The Safety Profiles of Adalimumab, Infliximab, Etanercept, Secukinumab and Ustekinumab in Psoriasis - A 30-month Observational Cohort Prospective Study of Adverse Events in Biologic Therapy.

BACKGROUND: Although biologic agents are very effective, long-term comparative studies demonstrating their safety relative to one another are still lacking. METHODS: A total of 124 patients with psoriasis were followed up for 30 months; 74 received anti-TNF-alpha inhibitors (adalimumab, etanercept, infliximab), 33 were on ustekinumab, and 17 were treated with secukinumab. The rates of adverse events in these groups were recorded and statistically analyzed. RESULTS: Infliximab-treated patients showed a high occurrence of asymptomatic, but increased liver enzymes, fatigue, and respiratory as well as dermatologic infections. Adalimumab-treated patients were more often affected by musculoskeletal disorders and infections of all types. Patients treated with secukinumab presented with higher rates of cardiovascular disorders as well as respiratory and dermatologic infections. The group receiving etanercept was more often diagnosed with musculoskeletal and reproductive disorders, specifically menstrual disorders. The rates of therapy discontinuation and serious adverse events did not reach statistically significant values. CONCLUSION: A higher incidence of adverse events was observed among adalimumab-, and infliximab-treated patients, with ustekinumab found to have the safest profile. Our results demonstrate that a personalized approach, including evaluation of a patient's risk profile, is necessary before commencing a biologic. Further research is warranted to confirm the findings of our study.

Synthetic neuroactive steroids.

This review discusses the topic of synthetic neuroactive steroids. A brief introduction to the mode of action of neuroactive steroids is followed by a short overview of the best-known synthetic neuroactive steroids used in clinical practice and the reasons for their withdrawal from the market. The paper examines various aspects of 6 specific synthetic neuroactive steroids which either have been approved for treatment or are currently in advanced phases of clinical trials, and lists their indications, current experience, and undesirable adverse effects. The authors conclude that the therapeutic potential of neuroactive steroids is still not made full use of. It is to be hoped that this particular class of drugs will find more widespread use also in the management and treatment neurological and psychiatric disorders other than those discussed in this article.

Pain and Analgesic Related Insomnia.

OBJECTIVES: The aim of this review is to describe the effects of analgesics on sleep. DATA SOURCES: Systematic search of the databases of PubMed and the Cochrane Library was performed between January and September 2021. REVIEW/ANALYSIS METHODS: The search included all articles on the topic published during the past 20 years (2000-2020). The search strategy was developed using a controlled vocabulary of known studies meeting the inclusion criteria and focused on the following terms: chronic pain, pain, sleep disturbance, insomnia, analgesic, analgesic medication, antidepressants, antiepileptic drugs, nonsteroidal drugs, opioids, and quality of life. Two reviewers independently considered the studies for inclusion in the review, assessed the risk of bias, and extracted data. DESIGN: Review and analysis. RESULTS: A total of 37 studies met the inclusion criteria: 15 analyzed the effects of opioids, 6 those of nonsteroidal anti-inflammatory drugs and acetaminophen, and 16 the effects of adjuvant analgesics. CONCLUSIONS: Sleep quality may be adversely affected by a variety of medications used in clinical practice, including those used in analgesic indications. The class of analgesics most affecting sleep quality are opioids.

Epidemiology of moderate-to-severe psoriasis: a comparison between psoriasis patients treated with biological agents, conventional systemic drugs and topical agents.

INTRODUCTION: Understanding how different comorbidities and epidemiological factors are related to psoriasis severity can help us estimating patients' clinical outcome. AIM: Establish possible prognostic factors of severe psoriasis. METHODS: Three groups of patients were included: 118 were on topical therapy, 83 used conventional systemic drugs, and 112 were treated with biological agents. Based on the fact that patients on topical therapy have a lower grade of disease severity than patients treated systemically, we compared a variety of comorbidities and epidemiological parameters between the three groups. RESULTS: Patients treated more aggressively have an increased risk of cardiovascular disease (p = .044), suffer more from depression (p = .020), hyperuricemia (p = .031) and nonspecific noninfectious liver disease (p = .005). Male gender (p < .001), increased height (p < .001), early age of disease onset (p < .001), viral upper respiratory infections (p = .049) and periods of hormonal changes (p = .045) are associated with these therapies. CONCLUSION: Psoriasis severity is directly related to an increased risk of cardiovascular disease, depression, hyperuricemia and nonspecific noninfectious liver disease. Male gender, increased height, early age of disease onset, viral upper respiratory infections and periods of hormonal changes seem to be prognostic of higher degrees of psoriasis severity. We are pioneering the use of increased height and puberty, menopause/andropause as independent prognostic factors of psoriasis severity.

