Influence of hand grip strength test and short physical performance battery on FRAX in post-menopausal women: a machine learning cross-sectional study.

BACKGROUND: Impaired physical performance and muscle strength are recognized risk factors for fragility fractures, frequently associated with osteoporosis and sarcopenia. However, the integration of muscle strength and physical performance in the comprehensive assessment of fracture risk is still debated. Therefore, this cross-sectional study aimed to assess the potential role of hand grip strength (HGS) and short physical performance battery (SPPB) for predicting fragility fractures and their correlation with Fracture Risk Assessment Tool (FRAX) with a machine learning approach. METHODS: In this cross-sectional study, a group of postmenopausal women underwent assessment of their strength, with the outcome measured using the HSG, their physical performance evaluated using the SPPB, and the predictive algorithm for fragility fractures known as FRAX. The statistical analysis included correlation analysis using Pearson's r and a decision tree model to compare different variables and their relationship with the FRAX Index. This machine learning approach allowed to create a visual decision boundaries plot, providing a dynamic representation of variables interactions in predicting fracture risk. RESULTS: Thirty-four patients (mean age 63.8±10.7 years) were included. Both HGS and SPPB negatively correlate with FRAX major (r=-0.381, P=0.034; and r=-0.407, P=0.023 respectively), whereas only SPPB significantly correlated with an inverse proportionality to FRAX hip (r=-0.492, P=0.001). According to a machine learning approach, FRAX major ≥20 and/or hip ≥3 might be reported for an SPPB<6. Concurrently, HGS<17.5 kg correlated with FRAX major ≥20 and/or hip ≥3. CONCLUSIONS: In light of the major findings, this cross-sectional study using a machine learning model related SPPB and HGS to FRAX. Therefore, a precise assessment including muscle strength and physical performance might be considered in the multidisciplinary assessment of fracture risk in post-menopausal women.

The Risk of Drug Interactions in Older Primary Care Patients after Hospital Discharge: The Role of Drug Reconciliation.

INTRODUCTION: Drug-drug interactions (DDIs) represent an important clinical problem, particularly in older patients, due to polytherapy, comorbidity, and physiological changes in pharmacodynamic and pharmacokinetic pathways. In this study, we investigated the association between drugs prescribed after discharge from the hospital or clinic and the risk of DDIs with drugs used daily by each patient. METHODS: We performed an observational, retrospective, multicenter study on the medical records of outpatients referred to general practitioners. DDIs were measured using the drug interaction probability scale. Potential drug interactions were evaluated by clinical pharmacologists (physicians) and neurologists. Collected data were analyzed using the Statistical Package for the Social Sciences. RESULTS: During the study, we evaluated 1772 medical records. We recorded the development of DDIs in 10.3% of patients; 11.6% of these patients required hospitalization. Logistic regression showed an association among DDIs, sex, and the number of drugs used (p = 0.023). CONCLUSIONS: This observational real-life study shows that the risk of DDIs is common in older patients. Physicians must pay more attention after hospital discharge, evaluating the treatment to reduce the risk of DDIs.

Ibuprofen in the Management of Viral Infections: The Lesson of COVID-19 for Its Use in a Clinical Setting.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for the management of fever, pain, and inflammation. However, they have always been considered to have a double-faced role, according to their capacity to manage inflammation but also their possible reduction of immune system response and diagnosis delay. This last point could favor a dramatic increase of viral infection diffusion, possibly leading to a more severe outcome. The advent of severe acute respiratory syndrome coronavirus 2 excluded the use of NSAIDs, particularly ibuprofen, and then indicated this drug as the better NSAID to manage infected outpatients and prevent complications. Several authors described the role of NSAIDs and ibuprofen in preventing cytokine storm and modulating the immune system. However, the development of both adverse drug reactions (i.e., gastrointestinal, renal, hepatic, and cardiovascular) and drug interaction recalled the necessity of prescribing the better NSAID for each patient. In this narrative review, we describe the role of NSAIDs, particularly of ibuprofen, in the management of viral symptoms, suggesting that the NSAID may be chosen considering the characteristics of the patient, the comorbidity, and the polytherapy.

