Effects Of Withdrawal Research Articles

Statin withdrawal and health-related quality of life in a primary cardiovascular prevention cohort.

While some work has been done on Health-Related Quality of Life (HRQoL) in statin users, none has focused specifically on statin-associated muscle symptoms (SAMS) sufferers. The objective was to assess self-reported HRQoL, before and after statin withdrawal, in patients reporting SAMS. We hypothesized that the presence of SAMS associated with decreased self-reported physical and mental well-being. Patients (50 men/28 women [M/W], aged 49 ± 9years [Mean ± SD]) in primary cardiovascular prevention were recruited into three cohorts: statin users with (SAMS, 29M/18W) or without symptoms (No SAMS, 10M/5W) and controls (11M/5W). The Short Form 36 Health Survey (SF-36) was used to assess HRQoL. All variables were measured before and after 2months of statin withdrawal, and repeated measures analyses were used to verify withdrawal and group effects as well as their interaction. SF-36 physical and mental component scores (respectively, PCS and MCS) were lower in the SAMS group compared with other groups (both p < 0.01). Statin withdrawal led to an increase in LDL cholesterol for statin users (+69.0%, p < 0.01) and an improvement in well-being in the SAMS group, other groups showing no change. A time x category interaction (p = 0.02) was seen for PCS and post hoc analyses showed that statin withdrawal improved PCS and MCS (respectively, +12.5% [ES 0.77] and +5.1% [ES 0.27], both p < 0.05) in the SAMS group. Patients self-reporting SAMS showed improved HRQoL following drug withdrawal, but this was mirrored by a rise in LDL cholesterol. These findings should be considered by clinicians in the evaluation and follow-up of treatment with statins.

Diurnal variation characteristics of thermal structure in a deep reservoir and the effects of selective withdrawal

Thermal structure significantly impacts the reservoir ecology and environment. The diurnal temperature variation (DTV) influences the photosynthesis and respiration of phytoplankton in day and night, and meanwhile changes the vertical density convection and current. Selective withdrawal is practical to control the withdrawal elevation and outflow temperature, and can also influence the thermal structure of reservoir area. Previous research mainly focusses on the long-term change pattern of thermal structure in reservoir, while the diurnal thermal dynamics is less studied, and the effects of selective withdrawal on the DTV is still unknow. Hence, this paper aims to illustrate the diurnal variation characteristics of thermal structure in reservoir, and moreover to reveal the corresponding effects of selective withdrawal. Taking the Sanbanxi Reservoir as study case, a hydrodynamic–temperature numerical model with hourly simulating resolution was built and validated using measured temperature profile during August 2015 to August 2016, based on the CE-QUAL-W2. The effects of selective withdrawal schemes, including different withdrawal elevation and withdrawal types, were illuminated. The discrete Fourier transform (DFT), energy spectrum and statistical analysis were used. This paper showed the following: (1) In the reservoir area, there were three main regions with significant DTV, i.e., the surface layer, the 10-m water layer and the 60-m water layer (withdrawal layer). For the baseline (existing intake), the average DTVs were 0.657, 0.497 and 0.174 °C, respectively, at the surface layer, the 10-m-depth layer and the 60-m-depth layer. (2) From the upstream to the downstream channels of reservoir, the DTV kept unchanged at the surface layer, and increased at the 10-m-depth layer and 60-m-depth layer. (3) A higher withdrawal elevation and the internal weir schemes (stoplog gate/temperature-control curtain) could increase the epilimnetic DTV and energy density, and were suggested to mitigate the hypoxia and nutrient enrichment, compared with a lower withdrawal elevation and the multi-level intake scheme. The results could provide technical support for the ecological management of reservoir and engineering design of the selective withdrawal.