Neurotoxic side effects of acyclovir: two case reports.

Acyclovir is an antiviral drug frequently used in clinical practice. It is indicated for the treatment of infections caused by herpes simplex virus and varicella zoster virus. The drug has a good safety profile; however, severe side effects may rarely occur during therapy. These include renal failure as a major risk factor for neurotoxic side effects potentially developing within 24-48 hours of therapy initiation. The paper presents the cases of two patients developing neurotoxic side effects while treated for herpes zoster. The aim of the authors is to highlight the potential for developing neurotoxic side effects in high-risk groups such as the elderly, patients with impaired renal function or multiple comorbidities on polypharmacy, or those using nephrotoxic drugs. Acyclovir use could lead to renal impairment and an increase in its plasma and CNS concentrations with severe neuropsychiatric side effects. The neurotoxic side effects are reversible after therapy withdrawal. Thus, in patients developing mental impairment or showing other neurological symptoms during acyclovir therapy, the patient should be promptly assessed for potential drug neurotoxicity, their therapy should be discontinued and drug elimination with forced diuresis or hemodialysis considered. Early recognition of acyclovir neurotoxic side effects can significantly improve a patient's prognosis.

The safety profile of biologic agents in comparison with non-biologic systemic agents, and topical compounds in the management of psoriasis-A 30-month prospective, observational cohort study.

BACKGROUND: Although biologic agents (BAs) are very effective, solid data proving they are safer than other therapies in psoriasis are still lacking. METHODS: A total of 289 psoriatic patients were followed for 30 months; of which number 118 were treated with topical agents alone, 112 received BAs, and the remaining 59 patients were on non-biologic systemic agents (NBSAs). The rates of adverse events in these groups were recorded and statistically analysed. RESULTS: Patients treated with BAs had higher rates of adverse events (P = .017), including overall infections (P = .003), respiratory infections (P < .001), renal, urinary (P < .001), musculoskeletal, connective tissue (P < .001, and P = .021) and oral cavity-related (P = .046) disorders. Except for the incidence of infections, all the above adverse events occurred more often in our study than in clinical trials. The occurrence of serious adverse events was P = .066, with the incidence of serious infections being P = .164. Unlike patients on topical therapy and NBSAs, patients treated with BAs were forced to discontinue their therapies (P = .001). The Psoriasis Area Severity Index (PASI) and body surface area (BSA) scores were the lowest among patients on BAs. CONCLUSION: While BAs were the most effective therapies, they were associated with higher rates of treatment discontinuation and adverse events in comparison with other forms of therapy.

Pitfalls of solving polypharmacy problems.

Polymedication is associated with a higher incidence of negative health indicators including falls, morbidity and mortality. Despite efforts, the solution to this problem is still unsatisfactory. The two main causes of polymedication are population aging and polymorbidity and, on the other hand, the development of the pharmaceutical industry and the availability of a wide range of medicines. The authors discuss the main shortcomings in the investigation of this issue, such as inconsistent terminology used, methodological shortcomings in data acquisition, lack of recommended guidelines for the polymorbid patients treatment, etc. They discuss whether polymedication is the cause or marker of increased falls, frailty and mortality. In the end they critically evaluate possible solution of polymedication in future - personalised medicine.

Drug-induced Cholelithiasis.

BACKGROUND: The prevalence of cholelithiasis in developed countries is high and its cause is multifactorial, with a negligible proportion of drug-induced cholelithiasis. METHODS: Relevant studies were identified by PubMed, Google Scholar and Science Direct. Reference lists of retrieved articles were also reviewed. The most relevant and up-to-date information was incorporated. RESULTS: There is a wide range of drugs that can induce lithiasis. While the risk of developing lithiasis is high with some drugs (ceftriaxone, atazanavir, somatostatin analogues), it is lower or even questionable with others. Some drugs precipitate in the bile and may account for up to 100% of the weight of the stone. CONCLUSION: Cholelithiasis can be induced by a wide range of drugs with different mechanisms of action. The aim of the article is to draw attention to this lesser known fact and the need to take into account the risk of developing lithiasis prior to therapy initiation.