The Pharmacological Treatment of Chronic Pain: From Guidelines to Daily Clinical Practice.

In agreement with the International Association for the Study of Pain, chronic pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage. To date, there are several types of pain: nociceptive, neuropathic, and nociplastic. In the present narrative review, we evaluated the characteristics of the drugs used for each type of pain, according to guidelines, and their effects in people with comorbidity to reduce the development of severe adverse events.

What Is the Role of Sex-Related Differences in the Effectiveness and Safety of Biological Drugs Used in Patients With Severe Asthma?

Biological drugs are used to treat severe asthma with an improvement of clinical symptoms. Data on sex difference of these drugs in patients with severe asthma are sparse. This study aimed to assess the effects of sex-related differences on biological drugs in patients with severe asthma. In this observational, open-label, prospective, noncontrolled, single-center cohort pilot study, we enrolled adult patients aged >18 years diagnosed with severe asthma and not previously treated with biological drugs. The first clinical end point was the statistical difference (P < .05) in the efficacy of biological drugs evaluated using the asthma control test and spirometry between sexes. The first safety end point was the statistical difference (P < .05) in developing adverse drug reactions between sexes. We enrolled 74 patients with severe asthma (48 women and 26 men) with a mean age of 59.4 (standard deviation, 11.8) years. The mean forced expiratory volume in 1 second was 6.9 (standard deviation, 13.9) for women and 9.4 (standard deviation, 10.7) for men and improved significantly after the treatment (P < .01), with no significant differences in sex (P = .8). Similarly, the asthma control test improved 12 months after the beginning of the treatment without significant differences between men and women (P = .5). The most common drug used was omalizumab (45.9% of the patients; P < .01) without significant differences between sex (P > .05). We did not observe the development of adverse drug reactions during the study. In conclusion, in asthmatic patients, sex does not have a role in either the effectiveness or safety of biological drugs.

Circulating MicroRNAs Expression Profile in Lung Inflammation: A Preliminary Study.

BACKGROUND: Bronchial asthma is an inflammatory airway disease with an ever-increasing incidence. Therefore, innovative management strategies are urgently needed. MicroRNAs are small molecules that play a key role in lungs cellular functions and are involved in chronic inflammatory diseases, such as bronchial asthma. This study aims to compare microRNA serum expression between subjects with asthma, obesity, the most common co-morbidity in asthma, and healthy controls to obtain a specific expression profile specifically related to lung inflammation. METHODS: We collected serum samples from a prospective cohort of 25 sex-matched subjects to determine circulating miRNAs through a quantitative RT-PCR. Moreover, we performed an in silico prediction of microRNA target genes linked to lung inflammation. RESULTS: Asthmatic patients had a significant lower expression of hsa-miR-34a-5p, 181a-5p and 146a-5p compared to both obese and healthy ones suggesting microRNAs' specific involvement in the regulation of lungs inflammatory response. Indeed, using in silico analysis, we identified microRNAs novel target genes as GATA family, linked to the inflammatory-related pathway. CONCLUSIONS: This study identifies a novel circulating miRNAs expression profile with promising potentials for asthma clinical evaluations and management. Further and larger investigations will be needed to confirm the potential role of microRNA as a clinical marker of bronchial asthma and eventually of pharmacological treatment response.

Effectiveness and Safety of a New Nutrient Fixed Combination Containing Pollen Extract Plus Teupolioside, in the Management of LUTS in Patients with Benign Prostatic Hypertrophy: A Pilot Study.

