Using sequential pharmacotherapy for the treatment of osteoporosis: an update of the literature.

Osteoporosis, which is characterized by compromised bone density and heightened susceptibility to fractures, is a substantial public health concern, especially among the aging population. Underdiagnosis, undertreatment, and therapy non-adherence contribute to its impact. Anabolic and dual-action agents like teriparatide, abaloparatide, and romosozumab have emerged as effective treatments, allowing rapid gains in bone mineral density (BMD) and reducing fracture risk. However, administering treatments in the correct order is paramount, with an 'anabolic first' approach gaining traction for patients at high risk of fractures. This strategy involves starting anabolic therapies, followed by antiresorptive agents as maintenance therapy. It is important to note that the effectiveness of anabolic agents differs between treatment-naive and previously treated patients: tailored treatment approaches are therefore necessary. This comprehensive strategy adheres to clinical guidelines, emphasizing individualized care, early intervention, and patient-centered management to mitigate the burden of osteoporosis and enhance patients' quality of life. The aim of this review is to summarize recent evidence on the sequential treatment of osteoporosis and to provide recommendations on the best treatment strategies. Effective treatments, such as anabolic agents, are key in high-risk patients, who require an 'anabolic first' approach. Sequential therapy, specifically tailored to a patient's history, can help to optimize prevention and management of fractures

Traitement de l’insuffisance cardiaque chez la personne âgée et inhibiteurs du SGLT2 - En avoir le cœur net [Treatment of congestive heart failure in older persons and SGLT2 inhibitors - Having your patient's best interests at heart]

The treatment and management of heart failure (HF) are constantly evolving. The latest guidelines recommend the use of SGLT2 inhibitors (SGLT2i) as an integral part to treating HF with reduced ejection fraction (< 40%). However, given that the patients included in these trials do not reflect the heterogeneity of the health of many elderly patients, we recommend basing the therapeutic decision on the patient's state of frailty. If a SGLT2i treatment at a standard dose (10 mg 1x/day) is recommended for robust patients, we suggest initiating treatment at 5 mg 1x/day for vulnerable patients, and then after 1 month increasing the dose to 10 mg 1x/day. Finally, for dependent patients, we recommend therapeutic abstention in the absence of sufficient scientific evidence

TRIzol-based RNA extraction for detection protocol for SARS-CoV-2 of coronavirus disease 2019

International audienceDiagnostic testing is important for managing the 2019 novel coronavirus (SARS-CoV-2). We developed an optimized protocol for SARS-CoV-2 RNA extraction from the surface of the respiratory mucosa with nasopharyngeal swabs and compared the sensitivity of RNA extraction methods. RNA extraction was performed using three different procedures (TRIzol, QIAamp, VMT-TRIzol) from nine positive SARS-CoV-2 samples. SARS-CoV-2 was detected by real-time reverse transcriptase PCR (RT-PCR) using a detection kit for SARS-CoV-2 (Sun Yat-sen University). Compared to RT-PCR results, there were no discernible differences in detection rates when comparing the three different extraction procedures. On the basis of these results, the use of TRIzol as a transport medium and RNA extraction method for SARS-CoV-2 detection may be a helpful alternative for laboratories facing shortages of commercial testing kits

Gériatrie [Geriatrics]

Sleeping enough is associated with a reduced risk of mortality and dementia. New evidence support regular physical exercise, including at home, as a corner stone intervention to prevent falls and fractures. In contrast, supplementation with high doses of vitamin D is ineffective and even deleterious in this indication and a routine screening in asymptomatic adults is not recommended. Several studies illustrate our difficulties in prescribing and deprescribing in frail older patients and a study suggests that statins in cardiovascular primary prevention should considered only when a patient's life expectancy exceeds 2.5 years. Finally, several studies have fueled the debate about screening for hearing impairment

Pharmacist intervention acceptance for the reduction of potentially inappropriate drug prescribing in acute psychiatry.

