groups 1, 2, and 3. Measurements of relative differences in the spatial position of dental and skeletal bilateral landmarks were obtained from the submentovertex and posteroanterior cephalometric (PA) radiographs. The t test for independent samples was used to compare group 1 with groups 2 and 3 at different times. Results from the submentovertex radiograph showed that asymmetric extractions in Class II subdivision malocclusions will maintain the differences in the anteroposterior positions of right and left, maxillary and mandibular first molars, as would be expected with the treatment protocols used. There were no significant skeletal changes that could be attributed to the treatment approaches investigated or transverse collateral effects with the asymmetric mechanics used. It was also demonstrated that treatment of Class II subdivision malocclusions with asymmetric extractions produced corrections of maxillary and mandibular dental midline deviations with the midsagittal plane, without canting the occlusal plane or any other investigated horizontal plane, as seen in the PA radiograph. Treatment of Class II subdivision malocclusions with asymmetric extractions constitutes a beneficial approach to this problem.     

Perceived occupational stress,affective, and physical well-being among telecommunication employees in Greece

The present study examined four potential roles of work-related negative affectivity on the associations between self-reported occupational stress and physical well-being among telecommunication employees in Greece. Participants (764, predominantly male) completed a battery of self-report measures on perceived occupational stress, negative affectivity, and illness symptoms. In line with previous research, negative affectivity exerted a nuisance effect, by inflating the association between reported stressors and illness symptoms, and significantly predicted illness symptoms, over and above the effects of stressors. In addition, negative affectivity influenced reported illness symptom indirectly, through the effects of stressors, and moderated the relationship between interpersonal conflict at work and illness symptoms. The findings suggest that negative affectivity can largely explain and influence in different ways the associations between self-reported stress and physical strain. It is recommended that future studies of occupational stress should control for the effects of negative affectivity, and that health professionals should be cautious of its effects when interpreting relationships between self-reported occupational stress and physical well-being.     

Arterial blood gases during cardiac arrest: markers of blood flow in a canine model.

Measures of CO2 have been shown to correlate with coronary perfusion pressure and cardiac output during cardiac arrest. We evaluated arterial pH (pHa) relative to blood flow during cardiac arrest in a canine electromechanical dissociation (EMD) model of cardiac arrest using different resuscitation techniques. Following 15 min of cardiac arrest, 24 mongrel dogs received epinephrine with continued CPR or closed-chest cardiopulmonary bypass. Central arterial blood gases, end-tidal carbon dioxide (PetCO2), coronary perfusion pressure and cardiac output were measured. During CPR, prior to epinephrine or bypass, there was no correlation of pHa, PACO2 and PetCO2, with cardiac output or coronary perfusion pressure. Immediately after instituting the resuscitation techniques, both pHa and PaCO2 showed a significant correlation with cardiac output (pHa; R = -0.78, P less than 0.001 and PaCO2; R = 0.87, P less than 0.001) and with coronary perfusion pressure (pHa; R = -0.75, P less than 0.001 and PaCO2; R = 0.75, P less than 0.001). Eventual survivors (n = 15) had an early significant decrease in pHa, base excess and a significant increase in PaCO2 which was not present in non-survivors (n = 9). Neither pHa nor PaCO2 correlate with blood flow under low flow conditions of CPR. However, with effective circulatory assistance, pHa and PaCO2 reflect systemic blood flow and reperfusion washout.     

Case report: Role of hepatitis E virus in the etiology of community-acquired non-A,non-B hepatitis in greece

The aim of this study was to determine the frequency of hepatitis E virus (HEV) infection in a population of Greek adults with community-acquired (sporadic) non-A, non-B hepatitis found to be seronegative for antibodies to hepatitis C virus (anti-HCV). All patients admitted to the Liver Unit of Western Attica General Hospital and diagnosed as having acute community-acquired non-A, non-B hepatitis between February, 1986, and May, 1990, were enrolled in follow up studies (n = 66). Nineteen patients with HCV infection and 11 patients with acute non-A, non-B, non-C hepatitis that progressed to chronicity were excluded. Convalescent sera were tested for antibody to HEV (anti-HEV) by a fluorescent antibody blocking assay in 33 of 36 eligible patients. One of the 33 (3%) patients was found to be positive for anti-HEV. Anti-HEV testing of all 20 available serum specimens from this patient showed evidence of anti-HEV seroconversion at the fourth week after the onset of hepatitis. The patient had not travelled abroad or within Greece or had not had apparent contact with people from foreign countries for the previous 3 months. These data show that HEV infection is not a major cause of community-acquired non-A, non-B hepatitis in Greece. However, the reported case of HEV hepatitis suggests that HEV may retain a low endemicity in Greece. More extensive seroprevalence studies are needed for an accurate estimation of the extent of HEV infection in the southeastern European countries. © 1994 Wiiey-Liss, Inc.     

