Placebo Medication Research Articles

Clinical course and radiographic resolution of pneumonia in dogs treated with a shorter versus longer course of antimicrobials: a randomized, double-masked, placebo-controlled study.

To describe clinical and radiographic outcomes in dogs with uncomplicated pneumonia receiving a shorter (2-week) versus longer (4-week) duration of antimicrobial therapy. 30 client-owned dogs with radiographic evidence of pneumonia. Dogs were randomly assigned to either a 2-week course of antimicrobials followed by a 2-week course of placebo medication (2-week group) or a 4-week course of antimicrobials (4-week group). All study investigators and owners were masked to the treatment group. Dogs were reevaluated at 12 ± 2 days and again at 28 ± 2 days for a physical examination and thoracic radiography. Standard documentation at visits included owner-reported clinical signs, nurse-acquired history, the clinician's physical examination, the number of affected lung lobe segments, and the global radiographic severity scores assigned. Outcomes investigated included the persistence of clinical and radiographic signs of pneumonia. 28 dogs (93.3%) experienced complete resolution of clinical signs by the first visit, and no dogs in either group experienced relapse of clinical signs during the study period. Eighteen of 30 dogs (60%) and 25 of 30 dogs (83%) experienced complete resolution of radiographic lesions at the first and second study visits, respectively. The remaining 5 dogs (17%) had either stable (4 dogs) or continued (1 dog) improvement in radiographic lesions. Resolution of clinical and radiographic signs followed similar courses in dogs with uncomplicated pneumonia receiving a 2-week course of antimicrobials compared to a 4-week course. Clinical signs may be more useful for guiding discontinuation of antimicrobial therapy for pneumonia than radiographic signs.

Does Cannabis-based Medicine Improve Pain and Sleep Quality in Patients With Traumatic Brachial Plexus Injuries? A Triple-blind, Crossover, Randomized Controlled Trial.

After traumatic brachial plexus injuries, despite treatment with appropriate medications, some patients experience uncontrollable pain, which can be devastating. Cannabis-based medicine is considered to have pain-relieving benefits in this situation, but the evidence is limited. Is cannabis-based medicine effective compared with the placebo in (1) reducing pain (measured by the VAS for pain) and neuropathic pain (measured by the DN4 questionnaire), and (2) improving sleep quality (measured by the VAS for sleep quality) in patients with traumatic brachial plexus injury? This prospective, triple-blinded (the researcher administering the substance, the patients, and the evaluator were all blinded to the substance used), two-period crossover, placebo-controlled, randomized controlled trial was conducted at a single center. Between January 2020 and January 2022, we treated 147 patients for neuropathic pain related to a traumatic brachial plexus injury. Our inclusion criteria were age between 20 and 60 years and moderate-to-severe pain (VAS for pain equal to or greater than 4 of 10 for more than 6 months), even with the use of appropriate medications. Based on these criteria, 20% (30) of patients were eligible. They were randomly allocated to receive either cannabis-based medicine followed by the placebo or vice versa. Fifteen patients received cannabis-based medicine first, and 15 patients received the placebo first. The groups did not differ at baseline in terms of demographic parameters. Participants received both the cannabis-based medicine and the placebo; they started with 10 days of the initial intervention, followed by a 14-day washout period, and then a 10-day period with the second intervention. The dosage regimen adhered strictly to the protocol. The outcomes were the (1) VAS for pain, which ranges from 0 to 10 and where 0 represents no pain and 10 signifies the worst pain; (2) the DN4 questionnaire which ranges from 1 to 10 and where a score of 4 or higher indicates a positive result for neuropathic pain; and (3) VAS for sleep quality, from 0 (worst) to 10 (best). The minimum clinically important difference of VAS for pain was defined as a 2-point improvement. After enrollment, 7% (2 of 30) of patients (one patient received the cannabis-based medicine first and another received the placebo first) were lost before the minimum study follow-up, leaving 93% (28 of 30) for analysis. With 28 patients in each group, the study was powered a priori at 90% to detect a clinically important difference of 2 points in the VAS for pain. No carryover or period effects were observed in the study. Four patients experienced mild dizziness during the cannabis-based medicine period but were able to continue the intervention. When comparing the use of cannabis-based medicine alongside pain control medications with the combination of placebo and pain control medications, the reduction in pain VAS from the preintervention resulted in a mean difference of 1 (99% CI -0.03 to 2.1; p = 0.01). Neuropathic pain was reported by 75% (21 of 28) of patients in both interventions (OR 1 [99% CI 0.07 to 14.1]; p > 0.99). The VAS for sleep quality favored cannabis-based medicine with a mean difference of 1.5 (99% CI 0.7 to 2.4; p < 0.001). Our study findings indicate that cannabis-based medicine did not improve pain by a clinically important margin. Consequently, our study advises against the addition of cannabis-based medicine to the standard medication treatment for pain in patients with traumatic brachial plexus injury. Level 1, therapeutic study.

