Showing papers in "Therapeutics and Clinical Risk Management in 2020"

N-Acetylcysteine to Combat COVID-19: An Evidence Review

Abstract: The novel coronavirus disease (COVID-19) is caused by a virus (SARS-Cov-2) and is known for inducing multisystem organ dysfunction associated with significant morbidity and mortality. Current therapeutic strategies for COVID-19 have failed to effectively reduce mortality rate, especially for elderly patients. A newly developed vaccine against SARS-Cov-2 has been reported to induce the production of neutralizing antibodies in young volunteers. However, the vaccine has shown limited benefit in the elderly, suggesting an age-dependent immune response. As a result, exploring new applications of existing medications could potentially provide valuable treatments for COVID-19. N-acetylcysteine (NAC) has been used in clinical practice to treat critically ill septic patients, and more recently for COVID-19 patients. NAC has antioxidant, anti-inflammatory and immune-modulating characteristics that may prove beneficial in the treatment and prevention of SARS-Cov-2. This review offers a thorough analysis of NAC and discusses its potential use for treatment of COVID-19.

Mirror Therapy in Stroke Rehabilitation: Current Perspectives.

Abstract: In contrast to varied therapy approaches, mirror therapy (MT) can be used even in completely plegic stroke survivors, as it uses visual stimuli for producing a desired response in the affected limb. MT has been studied to have effects not just on motor impairments but also on sensations, visuospatial neglect, and pain after stroke. This paper attempts to systematically review and present the current perspectives on mirror therapy and its application in stroke rehabilitation, and dosage, feasibility and acceptability in stroke rehabilitation. An electronic database search across Google, PubMed, Web of Science, etc., generated 3871 results. After screening them based on the inclusion and exclusion criteria, we included 28 studies in this review. The data collected were divided on the basis of application in stroke rehabilitation, modes of intervention delivery, and types of control and outcome assessment. We found that most studies intervened for upper limb motor impairments post stroke. Studies were equally distributed between intervention in chronic and acute phases post stroke with therapy durations lasting between 1 and 8 weeks. MT showed definitive motor and sensory improvements although the extent of improvements in sensory impairments and hemineglect is limited. MT proves to be an effective and feasible approach to rehabilitate post-stroke survivors in the acute, sub-acute, and chronic phases of stroke, although its long-term effects and impact on activities of daily living need to be analysed extensively.

Spotlight on Tocilizumab in the Treatment of CAR-T-Cell-Induced Cytokine Release Syndrome: Clinical Evidence to Date.

Abstract: Immune-based therapies such as chimeric antigen receptor (CAR)-T-cell therapy have revolutionized the landscape of cancer treatment in recent years. Although this class of therapy has demonstrated impressive clinical efficacy against cancers that were once thought to be incurable, its success is in part limited by unique toxicities which can be severe or even fatal. Cytokine release syndrome (CRS) is the most commonly observed toxicity and occurs as a result of non-antigen specific immune activation. Similar to macrophage activation syndrome (MAS)/hemophagocytic lymphohistiocytosis (HLH), CRS is associated with elevated levels of several cytokines including interleukin-6 (IL-6) that serve as a driver for host immune dysregulation. As a direct anti-cytokine drug, tocilizumab has been a cornerstone in the treatment of CAR-T-associated CRS through its ability to dampen CRS without compromising CAR-T-cell function. However, optimal timing of administration is yet unknown. Here, we review the use of tocilizumab in the management of CAR-T-associated CRS, emphasizing on the clinical efficacy across various CAR constructs and its role in current CRS management algorithms. We also discuss alternative therapies that may be considered for refractory CRS therapy and the use of tocilizumab in the current COVID-19 global pandemic.

Diagnosis and Treatment of Hereditary Transthyretin Amyloidosis (hATTR) Polyneuropathy: Current Perspectives on Improving Patient Care

Abstract: Hereditary transthyretin amyloidosis (hATTR) with polyneuropathy (formerly known as Familial Amyloid Polyneuropathy) is a rare disease due to mutations in the gene encoding transthyretin (TTR) and characterized by multisystem extracellular deposition of amyloid, leading to dysfunction of different organs and tissues. hATTR amyloidosis represents a diagnostic challenge for neurologists considering the great variability in clinical presentation and multiorgan involvement. Generally, patients present with polyneuropathy, but clinicians should consider the frequent cardiac, ocular and renal impairment. Especially a hypertrophic cardiomyopathy, even if usually latent, is identifiable in at least 50% of the patients. Therapeutically, current available options act at different stages of TTR production, including synthesis inhibition (liver transplantation and/or gene-silencing drugs) or tetramer TTR stabilization (TTR stabilizers), increasing survival at different disease stages.

