Analysis of 10 urinary BTEX metabolites using LC-MS/MS.

Benzene, toluene, ethylbenzene, and xylene (BTEX) are a group of volatile organic compounds that are ubiquitous in the environment due to numerous anthropogenic sources. Exposure to BTEX poses a health hazard by increasing the risk for damage to multiple organs, neurocognitive impairment and birth defects. Urinary BTEX metabolites are useful biomarkers for the evaluation of BTEX exposure, because of the ease of sampling and their longer physiological half-lives compared with parent compounds. A method that utilizes LC-MS/MS was developed and validated for simultaneously monitoring of 10 urinary BTEX metabolites. During the sample preparation an aliquot of urine was diluted with an equal volume of 1% formic acid; internal standard solution was added, and then the sample was centrifuged and analyzed. The analytes were separated on the Kinetex-F5 column by applying a linear gradient, consisting of 0.1% formic acid and methanol. The method was validated according to the FDA Bioanalytical Method Validation Guidance for Industry. The mean method's accuracies of the spiked matrix were 81-122%; the inter-day precision ranged from 4 to 20%; the limits of quantitation were 0.5-2 µg/L. The method was used for the evaluation of baseline levels of urinary BTEX metabolites in 87 firefighters.

Pregnancy outcomes following gestational exposure to papaverine: An observational comparative study.

AIMS: Papaverine is indicated for abdominal pain of various aetiologies. However, data on maternal and foetal safety following gestational exposure are lacking. The aim was to examine whether first trimester exposure to papaverine is associated with increased risk for major malformation and whether gestational exposure at any stage is associated with increased risk for preterm delivery, lower birthweight, small for gestational age, caesarean section (CS), lower Apgar score and perinatal death. METHODS: A retrospective comparative study consisted of pregnant women treated with papaverine between February 2010 and October 2019 at a large tertiary center. The control group comprised of livebirth deliveries randomly selected from the institutional obstetric database. RESULTS: The study group consisted of 498 pregnancies, which resulted in 537/544 (98.7%) live births, of whom 46/537 (8.6%) were exposed during the first trimester. The control group consisted of 498 pregnancies and 514 live births. Rate of major malformations did not differ between study group (2/46, 4.3%) and control (25/315, 4.9%, P = .67). Papaverine exposure was associated with higher rate of preterm delivery (22.3 vs. 10.3%, P < .001), CS (35.9 vs. 24.1%, P < .001) and lower birth weight (3207 vs. 3246 g, P = .02). Adjustment for treatment indication demonstrated that these remained significant only when given for obstetrical/surgical aetiologies. Comparable rates were observed for the remaining outcomes. CONCLUSIONS: Short-term gestational exposure to papaverine adjusted for indication was not associated with preterm deliveries, CS, lower birthweight, small for gestational age or perinatal death. Rate of major malformations among 46 first trimester exposures was comparable to controls.

Delayed versus classic orthostatic hypotension: clinical and prognostic implications.

Purpose: Orthostatic hypotension (OH) is a common disorder, especially among hospitalised patients. Classic OH is defined as occurring 3 or less minutes of orthostatic stress, and delayed OH as occurring after 3 min of stress. We aimed to compare clinical characteristics and prognosis between inpatients with classic vs. delayed OH.Methods: We performed a retrospective analysis of data from 358 inpatients, aged ≥60 years, who were evaluated for the occurrence of OH at the initial phase of ambulation in four previous prospective studies in our department. Demographic, clinical and prognostic data were compared between patients with (n = 191) vs. without (n = 167) OH, classic (n = 138) vs. delayed (n = 53) OH and seated (n = 115) vs. standing (n = 76) OH.Results: Demographic characteristics, duration of bed rest, the main reasons for admission and the use of offending medications were comparable between the delayed and classic OH groups. Mean maximal postural diastolic (p < .001) and systolic (p = .063) blood pressure falls were higher among patients with classic v. delayed OH. No statistically significant difference between the patients with classic and delayed OH were observed in the occurrence of OH-related symptoms (62.3 vs. 69.8%, p = .42). During a median follow-up of 5.5 years, no statistically significant differences in survival were observed between patients with vs. without OH (p = .14), classic vs. delayed OH (p = .68) and seated vs. standing OH (p = .067). On multivariate analysis, these variables remained not significantly associated with decreased survival.Conclusions: Among inpatients, delayed OH is associated with a lesser magnitude of orthostatic blood pressure fall than classic OH. However, rates of symptomatic OH and long-term mortality were comparable between the groups. Thus, among hospitalised patients, delayed OH should be considered as posing the same severity as classic OH.

