Invasive treatment of chronic vertebral pain

Background. The need to find new effective treatments for chronic pain today is beyond doubt. Pain resistant to nonsteroidal analgesics and gabapentin stimulates the introduction of invasive treatments for chronic pain. Materials and methods. The efficacy of the combination of diclofenac and gabapentin with epidural administration of dexamethasone 8 mg and epidural neurolysis of 30% ethyl alcohol in 1% lidocaine solution was compared. Results. The combination of diclofenac and gabapentin, as well as the use of epidural glucocorticoids, has not shown sufficient efficacy. After the use of glucocorticoids, a long-term assessment on the visual analog scale was at the level of 3.5 points, which corresponded to the results of a one-time neurolysis. At 2 injections of the neurolytic mixture or more, the score on the visual analog scale was lower by 1.5 points compared to the results of glucocorticoid administration. After the 3rd stage of neurolysis, the lack of need for analgesics to correct vertebral pain is accompanied by a reliable absence of conversions to other methods of analgesia. Conclusions. The safety and efficacy of three-time epidural neurolysis with 30% ethyl alcohol in 1% lidocaine solution allow recommending this procedure to patients with chronic resistant vertebrogenic pain, especially in case of low efficacy and poor tolerability of nonsteroidal analgesics.

Oxytocin as an Anti-obesity Treatment

Obesity is a growing health concern, as it increases risk for heart disease, hypertension, type 2 diabetes, cancer, COVID-19 related hospitalizations and mortality. However, current weight loss therapies are often associated with psychiatric or cardiovascular side effects or poor tolerability that limit their long-term use. The hypothalamic neuropeptide, oxytocin (OT), mediates a wide range of physiologic actions, which include reproductive behavior, formation of prosocial behaviors and control of body weight. We and others have shown that OT circumvents leptin resistance and elicits weight loss in diet-induced obese rodents and non-human primates by reducing both food intake and increasing energy expenditure (EE). Chronic intranasal OT also elicits promising effects on weight loss in obese humans. This review evaluates the potential use of OT as a therapeutic strategy to treat obesity in rodents, non-human primates, and humans, and identifies potential mechanisms that mediate this effect.

The WHO guideline on drugs to prevent COVID-19: small numbers- big conclusions

The World Health Organization (WHO) living guideline on drugs to prevent COVID-19 has recently advised that ongoing trials evaluating hydroxychloroquine in chemoprophylaxis should stop. The WHO guideline cites “high certainty” evidence from randomised controlled trials (RCTs) that hydroxychloroquine prophylaxis does not reduce mortality and does not reduce hospital admission, and “moderate certainty” evidence of poor tolerability because of a significantly increased rate of adverse events leading to drug discontinuation. Yet there is no such evidence. In the three pre-exposure chemoprophylaxis RCTs evaluated in the guideline there were no deaths and only two COVID-19-related hospital admissions, and there was a mistake in the analysis of the number of discontinuations (after correction there is no longer a statistically significant difference between those taking the drug and the controls). Guidelines on the prevention and treatment of COVID-19 should be based on sufficient verified evidence, understanding of the disease process, sound statistical analysis and interpretation, and an appreciation of global needs. The WHO living guideline on the prevention of COVID-19 should retract the advice to stop research on hydroxychloroquine chemoprophylaxis, should correct its errors, and should revise its guidance.

When Off Target Effects Are On Target: The Role Of Spironolactone In Patients With COVID-19

Aims: Spironolactone is a steroidal mineralocoricosteroid receptor antagonist (MRA) used for treatment of resistant hypertension, heart failure and edema. It exerts class specific adverse effects that are shared by other MRAs. Additionally, it exerts unique “off target” steroidal effects that include gynecomastia, impotence and loss of libido in males and menstrual irregularity in females. Together, these have led to a poor tolerability and limited use despite positive results in many randomized, controlled clinical trials. We review the off-target effects of spironolactone that may summate with its MRA action to provide an advantageous profile for prevention or treatment of patients with COVID-19. Methods: Literature review using PubMed Central. Results: The blockade by spironolactone of the androgen receptor should diminish the expression of transmembrane protease serine 2 (TMPRSS2) that has an androgen promoter while its MRA action should enhance the expression of protease nexin1 (PN1) that inhibits furin and plasmin. TMPRSS2, furin and plasmin cooperated to process the SARS-CoV-2 spike protein to increase its high affinity binding to the angiotensin converting enzyme 2 (ACE2) and thereby promote viral cell entry. Its actions as an MRA may reduce inflammation and preserve pulmonary, cardiac and vascular functions. Its anti-plasmin action may combat hemostatic dysfunction. Conclusion: The hypothesis that the off-target effects of spironolactone summate with its MRA actions to provide special benefits for COVID-19 is worthy of direct investigation and clinical trial.