Effects of Coenzyme Q10 Supplementation in Women with Metabolic Syndrome and Non-Alcoholic Fatty Liver Disease Evaluated by Magnetic Resonance Imaging—Coenzyme Q10 in Metabolic Syndrome and NAFLD

(1) Introduction: Coenzyme Q10 (CoQ10) is a component present in the transport chain of mitochondrial electrons with antioxidant property. Currently, there are limited studies which indicate the effects of its supplementation on Metabolic Syndrome (MetS) and Non-Alcoholic Fatty Liver Disease (NAFLD). (2) Objective: This work was conducted to determine the effects of CoQ10 supplementation in women with MetS and NAFLD. (3) Methodology: This double-blind randomized clinical-controlled trial was performed among 22 women with MetS and NAFLD. Patients were randomized into two groups: group A (n = 11), which received 200 mg/day of CoQ10; and group B (n = 11), which received a placebo medication for 12 weeks. The hepatic steatosis present in NAFLD, the volume of abdominal fat, and visceral fat volume were evaluated by Magnetic Resonance Imaging (MRI). Anthropometric, blood pressure, and marker serums that compound the MetS were also analyzed. (4) Results: A decrease in visceral fat volume (p = 0.02), abdominal circumference (p = 0.03/CI = 0.19–3.80), and increase in HDL-cholesterol (p = 0.01/CI = −9.80: −1.44) was observed in the CoQ10-supplemented group. We did not find significant changes in any of the other variables evaluated. (5) Conclusions: Supplementation with CoQ10 for 12 weeks, even if discreetly, brought some benefits for the supplemented group whereas no changes were observed in the control group.

Efficacy of Dequalinium Chloride vs Metronidazole for the Treatment of Bacterial Vaginosis

Bacterial vaginosis (BV) is a common cause of vaginal infection. First-line treatments of BV are metronidazole and clindamycin. Due to the increase in antibiotic resistance, effective nonantibiotic treatments for BV are needed. To examine whether dequalinium chloride, a broad-spectrum antiseptic, is noninferior to oral metronidazole for the treatment of BV. This phase 4, multicenter, triple-blind, double-dummy, parallel, noninferiority randomized clinical trial was conducted from July 29, 2021, to August 25, 2022, with a 1-month follow-up. Participants were premenopausal women 18 years or older with BV from 11 gynecologic practices and 1 hospital in Poland, Slovakia, and the Czech. Patients were randomized to treatment with dequalinium chloride vaginal tablets (10 mg once daily for 6 days) or oral metronidazole (500 mg twice daily for 7 days). Double-dummy medication kits contained vaginal and oral tablets with placebo and active medication. The main outcome was the noninferiority margin (of 15 percentage points) in the absolute difference in clinical cure rates between dequalinium chloride and metronidazole 7 to 11 days after start of treatment (visit 1). Noninferiority was met if the lower 95% CI for the difference in clinical cure rate was less than 15 percentage points at visit 1. A total of 147 women (mean [SD] age, 36.7 [9.0] years) were treated with dequalinium chloride (n = 72) or metronidazole (n = 75). The clinical cure rates at visit 1 were 64 of 69 (92.8%) for dequalinium chloride vs 69 of 74 (93.2%) for metronidazole in the intention-to-treat population, whereas in the per-protocol population, cure rates were 54 of 58 (93.1%) for dequalinium chloride vs 48 of 53 (90.6%) for metronidazole. The treatment differences of -0.5 percentage points (95% CI, -10.8 to 9.8 percentage points; P = .002) in the intention-to-treat population and 2.5 percentage points (95% CI, -9.4 to 14.4 percentage points; P = .001) in the per-protocol population confirmed the noninferiority of dequalinium chloride. The tolerability of dequalinium chloride was rated as very good by 30 of 50 patients (60.0%) but only by 21 of 54 (38.9%) for metronidazole. Three patients in the metronidazole group suspended treatment due to an adverse event. This randomized clinical trial showed that dequalinium chloride was not inferior to metronidazole for the treatment of BV. Dequalinium chloride had a similarly high cure rate but with better tolerability and fewer adverse events. With a similar efficacy to metronidazole and clindamycin, dequalinium chloride warrants consideration as first-line treatment for BV to help reduce antibiotic consumption. EudraCT: 2020-002489-15.

Psychosocial and medication interventions to stop or reduce alcohol consumption during pregnancy.