High compression leg bandaging prevents seated postural hypotension among elderly hospitalized patients.

Postural hypotension (PH) is a very common and often symptomatic disorder among elderly hospitalized patients. Little is known about measures for preventing previously unknown PH in this population. We evaluated the effectiveness of high compression leg bandaging in preventing seated PH during the initial phase of ambulation, among elderly inpatients without a history of PH. We compared the occurrence of seated PH between patients who were bandaged (n = 100) and unbandaged (n = 100). The rate of seated PH was significantly lower in the bandaged than the unbandaged group (27% vs. 51%, p < 0.001, relative risk reduction 47%, and the number of patients needed to treat 4.2). On multivariate analysis, not wearing leg bandaging was one of the variables most significantly associated with eventual occurrence of PH (p = 0.002, odds ratio 2.65, and 95% confidence interval 1.42-4.97). We conclude that during ambulation of elderly inpatients, high compression leg bandaging is beneficial to prevent seated PH.

Prognostic significance of platelet count changes during hospitalization for community-acquired pneumonia.

The prognostic significance of platelet count (PC) changes during hospitalization for community-acquired pneumonia (CAP) has not been investigated. For 976 adults, clinical data during hospitalization for CAP and all-cause mortality following discharge were compared according to ΔPC (PC on discharge minus PC on admission): groups A (declining PC, ΔPC < -50 × 109/l), B (stable PC, ΔPC ± 50 × 109/l), and C (rising PC, ΔPC >50 × 109/l), and according to the presence of thrombocytopenia, normal PC, and thrombocytosis on admission/discharge. Groups A, B, and C comprised 7.9%, 46.5%, and 45.6% of patients, respectively. On hospital admission/discharge, thrombocytopenia, normal PC, and thrombocytosis were observed in 12.8%/6.4%, 84.1%/84.4%, and 3.1%/9.2% of patients, respectively. The respective 90-day, 3-year, and total (median follow-up of 54 months) mortality rates were significantly higher: in group A (40.3%, 63.6%, and 72.7%), compared to groups B (12.3%, 31.5%, and 39.0%) and C (4.9%, 17.3%, and 25.4%), p < 0.001; and in patients with thrombocytopenia at discharge (27.4%, 48.4%, and 51.6%), compared to those with normal PC (10.2%, 26.9%, and 35.4%) and thrombocytosis (8.9%, 17.8%, and 24.4%) at discharge (p < 0.001). Mortality rates were comparable among groups with thrombocytopenia, normal PC, and thrombocytosis at admission (p = 0.6). In the entire sample, each 100 × 109/l increment of ΔPC strongly predicted lower mortality (p < 0.001, relative risk 0.73, 95% confidence interval 0.64-0.83). In conclusion, PC changes are common among CAP inpatients. Rising PC throughout hospitalization is a powerful predictor of better survival, while declining PC predicts poor outcome. Evaluation of PC changes during hospitalization for CAP may provide useful prognostic information.

A rise in mean platelet volume during hospitalization for community-acquired pneumonia predicts poor prognosis: a retrospective observational cohort study.

BACKGROUND: Clinical characteristics and the prognostic significance of changes in mean platelet volume (MPV) during hospitalization for community-acquired pneumonia (CAP) have not been investigated. METHODS: Among 976 adults hospitalized for CAP, clinical characteristics, in-hospital outcomes (transfer to the intensive care unit, treatment with mechanical ventilation, prolonged hospital stay and death), and all-cause mortality following discharge, were compared according to ΔMPV (MPV on discharge minus MPV on admission): groups A (no rising MPV, ΔMPV < 0.6 fL) and B (rising MPV, ΔMPV ≥ 0.6 fL). RESULTS: Groups A and B comprised 83.8% and 16.2% of patients, respectively. Patients with a rise in MPV were more likely to be older, and to present with renal dysfunction, cerebrovascular disorder and severe pneumonia than were patients with no rise in MPV. On discharge, lower values of platelets and higher levels of neutrophils were observed in group B. Rising MPV strongly predicted a need for mechanical ventilation and in-hospital death (the respective relative risks: 2.62 and 6.79; 95% confidence intervals: 1.54-4.45 and 3.48-13.20). The respective 90-day, 3-year and total (median follow-up of 54 months) mortality rates were significantly higher in group B (29.1%, 43.0% and 50.0%) than group A (7.3%, 24.2% and 32.6%), p < 0.001 for all comparisons. A rise in MPV was a powerful predictor of all-cause mortality (relative risk 1.26 and 95% confidence interval 1.11-1.43). CONCLUSIONS: Rising MPV during hospitalization for CAP is associated with a more severe clinical profile than no rise in MPV. A rise in MPV strongly predicts in-hospital and long-term mortality.

