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.

Metalloproteases in Pain Generation and Persistence: A Possible Target?

Matrix metalloproteinases (MMPs) are a large family of zinc-dependent proteolytic enzymes associated with extracellular matrix protein turnover and tissue degradation. They participate to many different physiological reactions but are also hyperactivated in several diseases. Various literature studies have documented that MMPs play a role in the modulation of neuropathic and nociceptive pain. The heterogeneity of clinical and pre-clinical data is an important issue in this experimental context. Despite the presence of a good number of studies on MMP inhibitors, these drugs showed scarce efficacy and relevant side effects. In the present manuscript, we reviewed studies in the literature that define a possible role of MMPs in pain and the effects of their modulation.

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.

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.

Audiovestibular Disorders after COVID-19 Vaccine: Is There an Association?

The SARS-CoV-2 vaccination campaign is probably one of the most historic public hygiene measures in modern medicine. The drama of the pandemic has forced the scientific community to accelerate the development and commercialization of vaccines, thereby enhancing the phases of active surveillance. Among the adverse events following immunization (AEFI) reported, those of an audiovestibular interest, such as sudden sensorineural hearing loss (SSNHL), tinnitus, dizziness, and vertigo, constitute a very small percentage. There are many plausible etiological hypotheses, and scientific research needs to pay more attention to the correct collection of data, which up until now have often been inadequate and fragmented, on which to base future studies. SSNHL, new onset tinnitus, vertigo, and dizziness require a prompt evaluation, while the proposed treatment is the same as it is for events unrelated to vaccination. These are uncommon adverse events, and the risk rates for these diseases have not increased in conjunction with the COVID-19 vaccinations, therefore there is no justification of any hesitation towards the vaccination campaign.

The Pharmacological Treatment of Pediatric Vertigo.

Vertigo in children is a challenging topic. The lack of dedicated trials, guidelines and papers causes inhomogeneity in the treatment of vertigo in children. Meniere's disease, migraine equivalents, vestibular neuritis, paroxysmal positional benign vertigo (BPPV), persistent postural-perceptual dizziness (PPPD) and motion sickness may affect children with various degrees of incidence and clinical severity compared to adults. Several drugs are proposed for the management of these conditions, even if their use is subordinated to the child's age. In this review, we summarize the existing evidence related to the use of drugs for this clinical condition in children as a start point for new trials, stating the urgent need for international guidelines.

A Fatal Case of Tuberculosis Meningitis in Previously Health Children.

Tuberculous meningitis (TBM) is a severe form of tuberculosis. We report the development of fatal TBM in a 2-year-old previously healthy child, suggesting that TBM must be evaluated in children of all ages with non-specific symptoms of central nervous involvement because a diagnostic delay induces a negative prognosis.

The pharmacological treatment of acute vestibular syndrome.

Acute vestibular syndrome (AVS) represents a clinical picture that involves urgent management due to the important procession of symptoms accompanying the event, which can be positively or negatively influenced by therapeutic choices and intervention timing. This forces a differential diagnosis and therapeutic choices to be made in conditions that are not always favorable and often not in the specialist field. In this work, we will examine in detail the pharmacological therapeutic possibilities, correlating them to the differential and, as far as possible, to the etiological diagnosis. In particular, the pharmacological possibilities for the two main conditions we can face will be investigated, namely, vestibular neuritis and posterior circulation stroke.

Oxygen-Ozone Therapy in Cervicobrachial Pain: A Real-Life Experience.

This prospective, open-label clinical study was carried out to evaluate both the efficacy and safety of intramuscular paravertebral injections of an oxygen−ozone (O2−O3) mixture in patients with cervicobrachial pain. We enrolled 540 subjects affected by cervicobrachial pain referred to the Ozone Therapy Ambulatory at the Mater Domini Hospital of Catanzaro (Italy) and to the Center of Pain in Taurianova (Reggio Calabria, Italy). All the subjects (n = 540) completed the treatment and the follow-up visits. The subjects received a mean of 11 cervical intramuscular treatments with an O2−O3 mixture (5 mL) with an O3 concentration of 10 µg/mL bis a week. The improvement of pain was measured by a change in the mean of the Visual Analog Scale (VAS) score from baseline to the end of treatment and during follow-ups. Patient satisfaction was assessed at the end of treatment using the SF-36 Questionnaire. The development of adverse drug reactions was recorded. The mean (±standard deviation) VAS pain score at baseline, at the end of treatment, and during follow-ups showed a significant reduction in pain over time (p < 0.001). All the patients who were enrolled (n: 540) were pain-free after one year. According to the pain distribution, all subjects showed a significant reduction in pain over time in each group (p < 0.05). No significant differences were observed with respect to sex or age. No adverse events were observed during the study. In conclusion, we documented that the intramuscular injection of an O2−O3 mixture is an effective and safe treatment option for patients with cervicobrachial pain.