Despite the known harms, alcohol consumption is common in pregnancy. Rates vary between countries, and are estimated to be 10% globally, with up to 25% in Europe. To assess the efficacy of psychosocial interventions and medications to reduce or stop alcohol consumption during pregnancy. We searched the Cochrane Drugs and Alcohol Group Specialised Register (via CRSLive), Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, Web of Science, and PsycINFO, from inception to 8 January 2024. We also searched for ongoing and unpublished studies via ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). All searches included non-English language literature. We handsearched references of topic-related systematic reviews and included studies. We included randomised controlled trials that compared medications or psychosocial interventions, or both, to placebo, no intervention, usual care, or other medications or psychosocial interventions used to reduce or stop alcohol use during pregnancy. Our primary outcomes of interest were abstinence from alcohol, reduction in alcohol consumption, retention in treatment, and women with any adverse event. We used standard Cochrane methodological procedures. We included eight studies (1369 participants) in which pregnant women received an intervention to stop or reduce alcohol use during pregnancy. In one study, almost half of participants had a current diagnosis of alcohol use disorder (AUD); in another study, 40% of participants had a lifetime diagnosis of AUD. Six studies took place in the USA, one in Spain, and one in the Netherlands. All included studies evaluated the efficacy of psychosocial interventions; we did not find any study that evaluated the efficacy of medications for the treatment of AUD during pregnancy. Psychosocial interventions were mainly brief interventions ranging from a single session of 10 to 60 minutes to five sessions of 10 minutes each. Pregnant women received the psychosocial intervention approximately at the end of the first trimester of pregnancy, and the outcome of alcohol use was reassessed 8 to 24 weeks after the psychosocial intervention. Women in the control group received treatment as usual (TAU) or similar treatments such as comprehensive assessment of alcohol use and advice to stop drinking during pregnancy. Globally, we found that, compared to TAU, psychosocial interventions may increase the rate of continuously abstinent participants (risk ratio (RR) 1.34, 95% confidence interval (CI) 1.14 to 1.57; I2 =0%; 3 studies; 378 women; low certainty evidence). Psychosocial interventions may have little to no effect on the number of drinks per day, but the evidence is very uncertain (mean difference -0.42, 95% CI -1.13 to 0.28; I2 = 86%; 2 studies; 157 women; very low certainty evidence). Psychosocial interventions probably have little to no effect on the number of women who completed treatment (RR 0.98, 95% CI 0.94 to 1.02; I2 = 0%; 7 studies; 1283 women; moderate certainty evidence). None of the included studies assessed adverse events of treatments. We downgraded the certainty of the evidence due to risk of bias and imprecision of the estimates. Brief psychosocial interventions may increase the rate of continuous abstinence among pregnant women who report alcohol use during pregnancy. Further studies should be conducted to investigate the efficacy and safety of psychosocial interventions and other treatments (e.g. medications) for women with AUD. These studies should provide detailed information on alcohol use before and during pregnancy using consistent measures such as the number of drinks per drinking day. When heterogeneous populations are recruited, more detailed information on alcohol use during pregnancy should be provided to allow future systematic reviews to be conducted. Other important information that would enhance the usefulness of these studies would be the presence of other comorbid conditions such as anxiety, mood disorders, and the use of other psychoactive substances.

Project harmony: A systematic review and network meta-analysis of psychotherapy and pharmacologic trials for comorbid posttraumatic stress, alcohol, and other drug use disorders.

We conducted a systematic review and network meta-analyses (NMA) of psychotherapy and pharmacologic treatments for individuals with co-occurring posttraumatic stress disorder (PTSD) and alcohol or other drug use disorder (AOD). A comprehensive search spanning 1995-2019 yielded a pool of 39 studies for systematic review, including 24 randomized controlled trials for the NMA. Study interventions were grouped by target of treatment (PTSD + AOD, PTSD-only, and AOD-only) and approach (psychotherapy or medication). Standardized mean differences (SMD) from the NMA yielded evidence that at the end of treatment, integrated, trauma-focused therapy for PTSD + AOD was more effective at reducing PTSD symptoms than integrated, non-trauma-focused therapy (SMD = -0.30), AOD-focused psychotherapy (SMD = -0.29), and other control psychotherapies (SMD = -0.43). End-of-treatment alcohol use severity was less for AOD medication compared to placebo medication (SMD = -0.36) and trauma-focused therapy for PTSD + placebo medication (SMD = -0.67), and less for trauma-focused psychotherapy + AOD medication compared to PTSD medication (SMD = -0.53), placebo medication (SMD = -0.50), and trauma-focused psychotherapy + placebo medication (SMD = -0.81). Key limitations include the small number of studies in the NMA for pharmacologic treatments and the lack of demographic diversity apparent in the existing literature. Findings suggest room for new studies that can address limitations in study sample composition, sample sizes, retention, and apply new techniques for conducting comparative effectiveness in PTSD + AOD treatment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Efficacy and Safety of Ketamine Compared with Placebo and Other Medications for Preventing Propofol Injection Pain in Adults: A Systematic Review and Meta-Analysis.

