Effects Of Pharmacological Therapy Research Articles

Effects of pharmacological therapy on sleep quality in a postoperative setting: A systematic review of randomized controlled trials

Abstract Background and Aims: Postoperative sleep disturbances are associated with delayed recovery and increased incidences of complications. This systematic review aims to determine the impact of perioperative pharmacological therapies on postoperative sleep quality in the hospital. Material and Methods: We searched MEDLINE, MEDLINE ePubs and In-Process Citations (Daily), Embase Classic + Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and PubMed for randomized controlled trials (RCTs) from inception to May 2022, with continued literature surveillance until August 2023. Studies included consisted of noncardiac surgical patients aged ≥18 years with postoperative sleep in the hospital. The primary outcome was improvement in postoperative sleep outcomes such as sleep quality, duration, efficiency, architecture, and insomnia ratings after pharmacological treatment. Additional outcomes included postoperative pain scores and opioid consumption. Results: The search strategy yielded 21 studies (n = 3276), and 18 reported improved sleep outcomes using eight validated sleep measurement tools. Eight of 10 studies using dexmedetomidine via patient-controlled analgesia or intravenous infusion reported better sleep quality versus controls. Opioids (nalbuphine, tramadol plus sufentanil), nonopioids (zolpidem, midazolam, pregabalin), propofol total intravenous anesthesia (TIVA), S-ketamine, and ropivacaine nerve blocks were superior to controls in enhancing postoperative sleep quality. Eleven studies (52%) which included the combination of dexmedetomidine with opioids reported concurrent improvements in postoperative pain and sleep. Dexmedetomidine also decreased postoperative opioid analgesia consumption. Conclusions: Evidence for the effects of perioperative pharmacological approaches on postoperative sleep are limited. High-quality RCTs of adequate power and methodology on the effects of pharmacology interventions on postoperative sleep are warranted.

Optimal Heart Failure Medical Therapy and Mortality in Survivors of Cardiogenic Shock: Insights From the FRENSHOCK Registry.

The effects of pharmacological therapy on cardiogenic shock (CS) survivors have not been extensively studied. Thus, this study investigated the association between guideline-directed heart failure (HF) medical therapy (GDMT) and one-year survival rate in patients who are post-CS. FRENSHOCK (French Observatory on the Management of Cardiogenic Shock in 2016) registry was a prospective multicenter observational survey, conducted in metropolitan French intensive care units and intensive cardiac care units. Of 772 patients, 535 patients were enrolled in the present analysis following the exclusion of 217 in-hospital deaths and 20 patients with missing medical records. Patients with triple GDMT (beta-blockers, renin-angiotensin system inhibitors, and mineralocorticoid receptor antagonists) at discharge (n=112) were likely to have lower left ventricular ejection fraction on admission and at discharge compared with those without triple GDMT (n=423) (22% versus 28%, P<0.001 and 29% versus 37%, P<0.001, respectively). In the overall cohort, the one-year mortality rate was 23%. Triple GDMT prescription was significantly associated with a lower one-year all-cause mortality compared with non-triple GDMT (adjusted hazard ratio 0.44 [95% CI, 0.19-0.80]; P=0.007). Similarly, 2:1 propensity score matching and inverse probability treatment weighting based on the propensity score demonstrated a lower incidence of one-year mortality in the triple GDMT group. As the number of HF drugs increased, a stepwise decrease in mortality was observed (log rank; P<0.001). In survivors of CS, the one-year mortality rate was significantly lower in those with triple GDMT. Therefore, this study suggests that intensive HF therapy should be considered in patients following CS.

COVID-19 and Pregnancy: An Updated Review about Evidence-Based Therapeutic Strategies.