Hypophosphatemia Associated with Intravenous Iron Therapies for Iron Deficiency Anemia: A Systematic Literature Review

Abstract: Background Iron deficiency anemia (IDA) is a prevalent yet underdiagnosed condition with a significant impact on quality of life. Oral iron supplementation is often poorly tolerated or yields inadequate response, requiring the use of intravenous iron (IVI) in some patients. Administration of certain IVI preparations has been associated with decreases in serum phosphate levels and clinically significant hypophosphatemia, which has been reported to lead to adverse events including serious fatigue and osteomalacia. Objective The purpose of this study was to systematically assess the prevalence, clinical consequences, and reporting of treatment-emergent hypophosphatemia within literature investigating IVI therapies marketed in the United States (US). Methods A systematic literature review (SLR) was conducted using the PubMed database to identify publications reporting serum phosphate levels or rates of hypophosphatemia within adult IDA patient populations receiving current US-marketed IVIs. Results The SLR yielded 511 unique publications, with 40 records meeting the final inclusion criteria. Most studies did not report phosphate monitoring methodology or an explicit definition of hypophosphatemia. Hypophosphatemia rates ranged from 0.0% to 92.1% for ferric carboxymaltose (FCM), 0.0% to 40.0% for iron sucrose, 0.4% for ferumoxytol, and 0.0% for low-molecular-weight (LMW) iron dextran. Randomized controlled studies described hypophosphatemia as "asymptomatic" or did not report on other associated sequelae. Eleven case reports detailed treatment-emergent hypophosphatemia in patients treated with FCM. Patients with acute hypophosphatemia primarily developed severe fatigue; those with repeated FCM dosing developed chronic hypophosphatemia associated with osteomalacia and bone deformities. Conclusion Studies analyzed in this SLR reported a range of hypophosphatemia rates, with the highest consistently seen in patients treated with FCM. Across the clinical literature, there appeared to be minimal standardization of phosphate monitoring and definitions of hypophosphatemia. Although multiple cases have documented serious clinical consequences of hypophosphatemia associated with certain IVIs, current trials neither consistently nor adequately assess the frequency and severity of treatment-emergent hypophosphatemia and may underestimate its prevalence.

Major Neurologic Adverse Drug Reactions, Potential Drug-Drug Interactions and Pharmacokinetic Aspects of Drugs Used in COVID-19 Patients with Stroke: A Narrative Review

Abstract: Stroke has been considered as one of the underlying diseases that increases the probability of severe infection and mortality Meanwhile, there are ongoing reports of stroke subsequent to COVID-19 infection In this narrative paper, we reviewed major neurologic adverse drug reactions (ADRs) and pharmacokinetics of drugs which are routinely used for COVID-19 infection and their potential drug-drug interactions (PDDIs) with common drugs used for the treatment of stroke It is highly recommended to monitor patients on chloroquine (CQ), hydroxychloroquine (HCQ), antiviral drugs, and/or corticosteroids about initiation or progression of cardiac arrhythmias, delirium, seizure, myopathy, and/or neuropathy In addition, PDDIs of anti-COVID-19 drugs with tissue plasminogen activator (tPA), anticoagulants, antiaggregants, statins, antihypertensive agents, and iodine-contrast agents should be considered The most dangerous PDDIs were interaction of lopinavir/ritonavir or atazanavir with clopidogrel, prasugrel, and new oral anticoagulants (NOACs)

Refractory Sarcoidosis: A Review.

Abstract: Sarcoidosis is a multi-system disease of unknown etiology characterized by granuloma formation in various organs (especially lung and mediastinohilar lymph nodes). In more than half of patients, the disease resolves spontaneously. When indicated, it usually responds to corticosteroids, the first-line treatment, but some patients may not respond or tolerate them. An absence of treatment response is rare and urges for verifying the absence of a diagnosis error, the good adherence of the treatment, the presence of active lesions susceptible to respond since fibrotic lesions are irreversible. That is when second-line treatments, immunosuppressants (methotrexate, leflunomide, azathioprine, mycophenolate mofetil, hydroxychloroquine), should be considered. Methotrexate is the only first-line immunosuppressant validated by a randomized controlled trial. Refractory sarcoidosis is not yet a well-defined condition, but it remains a real challenge for the physicians. Herein, we considered refractory sarcoidosis as a disease in which second-line treatments are not sufficient to achieve satisfying disease control or satisfying corticosteroids tapering. Tumor necrosis alpha inhibitors, third-line treatments, have been validated through randomized controlled trials. There are currently no guidelines or recommendations regarding refractory sarcoidosis. Moreover, criteria defining non-response to treatment need to be clearly specified. The delay to achieve response to organ involvement and drugs also should be defined. In the past ten years, the efficacy of several immunosuppressants beforehand used in other autoimmune or inflammatory diseases was reported in refractory cases series. Among them, anti-CD20 antibodies (rituximab), repository corticotrophin injection, and anti-JAK therapy anti-interleukin-6 receptor monoclonal antibody (tocilizumab) were the main reported. Unfortunately, no clinical trial is available to validate their use in the case of sarcoidosis. Currently, other immunosuppressants such as JAK inhibitors are on trial to assess their efficacy in sarcoidosis. In this review, we propose to summarize the state of the art regarding the use of immunosuppressants and their management in the case of refractory or multidrug-resistant sarcoidosis.