To systematically evaluate the effectiveness and safety of ketamine in preventing propofol injection pain (PIP). The electronic databases including PubMed, Embase, Web of Science, and Cochrane Library were searched from their inception until 2 August 2023. Randomized controlled trials (RCT) comparing ketamine with placebo or other interventions to alleviate PIP in adults were included. Fixed-effects or random-effects models were used to calculate pooled risk ratios (RR) and corresponding 95% confidence intervals (CI) based on the heterogeneity of the studies included. Thirteen RCTs involving 2105 patients were included. In terms of reducing the incidence of PIP, ketamine is more effective than placebo (RR = 0.43, 95% CI = [0.34, 0.55], P < 0.00001), lidocaine (RR = 0.70, 95% CI = [0.55, 0.90], P = 0.005), dexmedetomidine (RR = 0.52, 95% CI = [0.40, 0.66], P < 0.00001), and thiopental (RR = 0.25, 95% CI = [0.08, 0.83], P = 0.02). In reducing the incidence of severe PIP, ketamine is superior to placebo (RR = 0.12, 95% CI = [0.08, 0.19], P < 0.00001), and lidocaine (RR = 0.34, 95% CI = [0.21, 0.56], P < 0.0001), except dexmedetomidine (RR = 0.20, 95% CI = [0.04, 1.13], P = 0.07), and thiopental (RR = 0.33, 95% CI = [0.04, 3.10], P = 0.33). Compared with mixed injection, separate injection of ketamine and propofol showed no significant difference in the incidence of PIP (RR = 0.96, 95% CI = [0.31, 3.00], P = 0.95) and severe PIP (RR = 1.19, 95% CI = [0.07, 21.29], P = 0.90). Based solely on the reports from the studies included, subanesthetic doses of ketamine are generally safe in preventing PIP. A subanesthetic dose of ketamine can effectively and safely reduce the incidence of PIP and severe PIP in adults, and is more effective than lidocaine, dexmedetomidine, and thiopental. PROSPERO CRD42023455093.

The Effect of Dexlansoprazole on Gastroesophageal Reflux Disease: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis evaluated the efficacy of dexlansoprazole (a proton pump inhibitor-PPI) in resolving heartburn, reflux, and other symptoms and complications resulting from gastroesophageal reflux disease (GERD). The study followed PRISMA 2020 and was registered in PROSPERO (CRD42020206513). The search strategy used MeSH and free terms appropriately adapted for each database. Only randomized clinical trials (RCTs) were included. The Cochrane tool (RoB 2.0) was used to assess the risk of bias, and the certainty of evidence was rated using GRADE. Ten RCTs were included. Dexlansoprazole outperformed the placebo and other PPIs in the resolution of heartburn and reflux symptoms in patients with GERD, with benefits during and after treatment, especially in those with moderate and severe symptoms. The meta-analyses indicated that dexlansoprazole at doses of 30 and 60 mg had more 24 h heartburn-free days and nights compared to the placebo medications; no difference was reported between dexlansoprazole at doses of 30 and 60 mg in heartburn-free nights. A low bias risk and a moderate certainty of evidence were observed. This review confirms the therapeutic effect of dexlansoprazole (placebo-controlled) and its improvements in GERD symptoms compared to another PPI. However, the interpretation of the results should be carried out cautiously due to the small number of included studies and other reported limitations.

Ethics in placebo-controlled, acute treatment trials in schizophrenia: Two rival ethical frameworks

Placebo-controlled, acute treatment trials in schizophrenia enroll acutely symptomatic persons, randomize them to receive placebo or antipsychotic medication for several weeks, and evaluate whether symptoms improve. These trials can have scientific benefits, especially when they test drugs with novel mechanisms of action. However, the use of placebo is ethically problematic inasmuch as standard treatment is withheld and participants are subjected to prolonged psychotic symptoms and associated risks. We propose that both deontological (duty-based) and utilitarian analyses are relevant, that it may be impossible to satisfy the ideals of both frameworks, and that researchers who conduct these trials will unavoidably encounter ethical tension and criticism even when they give careful attention to ethical aspects of study design.

Neuroanatomical dimensions in medication-free individuals with major depressive disorder and treatment response to SSRI antidepressant medications or placebo

Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Our objective was to identify the neuroanatomical dimensions that characterize MDD and predict treatment response to selective serotonin reuptake inhibitor (SSRI) antidepressants or placebo. In the COORDINATE-MDD consortium, raw MRI data were shared from international samples (N = 1,384) of medication-free individuals with first-episode and recurrent MDD (N = 685) in a current depressive episode of at least moderate severity, but not treatment-resistant depression, as well as healthy controls (N = 699). Prospective longitudinal data on treatment response were available for a subset of MDD individuals (N = 359). Treatments were either SSRI antidepressant medication (escitalopram, citalopram, sertraline) or placebo. Multi-center MRI data were harmonized, and HYDRA, a semi-supervised machine-learning clustering algorithm, was utilized to identify patterns in regional brain volumes that are associated with disease. MDD was optimally characterized by two neuroanatomical dimensions that exhibited distinct treatment responses to placebo and SSRI antidepressant medications. Dimension 1 was characterized by preserved gray and white matter (N = 290 MDD), whereas Dimension 2 was characterized by widespread subtle reductions in gray and white matter (N = 395 MDD) relative to healthy controls. Although there were no significant differences in age of onset, years of illness, number of episodes, or duration of current episode between dimensions, there was a significant interaction effect between dimensions and treatment response. Dimension 1 showed a significant improvement in depressive symptoms following treatment with SSRI medication (51.1%) but limited changes following placebo (28.6%). By contrast, Dimension 2 showed comparable improvements to either SSRI (46.9%) or placebo (42.2%) (β = –18.3, 95% CI (–34.3 to –2.3), P = 0.03). Findings from this case-control study indicate that neuroimaging-based markers can help identify the disease-based dimensions that constitute MDD and predict treatment response.