The COVID-19 pandemic posed a significant challenge for clinicians in managing pregnant women, who were at high risk of virus transmission and severe illness. While the WHO declared in May 2023 that COVID-19 is no longer a public health emergency, it emphasized that it remains a global health threat. Despite the success of vaccines, the possibility of new pandemic waves due to viral mutations should be considered. Ongoing assessment of the safety and effectiveness of pharmacological therapies is crucial in clinical practice. This narrative review summarizes the evidence-based therapeutic strategies for pregnant women with COVID-19, considering over three years of pandemic experience. The review discusses the safety and effectiveness of various drug regimens (antivirals, anticoagulants, corticosteroids, immunoglobulins, monoclonal antibodies, and therapeutic gases) and procedures (prone positioning and extracorporeal membrane oxygenation). Drugs with contraindications, inefficacy during pregnancy, or unknown adverse effects were excluded from our evaluation. The aim is to provide healthcare professionals with a comprehensive guide for managing pregnant women with COVID-19 based on lessons learned from the pandemic outbreak.

Management of chronic non-cancer pain in primary care.

Management of chronic non-cancer pain in primary care.

Abstract 10020: Statins Are Associated With Lower Adjusted In-Hospital Mortality in Patients With COVID-19

Introduction: There are more than 250,000 publications on COVID-19. However, there is incomplete information on the effects of pharmacologic therapy in hospitalized patients. Hypothesis: We hypothesize that use of statin therapy will decrease all-cause mortality in patients hospitalized for COVID-19. Methods: A dataset of 1,064 patients with first admission for COVID-19 was used in this study. Predictive models using logistic regression, support-vector machines, and neural networks were used to predict all-cause in-hospital death. Results: In-hospital case fatality of patients admitted with COVID-19 was 17.5% and was higher in the first week after admission, among older individuals, those with higher body weight, and those with longer length of stay. The use of statins was associated with lower in-hospital mortality after adjustment for other medications and the factors mentioned above. The beneficial effect of statins may not be due to their effects on lipids but is probably due to their pleiotropic antioxidant effects. Using logistic regression, the duration of therapy was positively related to the beneficial effect of statins (p=0.0002). Conclusions: In conclusion, the in-hospital case fatality of COVID-19 patients was lower in patients receiving statins after adjustment for demographics, other medications, body weight, and length of stay (Figure).

Medications used in paediatric intensive care by continuous infusion: Do the technical aspects of the package inserts corroborate scientific evidence?

Hospitalized paediatric patients are three times more likely to experience medication errors with the potential to cause harm, when they are compared to adults. The lack of research in paediatrics, difficulties that are derived as indications and the parameters of safety and effectiveness of pharmacological therapy in children. To analyse whether the technical and legal aspects of the package insert for medicines used in paediatric intensive care units (ICU) using a continuous infusion (CI) pump corroborate the recommendations of clinical protocols and legal provisions. A documentary study, in which technical and legal information contained in the package inserts of medications commonly used via CI in neopediatric ICUs was analysed. The consultation of the medication package insert was carried out through the electronic portal of the National Health Surveillance Agency (Agência Nacional de Vigilância Sanitária - ANVISA). Information on the use of medications in the neonatal and paediatric populations via CI was sought in the medication package insert. To analyse the legal aspects, ANVISA's RDC no. 47/2009 was used. In order to compare the technical information, the Micromedex NeoFax®, Micromedex Paediatrics®, and Lexicomp® databases were consulted. Of the 13 medications analysed, 46% (n=6) had some non-compliance with RDC 47/2009. Only 46% (n=6) of the medications are indicated for paediatric use and only the medication package insert for midazolam (7.7%) contained the information considered essential for use via CI in paediatrics. This is an innovative study that identifies the weaknesses of the medication package inserts for medications used by CI in paediatric ICUs. Failure to comply with legal recommendations can make medication administration difficult and increase the probability that errors will occur; and the absence of specific technical information can make care difficult and compromise patient safety. It is important that there is supervision by regulatory agencies and the contribution of health professionals so that non-conformities are reported and corrected, to guarantee safe care for paediatric patients in intensive care.