Coronavirus Disease 2019 (COVID-19) and Transplantation: Pharmacotherapeutic Management of Immunosuppression Regimen

Abstract: The 2019 novel coronavirus disease (COVID-19) was first detected in Wuhan, Hubei Province, China, in late 2019. Since then, COVID-19 has spread to more than 200 countries in the world, and a global pandemic has been declared by the World Health Organization (WHO). At present, no vaccines or therapeutic regimens with proven efficacy are available for the management of COVID-19. Hydroxychloroquine/chloroquine, lopinavir/ritonavir, ribavirin, interferons, umifenovir, remdesivir, and interleukin antagonists, such as tocilizumab, have been recommended as potential treatment options in COVID-19. Transplant patients receiving immunosuppressant medications are at the highest risk of severe illness from COVID-19. At the same time, with regard to receiving polypharmacy and immunosuppressants, treatment options should be chosen with more attention in this population. Considering drug-drug interactions and adverse effects of medications used for the treatment of COVID-19, such as QT prolongation, the dose reduction of some immunosuppressants or avoidance is recommended in transplant recipients with COVID-19. Thus, this narrative review describes clinically important considerations about the treatment of COVID-19 and immunosuppressive regimens regarding modifications, side effects, and interactions in adult kidney or liver allograft recipients.

Changing Times for CLN2 Disease: The Era of Enzyme Replacement Therapy.

Abstract: Neuronal ceroid lipofuscinosis type 2 (CLN2 disease) is a progressive neurodegenerative disease that results in early-onset, severe, progressive, neurological disabilities, leading to death in late childhood or early adolescence. Management has relied on symptomatic care, and supportive and palliative strategies, but the approval of the enzyme replacement therapy cerliponase alfa in the USA and Europe in 2017 brought different treatment opportunities. We describe the natural history of CLN2 disease, its diagnosis and management, and the preclinical and clinical development of cerliponase alfa. A PubMed search was undertaken for cerliponase alfa and rhTPP1 to identify preclinical and clinical studies. The hallmark-presenting symptoms of CLN2 disease are unprovoked seizures and a history of language delay, and progression involves motor dysfunction, and cognitive and visual decline. Cerliponase alfa has shown efficacy and tolerability in mouse and canine models of CLN2 disease when delivered intracerebroventricularly. Administration of cerliponase alfa in patients with CLN2 disease has led to significant reductions in the rate of decline of motor and language functions in comparison with a natural history population. The approval of cerliponase alfa has brought a new era for CLN2 disease, highlighting the need to understand different patterns of disease progression and clinical needs in treated patients.

The Double Burden of the COVID-19 Pandemic and Polypharmacy on Geriatric Population - Public Health Implications

Abstract: COVID-19 pandemic is inducing acute respiratory distress syndrome, multi-organ failure, and eventual death. Respiratory failure is the leading cause of mortality in the elderly population with pre-existing medical conditions. This group is particularly vulnerable to infections due to a declined immune system, comorbidities, geriatric syndrome, and potentially inappropriate polypharmacy. These conditions make the elderly population more susceptible to the harmful effects of medications and the deleterious consequences of infections, including MERS-CoV, SARS-CoV, and SARS-CoV-2. Chronic diseases among elderlies, including respiratory diseases, hypertension, diabetes, and coronary heart diseases, present a significant challenge for healthcare professionals. To comply with the clinical guidelines, the practitioner may prescribe a complex medication regimen that adds up to the burden of pre-existing treatment, potentially inducing adverse drug reactions and leading to harmful side-effects. Consequently, the geriatric population is at increased risk of falls, frailty, and dependence that enhances their susceptibility to morbidity and mortality due to SARS-CoV-2 respiratory syndrome, particularly interstitial pneumonia. The major challenge resides in the detection of infection that may present as atypical manifestations in this age group. Healthy aging can be possible with adequate preventive measures and appropriate medication regimen and follow-up. Adherence to the guidelines and recommendations of WHO, CDC, and other national/regional/international agencies can reduce the risks of SARS-CoV-2 infection. Better training programs are needed to enhance the skill of health care professionals and patient's caregivers. This review explains the public health implications associated with polypharmacy on the geriatric population with pre-existing co-morbidities during the COVID-19 pandemic.

Diagnosis and Screening of Patients with Fabry Disease

Abstract: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by absence or deficient activity of α-galactosidase A (α-Gal A) due to mutations in the α-galactosidase A gene (GLA), leading to progressive accumulation of globotriaosylceramide (Gb3) in tissues and organs including heart, kidney, the eyes, vascular endothelium, the nervous system and the skin. Cardiac involvement is leading to fatal complications and reduced life expectancy. FD is treatable with disease-specific treatment (enzyme replacement therapy (ERT) or with chaperone therapy). Therefore, the early diagnosis of FD is crucial for reducing the morbidity and mortality. Screening of high-risk populations (eg, patients with unexplained left ventricular hypertrophy (LVH), young patients with unexplained stroke, and patients with unexplained renal failure proteinuria or microalbuminuria) yields good results. The diagnostic algorithm is gender-specific. Initially, the measurement of α-Gal A activity is recommended in males, and optionally in females. In males with non-diagnostic residual activity (5-10%) activity, genetic testing is afterwards done for confirming the diagnosis. In fact, diagnosis of FD is not possible without genetic testing for both males and females. Globotriaosysphingosine (lyso-Gb3) for identification of atypical FD variants and high- sensitive troponin T (hsTNT) for identification of cardiac involvement are also important diagnostic biomarkers. The aim of this review was to provide an update on diagnosis and screening of patients with FD.

