Gradual Discontinuation Research Articles

Heart failure treatment in the last years of life - a nationwide study of 364,000 individuals

Abstract Background Heart failure treatment patterns towards the end of life have rarely been studied at large scale. Yet, this is important to assess, since heart failure is a chronic condition with patients on treatment for potentially many years. Purpose To investigate treatment patterns in the last years of life in patients with heart failure. Methods In a register-based study covering the whole Swedish population between 2007 and 2020, we investigated treatment patterns in the last years of life in 364,480 individuals who died with heart failure. We combined binomial models (to estimate proportion on treatment at death) and Poisson models (to estimate discontinuation rate), to estimate the proportion on each heart failure treatment up to 5 years prior to death, using penalized splines to allow for non-linearities. We also assessed comorbidity patterns over time. Results All heart failure treatments saw a gradual discontinuation closer to death, but the discontinuation rate of beta blockers decreased over time, resulting in an increasing proportion of patients on treatment at the time of death (Fig). Also, the pattern of comorbidities changed over time, with an increase in e.g., hypertension and atrial fibrillation, but a decline in ischemic heart disease (63% in 2007 gradually declining to 54% in 2020). Conclusions In this nationwide study, we observed a changing pattern of medical treatment of heart failure during the last years of life, most notably with an increasing use of beta blockers. Comorbidities and the shares of heart failure etiologies also changed over time, with an increase in several conditions but a decline in ischemic heart disease. Taken together, this may have important implications for planning and optimizing care for these patients.

Cost-Utility Analysis of Antipsychotic Reduction and Discontinuation in Patients With Long-Term Schizophrenia and Psychosis in English Mental Health Trusts: The RADAR Study

ObjectivesThe current recommended treatment for patients with recurrent episodes of schizophrenia and related conditions is antipsychotic medication. However, many antipsychotic users remain functionally impaired and experience serious physical and mental side effects. This study aims to assess the cost-effectiveness of a gradual antipsychotic reduction and discontinuation strategy compared with maintenance treatment over 24 months from mental health services, health and social care, and societal perspectives. MethodsNineteen mental health trusts recruited patients to the Research into Antipsychotic Discontinuation and Reduction (RADAR) randomized controlled trial. Quality-adjusted life-years were calculated from patient-reported EQ-5D-5L, with years of full capability calculated from the patient-reported ICECAP-A. Mental health services use and medication was collected from medical records. Other resource use and productivity loss was collected using self-completed questionnaires. Costs were calculated from published sources. ResultsA total of 253 participants were randomized: 126 assigned to antipsychotic dose reduction and 127 to maintenance. There were no significant differences between arms in total costs for any perspectives. There were no significant difference in quality-adjusted life-years (−0.035; 95% CI: −0.123 to 0.052), whereas years of full capability were significantly lower in the reduction arm compared with the maintenance arm (baseline-adjusted difference: −0.103; 95% CI: −0.192 to −0.014). The reduction strategy was dominated by maintenance for all analyses and was not likely to be cost-effective. ConclusionsIt is unlikely that gradual antipsychotic reduction and discontinuation strategy is cost-effective compared with maintenance over 2-years for patients with schizophrenia and other recurrent psychotic disorders who are on long-term antipsychotics.

Ten years of maintenance treatment of severe melancholic depression in an adult woman including discontinuation experiences.

There are only few publications on long-term treatments for major depressive disorder (MDD) lasting 5 years or longer. Most clinical controlled trials lasted no longer than 2 years and some recent studies suggested an advantage of cognitive behavioral therapy (CBT) over antidepressants in relapse prevention of MDD. Exclusively outpatient "real world" treatment of severe melancholia, prospectively documented over 10 years with different serial treatment strategies, discontinuation phenomena and complications. Compared to CBT, agomelatine, mirtazapine, bupropion and high-dose milnacipran, high-dose venlafaxine (extended-release form, XR) was effective, even sustainably. Asymptomatic premature ventricular contractions (PVCs) were found at the beginning of the treatment of the MDD, which initially led to the discontinuation of high-dose venlafaxine (300 mg daily). Even the various treatment strategies mentioned above were unable to compensate for or prevent the subsequent severe deterioration in MDD (2 rebounds, 1 recurrence). Only the renewed use of high-dose venlafaxine was successful. PVC no longer occurred and the treatment was also well tolerated over the years, with venlafaxine serum levels at times exceeding 5 times the recommended upper therapeutic reference level (known bupropion-venlafaxine interaction, otherwise 2.5 to 3-fold increase with high-dose venlafaxine alone). During dose reduction or after gradual discontinuation of high-dose venlafaxine, rather mild withdrawal symptoms occurred, but as described above, also two severe rebounds and one severe recurrence happened. This long-term observation supports critical reflections on the discontinuation of successful long-term treatment with antidepressants in severe MDD, even if it should be under "the protection" of CBT. The PVC seemed to be more related to the duration of the severe major depressive episode than to the venlafaxine treatment itself. A particular prospective observation of this longitudinal case study is that relapses (in the sense of rebounds) during or after previous venlafaxine tapering seemed to herald the recurrence after complete recovery. Remarkably, neither relapses nor recurrence could be prevented by CBT. In this case, high-dose venlafaxine has a particular relapse-preventive (and "recurrence-preventive") effect with good long-term tolerability.