Сравнительное исследование эффективности препарата Прогепар у пациентов с неалкогольным стеатогепатитом

Неалкогольная жировая болезнь печени (НАЖБП) является одним из самых распространенных заболеваний печени в развитых странах. В среднем ее частота достигает 20 %. У части пациентов ­НАЖБП протекает с наличием воспаления, вакуолизации гепатоцитов и последующим развитием фиброза и цирроза. Такой вариант течения НАЖБП называют неалкогольным стеатогепатитом (НАСГ). Пациенты с НАСГ подвержены более высокому риску развития осложнений, например возникновению гепатоцеллюлярной карциномы или варикозного расширения вен пищевода. Специфическая терапия НАСГ на сегодняшний день еще не разработана. Основные рекомендации для пациентов заключаются в изменении стиля жизни, что имеет определенную эффективность в снижении уровня стеатоза и активности воспаления. Однако быстро прогрессирующее течение НАСГ не всегда возможно контролировать одним только снижением калорийности диеты и увеличением уровня физической активности. Для лечения пациентов с НАСГ также используется неспецифическая терапия, которая способна замедлять прогрессирование заболевания и снижать уровень воспаления. Так как основным механизмом патогенеза НАСГ является оксидативный стресс, исследователи активно изучают действие различных антиоксидантов и их комбинаций. На сегодняшний день представлено большое количество результатов исследований подобных препаратов. Существенным ограничением большой части данных исследований является отсутствие тщательного мониторинга комплайенса и длительности выполнения пациентами рекомендаций по изменению образа жизни. Ведь в данной ситуации особый интерес должны представлять именно те пациенты, у которых высокая степень активности НАСГ сохраняется, несмотря на строгую приверженность к рекомендациям по изменению стиля жизни. В связи с этим требуется проведение дополнительных исследований по оценке эффективности фармакологической терапии у пациентов с НАСГ на фоне длительного изменения образа жизни. В этой статье мы приведем описание и результаты одноцентрового контролируемого исследования по оценке эффективности препарата Прогепар у пациентов с НАСГ с персистенцией активности воспалительного процесса на фоне модификации образа жизни.

Effects and safety of high-frequency repetitive transcranial magnetic stimulation in trigeminal neuralgia

Background. Trigeminal neuralgia is the most common cause of facial pain. Insufficient effectiveness and frequent side effects of pharmacological therapy, as well as the risk of complications of invasive neurosurgical manipulations, determine the relevance of the development of new treatment approaches, one of which is repetitive transcranial magnetic stimulation (rTMS).The aim of the study is to determine the effectiveness of high‑frequency rTMS of the primary motor cortex in terms of pain intensity and quality of life in patients with trigeminal neuralgia, as well as to assess the safety of the stimulation course.Materials and methods. This open‑label non‑randomized single arm study included 20 patients with classic trigeminal neuralgia according to the ICHD‑3 classification. All patients received 10 sessions of navigated high‑frequency rTMS of the primary motor cortex (hand area) of the hemisphere, contralateral to pain syndrome localization. The maximum and average pain intensity was assessed before and after 10 rTMS sessions according to a Numeric Pain Rating Scale (NPRS), as well as quality of life was measured according to the SF‑36 questionnaire, and the severity of affective disorders according was measured to the Beck Depression Inventory (BDI). Safety and tolerability of rTMS were assessed using self‑developed questionnaires for adverse events that occurred during stimulation and within 24 hours after the previous session.Results. A significant decrease in the maximum (p = 0.01) and average (p &lt;0.01) pain intensity was shown after 10 sessions of rTMS. In 50 % of patients, the maximum pain intensity decreased by more than 30 % vs baseline. Significant changes were detected in the physical health measure of SF‑36 quality of life questionnaire, particularly, in the “bodily pain” domain, as well as in such aspects of the mental health measure as “vitality” and “social functioning”. The severity of affective disorders did not change significantly. A favorable profile of rTMS tolerability has been demonstrated.Conclusion. An open‑label study showed the possible effectiveness of 10 sessions of high‑frequency rTMS to reduceт the pain intensity in patients with trigeminal neuralgia. For the first time, the spectrum of adverse events both during stimulation and within a day after its completion was systematically analyzed.