Safety and efficacy of phosphodiesterase-5 (PDE-5) inhibitors in fetal growth restriction: a systematic literature review and meta-analysis.

Introduction: Fetal growth restriction (FGR) is associated with a higher risk of perinatal morbidity and mortality, as well as long-term health issues in newborns. Currently, there is no effective medicine for FGR. Phosphodiesterase-5 (PDE-5) inhibitors have been shown in pre-clinical studies to improve FGR. This study aimed to evaluate the latest evidence about the clinical outcomes and safety of PDE-5 inhibitors for the management of FGR. Methods: Eight databases (PubMed, Embase, Medline, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biomedical Database and WangFang Database) were searched for English and Chinese articles published from the database inception to December 2023. Randomized controlled trials (RCTs) reporting the use of PDE-5 inhibitors in FGR were included. The quality of the RCTs was assessed using the Cochrane Risk of Bias Tool. Odds ratio and mean difference (MD) (95% confidence intervals) were pooled for meta-analysis. Results: From 253 retrieved publications, 16 studies involving 1,492 pregnant women met the inclusion criteria. Only sildenafil (15 RCTs) and tadalafil (1 RCT) were studied for FGR. Compared with the control group (placebo, no treatment, or other medication therapies), sildenafil increased birth weight, pregnancy prolongation and umbilical artery pulsatility indices. However, it also increased the risk of pulmonary hypertension in newborns, as well as headache and flushing/rash in mothers. There were no significant differences in gestation age, perinatal mortality or major neonatal morbidity, stillbirth, neonate death, infants admitted to neonatal intensive care unit, intraventricular hemorrhage and necrotizing enterocolitis in infants, as well as pregnancy hypertension and gastrointestinal side effects in mothers between the treatment and the control groups. Discussion: Sildenafil was the most investigated PDE-5 inhibitors for FGR. Current evidence suggests that sildenafil can improve birth weight and duration of pregnancy but at the same time increase the risk of neonatal pulmonary hypertension. It remains uncertain whether the benefits of sildenafil in FGR outweigh the risks and further high-quality RCTs are warranted. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=325909.

Atractylodes macrocephala-Paeonia lactiflora Class Formula for the Treatment of Irritable Bowel Syndrome: A Systematic Review With Meta-Analysis and Trial Sequential Analysis.

Previous meta-analyses suggested that Chinese herbal medicine (CHM) is effective for irritable bowel syndrome (IBS). Formulas with Atractylodes macrocephala and Paeonia lactiflora as the core pairs have been widely used by traditional Chinese medicine (TCM) practitioners for the treatment of IBS. We aimed to examine the efficacy and safety of the Atractylodes macrocephala-Paeonia lactiflora class formula (A-P CHM) for IBS through a meta-analysis and trial-sequential analysis (TSA). The protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42023439087. We searched seven databases for data up to May 23, 2023. The primary outcome was global IBS symptom relief. The secondary outcomes included theIBS severity scoring system (IBS-SSS) score and treatment-related adverse events. The relative ratio (RR) (dichotomous variables), the standardized mean difference (SMD) (continuous variables), the number needed to treat (NNT), the number needed to harm (NNH), and the required information size (RIS) were calculated. Twenty-four eligible articles with 3,768 participants were included. Thirteen trials were at low risk of bias (RoB). Compared with placebo or Western medication, A-P CHM was associated with a significantly higher proportion of relief of global IBS symptoms. The TSA analysis verified the primary outcome. For the secondary outcome, the A-P CHM IBS-SSS score was lower than Western medication or placebo at the end of the treatment, which was further confirmed by the TSA analysis. We asserted that A-P CHM might be a potential candidate for patients with IBS, especially for IBS-D. It may provide a theoretical basis for future optimization of irritable bowel syndrome with diarrhea (IBS-D) herbal formulas. The overall certainty of the evidence was not high; more tightly designed randomized controlled trials (RCTs) are required in the future.

