Spectrum of Thoracic Imaging Findings in the Setting of Substance Abuse.

ABSTRACT: Substance abuse continues to be prevalent nationwide and can lead to a myriad of chest pathologies. Imaging findings are vast and can include nodules, masses, ground-glass opacities, airspace disease, and cysts. Radiologists with awareness of these manifestations can assist in early identification of disease in situations where information is unable to be obtained from the patient. This review focuses on thoracic imaging findings associated with various forms of substance abuse, which are organized by portal of entry into the thorax: inhalation, ingestion, and injection.

Efficacy of Hibiscus sabdariffa on Reducing Blood Pressure in Patients With Mild-to-Moderate Hypertension: A Systematic Review and Meta-Analysis of Published Randomized Controlled Trials.

We aimed to assess the efficacy of Hibiscus sabdariffa in patients with mild-to-moderate hypertension or metabolic syndrome (MetS) by comparing it against placebo, antihypertensive drugs, or other herbal products. Four databases were searched for randomized clinical trials (RCTs) examining the efficacy of H. sabdariffa in patients with mild-to-moderate hypertension or hypertension associated with MetS. Data on the change in systolic blood pressure (SBP) and diastolic blood pressure (DBP) were extracted and analyzed using Review Manager Version 5.3. A total of 13 RCTs (1205 participants) were analyzed. Hibiscus sabdariffa significantly reduced both SBP and DBP compared with placebo (mean difference -6.67, P = 0.004 and -4.35 mm Hg, P = 0.02). Subgroup analysis showed that change in SBP and DBP was statistically significant in patients with only hypertension, whereas not significant in patients with hypertension associated with MetS. When H. sabdariffa was compared with active controls (antihypertensive drugs or other herbals), the change in SBP and DBP was not statistically significant (all P > 0.05). Hibiscus sabdariffa is effective in reducing the SBP and DBP in patients with mild-to-moderate hypertension, but was neither effective in those with MetS nor superior to antihypertensive drugs. Further RCTs are required to determine the long-term efficacy of H. sabdariffa and to describe patients who would benefit most from this treatment.

Clinical profiles and outcomes of acute ST-segment elevation myocardial infarction in young adults in a tertiary care center in Saudi Arabia.

OBJECTIVES: To investigate the clinical profiles and outcomes of young adults presenting with ST-segment elevation myocardial infarction (STEMI). METHODS: We retrospectively reviewed King Saud Medical City, Riyadh, Saudi Arabia, registry between January 2016 and November 2017 for all patients younger than 45 years old who were admitted with STEMI. We compared this study population to a control group of patients aged 45 years and older who were enrolled in the same period. RESULTS: In total, 402 patients were enrolled; 197 were younger than 45 years. The incidence of newly diagnosed dyslipidemia was higher in younger patients (44% vs. 32%, p=0.01). Smoking was significantly more prevalent in the younger group (52% vs. 35%, p=0.001). The prevalence of pulmonary edema and cardiogenic shock on presentation was significantly higher in the older group (3% vs. 10; odds ratio, 4.43; 95% confidence interval, 1.750-10.94; p=0.002). Hospital stay was also longer in the older group (4±2 vs. 5±2 days, p=0.03). CONCLUSION: ST-segment elevation myocardial infarction in young patients has a favorable outcome. Smoking and dyslipidemia are the main risk factors for STEMI in young individuals. The majority of young patients with dyslipidemia were not aware of their pre-existing condition. Our findings recommend local adaptation and implementation of screening programs for dyslipidemia in the young and the reinforcement of smoking prevention programs.

Clinical Importance of Incidental Homogeneous Renal Masses That Measure 10-40 mm and 21-39 HU at Portal Venous Phase CT: A 12-Institution Retrospective Cohort Study.