Increased platelet activity in tinnitus patients.

OBJECTIVE: The aim of our study was to establish whether or not tinnitus patients have higher platelet activity, as measured by plasma 11-dehydro-thromboxane B2 levels, compared with individuals without tinnitus. METHODS: The study group included patients without documented organic causes of tinnitus or a cause of non-vascular hearing impairment. Laboratory tests included complete blood count, biochemistry, coagulation activity, and thromboxane levels. To exclude a pathology in the cerebellopontine angle, CT and MRI were performed together with an X-ray scan of cervical vertebrae. For the purpose of this study, blood samples were screened for 11-dehydro-thromboxane B2 levels using commercial kits. RESULTS: A comparison of the main marker of increased platelet activity i.e., thromboxane levels of tinnitus patients with those of a control group, showed increased thromboxane levels in the former. The average plasma concentrations of 11-dehydro-thromboxane B2 were 2.0234±1.80 ng/ml in the group of tinnitus patients and 1.3247±1.33 ng/ml in the control group. Our results showed that patients with tinnitus have significantly higher values of 11-dehydro-thromboxane B2. CONCLUSION: Tinnitus patients showed higher levels of increased platelet activity, a marker that may play an important role in the pathogenesis of tinnitus.

Antiplatelet therapy in secondary prevention of non-embolic ischaemic stroke.

The authors address the topic of antiplatelet therapy after a non-cardioembolic ischaemic stroke. They discuss some controversial issues in therapy such as monotherapy versus combination therapy, short-term versus long-term therapy and whether current therapy should be modified or continued in the event a patient has experienced a stroke. Other outstanding issues dealt with include e.g., the risk of such therapy in patients developing cerebral microbleeds. While consensus has been reached by experts regarding the utility of dual therapy in the initial period, divergent opinions exist as to the selection of drugs and therapy duration. Definition of the optimal strategy is hindered by the lack of evidence and robust data from clinical trials.

Controversies in the treatment of gout.

The authors discuss current options on the treatment of gout (acute gout attack, prophylaxis, management of hypouricemia) and asymptomatic hyperuricemia. They highlight the differences in individual guidelines in terms of the spectrum of drugs used, their preferences, dosing, dose titration, and goals of treatment as well as different positions over asymptomatic hyperuricemia. Further, the authors provide an overview of latest concepts related to uric acid and its association with some neurologic and cardiovascular diseases. Another issues discussed in the article are the completely different guidelines for general practitioners and their principles. In conclusion, the authors note that answers to some controversies in the treatment of gout can only be provided by data obtained from properly designed and conducted clinical trials. Key words: allopurinol - colchicine - glucocorticoids - gout - non-steroidal anti-inflammatory drugs - uric acid.

Cardiovascular risk of non-steroidal anti-inflammatory drugs.

Non-steroidal anti-inflammatory drugs (NSAIDs) belong to the most widely used drugs. Results of recent large meta-analyses have shown that the cardiovascular risk of NSAIDs is more serious than originally believed and is not associated exclusively with coxibs; it is also increased when using so called traditional NSAIDs. Data obtained to date show the safest drugs of this class in terms of cardiovascular risk are naproxen and ibuprofen at low doses. The position of naproxen as the safest NSAID has been challenged by some more recent findings. The authors examine some results of meta-analyses and conclusions of regulatory agencies.Key words: cardiovascular risk - coxibs - diclofenac - ibuprofen - naproxen - non-steroidal anti-inflammatory drugs.

[Citalopram and QT prolongation]. / Citalopram a prodlouzený QT interval.