Can selective withdrawal control algal blooms in reservoirs? The underlying hydrodynamic mechanism

Selective withdrawal is considered an effective and convenient method to mitigate thermal pollution and environmental problems in reservoirs and downstream rivers. However, the potential effects of selective withdrawal on harmful algal blooms in reservoirs remain uncertain, threatening sustainable reservoir management. This study developed and calibrated a three-dimensional (3D) hydro-ecological model for the Zipingpu reservoir to numerically investigate how selective withdrawal scenarios (including surface, middle, and bottom withdrawal) affect algal growth and hydrodynamic environments. The surface withdrawal scenario could inhibit algal growth efficiently, causing Chlorophyll a (Chl a) concentration below 10 μg L−1 consistently. The Chl a concentration decreased from 27.0 μg L−1 for bottom withdrawal and 21.2 μg L−1 for middle withdrawal to 3.3 μg L−1 for surface withdrawal in the bloom period. The nutrient, light, and temperature limitations among the three withdrawal scenarios showed slight differences and were not the main reason for the bloom differences. Compared with the bottom and middle withdrawal scenarios, the surface withdrawal scenario weakened stratification and decreased surface water temperature, suggesting inhibitory effects on algal blooms. The bottom and middle withdrawal scenarios significantly reduced surface flow velocity and made the flow direction against the water intake, indicating a favorable hydrodynamic environment for algal growth. The surface withdrawal scenario reduced hydraulic residence time, thereby restraining algal growth and accumulation in the reservoir. Implementing surface withdrawal might be an efficient and promising method to prevent algal blooms in reservoirs. These results not only highlight the potential of selective withdrawal for algal bloom control but also reveal that accelerating surface flow velocity is the key mechanism.

Abstract WP213: The Effect Of Nicotine Withdrawal On Stroke Outcome In Female Rats

Significance: Smoking-derived nicotine (N) is known to synergistically magnify the risk and severity of cerebral ischemia in females. Most importantly, smoking is the one preventable risk factor and giving up smoking reduces the risk for cerebral ischemia. However, how long the harmful effects of N on the brain persist after women stop smoking is unknown. In a laboratory study using an animal model of cerebral ischemia, we demonstrated that N alters brain energy metabolism and thus exacerbates ischemic brain damage. Therefore, the current study aims to investigate how long after N withdrawal (NW) N toxicity on brain energy metabolism persists and its impact on stroke outcomes in female rats. Methods: Female Sprague-Dawley rats (n=8/group) were randomly exposed to either saline or N (4.5 mg/kg) for 16-21 days after which point, they were withdrawn from N exposure and able to recover for 0, 15, or 30 days. These rats were then randomly assigned to either have their cortical tissue collected for global metabolomic (Metabolon Inc) and Western blot analysis or undergo a sham surgery or transient middle-cerebral artery occlusion (tMCAO; 90 min). Post-stroke cognition was tested with contextual fear conditioning at month following tMCAO, subsequently the brains were collected for infarct quantification. Results: Analysis of the metabolomics data revealed an increase in carbohydrate metabolites in the 30-day NW group when compared to the N-exposed group, suggesting persistence of N toxicity in the brain. Furthermore, fear conditioning data revealed a significantly lower freezing time in all NW groups when compared to the saline group implying that spatial memory deficits persist even after 30 days of NW. Lastly, the observed infarct volume was 26%(p&lt;0.05), 25%(p&lt;0.05), and 16%(p&lt;0.05) higher in the 0, 15, and 30 day NW groups respectively, when compared to the saline group. Conclusion: Even after 30 days of NW, N-induced global metabolomic changes in the brain persist and may be responsible for increased ischemic brain damage as well as cognitive deficits in female rats.

A Prediction Scoring Model for the Effect of Withdrawal or Addition of Inhaled Corticosteroids in Patients with Chronic Obstructive Pulmonary Disease.