Headache changes after kidney transplant

Headache is considered as a possible complication of dialytic treatment in chronic kidney disease (CKD). The aim of this study was to evaluate possible change in headache characteristics after kidney transplantation in patients with CKD. During a 1-year period, we enrolled 110 subjects submitted to a kidney transplant in the previous 5years. Headache characteristics before and after the transplant were investigated by a specific questionnaire. Possible effects of pharmacological therapies were also evaluated. 65.5% of patients complained of headache before the transplant (38.2% migraine and 14.5% dialysis headache). After transplant, 53.6% of patients reported changes in headache characteristics. In particular, 27.3% of the patients had a complete resolution, 19.1% presented a headache improvement and 7.2% showed a worsening. In both migraine and dialysis headache subgroups, steroids, beta-blockers and calcium channel blockers were associated with a significant improvement of headache. Kidney transplantation seems to impact significantly headache frequency and severity in patients with CKD. A careful evaluation and use of targeted treatments could improve both patients' compliance to therapies and quality of life.

Особенности клеточной регуляции нижних мочевыводящих путей как причина гиперактивности мочевого пузыря и снижения эффективности медикаментозной терапии

Overactive bladder (OAB) is a polyetiological nosology. Its symptoms are often characterized not only with detrusor hyperactivity, but also with the increased sensitivity of afferent fibers, which is clinically manifested as urgency. In addition, the disorders at the level of receptors expression and the synthesis of mediators lead to the development of bladder pain syndrome (BPS), which also significantly reduces the quality of life of patients. In recent years, the experimental animal studies achieved significant progress in understanding of the pathogenesis of lower urinary tract dysfunction. In particular, the broad understanding of the sensor properties of urothelium was obtained, which significantly increased the popularity of the urothelial theory of the development of idiopathic detrusor hyperactivity, as well as hypersensitivity and bladder pain. According to this theory, the pathological release of biologically active substance in the transitional epithelium in response to an extension of the bladder wall leads to clinical manifestations of the described conditions. In addition, due to the studies of the properties of receptors, ion channels, and mediators, the suggestion about the reduced efficiency of muscarinic receptor antagonists have been made in a large number of patients. Besides the acetylcholine control of the lower urinary tract, more and more attention is paid to other significant mechanisms of pathological conditions. The purpose of this part of the lecture is to systematize the available materials of basic research on the functioning of the lower urinary tract at the cellular level, as well as the mechanisms of action and questions of the effectiveness of pharmacological therapy for urinary disorders.

Nutritional Status in Patients with Probable Alzheimer's Disease: Effect of Rivastigmine.

Altough disease-modifying factors such as malnutrition and diet have been associated with Alzheimer's disease (AD), little is known about the effects of pharmacological therapies on the nutritional status of AD patients. To evaluate the nutritional status, prealbumin, and albumin serum levels and several anthropometric measurements in patients with probable moderate-stage AD, with and without rivastigmine drug treatment. A cross-sectional study. 34 patients were included, 17 with rivastigmine treatment and 17 without pharmacological treatment, over 60 years of both sexes. The nutritional status was evaluated using the Mini Nutritional Assessment (MNA). Albumin and prealbumin (transthyretin) levels and anthropometric evaluation were assessed using standard methods. A polarity of malnutrition was detected in the untreated group. According to the MNA survey, the risk of malnutrition is higher without rivastigmine treatment (p = 0.0001). There are a less loss of appetite, less psychological stress, greater mobility and independence in those patients receiving rivastigmine (p = 0.003, 0.008, 0.016 and 0.018, respectively). The body mass index does not show a statistical difference, however, categorizing it for older adults, this index was improved in those receiving rivastigmine (p = 0.016). The serum levels of albumin and prealbumin showed no significant statistical difference between the groups. Rivastigmine treatment shows a protective effect on malnutrition in patients with moderate-stage AD.