Inclisiran for the Treatment of Cardiovascular Disease: A Short Review on the Emerging Data and Therapeutic Potential.

Abstract: Proprotein convertase subtilisin kexin 9 (PCSK-9)-targeting therapy has arisen as a new line for the treatment of hyperlipidemia. Inclisiran is a double-stranded small RNA molecule that works by blocking the transcription of PCSK-9, leading to a reduction of PCSK9 levels in the hepatocytes, resulting in an increased expression of low-density lipoprotein (LDL) receptors in the hepatocyte membrane and, as a consequence, it reduces the circulating levels of LDL cholesterol (LDL-C). Compared to the other LDL-C-lowering medications, such as statins, ezetimibe and PCSK-9 inhibitors, inclisiran proposes an infrequent dosing of twice a year, while simultaneously providing a significant reduction of LDL-C. Its prolonged effect offers an advantage against medication non-compliance, which is one of the main causes for not achieving LDL-C goals with standard therapy. Inclisiran has also proven to have a relatively safe profile with adverse effects occurring in similar frequency as with placebo. This review aims to present and discuss the current clinical and scientific data pertaining to the role of inclisiran in the management of hypercholesterolemia and treatment of cardiovascular disease (CVD).

Uric Acid and Arterial Stiffness.

Abstract: Hyperuricemia is usually associated with hypertension, diabetes mellitus, metabolic syndrome and chronic kidney disease. Accumulating data from epidemiological studies indicate an association of increased uric acid (UA) with cardiovascular diseases. Possible pathogenic mechanisms include enhancement of oxidative stress and systemic inflammation caused by hyperuricemia. Arterial stiffness may be one of the possible pathways between hyperuricemia and cardiovascular disease, but a clear relationship between increased UA and vascular alterations has not been confirmed. The review summarizes the epidemiological studies investigating the relationship between UA and arterial stiffness and highlights the results of interventional studies evaluating arterial stiffness parameters in patients treated with UA-lowering drugs.

Cardiovascular Risk Profile in Prostate Cancer Patients Treated with GnRH Agonists versus Antagonists: An Italian Real-World Analysis.

Abstract: Purpose To evaluate and compare the incidence of cardiovascular (CV) events in a large contemporary cohort of patients diagnosed with prostate cancer (PCa) and in treatment with GnRH agonists or GnRH antagonists. Patients and methods An Italian observational retrospective cohort study based on administrative databases of three local health units and two Regions was performed. PCa patients treated with GnRH agonists or antagonist were included between January 01, 2013 and December 31, 2016. Index date (ID) was the date of first GnRH agonist/antagonist prescription during inclusion period. Follow-up was from ID to December 31, 2017. Patients were excluded if they were under abiraterone treatment or combination therapy with antiandrogens during follow-up. The incidence rate of CV events (acute myocardial infarction, ischemic heart diseases, cerebrovascular diseases, cardiac dysrhythmias, heart failure, atherosclerosis, aneurism, other CV-related conditions) was calculated among patients not switching to androgen deprivation therapy (ADT) in the overall cohort and in a sub-cohort of patients without previous CV events. Results In total, 9785 (mean age 76.8 ± 8.5) patients were included: 9158 (93.6%) were treated with a GnRH agonist and 627 (6.4%) with a GnRH antagonist. Of them, 9627 did not switch to ADT and were considered in the analyses. The incidence of CV events was significantly higher in patients treated with GnRH agonists rather than antagonists (8.8 vs 6.2, p=0.002). Mean time to CV event was beyond 1 year of treatment in both groups. In the multivariable regression analysis, the risk of experiencing CV events was significantly lower in patients treated with GnRH antagonist rather than those treated with GnRH agonists [HR (95% CI): 0.76 (0.60-0.95), p=0.018]. These findings were confirmed in the sub-cohort of patients without previous CV events. Conclusion This Italian observational study shows that most patients received a GnRH agonist rather than a GnRH antagonist prescription. GnRH antagonist seems to have a better CV risk profile than GnRH agonist, both in patients with and without a history of CV events.

Failure to Reach a Consensus in Polypharmacy Definition: An Obstacle to Measuring Risks and Impacts-Results of a Literature Review.