The aims of this study were to develop a scoring model that predicts the effects of withdrawing inhaled corticosteroids (ICSs) from triple therapy and to examine its adaptability when applied to assess the effect of adding ICSs to dual bronchodilators patients with chronic obstructive pulmonary disease (COPD). A scoring model was developed using the IMPACT study dataset, consisting of 2389 COPD patients treated with triple therapy before enrollment (ICS withdrawal dataset). The developed model consisted of COPD duration, Acute exacerbation history, Sex, Pulmonary function tests, blood Eosinophil count, and Race (CASPER) and was used to predict composite events of moderate-to-severe exacerbation, all-cause mortality, and pneumonia. Treatment heterogeneity was assessed using Cox interaction analyses. The CASPER model was applied to 540 COPD patients treated with dual bronchodilator before enrollment (ICS addition dataset). Validity was assessed using Harrell's C-index, time-dependent receiver operating characteristic curves, and calibration plots. The cumulative incidence of the composite event was 60.1% over 12 months in the ICS withdrawal dataset. Cox interaction analyses revealed that ICS was different according to race and blood eosinophil counts. The hazard ratios (HRs) for dual bronchodilator compared with triple therapy were 1.318 (95% confidence interval (CI)=1.170-1.485; P-value <0.001) in whites and 0.922 (95% CI = 0.712-1.195; P-value=0.541) in other races. The treatment effect was different in the eosinophil count ≥0.3 group (HR = 1.586; 95% CI = 1.274-1.975) and in the eosinophil count = 0.1-0.3 group (HR = 1.211; 95% CI = 1.041-1.408), but it was same in the eosinophil count <0.1 (HR = 1.009; P-value=0.940). The CASPER model performed well with good discrimination and calibration, which were superior to the prediction based on exacerbation history and blood eosinophil count. The presented CASPER model might be able to predict and compare the risk of composite events when dual bronchodilator or triple therapy is administered to COPD patients.

P413 Withdrawal versus continuation of thiopurine in vedolizumab-treated patients with Ulcerative Colitis (VIEWS): a multi-centre randomised controlled trial

Abstract Background The benefit of continuing thiopurine in ulcerative colitis (UC) responders to vedolizumab (VED) is unclear. We aimed to determine the effect of thiopurine withdrawal in VED-treated UC patients on combination therapy. Methods This prospective multi-centre, single-blind, randomised controlled trial recruited UC patients on VED 300mg IV every 8 weeks and a thiopurine for ≥6 months. Patients in steroid-free clinical remission (partial Mayo score[pMS]≤2, no subscore&amp;gt;1) and endoscopic remission/improvement (Mayo endoscopic subscore[MES]≤1) were randomised 2:1 to withdraw or continue thiopurine. Primary outcome was comparing week 48 VED trough levels. Secondary outcomes were disease relapse (pMS≥3 and faecal calprotectin&amp;gt;150μg/g or increase in MES≥1 from baseline), centrally-read endoscopic remission (MES=0), histologic remission (Nancy index=0), histo-endoscopic remission, faecal calprotectin (remission&amp;lt;150μg/g) and adverse events. Results Sixty-two consecutive patients (58% males, median follow-up 23.0 months) were randomised to withdraw (n=42) or continue (n=20) thiopurine. Randomisation was balanced. Complete data was available for 58 patients. There was a non-significant trend toward increased disease relapse in the withdrawal group (P=0.12, Fig. 1). In the withdrawal group, baseline histologic activity significantly increased disease relapse (HR:5.8, 95%CI:1.6-20.8, P=0.007, Fig. 2). There was a trend towards higher relapse rates in the withdrawal versus continue groups for bio-exposed patients (50.0% [6/12] vs 0.0% [0/4], P=0.07) but not bio-naïve patients (20.0% [6/30] vs 12.5% [2/16], P=0.52). At week 48, the continue group had significantly higher histologic remission (OR:4.6, 95%CI:1.1-18.9, P=0.03) and histo-endoscopic remission rates (OR:4.6, 95%CI:1.3-16.1, P=0.01, Fig. 3) versus the withdrawal group, but similar endoscopic remission rates (P=0.09, Fig. 3). Faecal calprotectin remission was significantly higher in the continue (94% [16/17]) versus withdrawal group (70% [28/40], P=0.047) with mean calprotectin 44.5μg/g±SD56.2 vs 209.6μg/g±SD344.2 (P=0.003) respectively. On multivariate analysis, histologic activity at baseline (HR:5.3, 95%CI:1.1-26.2,P=0.04) predicted disease relapse. Week 48 median VED levels were 15.9µg/mL (IQR:10.1-22.7) in the withdrawal group versus 14.7µg/mL (IQR:12.1-18.7) in the continue group (P=0.43). No patients had anti-VED antibodies. There was no significant difference in adverse events between groups. Conclusion Although thiopurine withdrawal did not affect VED trough level, it increased calprotectin, histologic and histo-endoscopic activity in UC. In patients with histological activity despite deep remission, thiopurine withdrawal significantly increased the risk of disease relapse.