Antipsychotic Medication Continuation vs Taper and Discontinuation in Patients With Schizophrenia and Other Nonaffective Psychotic Disorders.

Schizophrenia is a major mental illness that is managed with long-term antipsychotic medication as a standard of care. Antipsychotic medications, however, are associated with many subjective and objective adverse effects. These adverse effects have driven the study of risk-mitigation strategies such as targeted intermittent therapy and dose reduction and drug discontinuation. Randomized controlled trials (RCTs) of these strategies have been synthesized in meta-analysis; both strategies have been associated with no functional benefits and with an increased risk of relapse. The RCTs, however, have been criticized because, in many, patients were abruptly switched to the target dose or too rapidly tapered, thereby predisposing the RCT to failure of the intervention. Two important RCTs examined gradual individualized dose reduction and discontinuation. One, conducted in first-episode psychosis patients who were free from positive symptoms for 6 months, found that, at 18-month follow-up, dose reduction was associated with a higher risk of relapse (number needed to harm [NNH] = 5) and with no functional benefits. However, after return to routine clinical care, at a 7-year follow-up, the dose reduction group had better functional outcomes and similar clinical outcomes relative to the maintenance treatment group. The other RCT, conducted in patients with relapsing psychosis, found that, at a 2-year follow-up, dose reduction was associated with a higher risk of relapse (NNH = 5) and with no improvements in social, cognitive, quality of life, satisfaction, and other domains. Many large nationwide observational studies have found that antipsychotic discontinuation by patients with first-episode psychosis and schizophrenia is associated with increased relapse, rehospitalization, suicide mortality, cardiovascular mortality, and all-cause mortality. There is also the ethical matter that attempts to identify the few who may benefit from antipsychotic dose reduction and discontinuation may compromise the health and stability of the many who require long-term maintenance treatment.

Subjective discomfort and lack of volitional drive with neuroleptic pharmacotherapy - a phenomenological case study

IntroductionIn comparison to extrapyramidal and metabolic side effects, the subjective aspects of neuroleptic treatment have been less extensively researched. Nevertheless, they are equally significant given their potential to influence adherence and functional outcome. Historically, terms such as “neuroleptic dysphoria,” “neuroleptic-induced psychic indifference,” and “neuroleptic-induced deficit syndrome” were used to characterize a range of unpleasant mood states on the one hand and a documented and observable motivational deficit on the other. The latter aligns with the findings from preclinical neuroscientific studies and animal models highlighting the significant involvement of mesolimbic dopamine in motivational processes. Despite an abundance of anecdotal data these adverse effects are often undetectable in large-scale clinical studies that utilize standardized assessment measures.ObjectivesTo present adverse subjective changes in arousal, mood and volitional drive resulting from neuroleptic intake from a patient’s perspective.MethodsThe subject is a patient, with no reported negative symptoms or lasting functional impairment described, who underwent a gradual 6-month discontinuation of risperidone in an outpatient setting following a complete recovery after a single psychotic episode. A semi-structured interview modelled after The Clinical Assessment Interview for Negative Symptoms (CAINS) was conducted. We aimed to elicit descriptions of the subjective experience while ensuring our approach remained non-suggestive.ResultsIn addition to describing potential akathisia and lethargy at higher doses, the subject reported a significant lack of motivation and a notably reduced willingness to exert effort towards achieving specific goals or engaging in activities that he still found rewarding or pleasurable. Furthermore, he consistently noted gradual improvements across various psycho-social aspects following the discontinuation of the medication. These adverse and unpleasant experiences were presented as the primary reason for wanting to discontinue pharmacological treatment.ConclusionsCertain adverse effects of antipsychotic medications can only be elucidated by the clinician through the examination of the patient’s subjective experiences. Medication induced dysphoria and volitional deficits have the potential to profoundly impact treatment adherence, leading to unrecommended discontinuation of neuroleptics, and can cause important functional impairment.Disclosure of InterestNone Declared