Changes in Red Cell Distribution Width During Hospitalization for Community-Acquired Pneumonia: Clinical Characteristics and Prognostic Significance.

PURPOSE: We investigated outcomes of patients hospitalized with community-acquired pneumonia (CAP) according to the changes in red cell distribution width (RDW). METHODS: For 980 adults, clinical characteristics, outcomes during hospitalization for CAP (transfer to the intensive care unit, treatment with mechanical ventilation, prolonged hospital stay, and death), and all-cause mortality following discharge were compared: according to RDW changes versus stable RDW during hospitalization, and according to normal (≤14.7 %) versus high (>14.7 %) RDW values on admission/discharge. RESULTS: RDW changes (n = 386) during hospitalization were associated with more severe clinical and laboratory characteristics than stable RDW (n = 594). Changes in RDW strongly predicted poor in-hospital outcomes (p < 0.001). The respective 30, 90-day, and total (median follow-up 54 months) mortality rates were significantly higher (9.8, 16.0 and 43.5 %) among patients with RDW changes, compared to 4.0, 7.6 and 30.5 % among those with stable RDW (p < 0.001 for all comparisons). RDW changes, as well as high RDW (each 1 % increment) on admission and discharge, were powerful predictors of mortality (the respective relative risks 1.41, 1.13, and 1.15, and 95 % confidence intervals 1.13-1.74, 1.08-1.19, and 1.10-1.21). CONCLUSIONS: RDW changes during hospitalization for CAP are common and associated with a severe clinical profile. Time-dependent RDW changes strongly predict poor in-hospital outcomes and increased short- and long-term mortality. Repeated RDW determinations during hospitalization for CAP may provide useful prognostic information.

Acceptance rate of clinical pharmacists' recommendations-an ongoing journey for integration.

Introduction: Multidisciplinary expert team collaboration in the clinical setting, which includes clinical pharmacist involvement can facilitate significant improvements in outcomes and optimize patient management by preventing drug-related problems (DRP). This type of collaboration is particularly valuable in patients with multi-morbidity and polypharmacy such as diabetic foot patients. Evidence regarding the successful integration of a new clinical pharmacist, without previous experience into a unit is still scarce. Therefore, this study aimed to describe and evaluate the actual successful integration process of the clinical pharmacist into a diabetic foot unit by measuring the change in recommendation acceptance rate over time. Methods: A prospective, exploratory treatment effectiveness study based on the recommendation acceptance rate of a new clinical pharmacist introduced into the diabetic foot unit was conducted over a 9- month period. The clinical pharmacist identified medical and drug-related problems (DRP) or any discrepancies in the prescribing and administration of medications. Each identified DRP was documented and formulated as a recommendation by the clinical pharmacist. The main outcome measure was the acceptance rate of recommendations over time. Results: A total of 86 patients, of which 67% were men, averagely aged 66.5 (SD 11.8) years were evaluated. Calculated BMI was 30.2 (SD 6.2). The average number of medical diagnoses was 8.9 (SD3.2), and 11.1 (SD 3.7) prescribed drugs for each patient. Cardiovascular disease was presented by 95% (n = 82) of the patients and 33% of them (n = 28) had uncontrolled hyperglycemia. Averagely, 3.3 (SD 1.9) DRPs were identified pre patient. The efficacy-related DRP recommendation acceptance rate increased over the study period from 37.8% in the first 4 months to 79.4% after a period of 4.75 months. Safety-related DRP recommendation acceptance rate increased from 56% to 67.6%. Conclusion: Improved clinical outcomes and optimized pharmacologic patient management may be achieved by the successful integration of a clinical pharmacist into the team. This study provides evidence of the increasing recommendation acceptance rate of integrated, pharmacist-driven comprehensive medication management in an unexperienced unit. To overcome challenges, team members should collaborate to fully integrate the clinical pharmacist into the team-based structure and utilize proper strategies to minimize and transcend barriers.