OP37 Is the withdrawal of anti-tumour necrosis factor in inflammatory bowel disease patients in remission feasible without increasing the risk of relapse? Results from the randomised clinical trial of GETECCU (EXIT)

Abstract Background Background: The feasibility of anti-TNF discontinuation in inflammatory bowel disease (IBD) must be proven in clinical trials including patients in clinical, endoscopic, and radiologic remission at the time of anti-TNF withdrawal to make recommendations for clinical practice. Aims Primary: to compare the rates of clinical remission at 1 year in patients who discontinue anti-TNF treatment vs. those who continue treatment. Secondary objectives: to know the effect of anti-TNF withdrawal on relapse-free time, mucosal healing and safety; and to identify predictive factors for relapse. Methods Prospective, quadruple-blind, multicentre, randomised, controlled trial. Patients with ulcerative colitis (UC) or Crohn’s disease (CD) in clinical remission for &amp;gt; 6 months were randomised to maintain anti-TNF treatment [maintenance arm (MA)] or to withdraw it [withdrawal arm (WA)]. Patients who were on infliximab (IFX) received IFX 5 mg/kg or an intravenous placebo every 8 weeks, while patients on adalimumab (ADA) received subcutaneous ADA 40 mg or placebo every other week. Patients were followed-up until month 12 or up to the time of clinical relapse, whichever came first. Inclusion and exclusion criteria, trial scheme and definitions are summarized in figures 1a, 1b and 1c. Results were analysed by intention-to-treat (ITT) and by per-protocol (PP). Local investigators were blinded to faecal calprotectin (FC) and IFX and ADA trough levels. On-site monitoring was performed to assess data quality. Results 159 patients were screened, from whom 140 were randomised and comprised the ITT cohort: 70 allocated to the MA and 70 to the WA. Fifteen patients dropped out before the end of follow-up (12 months or relapse), leaving 63 patients in the MA and 62 patients in the WA for the PP analysis. The characteristics of patients in the MA and WA were similar (figure 2). The proportions of patients who maintained clinical remission -59/70 (84%), 95% confidence interval (CI)=74-92% in the MA vs. 53/70 (76%), 95%CI=64-85% in the WA- and who remained without significant endoscopic lesions at the end of follow-up were similar between groups (figures 3a, 3b, 3c). Only the proportion of patients with FC &amp;gt;250 mg/g was higher in the WA at the end of follow-up (figure 3d). Maintenance of clinical remission was no different between groups (figure 4). The same percentage of patients in both groups had at least one adverse event (69%). The proportion of patients with serious adverse events was also similar between groups (4% in MA vs. 7% in WA). Conclusion Anti-TNF withdrawal in selected IBD patients in clinical, endoscopic, and radiologic remission could be feasible without an increase in the risk of clinical relapse. Long-term follow-up of these patients is warranted.

Suvorexant, a Novel Dual Orexin Receptor Antagonist, for the Management of Insomnia.

The present investigation is a comprehensive review regarding the use of Suvorexant for insomnia treatment. It covers the background, pathophysiology, and significance of addressing insomnia, the pharmaceutical details of Suvorexant, and its safety, efficacy, and implications in treating insomnia. We further discuss Suvorexant's role in targeting insomnia with other comorbidities. Insomnia refers to poor quality and/or quantity of sleep. While there are many existing treatments such as benzodiazepines, melatonin agonists, TCAs, and atypical antipsychotics used to target various receptors involved in normal induction and maintenance of sleep, Suvorexant is an antagonist that specifically targets orexin receptors. Recent clinical studies suggest that Suvorexant is both clinically safe and effective. Quantity and quality of sleep are measured in various ways, yet the consensus points towards Suvorexant's effectiveness in improving sleep time, onset, latency, and quality compared to placebo. In addition to helping improve isolated insomnia, Suvorexant helps improve sleep in patients that have other comorbidities such as obstructive sleep apnea, Alzheimer's disease, dementia, acute stroke, and delirium. While Suvorexant is safe, there are still adverse effects associated with the drug that needs to be considered. The most common adverse effects include dizziness, somnolence, headaches, and cognitive impairment. Insomnia is a major public health concern that affects many people worldwide and has been linked to many adverse health outcomes. While there are existing treatments that target different receptors and pathways of normal sleep induction and maintenance, Suvorexant is a novel drug that targets dual orexin receptors. Its safety and efficacy, mechanism of action, pharmacokinetic parameters, and relative lack of rebound and withdrawal effects render suvorexant a reliable choice for the treatment of insomnia.