Clinical significance of bone marrow edema in the late stages of osteoarthritis

The use of magnetic resonance imaging (MRI) for osteoarthritis made it possible to simultaneously detail the state of cartilage, subchondral bone, menisci, ligaments, and synovial membrane. In some studies, a correlation was found between bone marrow edema (BME) and the intensity of the pain syndrome, the progression of OA and the risk of total knee replacement. In other studies, these data were not confirmed. It has been suggested that BME in OA, leading to debilitating pain, is not associated with trauma and is determined by an increase in extracellular fluid. Analysis of MRI images of 80 patients with 1-3 stages of knee osteoarthritis revealed a statistically significant relationship between the presence of bone marrow edema and the thickness of the cartilage of the femur and tibia, rupture and degradation of the medial menisci, the presence of Baker cysts and thickening of the synovial membrane. No reliable relationship was found with the presence and severity of synovitis. A review of data on the effect of various methods of conservative therapy on bone marrow edema in osteoarthritis is presented. The effect of anti-osteoporotic drugs, prostacyclin, Pentosan polysulfate sodium chondroitin sulfate is considered. Thus, OKM is of interest both in terms of the pathogenesis of OA and as an indicator of the effectiveness of the treatment of OA. Our data demonstrate a high incidence of OKM in the late stages of OA. The effect of pharmacological therapies on OKM requires further study.

Metabolic Syndrome and Pharmacological Treatment Measures

Metabolic syndrome is a set of several different pathological conditions and risk factors that are often the cause of many unwanted cardiac and cerebrovascular occurrences. It is highly represented around the world, especially in countries with excessive and inadequate nutrition, insufficient physical activity of the population and obesity, with a constant growth trend. The work included 1052 patients with HTA of which DM was 309 (29.4%). Out of the total number of 1052 patients with metabolic syndrome there were 675 (64.2%) patients. Observing certain determinants of the metabolic syndrome HTA was present in all observed patients. Low HDL cholesterol values were found in 503 (74.5%) patients and the lowest incidence was hyperglycaemia (252 mg / 37.3%). Implemented pharmacological treatment measures have led, in most patients, the blood pressure to optimal or normal. The effect of pharmacological therapy on glycaemic value in patients with metabolic syndrome led to the normalization of glycaemia in majority of patients. The results achieved have improved the quality of life of patients and motivated them for further treatment.

Positive Effects of Heme Oxygenase Upregulation on Adiposity and Vascular Dysfunction: Gene Targeting vs. Pharmacologic Therapy.