Does Slow and Steady Win the Race? Rates of Antipsychotic Discontinuation, Antipsychotic Dose, and Risk of Psychotic Relapse.

Antipsychotics are recommended for prevention of relapse in schizophrenia. It is unclear whether increased risk of relapse following antipsychotic discontinuation is predominantly associated with an absolute magnitude of dose reduction or rate of antipsychotic reduction. Establishing the responsible mechanism is important because prolonged withdrawal schedules have been suggested to reduce risk of relapse. Individual patient data from antipsychotic discontinuation studies were obtained. We estimated the occupancy of receptors over time using half-lives and median effective dose ED50 values obtained from pharmacokinetic and receptor occupancy studies. Hazard ratios for relapse events were calculated using Cox proportional hazards models to assess the influence of formulation (oral, 1-monthly, and 3-monthly injections). The change in hazard ratio over time was estimated, and the effect of time-varying covariates was calculated, including rate of occupancy reduction and absolute receptor occupancy. Five studies including 1388 participants with schizophrenia were identified (k = 2: oral, k = 2: 1-monthly injection, k = 1: 3-monthly injection). Withdrawal of long-acting injectable medication did not lead to a lower hazard ratio compared with withdrawal of oral medication, and this included the period immediately following randomization. Hazard ratios were not associated with the rate of decline of receptor occupancy; however, they were associated with reduced absolute occupancy in trials of long-acting injections (P = .038). Antipsychotic discontinuation is associated with an increased risk of psychotic relapse, related to receptor occupancy. Although relapse does not appear to be related to the rate of discontinuation, gradual discontinuation strategies may allow for easier antipsychotic reinstatement in case of symptomatic worsening.

Is the most really the best: a review for the most selective SSRI concept three decades later

IntroductionPharmaceutical slogans presuming a particular antidepressant molecule being the best solely based on a core concept could be proved “not accurate” especially following patients’ actual exposure to the antidepressant for longer than the usual six or twelve weeks’ trialsObjectivesReviewing the current situations of SSRI induced anhedonia recognition and its management. Distinguishing anhedonia as a core symptoms of depression from SSRI induced anhedonia and the combination of both.MethodsReview of literatures including theses related to the same topicResultsResearch suggests that, SSRIs might be more effective at treating some symptoms than others. More specifically, it has been suggested that, SSRIs might be more effective at improving symptoms such as low mood and anxiety but not anhedonia (Argyropoulos et al. psych.pharmaology, 2013; 27(10), 869-877). It has been proposed that, catecholaminergic antidepressants might be more effective treatments for anhedonia and emotional blunting in MDD than SSRIs (McCabe et al. Biological psychiatry, 2010; 67(5), 439–445. The primary effect of SSRIs is reduced processing of negative stimuli rather than increased positive stimuli. Emotional blunting is related to SSRI dose and possibly serotonergic effects on the frontal lobes and/or serotonergic modulation of midbrain dopaminergic systems projecting to the prefrontal cortex (PFC). By enhancing serotonergic transmission, SSRIs can activate the inhibitory Gamma Aminobutyric Acid (GABA) interneurons, thereby dampening the noradrenergic and dopaminergic input ( Blier. Int J Neuropsychopharmacol., 2014; 17:997–1008).Management of SSRI induced anhedonia includes lowering the current SSRI dose. Adding non SSRI antidepressant to the current SSRI dose or to a lowered SSRI dose. Gradual discontinuation of the SSRI and switching to another antidepressant with a different profile (SNRI) that might improve the patient’s emotional response (Koenigs. Behav Brain Res., 2009;201:239–43).Bupropion is an antidepressant with less possibility to give rise to emotional blunting. (Tomoko et al. Neuroscience Letters., 2021; 749, 135716. agomelatine(Thome et al. Journal of neural transmission., 2015; 122(1), 3-7.Vortioxetine and others (Bing et al. frontiers in psychiatry., Jan, 2019; 10-17. are of inrerest in this regard.Image 2:ConclusionsThe most selective SSRI concept assumes that most selective means less affinity to other receptors or secondary binding sites which might suggest less side effects and perhaps being the most efficacious. Not only serotonin but multiple neurotransmitters are in action at the downstream part of a cascade of events underpinning the etiology of MDD. MDD has heterogeneous etiology and this explains why patients respond differently. SSRI induced anhedonia could be tackled and we need to explore how many patients would benefit from that now and have not yet.Disclosure of InterestNone Declared