Withdrawal of sodium monensin when associated with virginiamycin during adaptation and finishing periods on feedlot performance, feeding behavior, carcass, rumen, and cecum morphometrics characteristics of Nellore cattle.

Feed additives such as monensin (MON) and virginiamycin (VM) are widely used in feedlots diets to maximize rumen fermentation. However, the knowledge about the effects of MON and VM combinations in specifics feedlot periods and the benefits of this association are still unclear. This study aimed to evaluate the effects of withdrawal of MON when associated with VM during the adaptation and finishing periods on feedlot performance of Nellore cattle. The experiment was designed as a completely randomized block replicated six times (four animals/pen) in which 120 Nellore bulls (378.4 ± 24.4 kg) were allocated in 30 pens and fed for 112 days according to the following treatments: (T1) MON during the entire feeding period; (T2) VM during the entire feeding period; (T3) MON+VM during the adaptation period and only VM during the finishing period 1 and 2; (T4) MON+VM during the entire feeding period; (T5) MON+VM during the adaptation and finishing period 1 and only VM during the finishing period 2. After 112 days on feed, no treatment effect was observed for DMI (P ≥ 0.12). However, bulls fed T5 had greater (P = 0.05) final BW and ADG when compared to T1, T2, and T4. Cattle from T3 and T5 groups presented heavier HCW (P = 0.05) than that fed T1, T2, and T4. Nellore bulls fed T1 and T5 had lower (P < 0.01) DMI variation than those receiving T2. The withdrawal of MON when associated with VM during the final third of the feedlot period improved overall final BW, ADG, and HCW when compared to bulls fed either MON or VM, but did not positively impact feedlot performance when compared to cattle that had MON withdrawn at the end of the adaptation period.

Clinical Research Updates.

Clinical Research Updates.

Sex-differences in anxiety, neuroinflammatory markers, and enhanced fear learning following chronic heroin withdrawal

Post-traumatic stress disorder (PTSD) and opioid use disorder (OUD) are comorbid in clinical populations. However, both pre-clinical and clinical studies of these co-occurring disorders have disproportionately represented male subjects, limiting the applicability of these findings. Our previous work has identified chronic escalating heroin administration and withdrawal can produce enhanced fear learning. This behavior is associated with an increase in dorsal hippocampal (DH) interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and glial fibrillary acidic protein (GFAP) immunoreactivity. Further, we have shown that these increases in IL-1β and TNF-α are mechanistically necessary for the development of enhanced fear learning. Although these are exciting findings, this paradigm has only been studied in males. The current studies aim to examine sex differences in the behavioral and neuroimmune effects of chronic heroin withdrawal and future enhanced fear learning. In turn, we determined that chronic escalating heroin administration can produce withdrawal in female rats comparable to male rats. Subsequently, we examined the consequence of heroin withdrawal on future enhanced fear learning and IL-1β, TNF-α, and GFAP immunoreactivity. Strikingly, we identified sex differences in these neuroimmune measures, as chronic heroin administration and withdrawal does not produce enhanced fear learning or immunoreactivity changes in females. Moreover, we determined whether heroin withdrawal produces short-term and long-term anxiety behaviors in both female and males. Collectively, these novel experiments are the first to test whether heroin withdrawal can sensitize future fear learning, produce neurobiological changes, and cause short-term and long-term anxiety behaviors in female rats.