POST-TRAUMATIC STRESS DISORDER AS PRESSING ISSUES OF OUR TIME

The issue of combat-related psychological trauma and the development of post-traumatic disorders during wartime are of great significance now. The ongoing conflict with the invasion of neighbouring forces and the large-scale war against Ukraine poses a threat that could extend for years, if not decades, and potentially affect other regions. The constant shelling of border areas, missile attacks, and the dire social, humanitarian, and epidemiological conditions in occupied territories of Kherson, Zaporizhzhia, Donetsk and Luhansk regions have resulted in profound psychological distress among not only military personnel but also the entire population of Ukraine. This situation has led to a complex and diverse development of post-traumatic stress disorder in the contemporary context. However, despite these tragic events, this topic is of interest due to its scientific, practical, epidemiological significance, among other aspects. There is still no universally accepted theoretical framework defining approaches to the study of the psychological and biological mechanisms underlying post-traumatic stress disorder. Several pathogenetic models of the development of this disorder are currently under development. This disorder is characterized by a wide range of symptoms, including asthenia, anxiety, affective, behavioural, and psychotic disorders, which often present challenges in therapy. The most effective approach involves the use of combined pharmacological and psychotherapeutic interventions, with antidepressants being the only pharmacological agents endorsed in international clinical guidelines as first-line treatments. While experimental treatment methods exist, they require further investigation. Nonetheless, only about half of the patients achieve remission. Consequently, symptomatic therapy, placebo medications, and polypharmacy have become common in clinical practice, as clinicians attempt to address various comorbid psychopathological symptoms. This approach, to some extent, reflects the lack of well-established effective therapeutic methods and often results in prolonged illness, the development of treatment resistance, and the occurrence of side effects. In general, the efficacy of comprehensive therapy is insufficiently studied and necessitates further representative placebo-controlled and comparative clinical studies, as well as the development of more suitable and effective experimental approaches to investigate novel treatment methods.

ANTIHISTAMINE AS AN ADJUNCTIVE TREATMENT IN ACNE VULGARIS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Approximately one-tenth of the global population suffer from acne vulgaris, which is a skin disease with considerable psychological impact. Recently, antihistamines have been used in the treatment of acne. However, their overall treatment effects for this indication remain unclear. This systematic review and meta-analysis aim to evaluate the clinical efficacy and safety of the antihistamines in the treatment of acne vulgaris. The following databases were searched: PubMed, Scopus, Embase, Cochrane Central Register of Controlled Clinical Trials, and Google Scholar. We included the randomized controlled trials on acne vulgaris patients which compared any H1- antihistamine drug in combination with other medications to placebo, no treatment, or other medications, with acne lesion (non-inflammatory and inflammatory) counts, acne severity score, patient satisfaction, acne flare, or adverse events as an outcome of interest. Six studies contributing to 388 patients were included, involving two H1 antihistamines (i.e., levocetrizine and desloratadine), isotretinoin, azithromycin, and topical azelaic acid cream. From the network meta–analysis, levocetirizine+isotretinoin was better than the isotretinoin alone in the inflammatory lesion count, but not in the non-inflammatory lesion count. The desloratadine+isotretinoin retained the best balance in terms of non-inflammatory lesion count, inflammatory lesion count, acne flare, and mucocutaneous adverse events. The desloratadine+isotretinoin and levocetirizine+isotretinoin were considered safe.

The Impact of Dapagliflozin on Cardiac LV Systolic Function in Patients with ST Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention Who Developed Post MI LV Dysfunction

Abstract Aim and objectives To study the impact of dapagliflozin on LV systolic function in patients with ST Elevation Myocardial Infarction undergoing primary percutaneous Coronary Intervention who developed post MI LV dysfunction. Patients and Methods The study included 80 patient who presented with ST-segment elevation myocardial infarction and underwent primary PCI at the catheterization lab unit, Cardiology department, Ain Shams University. The patients were divided into 2 groups. The standard treatment was given to all patients according to the ESC guidelines including: ACEI or ARNi, a beta-blocker, and an MRA[1] uptitrated according to the clinical state of the patient. The study medication was 10 mg of dapagliflozin[1] given once daily in the morning to the case group and a placebo medication to the control group. LVEF was assessed in both groups post primary PCI and at follow-up after 3 months by the same Echo machine GE VIVED S5 after the procedure since first of June 2021 till end of January 2022. Results There were no statistically significant difference between both groups regarding gender distribution, mean age, and the incidence of different risk factors of CAD (smoking, Diabetes and hypertension). Regarding pain to door (PTD) time, there was no statistically significant difference between case and control groups (P-value = 0.695), and anterior STEMI was the most common presentation in both groups (90% in the case group and 77.5% in the control group in the control group). Subsequently, there was no statistically significant difference between case and control groups regarding TIMI flow, and post-MI EF with mean range 34.88% ± 3.55% in the case group and 34.58% ± 3.65% in the control group (P = 0.711). On the other hand, there was statistically significant improvement in follow-up EF in the case group which showed a mean range of 45.36% ± 7.13% in comparison with the control group which showed a mean range of 41.80% ± 6.93% (P = 0.027). Conclusion Dapagliflozin administration in the early phase after STEMI results in significant improvement in LV systolic function in comparison with the placebo. Abbreviations ACE-I: Angiotensin-converting enzyme inhibitor; ACS: Acute coronary syndrome; ARNI: Angiotensin receptor-neprilysin inhibitor; CBC: Complete blood picture; DM: Diabetes Mellitus; ECG: Electrocardiogram; FH: Family History; GLS: Global longitudinal strain; HF: Heart Failure; HFrEF: Heart Failure reduced Ejection Fraction; HTN: Hypertension IV: Intravenous; LV: Left ventricle; LVEF: Left ventricular ejection fraction; MI: Myocardial Infarction; MRA: Mineralocorticoid receptor antagonists; PCI: Primary percutaneous coronary intervention; SD: Standard deviation; SGLT-2: Sodium-glucose cotransporter-2 inhibitors; SPSS: Statistical Package for the Social Science; STEMI: ST-segment elevation myocardial infarction; T2D: Type 2 Diabetes Mellitus