Use of Medical Cannabis in Patients with Gilles de la Tourette's Syndrome in a Real-World Setting.

Objective: Tourette's syndrome (TS) is a neurodevelopmental disorder characterized by vocal and motor tics and other comorbidities. Clinical recommendations for the use of medical cannabis are established, yet further guidance is needed. The aim of this study was to describe the experience of patients with TS with medical cannabis. Materials and Methods: TS patients were recruited from a registry of patients ("Tikun Olam" company). Questionnaires were answered before and after 6 months of treatment. Patients were divided into two groups: (A) patients who responded and (B) patients who did not respond to the follow-up questionnaire. In group A, an analysis was made to evaluate the presence and frequency of motor and vocal tics. The patients' general mood, employment status, quality of life, and comorbidities were also included in the analysis. Results: Seventy patients were identified. The tetrahydrocannabinol and cannabidiol mean daily dose was 123 and 50.5 mg, respectively. In group A, a statistically significant improvement was identified in quality of life (p<0.005), employment status (p=0.027), and in the reduction of the number of medications (p<0.005). Sixty-seven percent and 89% of patients with obsessive-compulsive disorder and anxiety comorbidities, respectively, reported an improvement. No statistically significant improvement was identified in motor tics (p=0.375), vocal tics (p>0.999), tics frequency (p=0.062), or general mood (p=0.129). The most frequent adverse effects were dizziness (n=4) and increased appetite (n=3). Conclusion: Subjective reports from TS patients suggest that medical cannabis may improve their quality of life and comorbidities. More studies are needed to evaluate the efficacy and safety of medical cannabis. Registry in the MOH: https://www.moh.gov.sg/ (Trial number: 0185-19-ASF).

Medical cannabis for the treatment of comorbid symptoms in children with autism spectrum disorder: An interim analysis of biochemical safety.

Background: Autistic Spectrum Disorder (ASD) is a common neurodevelopmental disorder and no effective treatment for the core symptoms is currently available. The present study is part of a larger clinical trial assessing the effects of cannabis oil on autism co-morbidities. Objectives: The aim of the present study was to assess the safety of a CBD-rich oil treatment in children and adolescents with ASD. Methods: Data from 59 children and young adults (ages 5-25 years) from a single-arm, ongoing, prospective, open-label, one center, phase III study was analyzed. Participants received the Nitzan Spectrum® Oil, with cannabis extracts infused in medium chain triglyceride (MCT) oil with a cannabidiol:THC ratio of 20:1, for 6 months. Blood analysis was performed before treatment initiation, and after 3 months. Complete blood count, glucose, urea, creatinine, electrolytes, liver enzymes (AST, ALT, gamma glutamyl transferase), bilirubin, lipid profile, TSH, FT4, thyroid antibodies, prolactin, and testosterone measurements were performed at baseline, prior to starting treatment and at study midpoint, after 3 months of treatment. Results: 59 children (85% male and 15% female) were followed for 18 ± 8 weeks (mean ±SD). The mean total daily dose was 7.88 ± 4.24 mg/kg body weight. No clinically significant differences were found in any of the analytes between baseline and 3 months follow up. Lactate dehydrogenase was significantly higher before treatment (505.36 ± 95.1 IU/l) as compared to its level after 3 months of treatment (470.55 ± 84.22 IU/L) (p = 0.003). FT4 was significantly higher after 3 months of treatment (15.54 ± 1.9) as compared to its level before treatment (15.07 ± 1.88) (p = 0.03), as was TSH [(2.34 ± 1.17) and (2.05 ± 1.02)] before and after 3 months of treatment, respectively (p = 0.01). However, all these values were within normal range. A comparison of the group with additional medications (n = 14) to those who received solely medical cannabis (n = 45) showed no difference in biochemical analysis, including liver enzymes, which remained stable, except for change in potassium level which was significantly higher in the group that did not receive additional medications (0.04 ± 0.37) compared to the group receiving concomitant drug therapy (-0.2 ± 0.33) (p = 0.04). A comparison of patients who received a high dose of the cannabis oil (upper quartile-16 patients), with those receiving a low dose (lower quartile-14 patients) showed no significant difference between the two groups, except for the mean change of total protein, which was significantly higher among patients receiving high dose of CBD (0.19 ± 2.74) compared to those receiving a low dose of CBD (1.71 ± 2.46 (p = 0.01), and mean change in number of platelets, that was significantly lower among patients who received high dose of CBD (13.46 ± 31.38) as compared to those who received low dose of CBD (29.64 ± 26.2) (p = 0.0007). However, both of these changes lack clinical significance. Conclusion: CBD-rich cannabis oil (CBD: THC 20:1), appears to have a good safety profile. Long-term monitoring with a larger number of participants is warranted.