BACKGROUND. Incidental homogeneous renal masses are frequently encountered at portal venous phase CT. The American College of Radiology Incidental Findings Committee's white paper on renal masses recommends additional imaging for incidental homogeneous renal masses greater than 20 HU, but single-center data and the Bosniak classification version 2019 suggest the optimal attenuation threshold for detecting solid masses should be higher. OBJECTIVE. The purpose of this article is to determine the clinical importance of small (10-40 mm) incidentally detected homogeneous renal masses measuring 21-39 HU at portal venous phase CT. METHODS. We performed a 12-institution retrospective cohort study of adult patients who underwent portal venous phase CT for a nonrenal indication. The date of the first CT at each institution ranged from January 1, 2008, to January 1, 2014. Consecutive reports from 12,167 portal venous phase CT examinations were evaluated. Images were reviewed for 4529 CT examinations whose report described a focal renal mass. Eligible masses were 10-40 mm, well-defined, subjectively homogeneous, and 21-39 HU. Of these, masses that were shown to be solid without macroscopic fat; classified as Bosniak IIF, III, or IV; or confirmed to be malignant were considered clinically important. The reference standard was renal mass protocol CT or MRI, ultrasound of definitively benign cysts or solid masses, single-phase contrast-enhanced CT or unenhanced MRI showing no growth or morphologic change for 5 years or more, or clinical follow-up 5 years or greater. A reference standard was available for 346 masses in 300 patients. The 95% CIs were calculated using the binomial exact method. RESULTS. Eligible masses were identified in 4.2% of patients (514/12,167; 95% CI, 3.9-4.6%). Of 346 masses with a reference standard, none were clinically important (0%; 95% CI, 0-0.9%). Mean mass size was 17 mm; 72% (248/346) measured 21-30 HU, and 28% (98/346) measured 31-39 HU. CONCLUSION. Incidental small homogeneous renal masses measuring 21-39 HU at portal venous phase CT are common and highly likely benign. CLINICAL IMPACT. The change in attenuation threshold signifying the need for additional imaging from greater than 20 HU to greater than 30 HU proposed by the Bosniak classification version 2019 is supported.

High success rates for the use of sofosbuvir/ombitasvir/paritaprevir/ritonavir + ribavirin and sofosbuvir/simeprevir/daclatasvir + ribavirin in retreatment of chronic hepatitis C infection after unsuccessful sofosbuvir/daclatasvir therapy: a real-life experience.

The aim of this work was assessment of the efficacy and tolerability of two different regimens for retreatment of hepatitis C virus (HCV) patients who failed to respond to SOF/DCV-based therapy. This prospective study included 104 HCV patients who failed to respond to SOF/DCV-based therapy. Patients were randomly allocated to two groups. Efficacy and tolerability were assessed. The 12-week sustained virological response (SVR12) rates were 96% and 94.4% in groups B and A, respectively, with no significant difference (p = 1.000). Most adverse events reported were mild to moderate, with no deaths during the study. Multi-target direct-acting antiviral (DAA) combinations are efficient for retreatment of HCV patients after failure of SOF/DCV-based therapy in real-world management.ClinicalTrials.gov identifier: NCT02992457.

Hepatitis C Virus: Efficacy of New DAAs Regimens.

BACKGROUND: HCV treatment showed dramatical change due to the introduction of potent, strong, direct antiviral drugs. Before the appearance of Direct-acting antivirals, multiple therapeutic interventions were used for hepatitis C, but none of these interventions were effective on patient-centered outcomes. Direct-acting antivirals cause disruption of viral replication because they target specific nonstructural viral proteins. AIM: To review the advantages of efficient HCV therapy and its long term drawbacks. METHODS: A search of the literature published in indexed databases (PubMed, Medline In-Process, and Embase) within the last 5 years was conducted. Any duplicated citations were excluded before first-pass screening. Citations (titles and abstracts) were screened for eligibility by a single reviewer. Full texts (including congress abstracts, posters and other congress communications) of citations deemed relevant during title and abstract screening were retrieved for second-pass review. RESULTS: Studies on the clinical effects of DAAs for hepatitis C show better tolerance, improved survival and fewer complications when compared to previous interferon therapy. CONCLUSION: HCV treatment has improved dramatically. Since that time, there are multiple approved oral therapies all with high efficacy. The most important factor which should be considered during choosing appropriate therapy is to ensure that it covers the viral genotype of the infected patients.

Safety and Efficacy of Levetiracetam for the Management of Levodopa- Induced Dyskinesia in Patients with Parkinson's Disease: A Systematic Review.