Age differences in routine formation: the role of automatization, motivation, and executive functions.

Medication adherence can be vital for one's health, especially in older adults. However, previous research has demonstrated that medication adherence is negatively affected by age-related cognitive decline. In the current study we investigated whether older adults are able to compensate for this decline by relying more on the formation of efficient, automatized routines. To this end, we directly compared daily (placebo) medication adherence in a healthy sample of 68 younger (18-29 years) and 63 older adults (65-86 years) over a period of 4 weeks. We show that despite an age-related decline in cognitive functions (i.e., poorer working memory, prospective memory, task switching, and goal-directed control), older adults adhered better to a daily pill intake routine than younger adults did and, in line with our hypothesis about increased routine formation, reported higher subjective automaticity of pill intake. Across age groups, automatization of pill intake was related to intake regularity and conscientiousness, but not to individual differences in habit tendency as measured in the lab nor to explicit strategic planning. Crucially, the age-related increase in pill intake adherence was mediated by experienced automatization as well as motivation. These findings demonstrate that intact habitual processes and high motivation aid older adults in successfully forming daily routines.

Improvement of synaptic plasticity and cognitive function in RASopathies—a monocentre, randomized, double-blind, parallel-group, placebo-controlled, cross-over clinical trial (SynCoRAS)

BackgroundCognitive impairment is a common medical issue in rat sarcoma (RAS) pathway disorders, so-called RASopathies, like Neurofibromatosis type 1 (NF1) or Noonan syndrome (NS). It is presumed to be caused by impaired synaptic plasticity. In animal studies, pathway-specific pharmacological interventions with lovastatin (LOV) and lamotrigine (LTG) have been shown to improve synaptic plasticity as well as cognitive function. The aim of this clinical trial is to translate the findings of animal studies to humans and to probe the effect of lovastatin (NS) and lamotrigine (NS and NF1) on synaptic plasticity and cognitive function/alertness in RASopathies.MethodsWithin this phase IIa, monocentre, randomized, double-blind, parallel-group, placebo-controlled, cross-over clinical trial (syn. SynCoRAS), three approaches (approaches I–III) will be carried out. In patients with NS, the effect of LTG (approach I) and of LOV (approach II) is investigated on synaptic plasticity and alertness. LTG is tested in patients with NF1 (approach III). Trial participants receive a single dose of 300 mg LTG or placebo (I and III) and 200 mg LOV or placebo (II) daily for 4 days with a cross-over after at least 7 days. Synaptic plasticity is investigated using a repetitive high-frequency transcranial magnetic stimulation (TMS) protocol called quadri-pulse theta burst stimulation (qTBS). Attention is examined by using the test of attentional performance (TAP). Twenty-eight patients are randomized in groups NS and NF1 with n = 24 intended to reach the primary endpoint (change in synaptic plasticity). Secondary endpoints are attention (TAP) and differences in short interval cortical inhibition (SICI) between placebo and trial medication (LTG and LOV).DiscussionThe study is targeting impairments in synaptic plasticity and cognitive impairment, one of the main health problems of patients with RASopathies. Recent first results with LOV in patients with NF1 have shown an improvement in synaptic plasticity and cognition. Within this clinical trial, it is investigated if these findings can be transferred to patients with NS. LTG is most likely a more effective and promising substance improving synaptic plasticity and, consecutively, cognitive function. It is expected that both substances are improving synaptic plasticity as well as alertness. Changes in alertness may be a precondition for improvement of cognition.Trial registrationThe clinical trial is registered in ClinicalTrials.gov (NCT03504501; https://www.clinicaltrials.gov; date of registration: 04/11/2018) and in EudraCT (number 2016–005022-10).