Prostatic Abscess Due to Idiopathic Granulomatous Disease: A Rare Complication of a Chameleon Disorder <br/>—Prostatic Abscess Due to Idiopathic Granulomatous Disease

Background: Prostatic abscesses are usually diagnosed in the setting of bacterial prostatitis. Rarely, they reveal or complicate granulomatous prostatitis (GP). Four cases of idiopathic xanthogranulomatous GP have been described previously and the present case report is the first of typical idiopathic variety. The case: A 60-year-old man presented with urine retention that was associated with pyuria and massively enlarged prostate. Cystoscopy revealed prostatic abscess (PA) that was opened. Urine and prostatic culture were negative for bacteria. Prostatic biopsy revealed multiple non-caseating granulomata surrounded by lymphocytes, plasma cells yet without foamy histiocytes, parasites and vasculitis. Special stains were negative for vasculitis, fungiand acid-fast organisms. The patient was treated with Solumedrol 1 g intravenously daily for 3 days followed by Prednisone 1 mg/kg/day for 1 month followed by gradual tapering till discontinuation by 3rd month. Moreover, he had received Mycophenolate mofetil (MMF) 1 g twice/daily. By the end of 2nd month; he was asymptomatic and without pyuria. Repeat cystourethroscopy and MRI scan of the prostate showed near normal prostate. In Conclusion: Idiopathic GP can present with PA that requires proper drainage and since it is a locally hyperimmune disease with genetic predisposition; MMF therapy will be maintained for a total of 2 years to prevent future disease-relapse.

Recommendations for the treatment of rheumatoid arthritis in Saudi Arabia: adolopment of the 2021 American College of Rheumatology guidelines

BackgroundThe 2021 American College of Rheumatology (ACR) rheumatoid arthritis (RA) guideline considers the specific context of the United States which differs from that of Saudi Arabia in many aspects that may impact recommendations. The objective of this project was to adapt a set of prioritized recommendations from the 2021 ACR guideline for the treatment of rheumatoid arthritis RA for the context of Saudi Arabia, by the Saudi Society for Rheumatology (SSR).MethodsThe process followed the GRADE-ADOLOPMENT methodology, and the reporting adhered to the RIGHT-Ad@pt checklist. Working groups included a coordination group and a 19-member panel representing different stakeholder groups. The Evidence to Decision (EtD) tables included evidence on health effects from the source guideline and contextual information from the Saudi setting.ResultsThe panel prioritized and adapted five recommendations from the source guideline. The process led to modifying two out of the five prioritized recommendations, all listed here. In naive patients with low disease activity, methotrexate (MTX) is conditionally recommended over sulfasalazine (SSZ) (modified direction); hydroxychloroquine (HCQ) is conditionally recommended over SSZ (unmodified). Initiation of csDMARDs with short-term glucocorticoids is conditionally recommended over csDMARDs alone in naive patients with moderate to high disease activity (modified direction). Switch to subcutaneous MTX is conditionally recommended over addition/switch to alternative DMARD(s) in patients taking oral MTX who are not at target (unmodified). Discontinuation of MTX is conditionally recommended over gradual discontinuation of the bDMARD or tsDMARD for patients taking MTX plus a bDMARD or tsDMARD who wish to discontinue a DMARD (unmodified).ConclusionRheumatologists practicing in Saudi Arabia can use the adoloped recommendations generated by this project while adopting the rest of the recommendations from the 2021 ACR guidelines.