Abstract: Introduction: The risk of polypharmacy is on the rise in most industrialized countries, threatening to burden their health systems. Although many definitions exist and numerous concepts are found in literature as synonyms, the phenomenon of polypharmacy remains poorly defined. The aim of this literature review is to provide an overview of available definitions of polypharmacy, to analyse their convergences and divergences and to discuss the consequences on the assessment of the problem. Methods: A literature review was conducted to identify all published systematic reviews on definitions of polypharmacy available via Scopus and Pubmed databases. The Assessment of Multiple Systematic Reviews (AMSTAR) tool was used to appraise the methodological quality of the selected reviews. Available definitions and other characteristics were extracted; summarised in a table and analysed. Results: Six systematic reviews were identified. They were published between 2000 and 2018. Three focussed on definitions of polypharmacy in the elderly; two in the general population and one in children. The strategy adopted in reviews is more rigorous in the most recent ones. However, they remain, at best, partially exhaustive. The definitions found in the literature used two main approaches, either (i) quantitative, applying varying thresholds and types of polypharmacy based on the number of medications being taken by the patient (ii) qualitative, based on the clinical indications and effects of a given drug regimen, with a growing number of characteristics to describe polypharmacy. The term “inappropriate” is increasingly associated with polypharmacy especially in studies that aimed to use this definition to identify possible solutions for healthcare providers in the field related to aging. Conclusion: This review confirms a high variability and an evolution in the approaches defining “polypharmacy” in the absence of a consensus following standardized criteria. That makes it very difficult to estimate and measure the outcomes associated with this phenomenon.

Therapeutic Potential of Dupilumab in the Treatment of Chronic Rhinosinusitis with Nasal Polyps: Evidence to Date

Abstract: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is one of the most severe forms of chronic rhinosinusitis. CRSwNP is characterized by nasal and facial congestion, loss of sense of smell, rhinorrhea, and post-nasal drip. Treatments have been ineffective at controlling disease recurrence, despite multiple courses of medical and surgical therapies. Oral glucocorticoid therapy is often used to control exacerbations leaving the patient exposed to steroid-induced adverse effects. Thus, there is a clear unmet need for new treatments to achieve better control of the disease. Advances in understanding Type 2 inflammatory processes that occur in about 80% of the Western world patients with CRSwNP have resulted in new avenues for disease control. Biologics in the form of monoclonal antibodies, which target Type 2 inflammation, have helped control the severest forms of atopic dermatitis and asthma. Treatment regimes for CRSwNP now include biologics. In July 2019, dupilumab was the first monoclonal antibody to gain FDA approval for the treatment of CRSwNP. In this review, we summarize the proof of concept clinical trials and Phase 3 trials leading to approval of dupilumab, an anti-IL4 alpha receptor antagonist that blocks the actions of both IL4 and IL13. These studies show that dupilumab is a proven treatment option to control disease. Collective studies demonstrate a high safety profile. Questions arise as to the best use of dupilumab in the context of current treatment paradigms, and for which sub-population of the varied heterogeneous endotypes of CRSwNP patients. Recognizing the high cost of biologics forces the need for cost-effectiveness analysis.

Behçet’s Disease in Children: Diagnostic and Management Challenges

Abstract: Behcet's Disease (BD) is an inflammatory disease of unknown etiology with multisystemic involvement, being the main clinical manifestations represented by recurrent oral and genital ulcerations and uveitis. The disease has typically a chronic-relapsing course and may cause significant morbidity and mortality due to eye, vascular and neurological involvement. Although BD is more frequently diagnosed in adulthood, the disease onset can also be in pediatric age. Pediatric-onset BD is commonly featured by an incomplete clinical picture, and therefore the diagnosis represents a considerable clinical challenge for the physicians. The first classification criteria for pediatric BD, based on a scoring system, have been proposed few years ago. This work focuses on the main difficulties concerning both the diagnostic approach and the treatment of BD in pediatric age. The recommendation for the treatment of pediatric BD has been recently updated and allowed a considerable improvement of the therapeutic strategies. In particular, the use of anti-TNFα drugs as a second-line option for refractory BD, and as a first-line treatment in severe ocular and neurological involvement, has demonstrated to be effective in improving the outcome of BD patients. The knowledge about the molecular pathogenesis is progressively increasing, showing that BD shares common features with autoimmune and autoinflammatory disorders, and thus leading to the use of new biologic agents targeting the main mediators involved in the determination of BD. Anti-IL-17, anti-IL-23, anti-IL-1 and anti-IL-6 agents have shown promising results for the treatment of refractory BD in clinical trials and will represent an important alternative for the therapeutic approach to the disease.

The Advantage of Implementation of Enhanced Recovery After Surgery (ERAS) in Acute Pain Management During Elective Cesarean Delivery: A Prospective Randomized Controlled Trial.

Abstract: Objective The aim of this study was to test whether the implementation of an enhanced recovery after surgery (ERAS) protocol for patients undergoing elective cesarean delivery has a positive impact on the postoperative status of the patients in terms of pain management, hospital stay, hospitalization costs, and adverse reactions. Methods Patients who underwent elective cesarean delivery were randomized into two groups - ERAS group and control group - and the groups were managed with the ERAS protocol and traditional protocol, respectively. Results Compared to the control group, the ERAS group had significantly fewer patients with intraoperative nausea, pain of visual analog scale (VAS) scores, and VAS grade >3 during rest in the first 24 h and during motion in the first 24 and 48 h after surgery. There were no intergroup differences in the requirement of extra analgesics, the incidence of vomiting, shivering, hypotension, postoperative nausea, and pruritus. None of the patients in either group had postoperative vomiting. Patient satisfaction rated as per the VAS was significantly higher in the ERAS group than in the control group. The total length of stay, postoperative length of stay, and the cost of anesthesia in both groups were comparable. Further, the average daily hospitalization cost was significantly lower in the ERAS group than in the control group. Conclusion The ERAS protocol shows promise and appears to be worthwhile for widespread implementation among patients undergoing elective cesarean delivery; it was found to be beneficial in reducing the postoperative pain, incidence of intraoperative nausea, and average cost of hospitalization and also improved patient satisfaction.