The WHO guideline on drugs to prevent COVID-19: small numbers- big conclusions

The World Health Organization living guideline on drugs to prevent COVID-19 has recently advised that ongoing trials evaluating hydroxychloroquine in chemoprophylaxis should stop. The WHO guideline cites “high certainty” evidence from randomised controlled trials (RCTs) that hydroxychloroquine prophylaxis does not reduce mortality and does not reduce hospital admission, and “moderate certainty” evidence of poor tolerability because of a significantly increased rate of adverse events leading to drug discontinuation. Yet there is no such evidence. In the three pre-exposure chemoprophylaxis RCTs evaluated in the guideline there were no deaths and only two COVID-19-related hospital admissions, and there was a mistake in the analysis of the number of discontinuations (after correction there is no longer a statistically significant difference between those taking the drug and the controls). Guidelines on the prevention and treatment of COVID-19 should be based on sufficient verified evidence, understanding of the disease process, sound statistical analysis and interpretation, and an appreciation of global needs.

Identification of clinical phenotypes in schizophrenia: the role of lurasidone

The treatment of schizophrenia includes the control of symptoms, the prevention of relapses, and amelioration of adaptive skills for patient re-integration into society. Antipsychotic drugs are the agents of choice for the treatment of schizophrenia, as they reduce the positive symptoms of psychosis. Lurasidone is a second-generation antipsychotic drug representing a novel and useful clinical tool for the management of schizophrenia. A board consisting of a panel of Italian expert psychiatrists was organized with the following aims: (a) defining the current modalities of use of lurasidone, highlighted through 17 specific questions; (b) defining and agreeing the main features of the drug and the principal reasons to suggest its administration. We established that lurasidone is suggested at any age, with no gender difference, at all stages of the disease. The switch from previous treatments is done primarily because of lack of efficacy as well as poor adherence/tolerability. Lurasidone is among the best-tolerated antipsychotics, and its use is indicated in the presence of different comorbidities. A wide range of dosages is available, allowing safe titration in particular cases, with the highest dose (148 mg) generally used for the treatment of the acute phase. The discontinuation rate due to poor tolerability, low compliance, and interactions with other drugs is very low. Akathisia is the most reported adverse event, but it may be controlled by dose reduction. Lurasidone does not possess a marked sedative action but, in agitated patients, can be associated with sedative drugs, such as benzodiazepines. The most frequent reason for switching to other therapies is the need for long-acting formulations, as in patients at risk of very low adherence or suicide. Lurasidone does not strongly impact metabolism or the cardiovascular system (QT interval), and does not influence the metabolism of other drugs, showing good efficacy and tolerability.

Triplet versus doublet therapy in multiple myeloma patients over 75 years.

e20519 Background: Clinical trials in multiple myeloma (MM) typically enroll patients that are younger and less frail while 33% patients are over the age of 75. Advanced age/frailty is associated with worse prognosis, partly due to poor tolerability of therapy. Compared to doublets, triplets improve progression-free and overall survival (PFS and OS), but these outcomes are not well studied in older patients. Here, we compare doublet and triplet therapy in newly diagnosed MM patients over 75. Methods: The MMRF’s CoMMpass trial is an international, longitudinal, observational study capturing disease progression and response to treatment. Using the MMRF database, we compared doublet versus triplet therapy in patients over 75. Primary outcome was PFS while secondary outcomes included OS, quality of life (QoL) and fatigue. QoL was assessed using EORTC QLQ-C30 questionnaire and fatigue was captured by the MM eCRF survey. Results: 146 patients were eligible for analysis. Median age was 80 years. 27 (18%) were ISS 1, 38 (26%) were ISS 2, and 59 (40%) were ISS 3. Amongst doublets (n = 62), 48% received Bortezomib/Dexamethasone while 48% received Lenalidomide/Dexamethasone. Amongst triplets (n = 71), 35% received both proteasome inhibitors (PI) and immunomodulatory drugs (IMIDs), whereas 58% received PI-based therapy with no IMID. Mean PFS for doublets was 467 days and for triplets was 608 days, with difference of 141 days (p = 0.0663). Mean OS for doublets was 757 days and for triplets was 920 days. Difference of 163 days was not statistically significant (p = 0.1784). In doublets, QoL remained at a median of 50% from baseline to 5 years. In triplets, QoL improved from a median 58% to 83% from baseline to 5 years. With respect to fatigue, levels remained unchanged from baseline to 5 years in doublets (43 to 44%) and dropped from 37% to 29% in triplets. Conclusions: There is a trend towards improved PFS, as well as an improvement in QoL and fatigue in MM patients over 75 that are treated with triplets as compared to those treated with doublets. Limitations include lack of randomization and selection bias.

Switching among branded and generic medication products during ongoing treatment of psychiatric illness

Switches between branded (reference) medications and the corresponding generic medications or between two different corresponding generic medications occur commonly during the treatment of central nervous system disorders. Prescribing a generic product in place of a reference product can reduce patient and pharmacy costs. But there can be implications. Planned or unplanned switches from one product to another during ongoing treatment may introduce variability in drug exposure which could in turn compromise efficacy and/or tolerability. Studies comparing the initiation of reference versus generic products do not provide clear evidence of the superiority of reference or generic products generally, whereas several studies examining a switch between reference and generic products suggest that reductions in efficacy or medication adherence and persistence may be associated with generic substitution. Clinicians should work with patients to facilitate a consistent supply of reference or generic drug product that provides stable exposure to avoid clinical deterioration or poor tolerability.