Management of cerebral vascular spasm in posttraumatic subarachnoid hemorrhage using a combination therapy of oral nimodipine and intravenous milrinone

Background Intravenous milrinone has been investigated for management of vasospasm after aneurysmal subarachnoid hemorrhage (SAH); however, its role in vasospasm after traumatic SAH is still under evaluation. Patients and methods A total of 30 patients with cerebral vascular spasm after traumatic SAH were randomly divided into two equal groups. Group H was given nimodipine (60 mg/4 h) orally or via nasogastric tube and then combination of induced hypertension, hypervolemia, and hemodilution (triple-H therapy). Group M was given nimodipine (60 mg/4 h) orally or in the nasogastric tube and then intravenous milrinone bolus of 0.1–0.2 mg/kg followed by intravenous infusion of 0.75–1.25 μg/k/min. The infusion was continued for 72 h before gradual discontinuation at a rate of 0.25 μg/kg/min every 24 h until complete weaning. For refractory cases in both groups, emergency angioplasty was done. Primary outcome was the transcutaneous cerebral regional oxygen saturation 14 days after starting treatment. Secondary outcomes were the Glasgow coma score 14 days after starting treatment, infarction rate, ICU and hospital stays, and modified Rankin scale and Glasgow outcome scale at 3 and 6 months after starting treatment. Results Group M showed significant increase in regional oxygen saturation and Glasgow coma score; decrease in infarction rate, ICU stay, and hospital stay; and improvement in modified Rankin scale and Glasgow outcome scale. Significance was set at P value less than 0.05. Conclusion The combination of oral nimodipine and intravenous milrinone improves the outcome of vasospasm in posttraumatic SAH.

Designing Flexible Longitudinal Regimens: Supporting Clinician Planning for Discontinuation of Psychiatric Drugs.

Clinical decision support tools have typically focused on one-time support for diagnosis or prognosis, but have the ability to support providers in longitudinal planning of patient care regimens amidst infrastructural challenges. We explore an opportunity for technology support for discontinuing antidepressants, where clinical guidelines increasingly recommend gradual discontinuation over abruptly stopping to avoid withdrawal symptoms, but providers have varying levels of experience and diverse strategies for supporting patients through discontinuation. We conducted two studies with 12 providers, identifying providers’ needs in developing discontinuation plans and deriving design guidelines. We then iteratively designed and implemented AT Planner, instantiating the guidelines by projecting taper schedules and providing flexibility for adjustment. Provider feedback on AT Planner highlighted that discontinuation plans required balancing interpersonal and infrastructural constraints and surfaced the need for different technological support based on clinical experience. We discuss the benefits and challenges of incorporating flexibility and advice into clinical planning tools.

Association of Opioid Dose Reduction With Opioid Overdose and Opioid Use Disorder Among Patients Receiving High-Dose, Long-term Opioid Therapy in North Carolina

Rapid reduction or discontinuation of long-term opioid therapy may increase risk of opioid overdose or opioid use disorder (OUD). Current guidelines for chronic pain management caution against rapid dose reduction but are based on limited evidence. To characterize the association between rapid reduction or abrupt discontinuation of opioid therapy (vs maintained or gradual reduction) and incidence of opioid overdose and OUD among patients prescribed high-dose, long-term opioid therapy (HDLTOT). This retrospective cohort study was conducted among patients aged 18 to 64 years who were prescribed HDLTOT (≥90 daily morphine milligram equivalents for ≥90% of 90 days) from January 2006 to September 2018, with follow-up up to 4 years after cohort entry. Claims data were drawn from a large private health insurer in North Carolina and analyzed from March 1, 2006, to September 30, 2018. Time-varying exposure of rapid dose reduction or discontinuation (>10% dose reduction/week) vs maintenance, increase, or gradual reduction or discontinuation. The main outcome was incident opioid overdose (fatal or nonfatal) or diagnosed OUD. Inverse probability-weighted cumulative incidence of outcomes were estimated using the cumulative incidence function and hazard ratios (HRs) using marginal structural Fine-Gray models as a function of rapid dose tapering or discontinuation (vs gradual reduction or discontinuation or maintained or increased), accounting for competing risks. A total of 19 443 patients (median [IQR] age, 49 [41-55] years; 10 073 [51.8%] men) who received HDLTOT were identified. Rapid reduction or discontinuation was associated with higher risk of fatal and nonfatal overdoses compared with gradual reduction after the first year (year 1: HR, 1.43; 95% CI, 0.94-2.18; years 2-4: HR, 1.95; 95% CI, 1.31-2.90). There was no association between rapid reduction or discontinuation and diagnosed OUD through 2 years of follow-up; however, the hazard of incident OUD among patients exposed to rapid tapering or discontinuation was greater 25 to 48 months after the start of follow-up (HR, 1.28; 95% CI, 1.01-1.63). In this cohort study, rapid dose reduction or discontinuation was associated with increased risk of opioid overdose and OUD during long-term follow-up. These findings reinforce prior concerns about safety of rapid dose reductions for patients receiving HDLTOT and highlight the need for caution when reducing opioid doses.