Maternal and Newborn Thyroid Hormone, and the Association With Polychlorinated Biphenyls (PCBs) Burden: The EHF (Environmental Health Fund) Birth Cohort.

Background: Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants found in human tissues. PCBs can be transferred through the placenta and may disrupt the maternal thyroid homeostasis, and affect fetal thyroid hormone production. Several studies have shown that intrauterine exposure to PCBs might be associated with abnormal levels of thyroid hormones in mothers and their offspring. Objectives: To examine the associations between environmental exposure to PCBs and thyroid hormone levels in mothers and newborns. Methods: The EHF-Assaf-Harofeh-Ichilov cohort includes 263 mothers-newborns dyads. A total of 157 mother-newborn dyads had both PCBs and thyroid function measures. Regression models were used to estimate associations between maternal PCB exposure and maternal and newborn thyroid function, controlling for possible confounders. Results: Four PCBs congeners were analyzed: PCBs 118, 138, 153, and 180. ∑PCBs median (IQR) level was 14.65 (2.83-68.14) ng/g lipids. The median maternal thyroid-stimulating hormone (TSH) level was 2.66 (0.70-8.23) µIU/ml, the median maternal free thyroxine (FT4) level was 12.44 (11.27-13.53) µg/dL, the median maternal thyroid peroxidase antibodies (TPO Ab) level was 9.6 (7.36-12.51) IU/mL. Newborns' median total thyroxine (T4) level was 14.8 (7.6-24.9) µg/dL. No association was found between exposure to different congeners or to ∑PCBs and maternal TSH, FT4, thyroglobulin autoantibodies (Tg Ab), TPO Ab and newborn total T4 levels. In multivariable analysis a 1% change in ∑PCBs level was significantly associated with a 0.57% change in maternal TSH levels in women with body mass index (BMI) < 19. The same association was observed for each of the studied PCB congeners. Maternal TPO Ab levels statistically significantly increased by 0.53 and 0.46% for 1% increase in PCB 118 and 153 congeners, respectively. In women with BMI > 25, the association between the PCBs levels and maternal TSH levels was in the opposite direction. No association was found in women with normal BMI (19-24.9). Conclusions: Background exposure to environmentally relevant concentrations of some PCBs can alter thyroid hormone homeostasis in pregnant women and might be associated with abnormal TSH levels and TPO-Ab in women with low BMI. However, these findings require further investigation.

Platelet distribution width: a novel prognostic marker in an internal medicine ward.

Background: Platelet distribution width (PDW) has demonstrated clinical significance in populations with specific disorders; its prognostic significance in internal medicine wards has not been investigated. Methods: Demographic, clinical and laboratory data were collected prospectively for 1036 internal medicine inpatients. The primary outcome was 90-day mortality, secondary outcomes were: treatment with mechanical ventilation, prolonged hospital stay, in-hospital death, and all-cause mortality following discharge. Data were assessed according to PDW values on admission ≤16.7% (group A) and >16.7% (group B). Results: Compared to group A patients (n = 273), group B patients (n = 763) were more likely to be older, admitted for cardio-cerebrovascular disorder, to present with comorbidities, to be mechanically ventilated, to have prolonged hospital stay and to die during the current hospitalization. The respective 90-day and total (median follow-up of 5 months) mortality rates were significantly higher in group B (13.2% and 16.3%) than in group A (6.6% and 9.5%), P < 0.01. On multivariate analysis, higher PDW values on admission predicted 90-day mortality and shortened survival (relative risks 1.58 and 1.26; 95% confidence intervals 0.89 - 2.78 and 0.97-1.64, respectively). Conclusion: Higher PDW values on admission to internal medicine wards are associated with a more severe clinical profile and increased risk of 90-day mortality.

International Normalized Ratio as a Screening Test for Assessment of Anticoagulant Activity for Patients Treated With Rivaroxaban or Apixaban: A Pilot Study.