A dangerous consequence of the recent pandemic: Early lung fibrosis following covid-19 pneumonia – case reports

Abstract: The outbreak of the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) started in China in December 2019. COVID-19 patients at presentation show a wide spectrum of clinical and pathological involvement. We report two cases of respiratory insufficiency due to COVID-19 pneumonia that occurred in adults without a history of respiratory diseases. Although these patients improved and were discharged from the acute ward, during the hospitalization they both progressed with a subsequent clinical and radiological worsening, pointing out one of the main concerns for these patients at discharge: the possibility of developing persistent lung abnormalities also in healthy people not having other risk factors. In conclusion, these cases represent two examples of early lung fibrosis in patients with COVID-19 pneumonia with different severity disease evolution and highlight the need for long-term follow-up strategies. The etiology of this fibrosis is under discussion: we suppose that it could be due to either a possible outcome of natural history of lung damage produced by ARDS, or to the lung injury related to high oxygen level or to the lung damage directly induced by viral infection or finally to the autoimmune response. At this moment, it is not possible to predict how many people will have consequences due to COVID-19 pneumonia, and therefore we believe that careful follow-up should be mandatory.

HIV Treatment Outcomes Among Patients Initiated on Antiretroviral Therapy Pre and Post-Universal Test and Treat Guidelines in South Africa.

Abstract: Introduction Officially rolled out on 01 September 2016, South Africa's Universal Test and Treat (UTT) policy calls for first-line antiretroviral treatment (ART) initiation among all known HIV-positive patients, irrespective of CD4 cell count. We evaluate treatment outcomes of patients initiated on first-line ART directly before and after the implementation of UTT. Methods We analysed prospectively collected clinical cohort data among ART-naive adult patients within two HIV clinics in Johannesburg, South Africa. We compare two groups: 1) an unexposed pre-UTT group initiating treatment from 01 December 2014 to 31 May 2015; and 2) an exposed UTT group initiating treatment from 01 December 2016 to 31 May 2017. Primary treatment outcomes included lost to follow-up (LTFU) (>90 days late for the last scheduled visit with no subsequent clinical visit). Cox proportional hazards models were used to estimate the association between pre-UTT vs UTT initiation on LTFU by 12 months. Results We included 2410 patients. A total of 1267 (52.6%) patients initiated ART before UTT implementation and 1143 (47.4%) after the change in policy. LTFU (adjusted Hazard Ratio (aHR): 1.51; 95% Confidence Interval (CI): 1.16-1.98) between groups and specifically among those initiating with a CD4 cell count ≤500 cells/mm3 (aHR: 1.59; 95% CI: 1.21-2.10) was higher among patients initiating ART under UTT. Conclusion LTFU under UTT proved higher than that of previous periods. Patients initiating first-line therapy under the treat-all policy may often start treatment in better health, subsequently not perceiving a direct benefit to treatment which may deter patients from consistent engagement in HIV treatment programmes.

Prevention and Treatment of Postoperative Nausea and Vomiting (PONV): A Review of Current Recommendations and Emerging Therapies

Abstract: Postoperative nausea and vomiting is one of the most frequent adverse events after surgery and anesthesia. It is distressing for the patient and can lead to other postoperative complications. Management of PONV involves a framework of risk assessment, multimodal risk reduction, and prophylactic measures, as well as prompt rescue treatment. There has been a significant paradigm shift in the approach towards PONV prevention. There have also been several emerging therapeutic options for PONV prophylaxis and treatment. In this review, we will discuss the up-to-date PONV management guidelines and highlight novel therapeutic options which have emerged in the last few years.

Diagnosis and Screening of Patients with Hereditary Transthyretin Amyloidosis (hATTR): Current Strategies and Guidelines.

Abstract: The outlook for transthyretin amyloidosis (ATTR) is changing with the availability of new and emerging treatments. ATTR now appears to be more common than previously thought and is no longer viewed as an obscure diagnosis with a grim prognosis. Now more than ever, there is growing emphasis on the need for early diagnosis because the treatments appear to be most effective if started in earlier stages of the disease. Diagnosing ATTR is a challenge as it may initially present with nonspecific symptoms and it is often thought of as a diagnosis of exclusion. Increased awareness is imperative as new treatments offer hope and have the potential to change the disease trajectory. ATTR commonly presents with neurological and cardiac features. Transthyretin (TTR) is a protein produced in the liver which misfolds either due to genetic mutations or due to aging and results in deposition of amyloid fibrils in organs and tissues. Apart from the traditional imaging modalities, newer techniques including echocardiographic strain imaging, magnetic resonance imaging (MRI), and nuclear scintigraphy, as well as the increased availability of genetic testing are aiding in making a timely diagnosis. In this review, we present the current understanding of the ATTR disease process, diagnostic and surveillance approaches, newer treatment modalities, and the future directions.