Benign prostatic hyperplasia (BPH) is a common cause of male lower urinary tract symptoms (LUTS) that can reduce quality of life. Even if several drugs can be used in its treatment, the development of adverse drug reactions (ADRs) represents the most common cause of low adherence. In the present study, we evaluate both the efficacy and the safety of a new nutrient fixed combination of Pollen Extract plus Teupolioside, named Xipag®, in patients with LUTS. We conduct a pilot single center open label clinical study between 1 March 2020 and 30 June 2020 in patients with BPH referred to general practitioner's ambulatories. Male patients > 45 years, sexually active, with clinical symptoms of LUTS and with a diagnosis of HPB were enrolled and received one tablet/day of Xipag® (T0), for three months (T1: end of treatment). The IPSS and IIEF-5 questionnaires were carried out at T0 and T1 and represent the first end point, whereas the primary safety end point was considered the absence of ADR or of drug−drug interactions related to Xipag® administration. During the study period, 25 subjects aged 43 to 76 years (mean 62.7 ± 9) were enrolled and completed the study. The clinical evaluation in T1 documented that Xipag® induced a statistically significant improvement (p < 0.01) in symptoms, as documented by the IPSS questionnaire (range 22.7−88.9; mean 55.2 ± 23.6), without the development of ADRs. In conclusion, this is the first real-world study that showed the efficacy and the safety of Xipag® in the BPH patients with LUTS.

Vitamin D Deficiency in Women with Breast Cancer: A Correlation with Osteoporosis? A Machine Learning Approach with Multiple Factor Analysis.

Breast cancer (BC) is the most frequent malignant tumor in women in Europe and North America, and the use of aromatase inhibitors (AIs) is recommended in women affected by estrogen receptor-positive BCs. AIs, by inhibiting the enzyme that converts androgens into estrogen, cause a decrement in bone mineral density (BMD), with a consequent increased risk of fragility fractures. This study aimed to evaluate the role of vitamin D3 deficiency in women with breast cancer and its correlation with osteoporosis and BMD modifications. This observational cross-sectional study collected the following data regarding bone health: osteoporosis and osteopenia diagnosis, lumbar spine (LS) and femoral neck bone mineral density (BMD), serum levels of 25-hydroxyvitamin D3 (25(OH)D3), calcium and parathyroid hormone. The study included 54 women with BC, mean age 67.3 ± 8.16 years. Given a significantly low correlation with the LS BMD value (r2 = 0.30, p = 0.025), we assessed the role of vitamin D3 via multiple factor analysis and found that BMD and vitamin D3 contributed to the arrangement of clusters, reported as vectors, providing similar trajectories of influence to the construction of the machine learning model. Thus, in a cohort of women with BC undergoing Ais, we identified a very low prevalence (5.6%) of patients with adequate bone health and a normal vitamin D3 status. According to our cluster model, we may conclude that the assessment and management of bone health and vitamin D3 status are crucial in BC survivors.

Direct-acting Antivirals Inducing HCV-RNA Sustained Suppression Improve Xerophthalmia in HCV-infected Patients.

BACKGROUND: Hepatitis C Virus (HCV) infection represents a global problem, and it is related to both hepatic and extra-hepatic manifestations (e.g., xerophthalmia). New direct-acting antivirals (DAAs), IFN-free treatments, are commonly used to manage HCV infection. However, the impact of new DAAs on dry eyes (xerophthalmia) is lacking. In this study, we evaluated its incidence in HCV patients and the effect of DAAs on this manifestation. METHODS: We performed an observational open-label non-randomized study in HCV patients from 01 April 2018 to 01 June 2020. RESULTS: Patients who satisfied the inclusion criteria underwent clinical and laboratory evaluation, Schirmer's test, and Break-up time test. Enrolled patients were divided in two groups: Group 1: HCV patients with xerophthalmia: 24 patients (16 male and 8 female), HCV-RNA 2,685,813 ± 1,145,698; Group 2: HCV patients without xerophthalmia: 35 patients (19 male and 16 female), HCV-RNA 2,614,757 ± 2,820,433. The follow-ups (3 and 6 months after the enrollment) documented an improvement in both eyes' manifestations and HCV-infection (HCV-RNA undetected). CONCLUSION: In conclusion, in this study, we reported that xerophthalmia could appear in HCV patients, and DAAs treatment reduces this manifestation without the development of adverse drug reactions.