BACKGROUND: Levetiracetam, a novel antiepileptic drug, has shown antidyskinetic effects in experimental animal models of Parkinson's disease (PD). The tolerability and efficacy of levetiracetam in reducing the levodopa-induced dyskinesia (LID) in PD patients have not been established. Therefore, this study aims to synthesize evidence from published prospective clinical trials about the efficacy of levetiracetam for the management of LID in PD patients. METHODS: We followed the PRISMA statement guidelines during the preparation of this systematic review. A computer literature search of PubMed, EBSCO, Scopus, MEDLINE, and the web of science was carried out. We selected prospective clinical trials assessing the anti-dyskinetic efficacy of levetiracetam for treating LID in patients with PD. The Abnormal Involuntary Movement Scale (AIMS), Clinical Global Impression Score (GCI), UPDRS III, and UPDRS IV were considered as the primary outcome measures; their data were extracted and reviewed. RESULTS: Our review included seven clinical trials with a total of 150 patients. Of them, three studies were randomized controlled trials, and the remaining were open-label single arm trials. Four studies reported poor tolerability of the levetiracetam with mild anti-dyskinetic effects. Levetiracetam slightly improved the UPDRS-IV and AIMS scores with small effect size. In the remaining three studies, levetiracetam failed to exhibit any anti-dyskinetic effects. CONCLUSION: Current evidence does not support the efficacy of the levetiracetam for treating LID in PD patients, however, due to the limited number of published randomized control trials (RCTs), further RCTs are required.

Efficacy of Alpha-lipoic Acid in The Management of Diabetes Mellitus: A Systematic Review and Meta-analysis.

Alpha-lipoic acid (ALA) is a naturally-occurring compound that has shown promising antioxidant and anti-inflammatory effects in experimental and human studies. The aim of this study was to assess the efficacy of ALA in the management of patients with diabetes mellitus (DM). We searched Medline (via PubMed), EBSCO, Scopus, and Web of Science for relevant randomized controlled trials. Data on glycated hemoglobin (HbA1c), blood glucose levels, lipid profile components, HOMA, and glutathione peroxidase (GPx) were extracted and pooled as the standardized mean difference (SMD) in a random effect model meta-analysis using RevMan version 5.3. Ten studies (n = 553 patients) were included. In the term of HBA1C, the overall SMD did not favor either of the two groups (SMD = 0.01, 95% CI [-0.32,0.35]; p = 0.94) in uncomplicated T2DM patients. Moreover, there was no statistically significant difference between the two groups in terms of FBG (SMD = -0.06, 95% CI [-0.44,0.33]; p = 0.78), PPBG (SMD = 0.04, 95% CI [-0.27,0.34]; p = 0.82), HDL (SMD = -0.05, 95% CI [-0.35,0.25]; p = 0.75), LDL (SMD = -0.05, 95% CI [-0.33,0.23]; p = 0.75). In terms of GPx, ALA was superior to placebo (SMD = 0.43, 95% CI [0.07,0.8]; p = 0.02). Our analysis showed that ALA was not superior to placebo in terms of HBA1C, LDL, HDL, TC, TG reduction in uncomplicated T2DM. However, in terms of GPx, ALA was significantly superior to the placebo. Further studies with larger sample sizes should investigate different doses of ALA in DM patients.

Essential oils of green cumin and chamomile partially protect against acute acetaminophen hepatotoxicity in rats.

Essential oils of green cumin (Cuminum cyminum) and chamomile (Chamomilla recutita) have antioxidant and anti-inflammatory effects. Acetaminophen, N-acetyl-p-amino-phenol, is an over-the-counter analgesic and antipyretic. Despite being safe at therapeutic doses, acetaminophen overdose is a leading cause of acute liver failure. This study aimed to compare the possible protective effects of cumin and chamomile essential oils against acute acetaminophen hepatotoxicity in male rats. Cumin oil (400 mg/kg) and chamomile oil (250 mg/kg) were orally administered for 2 weeks prior to a single acetaminophen dose (1g/kg). Serum liver function enzymes, oxidative stress markers in the liver and histopathological features were evaluated. Acetaminophen caused marked damage to hepatocytes evidenced by a significant rise in the levels of liver function enzymes, including alanine aminotransferase and aspartate aminotransferase, and disruption to the liver antioxidant protective system. Whereas the cumin oil normalized acetaminophen-induced liver enzymes elevation, the chamomile oil slightly attenuated the increase in alanine aminotransferase levels in acetaminophen-intoxicated rats. The Chamomile oil moderately ameliorated glutathione depletion and the decrease in superoxide dismutase activity in the liver of acetaminophen-administered rats. The Cumin oil preserved the liver structure to a greater extent than chamomile oil in acetaminophen-intoxicated rats. Essential oils of cumin and chamomile partially counteracted acute acetaminophen hepatotoxicity.