In 2011/2012, the US Food and Drug Administration issued a warning about the effect of citalopram on the QT interval and decreased its dosing. Further studies addressing this issue have been published since then. The authors were interested to know whether or not the studies have furnished new information that could modify or further specify the FDA-issued recommendations. After analyzing the most relevant studies, the authors concluded that even papers published within the last 5 years confirmed that, of the SSRI class of drugs, citalopram prolongs the QT interval most significantly. While the QT interval prolongation in young and otherwise healthy individuals is small and treatment with citalopram relatively safe, in elderly comorbid patients with polypharmacy, use of even currently recommended doses may result in significant QT interval prolongation. Hence, the decision about future therapy will depend on the degree of risk of each individual patient. Judging by the most recent data, citalopram is not more effective compared with the other SSRIs. As a result, therapy with citalopram will presumably show a declining trend, particularly in elderly patients.Key words: citalopram - escitalopram - QT interval - SSRI.

[Drug induced tendon injury]. / Poskození slach vyvolané léky.

Tendon injury belongs to the less known side effects of some drugs, reported until recently only for glucocorticoids and fluoroquinolones. To date, some other classes of drugs such as statins, aromatase inhibitors, anabolic steroids, potentially causing tendon injury, have been added to the list. The authors discuss the most common clinical presentations, diagnosis, and management as well as latest experimental data regarding this issue. The most often, the Achilles tendon is affected, however, nearly every tendon of the entire body may be affected. Tendon rupture or drug induced tendinopathy should be strongly considered in those who have a tendon injury and have recently taken these drugs.Key words: anabolic steroids - aromatase inhibitors - fluoroquinolones - glucocorticoids - statins - tendon injury.

Circulating steroids negatively correlate with tinnitus.

While not a disease entity in itself; symptoms of tinnitus (from Latin tinnio - clink) accompany a number of diseases. Tinnitus prevalence increases with age, deteriorates one's quality of life, and may even result in suicidal behavior. Tinnitus develops in response to a variety of risk factors, otoxic substances, noise exposure, hearing disorders, and psychological alterations. Tinnitus is closely related to mood, depression, and psychological state. In the present study, we focused on alterations of the steroid metabolome and particularly neuroactive, neuroprotective, and immunomodulatory steroids in patients with tinnitus. The study group consisted of 28 patients without evidence of an organic cause of tinnitus as well as without associated diseases or the effect of ototoxic medications. All patients underwent a complete audiological assessment and laboratory tests including routine biochemical markers and quantification of circulating steroids using gas chromatography/mass spectrometry and immunoassays. To rule out a pathology in the cerebellopontine angle area, CT scan or MRI were performed. To diagnose stem lesions, evoked potentials were also measured. Pearson's correlations and multivariate regression were used to assess any links between tinnitus intensity and frequency on the one hand, and steroid levels on the other. Results indicated a significant and consistent negative correlation between tinnitus indices and intensity of adrenal steroidogenesis. The circulating steroid metabolome including hormones and neuroactive, neuroprotective, and immunomodulatory steroids negatively correlates with the degree of tinnitus due to hypothalamo-pituitary-adrenal axis malfunction. Our results may help explain the pathophysiology of tinnitus and improve its diagnosis. However, further studies are needed to verify our postulation.

Suppressive effect of citalopram on plasma concentrations of thromboxane B2.

BACKGROUND: Citalopram, a selective serotonin reuptake inhibitor (SSRi), is widely used to treat major depression. Patients treated with SSRIs suffer more frequently from bleeding disorders caused by the antiplatelet effect of SSRIs. METHODS: To investigate the potential suppressive effect of citalopram treatment on plasma thromboxane B2 levels and its possible correlation with actual plasma concentration of citalopram. Plasma concentrations of thromboxane B2 and citalopram were examined in a cohort of 77 aspirin-treated geriatric patients before and in the third week of citalopram therapy. RESULTS: Citalopram therapy led to a significant decrease of plasma concentrations of thromboxane B2 compared to its levels before initiation of the therapy. Furthermore, we have shown negative correlation in thromboxane B2 levels and actual plasma concentration of citalopram. Actual plasma concentrations of citalopram were significantly higher compared to younger adult patients treated with similar dose. CONCLUSIONS: In this study we have shown that even short-term citalopram therapy led to a suppression of thromboxane B2 production in aspirin-treated patients. This suppressive effect correlates with actual plasma concentration of citalopram.

Serotonin syndrome.