Objective: Heme oxygenase (HO-1) plays a critical role in adipogenesis and it is important to understand its function in obesity. Many studies have shown that upregulation of HO-1 can affect the biologic parameters in obesity-mediated diabetes, hypertension and vascular endothelial cell function. Thus, we aimed to explore the hypothesis that upregulation of HO-1, using a pharmacologic approach as well as gene targeting, would improve both adiposity and endothelial cell dysfunction by direct targeting of endothelial cells. Our second aim was to compare the short-term effect of a HO-1 inducer, cobalt-protoporphrin IX (CoPP), with the long-term effects of gene targeted therapy on vascular and adipocyte stem cells in obese mice. Method: We examined the effect of CoPP on fat pre-adipocytes and mesenchymal stem cells (MSC) in mice fed a high-fat diet (HFD). We also used a lentiviral construct that expressed heme oxygenase (HO-1) that was under the control of an endothelium specific promoter, vascular endothelium cadherin (VECAD) heme oxygenase (VECAD-HO-1). We targeted endothelial cells using vascular endothelium cadherin/green fluorescent protein fusion construct (VECAD-GFP) as the control. Conditioned media (CM) from endothelial cells (EC) was added to fat derived adipocytes. Additionally, we treated renal interlobar arteries with phenylephrine and dosed cumulative increments of acetylcholine both with and without exposure to CoPP. We did the same vascular reactivity experiments with VECAD-HO-1 lentiviral construct compared to the control. Results: CoPP improved vascular reactivity and decreased adipogenesis compared to the control. MSCs exposed to CM from EC transfected with VECAD-HO-1 showed decreased adipogenesis, smaller lipid droplet size and decreased PPAR-γ, C/EBP and increased Wnt 10b compared to the control. HO-1 upregulation had a direct effect on reducing adipogenesis. This effect was blocked by tin mesoporphrin (SnMP). EC treated with VECAD-HO-1 expressed lower levels of ICAM and VCAM compared to the control, suggesting improved EC function. This also improved ACH induced vascular reactivity. These effects were also reversed by SnMP. The effect of viral transfection was much more specific and sustained than the effects of pharmacologic therapy, CoPP. Conclusion: This study demonstrates that a pharmacological inducer of HO-1 such as CoPP improves endothelial cell function while dampening adipogenesis, but long-term HO-1 expression by direct targeting of endothelial cells by gene transfer therapy may offer a more specific and ideal solution. This was evidenced by smaller healthier adipocytes that had improved insulin sensitivity, suggesting increased adiponectin levels. HO-1 upregulation reestablished the “crosstalk” between perivascular adipose tissue and the vascular system that was lost in the chronic inflammatory state of obesity. This study demonstrates that gene targeting of EC may well be the future direction in treating obesity induced EC dysfunction, with the finding that targeting the vasculature had a direct and sustained effect on adipogenesis.

Drug Use, a Valid Indicator of Effective Implementation of Medical Protocols

The effectiveness of pharmacological therapies is supported and guaranteed by medical protocols, which are the result of long-lasting experiments and scientific research, of course adapted to the level of competence and functional capacity of the healthcare provider. Besides pharmacological effectiveness, the therapeutic regimens should be evaluated from the point of view of economic efficiency, by assessing the financial impact of drug consumption, in correlation with other indicators specific to medical management. A retrospective comparative study of drug used in a surgical section with a capacity of 25 beds, from a county hospital is described. Study objective was to identify the relationship of influence and determination between costs with drugs and other economic and financial indicators and the use of services; objectively evaluate the effectiveness of the protocols used to limit the development of antibiotic resistance, avoiding polypharmacy and improving costs related to drug use, but especially to determine the existence of deviations from these and generating causes. The implementation of medical protocols has led to a decrease in drug costs. Tracking drug use is an effective tool to increase the quality of medical services by avoiding polypharmacy, therapeutic errors and preventing the development of antibiotic resistance. All these aspects are supported by the implementation of medical protocols and, thus, drug use can be appreciated as a valid indicator of their effectiveness and efficiency.

Postural orthostatic tachycardia syndrome: clinical presentation, aetiology and management.

Postural orthostatic tachycardia syndrome (POTS) is a variant of cardiovascular autonomic disorder characterized by an excessive heart rate increase on standing and orthostatic intolerance. POTS affectsyounger individuals 15-45years old with a distinct female predominance (≈80%). The prevalence ranges between 0.2% and 1.0% in developed countries. The onset of POTS is typically precipitated by immunological stressors such as viral infection, vaccination, trauma, pregnancy, surgery or psychosocial stress. The most common complaints are dizziness, weakness, rapid heartbeat and palpitation on standing. Moreover, patients often report physical deconditioning and reduced exercise capacity as well as headache, 'brain fog', dyspnoea, gastrointestinal disorders and musculoskeletal pain. The aetiology of POTS is largely unknown and three main hypotheses include an autoimmune disorder, abnormally increased sympathetic activity and catecholamine excess, and sympathetic denervation leading to central hypovolaemia and reflex tachycardia. The golden standard for POTS diagnosis is head-up tilt test with a non-invasive beat-to-beat haemodynamic monitoring. Although long-term prognosis of POTS is poorly explored, around 50% of patients spontaneously recover within 1-3years. After the diagnosis has been established, patient should be thoroughly educated about non-pharmacological measures alleviating the symptoms. Exercise training may be very effective and counteract deconditioning. In more symptomatic patients, different drugs directed at controlling heart rate, increasing peripheral vasoconstriction and intravascular volume can be tested. However, the overall effects of pharmacological therapy are modest and the most affected patients remain handicapped. Future efforts should focus on better understanding of POTS pathophysiology and designing randomized controlled trials for selection of more effective therapy.