Trajectories of prescription opioid dose and risk of opioid-related adverse events among older Medicare beneficiaries in the United States: A nested case-control study.

BackgroundDespite the rising number of older adults with medical encounters for opioid misuse, dependence, and poisoning, little is known about patterns of prescription opioid dose and their association with risk for opioid-related adverse events (ORAEs) in older patients. The study aims to compare trajectories of prescribed opioid doses in 6 months preceding an incident ORAE for cases and a matched control group of older patients with chronic noncancer pain (CNCP).Methods and findingsWe conducted a nested case–control study within a cohort of older (≥65 years) patients diagnosed with CNCP who were new users of prescription opioids, assembled using a 5% national random sample of Medicare beneficiaries from 2011 to 2018. From the cohort with a mean follow-up of 2.3 years, we identified 3,103 incident ORAE cases with ≥1 opioid prescription in 6 months preceding the event, and 3,103 controls matched on sex, age, and time since opioid initiation. Key exposure was trajectories of prescribed opioid morphine milligram equivalent (MME) daily dosage over 6 months before the incident ORAE or matched controls. Among the cases and controls, 2,192 (70.6%) were women, and the mean (SD) age was 77.1 (7.1) years. Four prescribed opioid trajectories before the incident ORAE diagnosis or matched date emerged: gradual dose discontinuation (from ≤3 to 0 daily MME, 1,456 [23.5%]), gradual dose increase (from 0 to >3 daily MME, 1,878 [30.3%]), consistent low dose (between 3 and 5 daily MME, 1,510 [24.3%]), and consistent moderate dose (>20 daily MME, 1,362 [22.0%]). Few older patients (<5%) were prescribed a mean daily dose of ≥90 daily MME during 6 months before diagnosis or matched date. Patients with gradual dose discontinuation versus those with a consistent low dose, moderate dose, and increase dose were more likely to be younger (65 to 74 years), Midwest US residents, and receiving no low-income subsidy. Compared to patients with gradual dose discontinuation, those with gradual dose increase (adjusted odds ratio [aOR] = 3.4; 95% confidence interval (CI) 2.8 to 4.0; P < 0.001), consistent low dose (aOR = 3.8; 95% CI 3.2 to 4.6; P < 0.001), and consistent moderate dose (aOR = 8.5; 95% CI 6.8 to 10.7; P < 0.001) had a higher risk of ORAE, after adjustment for covariates. Our main findings remained robust in the sensitivity analysis using a cohort study with inverse probability of treatment weighting analyses. Major limitations include the limited generalizability of the study findings and lack of information on illicit opioid use, which prevents understanding the clinical dose threshold level that increases the risk of ORAE in older adults.ConclusionsIn this sample of older patients who are Medicare beneficiaries, 4 prescription opioid dose trajectories were identified, with most prescribed doses below 90 daily MME within 6 months before ORAE or matched date. An increased risk for ORAE was observed among older patients with a gradual increase in dose or among those with a consistent low-to-moderate dose of prescribed opioids when compared to patients with opioid dose discontinuation. Whether older patients are susceptible to low opioid doses warrants further investigations.

Triggers and Characteristics of Brain Zaps According to the Findings of an Internet Questionnaire.