Indomethacin for heterotopic ossification prophylaxis following surgical treatment of elbow trauma: a randomized controlled trial

Heterotopic ossification is a frequent complication following surgical treatment of elbow trauma. The use of indomethacin to prevent heterotopic ossification is reported in the literature; however, its effectiveness is controversial. The purpose of this randomized, double-blind, placebo-controlled study was to determine whether indomethacin is effective in reducing the incidence and severity of heterotopic ossification after surgical management of elbow trauma. Between February 2013 and April 2018, 164 eligible patients were randomized to receive postoperative indomethacin or placebo medication. The primary outcome was the incidence of heterotopic ossification on elbow radiographs at 1-year follow-up. Secondary outcomes included the Patient Rated Elbow Evaluation score, Mayo Elbow Performance Index score, and Disabilities of the Arm, Shoulder and Hand score. Range of motion, complications, and nonunion rates were also obtained. At 1-year follow-up, there was no significant difference in the incidence of heterotopic ossification between the indomethacin group (49%) and the control group (55%) (relative risk, 0.89; P=.52). There were no significant differences in postoperative Patient Rated Elbow Evaluation, Mayo Elbow Performance Index, and Disabilities of the Arm, Shoulder and Hand scores or range of motion (P=.16). The complication rate was 17% in both the treatment and control groups (P>.99). There were no nonunions in either group. This Level I study demonstrated that indomethacin prophylaxis against heterotopic ossification in the setting of surgically treated elbow trauma was not significantly different from placebo.

PHARMACOLOGICAL AND INTERVENTIONAL TREATMENT OF RESISTANT HYPERTENSION. A NETWORK META-ANALYSIS

Objective: Resistant hypertension is associated with a high risk of cardiovascular disease, chronic kidney disease and mortality. Yet, its management is still challenging. This study aims to establish the comparative effectiveness of pharmacologic and interventional treatments by conducting a network meta-analysis. Design and method: We systematically searched MEDLINE, Cochrane Register of Controlled Trials (CENTRAL) and Web of Science Core Collection in March 2022. Randomized controlled trials comparing treatment options as add-on therapy for management of resistant hypertension were included. Outcomes were blood pressure changes, measured in the office and in 24h ABPM. We applied a frequentist random effects model to perform a network meta-analysis combining placebo medication and sham procedure as the reference comparator. Results: From 4771 records, 24 studies met our inclusion criteria with 3458 included patients in total. 12 active treatment alternatives were analyzed. Among all comparators, spironolactone had the highest-ranking probability and was considered as the most effective treatment to reduce office systolic blood pressure (-13.30 mmHg [-17.89; -8.72]; P &lt; 0.0001) and 24h systolic blood pressure (-8.46 mmHg [-12.54; -4.38]; P &lt; 0.0001) in patients with resistant hypertension. Conclusions: Among all pharmacologic and interventional treatments, spironolactone has been found to be most effective in reducing office and 24h systolic blood pressure as an add-on therapy for resistant hypertension. Our study provides an evidence-based and valid reference in clinical decision-making.

Effectiveness of auricular acupoint therapy targeting menstrual pain for primary dysmenorrhea: A systematic review and meta-analysis of randomized controlled trials.

Primary dysmenorrhea (PD) is a global public health concern affecting women's health and quality of life, leading to productivity loss and increased medical expenses. As a non-pharmacological intervention, auricular acupoint therapy (AAT) has been increasingly applied to treat PD, but the overall effectiveness remains unclear. The aim of this review was to synthesize the effects of AAT targeting menstrual pain among females with PD. Eight databases (PubMed, EMBASE, AMED, CINAHL Plus, Cochrane Library, Web of Science, China National Knowledge Infrastructure and Wanfang Data) and three registries (ClinicalTrials.gov, ISRCTN Registry and the Chinese Clinical Trial Registry) were searched to identify existing randomized controlled trials (RCTs) from inception to 21 August 2022. Two reviewers independently screened, extracted the data, and appraised the methodological quality and the evidence strength using the Cochrane risk-of-bias tool for randomized trials (RoB 2) and the GRADE approach. A total of 793 participants from 11 RCTs were included. Despite substantial heterogeneity, AAT was more effective in reducing menstrual pain and related symptoms than placebo and nonsteroidal anti-inflammatory medications (NSAIDs). No significant subgroup differences were found between study locations as well as invasiveness, duration, type, acupoints number, ear selection and provider of AAT. Only minor adverse effects of AAT were reported. AAT can help women with PD, particularly those who are refrained from pharmaceuticals. Primary healthcare professionals, including nurses, can be well-equipped to provide evidence-based and effective AAT for people with PD. AAT can be used in a broader global clinical community. To provide an optimal effect and have wider usability, a unified practice standard is required, which would necessitate further adaptation of clinical care of people with PD. AAT effectively decreased menstrual pain and other accompanying symptoms of PD. More research is needed to identify effective AAT features and explore optimal therapy regimes for PD.