The effect of thyroid hormone withdrawal performed to evaluate the success of I-131 ablation on quality of life and psychological symptoms in female patients with low-risk differentiated thyroid cancer

Aim: There is a need to evaluate the treatment response in patients who have undergone radioiodine treatment (RIT) for differentiated thyroid cancer. Diagnostic tests that are used for this purpose include radioiodine whole-body scan (WBS) and serum thyroglobulin (Tg) measurement, which are most accurate during thyroid-stimulating hormone (TSH) stimulation. However, temporary discontinuation of thyroid hormone therapy to increase TSH (withdrawal) may be associated with the morbidity of hypothyroidism. The study aimed to show the effects of thyroid hormone withdrawal (THW) on quality of life and psychological symptoms in female patients with low-risk, well-differentiated papillary thyroid cancer. Methods: We applied the short form-36 (SF-36) and Symptom Checklist-90-R (SCL-90-R) questionnaires to the patients in the euthyroid state who have referred a median of 9 months (6-13 months) after RIT to perform a dWBS and to evaluate stimulated Tg. We applied the same questionnaire again when thyroid-stimulating hormone (TSH) was &gt; 30 μIU/mL 4 weeks after THW (hypothyroid state). Results: 52 patients were evaluated (median age 48 years, range 23-65 years). There was a statistically significant worsening in anxiety, psychosis, additional items, and general symptoms of the SCL-90-R questionnaire, physical functioning, role limitation due to physical health, energy/fatigue, emotional well-being, social function, and general health change in the SF-36 questionnaire. Conclusions: THW worsened the patients’ psychological symptoms and quality of life. To reduce the side effects of hypothyroidism, treatment response assessment with TSH stimulation should be used only in a selected group of patients with a higher risk of recurrence.

Effect of withdrawal of thyroid hormones versus administration of recombinant human thyroid-stimulating hormone on renal function in thyroid cancer patients

This study was conducted to investigate the effects of thyroid hormone withdrawal (THW) and recombinant human thyroid-stimulating hormone (rhTSH) administration on renal function in patients with thyroid cancer after total thyroidectomy. This study included 202 patients who discontinued thyroid hormone therapy and/or received rhTSH after total thyroidectomy. Creatinine (Cr), blood urea nitrogen (BUN) levels, and estimated glomerular filtration rate (eGFR) were assessed at the following three time points: before thyroidectomy, at least 3 weeks after THW, and 1 day after the second injection of rhTSH. The median serum Cr level was significantly higher following THW compared to that before thyroidectomy (0.95 versus 0.70). In contrast, the median BUN level was significantly lower after THW compared to that before thyroidectomy (9.8 versus 11.3). Over a fifth (22.2%) of patients had abnormal eGFR values after THW, which was significantly greater than that before thyroidectomy. In contrast, renal parameter values after rhTSH administration were not significantly different than those before thyroidectomy. In conclusion, THW affects renal function in patients with thyroid cancer who have undergone total thyroidectomy. However, renal function in such patients is not affected by rhTSH administration.

Effect of cropland withdrawal on soil organic carbon in China, 1990–2018

AbstractSoil organic carbon (SOC) is one of the most important soil attributes responsible for the sustainable maintenance of soil quality. In recent years, cropland withdrawal (CWD) (i.e., conversion into natural landscapes) in China has become a remarkable phenomenon of land use changes, driven by the spontaneous cropland abandonment by rural households and government‐led conversion of cropland to forest and grassland. The CWD may affect SOC content and storage in China. Therefore, this study estimated the variation in SOC caused by CWD between 1990 and 2018 based on the grid data of land use and soil organic matter (SOM). The results showed that CWD had a significant effect on SOC. (1) From 1990 to 2018, the total area of CWD was about 358 × 103 km2, an area that represented about 20% of the total area of cropland in China in 1990. In addition, within the total area of CWD, the proportions represented by the conversion of cropland to forest and grassland were the highest, reaching 58% and 39%, respectively. The former was mainly distributed in the southern part of China, especially in the southwestern mountainous area. The latter was largely concentrated in the northern part of China, especially in the Loess Plateau; (2) From 1990 to 2018, the average SOC content of CWD increased by about 10%, representing an increase of 193 Tg in soil organic carbon storage (SOCS). This is equivalent to six times the carbon emissions from agricultural land in China in 2019; (3) Among eight agricultural regions in China, the middle‐lower Yangtze Plain had the largest area of CWD, which accounted for 19.9% of the total CWD of the whole country.