Systemic Inflammatory Response Markers Associated with Infertility and Endometrioma or Uterine Leiomyoma in Endometriosis

Abstract: Purpose The aim of this study was to find the most useful marker of endometriosis-related infertility and evaluate predictive and diagnostic values of systemic inflammatory response markers (preoperative white blood-cell subtypes, neutrophil:lymphocyte ratio [NLR], platelet:lymphocyte ratio [PLR], and monocyte:lymphocyte ratio [MLR]) and CA125 levels in endometriosis patients. Methods This study comprised 662 women who had undergone laparoscopic surgery and been pathologically confirmed as having endometriosis and 83 patients pathologically confirmed with benign ovarian tumors. Related inflammatory factors in endometriosis complicated by infertility were analyzed via logistic regression analysis. Diagnostic values of the inflammatory response markers were obtained by receiver operating-characteristic analysis. Results We firstly identified that lower NLR level was an independent risk factor of infertility. Serum lymphocytes were significantly higher in endometriosis patients, while serum CA125, NLR, MLR, and PLR were elevated. For differentiating endometriosis from other benign ovarian tumors, the combination of NLR and CA125 achieved greater sensitivity than CA125 alone. In addition, both CA125 and NLR were positively correlated with stage, oviduct adhesion, and diameter of ovarian ectopic cysts. Conclusion NLR may be used as a simple and easily obtained predictive marker for endometriosis with infertility. Moreover, NLR can be a neoadjuvant biomarker for serum CA125 to diagnose endometriosis.

Update on Safety Profiles of Vitamins B1, B6, and B12: A Narrative Review.

Abstract: The neurotropic B vitamins B1 (thiamine), B6 (pyridoxine), and B12 (cobalamin) are essential for proper functioning of the nervous system. Deficiencies may induce neurological disorders like peripheral neuropathy (PN) and mainly occur in vulnerable populations (eg, elderly, diabetics, alcoholics). As epidemiologic cohort studies raised safety concerns about vitamin B6/B12 intake being potentially associated with increased risks of hip fracture (HF) and lung cancer (LC), we explored these aspects and performed comprehensive literature searches. However, we suggest not to neglect actual high-risk factors (eg, smoking in LC, higher age in HF) by focusing on individual nutrients, but to examine the complex interaction of numerous factors involved in disease development. Because it warrants continued consideration, we also provide an update on neurotoxicity associated with vitamin B6. We consider that neurological side effects due to vitamin B6 intake are rare and only occur with high daily doses and/or longer treatment duration. The benefit-risk ratio of high-dose treatment with neurotropic B vitamins in indications like PN is therefore considered advantageous, particularly if dosing recommendations are followed and serum levels monitored.

Safe Use of Opioids in Chronic Kidney Disease and Hemodialysis Patients: Tips and Tricks for Non-Pain Specialists.

Abstract: In patients suffering from moderate-to-severe chronic kidney disease (CKD) or end-stage renal disease (ESRD), subjected to hemodialysis (HD), pain is very common, but often underestimated. Opioids are still the mainstay of severe chronic pain management; however, their prescription in CKD and HD patients is still significantly low and pain is often under-treated. Altered pharmacokinetics and the lack of clinical trials on the use of opioids in patients with renal impairment increase physicians' concerns in this specific population. This narrative review focused on the correct and safe use of opioids in patients with CKD and HD. Morphine and codeine are not recommended, because the accumulation of their metabolites may cause neurotoxic symptoms. Oxycodone and hydromorphone can be safely used, but adequate dosage adjustments are required in CKD. In dialyzed patients, these opioids should be considered as second-line agents and patients should be carefully monitored. According to different studies, buprenorphine and fentanyl could be considered first-line opioids in the management of pain in CKD; however, fentanyl is not appropriate in patients undergoing HD. Tapentadol does not need dosage adjustment in mild-to-moderate renal impairment conditions; however, no data are available on its use in ESRD. Opioid-related side effects may be exacerbated by common comorbidities in CKD patients. Opioid-induced constipation can be managed with peripherally-acting-μ-opioid-receptor-antagonists (PAMORA). Unlike the other PAMORA, naldemedine does not require any dose adjustment in CKD and HD patients. Accurate pain diagnosis, opioid titration and tailoring are mandatory to minimize the risks and to improve the outcome of the analgesic therapy.

Octreotide-Resistant Acromegaly: Challenges and Solutions

Abstract: Acromegaly is a rare and severe disease caused by an increased and autonomous secretion of growth hormone (GH), thus resulting in high circulating levels of insulin-like growth factor 1 (IGF-1). Comorbidities and mortality rate are closely related to the disease duration. However, in most cases achieving biochemical control means reducing or even normalizing mortality and restoring normal life expectancy. Current treatment for acromegaly includes neurosurgery, radiotherapy and medical therapy. Transsphenoidal surgery often represents the recommended first-line treatment. First-generation somatostatin receptor ligands (SRLs) are the drug of choice in patients with persistent disease after surgery and are suggested as first-line treatment for those ineligible for surgery. However, only about half of patients treated with octreotide (or lanreotide) achieve biochemical control. Other available drugs approved for clinical use are the second-generation SRL pasireotide, the dopamine agonist cabergoline, and the GH-receptor antagonist pegvisomant. In the present paper, we revised the current literature about the management of acromegaly, aiming to highlight the most relevant and recent therapeutic strategies proposed for patients resistant to first-line medical therapy. Furthermore, we discussed the potential molecular mechanisms involved in the variable response to first-generation SRLs. Due to the availability of different medical therapies, the choice for the most appropriate drug can be currently based also on the peculiar clinical characteristics of each patient.