Assessment of liver fibrosis in Egyptian chronic hepatitis B patients: A comparative study including 5 noninvasive indexes.

Fibrosis assessment in chronic hepatitis B (CHB) is essential for prediction of long-term prognosis and proper treatment decision. This study was conducted to assess predictability of 5 simple noninvasive fibrosis indexes in comparison to liver biopsy in CHB patients.A total of 200 CHB adult Egyptian patients were consecutively included in this study, all were subjected to liver biopsy with staging of fibrosis using METAVIR scoring system. Fibrosis indexes including S-index, red cell distribution width to platelets ratio index (RPR), fibrosis-4 index (Fib-4), AST to platelets ratio index (APRI), and AST/ALT ratio index (AAR) were compared to biopsy result and their predictabilities for the different fibrosis stages were assessed using area under receiver operating characteristic curve (AUROC) analysis.S-index showed the highest AUROCs for predicting fibrosis among the studied indexes. AUROCs of S-index, RPR, Fib-4, APRI, and AAR were: 0.81, 0.67, 0.70, 0.68, and 0.60 for prediction of significant fibrosis (F2-F4), 0.90, 0.66, 0.68, 0.67, and 0.57 for advanced fibrosis (F3-F4), and 0.96, 0.62, 0.61, 0.57, and 0.53 for cirrhosis (F4), respectively. The optimal S-index cutoff for ruling in significant fibrosis was ≥0.3 with 94% specificity, 87% PPV, and 68% accuracy, while that for ruling out significant fibrosis was <0.1 with 96% sensitivity, 91% NPV, and 67% accuracy. Accuracy of S-index was higher for predicting cirrhosis (91%) than that for predicting advanced fibrosis (79%) and significant fibrosis (68%).S-index has the highest predictability for all fibrosis stages among the studied fibrosis indexes in HBeAg-negative CHB patients, with higher accuracy in cirrhosis than in the earlier fibrosis stages.

Drug repurposing may generate novel approaches to treating depression.

OBJECTIVES: The breakthrough advancements in scientific medical research have greatly improved our understanding of the pathogenesis of depression, encouraging drug discoverers to take a shorter path than ever through drug repurposing to generate new antidepressant medications. In addition to reduced noradrenergic and serotonergic neurotransmission in the brain, other coincidence features such as glutamate neurotoxicity, inflammation and/or cerebrovascular insufficiency are implicated in the pathogenesis of major depressive disorder and late-life depression. This short review discusses the progress made in repurposing drugs for antidepressant actions. KEY FINDINGS: Drugs being repurposed as antidepressants act on novel drug targets, thereby treating resistant depression and improving remission rate. Drugs such as ketamine, dextromethorphan/quinidine and scopolamine are rapidly acting antidepressants targeting glutamate receptors. Nimodipine and quetiapine are efficient add-on therapy for late-life depression. Anti-inflammatory drugs, statins, insulin sensitizers, minocycline could remarkably contribute to treating refractory depression. SUMMARY: Drug repurposing represents an alternative approach to cope with major obstacles, including financial insufficiency and unavoidable long lag evaluation time, undermining the classical pathway of developing new hit compounds into clinically approved antidepressants.

Demographic and Socioeconomic Characteristics of Outpatients Could Modify Their Attitude Towards Misusing Medications in Northern Jordan.