Neurological Effects of Combining Low Toxic Dose of Tramadol and Nicotine: An Animal Model Evidence of Endoplasmic Reticulum Stress.

Tramadol abuse is a common problem in the Middle East in conjunction with smoking. The current study applied immunohistochemistry, western blot, real-time PCR, and ELISA to test the combination toxicity. Low toxic doses of tramadol induced animal brain cortex inflammation and hippocampus injury. Adding nicotine reverted hippocampus pathological changes without triggering marked brain injury. The expression of CHOP protein with real-time PCR showed mild endoplasmic reticulum stress (ER) in rat's brain. Histological, immunohistochemical, and western blotting analysis of CHOP (CCAAT-enhancer-binding protein homologous protein) and BIP (immunoglobulin heavy chain-binding protein) chaperones demonstrated endoplasmic reticulum stress in the brains of animals. Furthermore, the levels of apoptosis and autophagy markers demonstrated a mild reaction. The blood level of serotonin was high in all study groups, with a marked increase in the combined one. The high serotonin levels in the blood can be critical and associated with a high risk of serious withdrawal and pathological consequences. Serotonin receptor blockers such as olanzapine may increase systemic serotonin levels and need further investigation to utterly pinpoint their roles in managing mood disorders. In conclusion, the combination of tramadol and nicotine is less harmful than expected. However, serious withdrawal effects can occur as a result of high systemic serotonin effects.

Diarrhea after kidney transplantation: A study of risk factors and outcomes.

Diarrhea in kidney transplant recipients (KTRs) can be associated with significant morbidity. We evaluated 198 KTRs for a history of diarrhea post-kidney transplant at a tertiary care center in western India over 1 year. A protocol-based evaluation of diarrhea was done with respect to clinical features, diagnostic evaluation, associated acute allograft dysfunction, and its impact on long-term allograft function. Primary outcomes of interest were: chronic allograft injury (CAI) and the need for mycophenolate mofetil (MMF) withdrawal. We also assessed the effect of MMF withdrawal on the risk of the development of CAI. Eighty-five of 198 (42.5%) recipients experienced diarrhea and a total of 140 diarrheal episodes were evaluated. The mean age of these 85 recipients was 38 ± 12 years and 72 (84.7%) were males. 73 of 85 recipients were on MMF at the time of diarrhea and in 35 (48%) of them MMF withdrawal was needed for chronic and persistent symptoms. Diarrhea was attributed to infective etiologies in 90 of 140 (64.2%) cases. Among the microbiologically confirmed infective diarrheal episodes, giardia and cryptosporidium were the common pathogens in 11/28 (39%) and 6/28 (21.4%) episodes respectively. One hundred and twenty-eight episodes out of 140 (91.4%) episodes were complicated by acute allograft dysfunction. Forty-one of 85 recipients (48.2%) developed chronic allograft injury and 12 (14.1%) developed allograft rejection (acute and/or chronic). Probability of chronic allograft injury was higher in those with MMF withdrawal. Diarrhea post-kidney transplant adversely affects graft function, especially after MMF withdrawal.

A Clinical Study of Pippalyadi gana kashaya’efficacy in Amavata (R.A)

Amavata is among the most common health complaints in medical practice specially In females and most prevalent of all musculoskeletal disorders. Recent studies have shown that womern are three times more affected that men from amavata (RA).It is the most common form of chronic inflammation affecting approximately 1% of adult population.In this modern era of improper lifestyle and unstable diet pattern, it is the most neglected part of life where one gives least importance to the timing, duration and quality of dietary habit and pattern. Mandagni plays an important role in causing ama formation and it is sensitive to disturbances due to many internal and external influences like diet and enviormental factors.In modern science, amavata is correlated with Rheumatoid Arthritis (RA).it is a chronic autoimmune inflammatory systemic disease.Modern DMARDs,Steroids are immune depressent due to its patients have hazardous withdrawal effects.

Implementing gradual, hyperbolic tapering of long-acting injectable antipsychotics by prolonging the inter-dose interval: an in silico modelling study.