Objective: To build on the findings of our prior study of spontaneous posts made about brain zaps on a popular lay mental health website using questions specifically targeting brain zaps in a web-based questionnaire.Methods: 3,141 responses were examined from an online questionnaire made available between June 2016 and February 2018. The questions probed the specifics of the medications taken, the temporal characteristics of medication taken, the symptoms associated with the brain zaps, the specifics of the "zap" experience itself, and their effect on quality of life. Special attention was paid to gathering data regarding the triggers of brain zaps, because in our previous study, eye movements triggering brain zaps emerged as an unexpected finding. As this was a convenience sample, qualitative analysis was primarily performed, except regarding the interaction between the half-life of antidepressants and the time to the onset of the first brain zaps, for which the numerical data appeared to be specific enough to allow such analyses.Results: The data from the targeted questionnaire showed a pattern of responses that was very similar to that obtained from analysis of the spontaneous posts. These data include the types of medications taken, the length of time these medications were taken before the onset of the zaps, the length of the zaps, the feeling quality of the zaps, and the effect of gradual versus sudden discontinuation on their onset and presence. Lateral eye movement as a trigger emerged with even more clarity than in the previous study. The positive correlation between the time from onset of the brain zaps and the half-life of the drugs strongly suggests that brain zaps are indeed associated with antidepressant discontinuation.Conclusions: Brain zaps remain a barely examined and poorly understood symptom of antidepressant discontinuation. Further studies are needed from both a prevention and treatment perspective. There is now an even stronger indication that brain zaps are typically triggered by lateral eye movements, which may open avenues for investigating this process.

Generalized pustular psoriasis and Cushing’s syndrome in childhood due to corticosteroids misuse

Background : Generalized pustular psoriasis (GPP) is characterized clinically by yellow ish sterile pustules surrounded by erythema. GPP in children is very rare and may appear following steroid withdrawal in psoriasis vulgaris. Case Illustration : A 14-year-old female presented to the emergency unit with generalized erythematous plaques and multiple pustules with lake of pus after abruptly stopped oral and topical corticosteroid for two weeks. The patient had used topical and oral corticosteroids for almost a year to treat psoriasis. Physical examination revealed moderately ill and tachycardic, with short stature, moon face, amenorrhea, and multiple erythematous plaques with multiple pustules and lake of pus along with red-purple striae all over the body. Discussion: Adverse effects of steroid-induced adrenal insufficiency are time-dependent and generally reversible. Gradual discontinuation of steroids must adhere to physiological dose of steroids, mostly in 3.49 &plusmn; 2.92 months. Other treatments available are emollients, salicylic acid, calcipotriol, coal tar, topical steroids, phototherapy, retinoids, and cyclosporine. Topical steroids cannot be the main therapy in severe psoriasis due to the possible side effects of excessive usage. Conclusion : Misuse of topical and systemic steroid in children could lead to Cushing&rsquo;s syndrome, a multisystem disorder resulting from prolonged exposure to excess glucocorticoids, either both systemic or topical. Children could easily develop systemic reactions to topical steroids due to their higher total body surface area to body weight ratio. &nbsp; Keywords : childhood, Cushing&rsquo;s syndrome, pustular psoriasis, steroid misuse

Mech jako materiał do uszczelniania belek w budownictwie drewnianym Karpat

The article examines the tradition of the chinking of log cabins with moss in chosen villages of the Carpathian Foothills (SE Poland) in the counties of Krosno, Strzyżów, and Sanok. Moss used to be the main material used for chinking. After being gathered in pastures and forests by children and women, it was dried, sprinkled withwater and packed with the help of the metal part of a plough. For the most efficient chinking, the space between logs had to be about 5 cm wide. The main species of moss used for this purpose were Rhytidiadelphus squarrosus (collected on pastures) and Pleurozium schreberi (collected in pine forests). The 1940s and 1950s saw a gradual discontinuation of this practice. In the course of the research, the author chinked two houses in cooperation with a person who was also a key source of information. The article also addresses the legal limitations of reviving the tradition, which include laws concerning the collecting of understorey plants in state forests, fines for using plants from other owners’ forests, and the protection of some moss species.

Development of pulmonary tuberculosis in the patient with systemic sarcoidosis and brain involvement

The article presents a clinical case of pulmonary tuberculosis with destruction and bacterial excretion in the patient with systemic sarcoidosis and cerebral lesions. Tuberculosis was characterized by the infiltrate and cavity in S1+2 of the left lung, tuberculous mycobacteria were detected by microscopy, GeneXpertMBT/Rif, and culture. Systemic sarcoidosis with brain involvement was diagnosed based on intrathoracic lymphadenopathy in 2015, development of dissemination in the lungs and neurological symptoms by 2018, deterioration of changes by 2019, rapid partial resolution of foci in the lungs, and moderate regression of neurological disorders during the treatment with prednisolone. A full course of anti-tuberculosis chemotherapy (316 doses) resulted in persistent sputum conversion, resolution of the infiltrate and cavity healing. Prednisolone was administered simultaneously for 318 days with increased doses (45-35 mg) for the first 2 months, then titrated down to 15 mg and remained so until the end of the treatment with gradual reduction and discontinuation. Changes in the lungs and improvement of clinical and radiological manifestations of neurosarcoidosis were documented.