Serotonin syndrome is a potentially serious clinical condition. In this article, the authors put serotonin syndrome into historical context, discuss its pathophysiology, review in detail its clinical presentations, diagnostic criteria, differential diagnosis and treatment. Special attention is given to drugs that most often cause serotonin syndrome, and the gene polymorphisms involved in the metabolism of these drugs.

The non-antidepressant effects of citalopram: a clinician's perspective.

The authors present an overview of the most often discussed questions concerning citalopram, i.e. its proven effect on the QT interval and related dose reductions. They discuss citalopram's antiplatelet effect including the most recent data and draw attention to serotonin syndrome as its incidence is still underestimated. They go on to discuss hyponatremia pointing out that this condition may develop even in those taking low doses of citalopram. Finally, the authors provide a brief overview of the latest findings on osteoporosis and the serotonergic mechanism inducing it in individuals treated with a selective serotonin reuptake inhibitor.

The purification step is not crucial in EIA measurements of thromboxane B2 and 11-dehydrothromboxane B2 in human plasma.

BACKGROUND: Thromboxane B2 (TxB2) and particularly 11-dehydrothromboxane B2 (11-dTxB2) are widely used as prognostic risk markers of platelet activation in cardiovascular diseases. The main errors in TxB2 and 11-dTxB2 determination include either low concentrations of circulating TxB2 (1 - 2 pg/mL) and 11-dTxB2 (0.9 - 4.3 pg/mL) or rather high transiency (mean TxB2 half-life is approximately 5 minutes) as well as an incorrect pre-analytical phase set up. The aim of this study was to investigate the impact of a widely used purification step on the results of enzyme immunosorbent assay (EIA)--based measurement of the two selected thromboxanes. METHODS: For the purpose of this study, 20 plasma samples (10 healthy donors, 10 patients under treatment with acetylsalicylic acid) were screened for TxB2 and 11-dTxB2 concentrations using commercial competitive EIA kits (Cayman Chemicals, Tallinn, Estonia; Neogen, Lexington, KY, USA) with or without the introduction of the purification procedure. RESULTS: The purification step does not significantly affect the results of EIA measurements of the two of TxA2 metabolites (TxB2, 11-dTxB2) in human plasma. The levels of TxB2 and 11-dTxB2 determined in the plasma samples were not significantly changed (p < 0.05) when the purification step was omitted compared to the purified samples. CONCLUSIONS: This study establishes a protocol allowing for reliable and reproducible plasma TxB2 and 11-dTxB2 EIA measurement for routine basic screening of platelet function.

Evaluation of aspirin's effect on platelet function early after coronary artery bypass grafting.

OBJECTIVE: Aspirin therapy decreases mortality and ischemic complication rates after coronary artery bypass grafting (CABG). However, platelet inhibition after oral aspirin seems to be insufficient in the early postoperative period. There are incomplete data reporting aspirin efficacy early after CABG. The aim of this study was to assess the pharmacologic effect of aspirin on platelets in the first postoperative days using the most specific laboratory tests for the evaluation of aspirin efficacy. DESIGN: A prospective study. SETTING: A clinical study in one cardiac surgery center and measurements in two pharmacologic institutions. PARTICIPANTS: Thirty patients. INTERVENTIONS: Postoperative aspirin efficacy (200 mg/d) was assessed by the suppression of serum thromboxane B(2) (TxB(2)) and by arachidonic acid-induced aggregometry using the MULTIPLATE analyzer. Samples were collected before surgery and on postoperative days 1-5. METHODS AND MAIN RESULTS: The median baseline value (range) of serum TxB(2) was 1.6 ng/mL (1.4-1.9). The median TxB(2) inhibition >90% (the value required for full platelet inhibition) was not achieved until day 5 (-91%, 0.13 ng/mL [0.08-0.22], p < 0.001) and in only 55% of patients. The median baseline ASPI value was 805 (640-975) aggregation units (AU)*min. A significant decrease in aspirin insufficiency was not seen before postoperative day 5 (390 [243-621], p < 0.003) and only 34% of patients reached an effective platelet inhibition on day 5 (cutoff < 300 AU*min). CONCLUSIONS: The effect of aspirin on inhibition of TxB(2) production and arachidonic acid-induced platelet aggregation is impaired during the first postoperative days after CABG. A more effective antiplatelet strategy presumably could increase early graft patency and improve clinical outcomes after CABG.