Response rates in metastatic neuroendocrine tumors receiving peptide receptor radionuclide therapy and implications for future treatment strategies

BackgroundPeptide receptor radionuclide therapy is a targeted therapy used to treat unresectable somatostatin receptor-positive neuroendocrine tumors. The objective of this study was to evaluate response rates among neuroendocrine tumors of different primaries and identify factors relevant to future treatment strategies.MethodsWe retrospectively reviewed patients who received peptide receptor radionuclide therapy for neuroendocrine tumors from 2018 to 2019 at our institution. Patients were assessed with computed tomography/magnetic resonance imaging and ⁶⁸Ga-DOTATATE-positron emission tomography before and after 2 or 4 cycles of peptide receptor radionuclide therapy. Tumor response was evaluated by RECIST 1.1. Statistics included multinomial logistic regression models and Fisher exact test.ResultsTwenty-seven patients underwent 92 cycles of peptide receptor radionuclide therapy: pancreas (n = 11), small bowel (n = 7), and other (n = 9) neuroendocrine tumors. Overall, 30% (8 of 27) had partial response, 59% (16 of 27) stable disease, and 11% (3 of 27) progressed. Pancreatic neuroendocrine tumors responded differently from small bowel neuroendocrine tumors regardless of cycle number (P = .01). The majority of pancreatic neuroendocrine tumors (6 of 11) had partial response to peptide receptor radionuclide therapy, while all small bowel neuroendocrine tumors had stable disease. Pancreatic neuroendocrine tumors stable after 2 cycles were more likely to respond to additional cycles versus other neuroendocrine tumors (probability: 60% vs 11%).ConclusionPatients with unresectable advanced or metastatic pancreatic neuroendocrine tumors may benefit from a full course of peptide receptor radionuclide therapy, whereas other neuroendocrine tumors appear less likely to respond. Large prospective studies are needed to confirm these findings.     

Clinical evaluation of an HIV-1 and HCV assay and demonstration of significant reduction of the HCV detection window before seroconversion

BACKGROUND: One HIV-1 and HCV assay simultaneously detects HIV-1 and HCV RNA (Procleix, Chiron Corp.). The main intended use of the assay is the testing of blood and blood products in blood banking. STUDY DESIGN AND METHODS: To evaluate the clinical sensitivity of the assay, 164 anti-HIV-1+ and 160 anti-HCV+ patients of different viral load were tested. The assay specificity was determined in 1000 HIV-1- and HCV-seronegative blood donors. The ability of the assay to detect different HCV genotypes was investigated in a total of 40 patients of different genotypes (1-4). Furthermore, to investigate the reduction of the HCV window phase before seroconversion, serial samples of 25 hemodialysis patients who seroconverted to anti-HCV were also tested. RESULTS: The assay detected all 60 HIV-1-infected patients with a viral load of greater than 50 copies per mL and 48 of 104 patients with a viral load of less than 50 copies per mL. Moreover, all 60 patients with an HCV RNA load of greater than 521 IU per mL and 7 of 100 patients with a viral load of less than 50 IU per mL tested positive. The assay specificity was found to be 100 percent. In addition, all 40 patients of different HCV genotypes were successfully detected. Finally, the median time that the assay detected HCV infection before second- and third-generation anti-HCV assay was found to be 183 and 91 days, respectively. CONCLUSION: The assay sensitivity and specificity, its ability to detect different HCV genotypes, and the significant reduction of window period of HCV infection further support its use for improving the safety of blood and blood products.     

Serum osmolal gap in clinical practice: usefulness and limitations

Background: Although serum osmolal gap can be a useful diagnostic tool, clinicians are not familiar with its use in clinical practice.

Objectives: The review presents in a series of questions-answers and under a clinical point of view the current data regarding the use of osmolal gap.

Discussion: The definition and the best formula used for the calculation of osmolal gap, the main causes of increased osmolal gap with or without increased anion gap metabolic acidosis, as well as the role of concurrent lactic acidosis or ketoacidosis are presented under a clinical point of view.

Conclusions: The calculation of osmolal gap is crucial in the differential diagnosis of many patients presenting in emergency departments with possible drug or substance overdose as well as in comatose hospitalized patients.