Diestrous diabetes mellitus remission in a Yorkshire terrier bitch

AbstractRemission of diabetes mellitus in dogs is a very rare condition. In our case, the clinical signs of diabetes mellitus in the nine‐ year‐old Yorkshire terrier bitch disappeared three months after a therapeutic ovariohysterectomy. The diagnosis of diestrous diabetes mellitus, requiring insulin supplementation, was confirmed on the basis of anamnesis, symptomatology, clinical examination and specific laboratory tests. The chosen therapy and a change in diet led to the stabilization of the patient and its preparation for surgery. Repeated follow‐ups, consisting of control blood samplings for glucose and progesterone levels and urinanalysis, has ensured control of insulin therapy and proper insulin dosing. Three weeks after ovariohysterectomy, normoglycaemia, confirmed by control trials, resulted in gradual discontinuation of insulin administration. The stable health status of the patient two months after the performance of therapeutic ovariohysterectomy confirmed the remission of the disease without the need for further insulin supplementation and regular monitoring.

Tacrolimus as a therapeutic option in patients with acquired neuromyotonia

ObjectiveTo analyze the clinical characteristics and outcomes of patients diagnosed with acquired neuromyotonia and who were treated with tacrolimus. MethodsA single center, retrospective study was performed on patients with acquired meuromyotonia whose treatment included tacrolimus. The clinical information, antibody tests, and electromyography results were reviewed. The Numeric Rating Scale for pain and modified Rankin scale were used to quantify outcomes. ResultsThis study included four patients who presented with fasciculation or myokymia in their limbs. Electromyography suggested peripheral nerve hyperexcitability. Autoantibodies including contactin-associated protein 2 (CASPR2), leucine-rich glioma inactivated protein 1 (LGl1) or IgLON5 antibody were detected in three patients, and another patient had Sjogren's syndrome. Initial treatment included membrane-stabilizing drugs and/or corticosteroids. Tacrolimus was administered at a dose of 3 mg once daily to all patients. All patients showed clinical improvement after the treatment. No recurrence was observed after gradual tapering or discontinuation of therapy during follow-up. ConclusionsTacrolimus may be a therapeutic option for acquired neuromyotonia. Further studies on tacrolimus in larger patient cohort should be performed.

Impact of anticholinergic drugs withdrawal on motor function in patients with Parkinson’s disease

ObjectivesPhysicians have prescribed anticholinergic agents as monotherapy or adjuvant therapy in patients with Parkinson’s disease for decades. However, these medications can cause many adverse effects including gait freezing and falling. Herein we assessed the effects of anticholinergic medications on motor function, freezing of gait and falling in a group of patients with PD. Patients and MethodsThis prospective study evaluated the effect of gradual discontinuation of anticholinergics on motor function in 131 outpatients with Parkinson’s disease. We assessed patients’ motor function at baseline six and twelve months later using the UPDRS-III. We also evaluated freezing of gait and falling in patients using UPDRS-II part 14 and 13 respectively. The anticholinergics were tapered and gradually discontinued and additional levodopa doses were added as patients needed. Results131patients successfully discontinued their anticholinergic medications. Stopping anticholinergics significantly improved the motor symptoms in PD patients as reflected in the change between the mean (±SD) UPDRS-III score of 36.85(±11.5) at the baseline to 32.51(±11.4) and 31.43 (±11.3) after six and twelve months (P < 0.001). The mean (±SD) scores of freezing of gait (FOG)significantly changed from 1.34(±1) to 1.17(±1) and 0.6(±0.7) and for falling down from 0.62(±0.8) to 0.5 (±0.8) and 0.29(±0.5) respectively (p-value of <0.001). ConclusionOur finding demonstrated an improvement in motor function and FOG and falling incidences in PD patients, after discontinuation of anticholinergic drugs. As motor complications adversely affect the quality of life in PD patients, clinicians must be careful with the unnecessary use of anticholinergic drugs in their treatment strategies.