Is there a Link between Non Melanoma Skin Cancer and Hydrochlorothiazide?

AIMS: Here in we evaluated the association between the use of Hydrochlorothiazide (HCTZ) and the risk of NMSC both, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). BACKGROUND: Even though the use of HCTZ is not linked with the development of serious adverse drug reactions, non-melanoma skin cancer (NMSC) has been reported in patients treated with the drug in recent years, most likely due to its photosensitizing ability. OBJECTIVE: To evaluate the statistically significant difference (P<0.05) in the development of NMSC between HCTZ users and non-users and the correlation (P<0.05) between HCTZ use and NMSC. METHODS: We performed a retrospective study on patients referred to general practitioners who developed skin cancer or NMSC whether or not they were treated with antihypertensive drugs. Controls were matched with the test by age and sex. We calculated odds ratios (ORs) for skin cancer and NMSC associated with hydrochlorothiazide using conditional logistic regression. RESULTS: We enrolled 19,320 patients in the present study, out of a total of 10,110 (52.3%) who were treated with antihypertensive drugs. Of 10,110 patients, 3,870 were treated with HCTZ (38.3%). During the study, we failed to report an increased risk of NMSC in HCTZ-treated vs. untreated patients. Gender stratification revealed an OR for NMSC of 1.36 for men and 0.56 for women. We did not find a dose-response relationship between HCTZ use and NMSC. CONCLUSION: In the present study, we failed to report an association between the use of HCTZ and the development of NMSC.

Drug-Drug Interactions in Vestibular Diseases, Clinical Problems, and Medico-Legal Implications.

Peripheral vestibular disease can be treated with several approaches (e.g., maneuvers, surgery, or medical approach). Comorbidity is common in elderly patients, so polytherapy is used, but it can generate the development of drug-drug interactions (DDIs) that play a role in both adverse drug reactions and reduced adherence. For this reason, they need a complex kind of approach, considering all their individual characteristics. Physicians must be able to prescribe and deprescribe drugs based on a solid knowledge of pharmacokinetics, pharmacodynamics, and clinical indications. Moreover, full information is required to reach a real therapeutic alliance, to improve the safety of care and reduce possible malpractice claims related to drug-drug interactions. In this review, using PubMed, Embase, and Cochrane library, we searched articles published until 30 August 2021, and described both pharmacokinetic and pharmacodynamic DDIs in patients with vestibular disorders, focusing the interest on their clinical implications and on risk management strategies.

Vitamin D Serum Levels in Subjects Tested for SARS-CoV-2: What Are the Differences among Acute, Healed, and Negative COVID-19 Patients? A Multicenter Real-Practice Study.

Vitamin D might play a role in counteracting COVID-19, albeit strong evidence is still lacking in the literature. The present multicenter real-practice study aimed to evaluate the differences of 25(OH)D3 serum levels in adults tested for SARS-CoV-2 (acute COVID-19 patients, subjects healed from COVID-19, and non-infected ones) recruited over a 6-month period (March-September 2021). In a sample of 117 subjects, a statistically significant difference was found, with acute COVID-19 patients demonstrating the lowest levels of serum 25(OH)D3 (9.63 ± 8.70 ng/mL), significantly lower than values reported by no-COVID-19 patients (15.96 ± 5.99 ng/mL, p = 0.0091) and healed COVID-19 patients (11.52 ± 4.90 ng/mL, p > 0.05). Male gender across the three groups displayed unfluctuating 25(OH)D3 levels, hinting at an inability to ensure adequate levels of the active vitamin D3 form (1α,25(OH)2D3). As a secondary endpoint, we assessed the correlation between serum 25(OH)D3 levels and pro-inflammatory cytokine interleukin-6 (IL-6) in patients with extremely low serum 25(OH)D3 levels (<1 ng/mL) and in a subset supplemented with 1α,25(OH)2D3. Although patients with severe hypovitaminosis-D showed no significant increase in IL-6 levels, acute COVID-19 patients manifested high circulating IL-6 at admission (females = 127.64 ± 22.24 pg/mL, males = 139.28 ± 48.95 ng/mL) which dropped drastically after the administration of 1α,25(OH)2D3 (1.84 ± 0.77 pg/mL and 2.65 ± 0.92 ng/mL, respectively). Taken together, these findings suggest that an administration of 1α,25(OH)2D3 might be helpful for treating male patients with an acute COVID-19 infection. Further studies on rapid correction of vitamin D deficiency with fast acting metabolites are warranted in COVID-19 patients.