BACKGROUND: Potentially inappropriate drug use, including prescribed and over-the-counter medications, is associated with increased morbidity and mortality. It also contributes to unnecessary expenditure on health services. This survey was undertaken to investigate the incidence of drug misuse and associated socioeconomic/demographic characteristics in Irbid, Jordan. DESIGN AND METHODS: The present cross section study was conducted using a validated 5-point Likert scale questionnaire to be self-reported by 480 outpatients visiting clinics in three major medical centres in Irbid, Jordan between 20th October 2015 and 27th November 2015. Descriptive analysis, chi-square tests and ordinal logistic regression models were performed. RESULTS: Patients demonstrated distinctive attitudes towards medication misuse (P<0.001). Whereas around 40% of patients sometimes stopped taking medications earlier than prescribed or doubled the dose in case of missing a dose, three quarters and two fifth of participants neither used expired drugs nor continued to take a drug when adverse drug reactions occurred, respectively. Also, there were significant associations (P<0.05) between patients' attitudes towards misusing medications and characteristics like age, gender, income and marital status. For instance, senior patients (>45 years) tended to double a medication's dose in case of no improvement, and to use others' leftover drugs without medical supervision. Further, male and female patients exhibited different attitude towards misusing medications. Unemployment and little earnings increased the risk for not using drugs properly. Furthermore, married patients were less likely to misuse medications. In particular, the educational level of patients was found to play a major role in modifying patients' attitudes towards potentially inappropriate drug use. Patients holding one or more university degrees were at lower risk for using medications inappropriately. CONCLUSIONS: This survey indicated that northern Jordanians inappropriately used medications to a great extent, suggesting that the current policies should be revised, and emphasising the importance of running public antidrug misuse awareness campaigns and establishing advanced educational/training events targeting healthcare professionals.

Corticosterone and dopamine D2/D3 receptors mediate the motivation for voluntary wheel running in C57BL/6J mice.

Physical exercise can improve cognition but whether this is related to motivation levels is unknown. Voluntary wheel running is a rewarding activity proposed as a model of motivation to exercise. To question the potential effects of exercise motivation on subsequent behaviour, we used a pharmacological approach targeting some reward mechanisms. The stress hormone corticosterone has rewarding effects mediated by activation of low affinity glucocorticoid receptors (GR). To investigate whether corticosterone synthesis motivates exercise via activation of GRs and subsequently, impacts on behaviour, we treated C57BL/6J mice acutely with the inhibitor of corticosterone synthesis metyrapone (35mg/kg) or repeatedly with the GR antagonist mifepristone (30mg/kg) prior to 1-h running wheel sessions. To investigate whether reducing motivation to exercise impacts on behaviour, we antagonised running-induced dopamine D2/D3 receptors activation with sulpiride (25 or 50mg/kg) and assessed locomotor, anxiety-related and memory performance after 20 running sessions over 4 weeks. We found that corticosterone synthesis contributes to running levels, but the maintenance of running behaviour was not mediated by activation of GRs. Intermittent exercise was not associated with changes in behavioural or cognitive performance. The persistent reduction in exercise levels triggered by sulpiride also had limited impact on behavioural performance, although the level of performance for some behaviours was related to the level of exercise. Altogether, these findings indicate that corticosterone and dopamine D2/D3 receptor activation contribute to the motivation for wheel running, but suggest that motivation for exercise is not a sufficient factor to alter behaviour in healthy mice.

Corticosterone protects against memory impairments and reduced hippocampal BDNF levels induced by a chronic low dose of ethanol in C57BL/6J mice.

Acute low doses of ethanol can produce reversible memory deficits, but it is unknown whether they persist upon chronic use. We investigated whether the chronic intake of a low dose of ethanol induces memory impairments in the ethanol-preferring C57BL/6J mouse strain. Because stress precipitates alcohol abuse and the stress hormone corticosterone contributes to memory processes, ethanol consumption and toxic effects, we also determined the impact of co-treatment with corticosterone on these effects. BDNF contributes to memory function and toxic effects of ethanol, therefore its levels were quantified in the hippocampus and frontal cortex. Ethanol (1% in drinking water) and corticosterone (250 µg/mL) were administered using the two-bottle choice test to monitor their appetitive properties. Spatial and non-spatial memory performance was assessed using the spontaneous alternation, object recognition and object location tests. The chronic exposure to a low dose of ethanol caused spatial and non-spatial memory deficits after withdrawal associated with a reduction in hippocampal BDNF levels, which were prevented by co-treatment with corticosterone (~21 mg/kg/day). The protective effect of corticosterone on memory was no longer observed at higher doses (~41 mg/kg/day), but persisted for hippocampal BDNF levels. C57BL/6J mice did not develop an appetence for 1% ethanol, but the addition of corticosterone increased voluntary consumption of and preference for the ethanol+corticosterone solutions. Although acute low doses of corticosterone (1 mg/kg) were found to rescue established memory impairments, this is the first report of a protective effect of chronic doses of corticosterone in the range of 20-32 mg/kg, and particularly against memory deficits induced by alcohol.