TDCS effects on cortical excitability in multiple sclerosis fatigue

Objectives Fatigue could affect up to 90% of patients with multiple sclerosis (MS) [1] . Facing the modest benefits and numerous side effects of pharmacological therapies, transcranial direct current stimulation (tDCS) has recently emerged as an appealing tool to treat several neuropsychiatric complaints, including MS fatigue [3] . Previous tDCS protocols did not assess long-term effects of tDCS on MS fatigue, neither did they investigate its potential mechanism of action in this context. Methods We hereby present the case of a 37-year-old MS patient who sought medical attention for debilitating fatigue. The patient has previously participated in a sham-controlled tDCS trial and was found to be among responders to real but not sham stimulation [3] . At presentation, he did not have secondary causes of fatigue. The protocol lasted for 9 weeks (5 consecutive daily sessions in week 1; 4 sessions per week in week 2 and 3; 3 sessions in week 4; 2 sessions in week 5; 1 session in week 6 and a follow-up in week 9). We tested tDCS effects over fatigue as well as other neuropsychological symptoms. Cortical excitability measures were obtained at baseline [2] and then at the end of week 1, week 3 and week 6. Results tDCS resulted in a significant improvement of fatigue which was obtained after the first week, but the most important anti-fatigue effects were documented after week 5. This effect was paralleled by amelioration of cognition and mood scores as well as changes in cortical excitability parameters (increase in short-interval intracortical inhibition and decrease in short-interval intracortical facilitation). Conclusion This is the first report that presents long-term assessment of tDCS effects in the context of fatigue and other MS-related symptoms. Left prefrontal tDCS appears to improve MS fatigue and seems to have a modulatory effect on inhibitory and facilitatory intracortical circuits.

Pharmacotherapies for fatigue in chronic liver disease (CLD): a systematic review and meta-analysis (protocol)

BackgroundThis is the protocol for a systematic review (and meta-analysis) of an intervention. The primary objective of this systematic review will be to assess the benefits and harms of pharmacological therapies (pharmacotherapies) for the management of fatigue in adults with CLD of any etiology. The effects of pharmacological therapies on fatigue in CLD will be compared against those of placebo, no intervention, or non-pharmacological interventions. Specifically, this review will examine whether pharmacological therapies improve CLD-associated fatigue, and if they do, what key elements are associated with their effectiveness. The results of this systematic review will assist clinicians, policy-makers, researchers, and people with CLD in decision-making on how best to manage fatigue and its associated symptoms.MethodsMEDLINE, SCOPUS, EMBASE, EU Clinical Trials Register, WHO International Clinical Trials Registry Platform, CENTRAL (The Cochrane Library), ClinicalTrials.gov, reference lists of articles and conference proceedings will be searched for relevant studies. No language or date restrictions will be applied. Eligible studies will include adults with CLD of any etiology. Included studies will be randomized controlled trials. From included studies, data on participant characteristics, study design, setting, research ethics compliance, and intervention outcomes will be extracted. Risk of bias in included studies will be assessed using the Cochrane Risk of Bias Tool. A random-effects meta-analysis will be conducted. If substantial or considerable levels of heterogeneity are detected, analysis will be limited to a narrative synthesis.DiscussionThis systematic review will examine the effectiveness of pharmacological therapies on fatigue reduction in people with CLD. Such therapies may be more effective than non-pharmacological interventions in treating fatigue symptoms in CLD. Evidence derived from the findings of this study will guide future practice, policy, and research.Systematic review registrationPROSPERO, CRD42017076957