Background Prescribing for the elderly is challenging. A previous observational study conducted in our geriatric psychiatry admission unit (GPAU) using STOPP/START criteria showed a high number of potentially inappropriate drug prescriptions (PIDPs). A clinical pharmacist was added to our GPAU as a strategy to reduce PIDPs. Objective The objective of the present study was to assess the impact of a clinical pharmacist on PIDPs by measuring acceptance rates of pharmacist interventions (PhIs). Setting This study was conducted at the GPAU of Lausanne University Hospital. Method The clinical pharmacist attended four GPAU meetings weekly. Complete medication reviews were performed daily. The clinical pharmacist conducted standard analyses based on clinical judgment and STOPP/START criteria assessment. A PhI was generated when a PIDP was detected. When a PhI was accepted, the PIDP was considered as eliminated. Acceptance rate of PhI was calculated (number of PhI accepted/total number of PhI). Main outcome measure PhIs acceptance rates. Results In a cohort of 102 patients seen between July 2013 and February 2014, a total of 697 PhIs (average 6.8/patient) were made based on standard evaluation (n = 479) and STOPP/START criteria (n = 243). The global acceptance rate was 68% (standard, 78%; STOPP/START, 47%). Conclusion Good PhIs acceptance rates demonstrated that a clinical pharmacist can reduce PIDPs in a GPAU. PhIs based on standard evaluation had a higher acceptance than those based on STOPP/START criteria, probably because they are better adapted to individual patients. However, these two evaluation approaches can be used in a complementary manner

A Systems Approach Dissociates Fructose-Induced Liver Triglyceride from Hypertriglyceridemia and Hyperinsulinemia in Male Mice

The metabolic syndrome (MetS), defined as the co-occurrence of disorders including obesity, dyslipidemia, insulin resistance, and hepatic steatosis, has become increasingly prevalent in the world over recent decades. Dietary and other environmental factors interacting with genetic predisposition are likely contributors to this epidemic. Among the involved dietary factors, excessive fructose consumption may be a key contributor. When fructose is consumed in large amounts, it can quickly produce many of the features of MetS both in humans and mice. The mechanisms by which fructose contributes to metabolic disease and its potential interactions with genetic factors in these processes remain uncertain. Here, we generated a small F2 genetic cohort of male mice derived from crossing fructose-sensitive and -resistant mouse strains to investigate the interrelationships between fructose-induced metabolic phenotypes and to identify hepatic transcriptional pathways that associate with these phenotypes. Our analysis indicates that the hepatic transcriptional pathways associated with fructose-induced hypertriglyceridemia and hyperinsulinemia are distinct from those that associate with fructose-mediated changes in body weight and liver triglyceride. These results suggest that multiple independent mechanisms and pathways may contribute to different aspects of fructose-induced metabolic disease

Hepatic PPARα is critical in the metabolic adaptation to sepsis.

Although the role of inflammation to combat infection is known, the contribution of metabolic changes in response to sepsis is poorly understood. Sepsis induces the release of lipid mediators, many of which activate nuclear receptors such as the peroxisome proliferator-activated receptor (PPAR)α, which controls both lipid metabolism and inflammation. We aimed to elucidate the previously unknown role of hepatic PPARα in the response to sepsis. Sepsis was induced by intraperitoneal injection of Escherichia coli in different models of cell-specific Ppara-deficiency and their controls. The systemic and hepatic metabolic response was analyzed using biochemical, transcriptomic and functional assays. PPARα expression was analyzed in livers from elective surgery and critically ill patients and correlated with hepatic gene expression and blood parameters. Both whole body and non-hematopoietic Ppara-deficiency in mice decreased survival upon bacterial infection. Livers of septic Ppara-deficient mice displayed an impaired metabolic shift from glucose to lipid utilization resulting in more severe hypoglycemia, impaired induction of hyperketonemia and increased steatosis due to lower expression of genes involved in fatty acid catabolism and ketogenesis. Hepatocyte-specific deletion of PPARα impaired the metabolic response to sepsis and was sufficient to decrease survival upon bacterial infection. Hepatic PPARA expression was lower in critically ill patients and correlated positively with expression of lipid metabolism genes, but not with systemic inflammatory markers. During sepsis, Ppara-deficiency in hepatocytes is deleterious as it impairs the adaptive metabolic shift from glucose to FA utilization. Metabolic control by PPARα in hepatocytes plays a key role in the host defense against infection. As the main cause of death in critically ill patients, sepsis remains a major health issue lacking efficacious therapies. While current clinical literature suggests an important role for inflammation, metabolic aspects of sepsis have mostly been overlooked. Here, we show that mice with an impaired metabolic response, due to deficiency of the nuclear receptor PPARα in the liver, exhibit enhanced mortality upon bacterial infection despite a similar inflammatory response, suggesting that metabolic interventions may be a viable strategy for improving sepsis outcomes