Oxygen-Ozone (O 2 -O 3 ) Therapy in Peripheral Arterial Disease (PAD): A Review Study

Abstract: The purpose of this study is to review the current knowledge of oxygen-ozone (O2-O3) therapy and its effects on peripheral artery disease (PAD) risk factors, symptoms, as well as on PAD patients' quality of life From the in vitro studies, it has been concluded that the oxygen-ozone therapy exerts a positive effect on the platelet aggregation, cell remodeling, cytoskeletal elements organization and mitochondria structure In animal studies, it has been shown that the O2-O3 therapy is an effective method in hypertension, and it diminishes the hypoxia state of various tissues Clinical studies have provided evidence on the oxygen-ozone therapy effectiveness in low perfusion syndromes and hyperglycemia, as well as conditions with oxidative stress and inflammation The oxygen-ozone therapy promotes faster recovery and enhances healing processes It appears to be an effective adjunctive therapy in preventing peripheral artery disease complications such as occurrence of cardiovascular event, amputation or other extreme surgical solutions It has been concluded that the O2-O3 therapy improves the quality of life of PAD patients The oxygen-ozone therapy appears to have no adverse events or side effects Moreover, it is very cost-effective, as standard treatment costs can be reduced by 25% Easy clinical protocols allow the implementation of oxygen-ozone therapy into the usual care of PAD patients Finally, the O2-O3 therapy may be meaningful especially for older patients and patients who are not eligible for standard revascularization

Diagnosis and Management of Patients with Heart Failure with Preserved Ejection Fraction (HFpEF): Current Perspectives and Recommendations.

Abstract: Heart failure with preserved ejection fraction (HFpEF) is a major global public health problem. Diagnosis of HFpEF is still challenging and built based on the comprehensive echocardiographic analysis. Currently, there are no universally accepted therapies that alter the clinical course of HFpEF. This review attempts to summarize the current advances in the diagnosis of HFpEF and provide future directions of the patients´ management with this very widespread, heterogeneous clinical syndrome.

Lung Function Assessment by Impulse Oscillometry in Adults

Abstract: Over the past decades, impulse oscillometry (IOS) has gained ground in the battery of pulmonary function tests. Performing the test requires minimal cooperation of the patient; therefore, it is a useful tool, especially in evaluating lung mechanics in children, elderly patients, and those who cannot perform spirometry. Oscillometry has also been used in both clinical and research departments. Studies were published mainly in asthma regarding detection of bronchodilator response and the therapeutic response to different drugs. Furthermore, it has been shown to be a sensitive technique to evaluate disease control. Other studied diseases were COPD, interstitial lung diseases, small airway disease, impairment of lung function due to exposure to occupational hazards or smoking, central airways obstruction, cystic fibrosis, monitoring lung mechanics during mechanical ventilation and sleep, neuromuscular diseases, lung transplant, and graft function. The aim of this review is to present the utility of oscillometry on the previously mentioned clinical fields.

Comparison of Percutaneous Endoscopic Lumbar Discectomy with Minimally Invasive Transforaminal Lumbar Interbody Fusion as a Revision Surgery for Recurrent Lumbar Disc Herniation after Percutaneous Endoscopic Lumbar Discectomy.

Abstract: Objective The purpose of this study was to compare the outcomes between percutaneous endoscopic lumbar discectomy (PELD) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) for the revision surgery for recurrent lumbar disc herniation (rLDH) after PELD surgery. Patients and Methods A total of 46 patients with rLDH were retrospectively assessed in this study. All the patients had received a PELD in Peking University First Hospital between January 2015 and June 2019, before they underwent a revision surgery by either PELD (n=24) or MIS-TLIF (n=22). The preoperative data, perioperative conditions, complications, recurrence condition, and clinical outcomes of the patients were compared between the two groups. Results Compared to the MIS-TLIF group, the PELD group had significantly shorter operative time, less intraoperative hemorrhage, and shorter postoperative hospitalization, but higher recurrence rate (P<0.05). Complication rates were comparable between the two groups. Both groups had satisfactory clinical outcomes at a 12-month follow-up after the revision surgery. The PELD group also showed significantly lower visual analog scale (VAS) scores of back pain and Oswestry disability index (ODI) in one month after the revision surgery, whereas the difference was not detectable at six- and 12-month follow-ups. Conclusion Both PELD and MIS-TLIF are effective as a revision surgery for rLDH after primary PELD. PELD is superior to MIS-TLIF in terms of operative time amount of intraoperative hemorrhage and postoperative hospitalization. However, its higher postoperative recurrence rate must be considered and patients should be well informed, when making a decision between the two surgical approaches.