Morphological changes in the bladder of spinal cord injured patients affected by detrusor overactivity

It is well known that the neurogenic detrusor over activity (NDO) represents one of the most disabling condition in patients with suprasacral spinal cord injury (SCI). The treatments with anti-muscarinic drugs and botulinum toxin local injection show a temporary efficacy in controlling the bladder impairment; after that, the typical NDO urodynamical signs, such as reduced bladder capacity, high intravesical pressure with potentially upper urinary tract damage, reoccurs (1). At this stage, these patients can choice to perform a cystectomy with or without bladder augmentation. In order to investigate the pathological remodelling of bladder wall, we collected bladder specimens from SCI patients underwent to cystectomy. Control specimens were obtained from patients underwent to surgery for bladder cancer. Data obtained from clinical records, histology and immunohistochemistry were paralleled. The group of SCI patients were uniform on the basis of age, legion level, previous therapies and urodinamic parameters. These latter indicated a strong reduction of bladder capacity and reflex volume. Histologically, SCI bladder showed an important inflammatory state with oedema and congestive blood vessels in the submucosa and lamina propria; in the most serious cases, phlogosis was present also in the detrusor and characterized by eosinophilic infiltrate. Moreover, an important alteration of smooth muscle cell organization was appreciable. The immunohistochemical experiments demonstrated a redistribution of alpha-smooth muscle actin filaments (αSMA) in the smooth muscle cells associated with an altered distribution of caveolin 1 (cav1). Present findings show consistent alteration of the contractile structures and molecules that might explain the recurrence of NDO sign and symptoms in SCI patients. It remains to understand whether these changes are side effects of pharmacological therapies or instead the typical evolution of the disease that the therapies, eventually, postponed.

Clinical Weighting of Drug-Drug Interactions in Hospitalized Elderly.

Adverse drug reactions impact on patient health, effectiveness of pharmacological therapy and increased health care costs. This investigation intended to detect the most critical drug-drug interactions in hospitalized elderly patients, weighting clinical risk. We conducted a cross-sectional study between January and April 2014; all patients 70years or older, hospitalized for >24hr and prescribed at least one medication were included in the study. Drug-drug interactions were estimated by combining Stockley's, Hansten and Tatro drug interactions. Drug-drug interactions were weighted using a risk-analysis method based on failure modes, effects and criticality analysis. We calculated a criticality index for each drug involved in the drug-drug interactions based on the severity of the interaction mechanism, the frequency the drug was involved in drug-drug interactions and the risk of drug-drug interactions in patients with impaired renal function. The average number of drugs consumed in the hospital was 6±2.69, involving 160 active ingredients. The most frequent were as follows: Furosemide, followed by Enalapril. Of drug-drug interactions, 2% were classified as contraindicated, 14% advised against and 83% advised caution during the hospital stay. Thirty-four drug-drug interactions were assessed, of which 23 were pharmacodynamic drug-drug interactions and 12 were pharmacokinetic drug-drug interactions (1 was both). The clinical risk calculated for each drug-drug interaction included heparins+non-steroidal anti-inflammatory drugs (NSAIDs) or Digoxin+Calcium Gluconate, cases which are pharmacodynamic drug-drug interactions with agonist effect and clinical risk of bleeding, one of the most common clinical risks in the hospital. An index of clinical risk for drug-drug interactions can be calculated based on severity by the interaction mechanism, the frequency that the drug is involved in drug-drug interactions and the risk of drug-drug interactions in an elderly patient with impaired renal function.