Effect of Statins on Lung Cancer Molecular Pathways: A Possible Therapeutic Role.

Lung cancer is a common neoplasm, usually treated through chemotherapy, radiotherapy and/or surgery. Both clinical and experimental studies on cancer cells suggest that some drugs (e.g., statins) have the potential to improve the prognosis of cancer. In fact, statins blocking the enzyme "hydroxy-3-methylglutaryl-coenzyme A reductase" exert pleiotropic effects on different genes involved in the pathogenesis of lung cancer. In this narrative review, we presented the experimental and clinical studies that evaluated the effects of statins on lung cancer and described data on the effectiveness and safety of these compounds. We also evaluated gender differences in the treatment of lung cancer to understand the possibility of personalized therapy based on the modulation of the mevalonate pathway. In conclusion, according to the literature data, statins exert multiple effects on lung cancer cells, even if the evidence for their use in clinical practice is lacking.

FT-IR Analysis of Structural Changes in Ketoprofen Lysine Salt and KiOil Caused by a Pulsed Magnetic Field.

High-intensity, low-frequency magnetic fields (MFs) have been widely used in the treatment of diseases and in drug delivery, even though they could induce structural changes in pharmacological molecules. Morphological changes in ketoprofen and KiOil were investigated through Fourier-transform infrared spectroscopy (FT-IR). Unsupervised principal component analysis was carried out for data clustering. Clinical validation on 22 patients with lower back pain was managed using diamagnetic therapy plus topical ketoprofen or KiOil. The Numerical Rating Scale (NRS) and Short-Form Health Survey 36 (SF-36) were used to evaluate clinical and functional response. Ketoprofen showed clear clustering among samples exposed to MF (4000−650 cm−1), and in the narrow frequency band (1675−1475 cm−1), results evidenced structural changes which involved other excipients than ketoprofen. KiOil has evidenced structural modifications in the subcomponents of the formulation. Clinical treatment with ketoprofen showed an average NRS of 7.77 ± 2.25 before and an average NRS of 2.45 ± 2.38 after MF treatment. There was a statistically significant reduction in NRS (p = 0.003) and in SF-36 (p < 0.005). Patients treated with KiOil showed an average NRS of 7.59 ± 2.49 before treatment and an average NRS of 1.90 ± 2.26 after treatment (p < 0.005). SF-36 showed statistical significance for all items except limitations due to emotional problems. A high-intensity pulsed magnetic field is an adjunct to topical treatment in patients with localized pain, and the effect of MF does not evidence significant effects on the molecules.

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.

Nutraceuticals for Peripheral Vestibular Pathology: Properties, Usefulness, Future Perspectives and Medico-Legal Aspects.

Vestibular disorders may generate complex signs and symptoms, which may alter patients' balance and the quality of life. Dizziness and vertigo can strongly affect daily activities and relations. Despite the presence of conventional drugs, maneuvers, and surgery, another interesting therapeutic opportunity is offered by nutraceuticals. These molecules are often used in the treatment of dizziness and vertigo, but the rationale of their application is not always solidly demonstrated by the scientific evidence. Several substances have shown a variable level of efficacy/usefulness in this field, but there is lack of important evidence for most of them. From a medico-legal point of view, specific information must be provided to the patient regarding the efficacy and possibilities that the use of these preparations can allow. Administering the right nutraceutical to the proper patient is a fundamental clinical skill. Integrating conventional drug treatment with nutraceutical administration seems to be easy, but it may be difficult considering the (in part unexplored) pharmacodynamics and pharmacokinetics of nutraceuticals. The aim of the scientific community should be to elevate nutraceuticals to the same law and technical dignity of conventional drugs.

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.