Data Recorded in Real Life Support the Safety of Nattokinase in Patients with Vascular Diseases.

Nattokinase (NK) is a serine protease enzyme with fibrinolytic activity. Even if it could be used for the treatment of several diseases, no data have been published supporting its use patients who underwent vascular surgery. In this study, we evaluated both the efficacy and the safety of nattokinase (100 mg/day per os) in patients admitted to vascular surgery. Patients were of both sexes, >18 years of age, with vascular diseases (i.e., deep vein thrombosis, superficial vein thrombosis, venous insufficiency), and naïve to specific pharmacological treatments (anticoagulants or anti-platelets). Patients were divided into three groups. Group 1: patients with deep vein thrombosis, treated with fondaparinux plus nattokinase. Group 2: patients with phlebitis, treated with enoxaparin plus nattokinase. Group 3: patients with venous insufficiency after classical surgery, treated with nattokinase one day later. During the study, we enrolled 153 patients (age 22-92 years), 92 females (60.1%) and 61 males (39.9%;), and documented that nattokinase was able to improve the clinical symptoms (p < 0.01) without the development of adverse drug reactions or drug interactions. Among the enrolled patients, during follow-up, we did not record new cases of vascular diseases. Attention to patients' clinical evolution, monitoring of the INR, and timely and frequent adjustment of dosages represent the cornerstones of the safety of care for patients administered fibrinolytic drugs as a single treatment or in pharmacological combination. Therefore, we can conclude that the use of nattokinase represents an efficient and safe treatment able to both prevent and treat patients with vascular diseases.

Efficacy of a Low-Dose Diosmin Therapy on Improving Symptoms and Quality of Life in Patients with Chronic Venous Disease: Randomized, Double-Blind, Placebo-Controlled Trial.

Chronic Venous Disease (CVD) is a common medical condition affecting up to 80% of the general population. Clinical manifestations can range from mild to more severe signs and symptoms that contribute to the impairment of the quality of life (QoL) of affected patients. Among treatment options, venoactive drugs such as diosmin are widely used in the symptomatic treatment in all clinical stages. The aim of this study is to determine the effectiveness of a new formulated diosmin in relieving symptoms and improving QoL in patients suffering from CVD. In this randomized, double-blind, placebo-controlled, multicenter clinical study, CVD patients with a Clinical-Etiology-Anatomy-Pathophysiology (CEAP) classification system between C2 and C4 were randomized to receive a bioavailable diosmin (as µsmin® Plus) 450 mg tablet once daily or a placebo for 8 weeks. Clinical symptoms and QoL were monitored using the measurement of leg circumference, visual analogue scale (VAS) for pain, Global Index Score (GIS) and Venous Clinical Severity Score (VCSS). A total of 72 subjects completed the study. From week 4, leg edema was significantly decreased in the active group (p < 0.001). An improvement in the VAS score was observed in the active group compared to placebo at the end of treatment (p < 0.05). GIS and VCSS scores were significantly improved in the active group at week 8 (p < 0.001). No treatment related-side effects were recorded. The results of this study showed that the administration of low-dose µsmin® Plus was safe and effective in relieving symptoms and improving QoL in subjects with CVD.