Gradual, hyperbolic tapering has been proposed as a method to reduce the risk of withdrawal effects and potential relapse of an underlying condition by minimising disruption of existing equilibria. We applied hyperbolic tapering principles in silico to long-acting aripiprazole to generate regimens for withdrawal in clinical practice. We derived thresholds for taper rates using existing studies and consensus. Using pharmacokinetic data for aripiprazole long-acting injectable antipsychotic (ALAI), we conducted in silico modelling to examine the impact of abrupt cessation of long-acting injectable antipsychotic (LAI) medication and the effect of prolonging inter-dose interval on plasma aripiprazole levels and consequent D2 occupancy. We also modelled transitions from LAI medication to oral medication. Regimens were designed to afford a rate of reduction between 5 and 12.5 percentage points of D2 occupancy per month. Abrupt discontinuation of ALAI was shown to lead to a maximal D2 occupancy reduction of 16.8 percentage points per month; prolongation of the inter-dose interval of ALAI produced a slower reduction. Specifically, hyperbolic tapering was afforded by prolongation of a 400 mg ALAI inter-dose interval from 4 to 7 weeks, before reducing the dose to 300 mg ALAI. This could then be administered at up to 4-week (for 6% maximal D2 occupancy change), 6-week (9% change) or 7-week (11% change) intervals. Switching to oral medication - 5, 2.5 and 1.25 mg for the three regimens, respectively - is required for ALAI to complete full cessation to prevent too rapid a reduction in D2 occupancy. Oral medication should probably be maintained at a consistent dose for 3-6 months before further reductions to account for residual LAI being concurrently eliminated. Hyperbolic dose tapering is possible with ALAI through prolongation of the inter-dose interval and may reduce the risk of relapse compared to abrupt discontinuation of LAI medication.

Feasibility study of a Behavioural Intervention for Opioid Reduction (BIOR) for patients with chronic non-cancer pain in primary care: a protocol

IntroductionAround 30%–50% of adults suffer moderate to severe chronic pain not caused by cancer. Significant numbers are treated with opioids which over time may cease to be effective and produce...

Chocolate amargo (70% cacau) reduz fissura em tabagistas com comorbidades cardiovasculares graves sem interferir nas medidas antropométricas

ABSTRACT Objective: Analyze craving in smokers with cardiovascular comorbidities submitted to a nutritional approach. Methods: Two groups were randomized and submitted to clinical intervention (n = 32): Group 1 (G1, n = 15): ingested 40 g of chocolate containing 70% cocoa/day and behavioral intervention for smoking cessation for one month; Group 2 (G2, n = 17): control group, only behavioral intervention. Questionnaire of Smoking Urges-Brief (QSU-Brief) - Brazil version measured total craving and its factors. Anthropometric measurements verified the nutritional interference of the procedure and the serum assessment verified the interference of inflammatory processes related to smoking. The study was registered on the Brazilian Registry of Clinical Trials (ReBEC): RBR-83jr3. Results: After one month, compared to the initial evaluation, the G1 reduced the craving evaluated by the QSU-Brief and its Factors 1 and 2. Total QSU-Brief: 44.27 ± 15.82 x 27.00 ± 18.03 (p = 0.008); Factor 1: 21.90 ± 7.70 x 12.90 ± 8.87 (p = 0.006); Factor 2: 11.90 ± 6.30 x 7.00 ± 6.63 (0.007). G2 showed a reduction in total QSU-Brief and Factor 1, but not in Factor 2. QSU-Brief total 28.17 ± 17.24 x 19.52 ± 9.50 (p = 0.049); Factor 1: 14.47 ± 8.74 x 9.23 ± 6.11 (p = 0.046). Serum levels of cortisol, leptin, serotonin, C-Reactive Protein (CRP) and insulin did not show differences (p &gt; 0.05). No anthropometric differences were found. Conclusion: The results demonstrate that daily consumption of chocolate for one month (70%) reduced craving in smokers at the beginning of treatment. Chocolate potentiated the well-known effect of behavioral counseling on Factor 1 (pleasurable drug effects) and also interfered with factor 2 (unpleasant withdrawal effects).