Introduction: In patients treated with direct oral anti activated factor X (anti-FXa) anticoagulants such as apixaban and rivaroxaban, there are several emergency and non-emergency conditions in which anticoagulation activity should be measured. The validity of the common global clotting tests, prothrombin time and international normalized ratio (PT/INR) for determination of blood levels of these drugs, has been widely investigated. As the anticoagulation activity evaluation "calibrated anti-FXa" of these drugs is relatively more expensive and less available, we aimed to build a prediction model for anticoagulation activity assessment based on INR values. Methods and Findings: One hundred sixty samples from 80 hospitalized patients treated with apixaban or rivaroxaban were tested using PT/INR and Anti-FXa chromogenic assay. Two blood samples, trough and peak, were collected from each subject. Participants were randomly divided into two equal groups. One group (n = 40) was used to build the model, which was validated by the second group (n = 40). There was a strong correlation between anti-FXa concentrations and INR in rivaroxaban treated patients (r = 0.899, p < 0.001). Therefore, we were able to build a formula for rivaroxaban patient group which reliably represent the relationship between these two parameters. The correlation in apixaban treated patients was less predictive (r = 0.798, p < 0.001) and the formula suggested could not be validated. Conclusions: In our study, we developed a formula that estimates the anticoagulant activity of rivaroxaban by obtaining INR values. Where anti-FXa assay is unavailable, our proposed formula may be considered as a screening test for rivaroxaban.

Therapeutic levetiracetam monitoring during pregnancy: "mind the gap".

BACKGROUND: Epilepsy is one of the most common chronic neurological conditions and its treatment during pregnancy is challenging. Levetiracetam (LEV) is an antiepileptic medication frequently used during pregnancy. Only a few small studies have been published on LEV monitoring during pregnancy, demonstrating decreased serum LEV levels during the first and second trimester; however, the most significant decrease was observed during the third trimester of pregnancy. In this study we aimed to evaluate LEV pharmacokinetics during different stages of pregnancy. METHODS: We followed up and monitored serum levels of pregnant women treated with LEV for epilepsy. RESULTS: Fifty-nine women with 66 pregnancies during the study period were included. The lowest raw LEV serum concentrations were observed during the first trimester. Compared with the pre-pregnancy period, raw serum concentration was lower by 5.76 mg/L [95% confidence interval (CI) (2.78, 8.75), p = 0.039] during the first trimester. Comparing the decrease in the first trimester with either the second or the third, no significant changes were observed (p = 0.945, p = 0.866). Compared with pre-pregnancy measurements, apparent clearance was increased by 71.08 L/day [95%CI (16.34, 125.83), p = 0.011] during the first trimester. About 30% of LEV serum levels during pregnancy were below the laboratory quoted reference range. CONCLUSIONS: Raw LEV serum levels tend to decrease during pregnancy, mainly during the first trimester contrary to previous reports. Monitoring of LEV serum levels is essential upon planning pregnancy and thereafter if pre-pregnancy LEV levels are to be maintained. However, more studies are needed to assess the correlation with clinical outcome.

Oral Cannabidiol Use in Children With Autism Spectrum Disorder to Treat Related Symptoms and Co-morbidities.

Objective: Children with autism spectrum disorder (ASD) commonly exhibit comorbid symptoms such as aggression, hyperactivity and anxiety. Several studies are being conducted worldwide on cannabidiol use in ASD; however, these studies are still ongoing, and data on the effects of its use is very limited. In this study we aimed to report the experience of parents who administer, under supervision, oral cannabinoids to their children with ASD. Methods: After obtaining a license from the Israeli Ministry of Health, parents of children with ASD were instructed by a nurse practitioner how to administer oral drops of cannabidiol oil. Information on comorbid symptoms and safety was prospectively recorded biweekly during follow-up interviews. An independent group of specialists analyzed these data for changes in ASD symptoms and drug safety. Results: 53 children at a median age of 11 (4-22) year received cannabidiol for a median duration of 66 days (30-588). Self-injury and rage attacks (n = 34) improved in 67.6% and worsened in 8.8%. Hyperactivity symptoms (n = 38) improved in 68.4%, did not change in 28.9% and worsened in 2.6%. Sleep problems (n = 21) improved in 71.4% and worsened in 4.7%. Anxiety (n = 17) improved in 47.1% and worsened in 23.5%. Adverse effects, mostly somnolence and change in appetite were mild. Conclusion: Parents' reports suggest that cannabidiol may improve ASD comorbidity symptoms; however, the long-term effects should be evaluated in large scale studies.

Prognostic significance of changes in red cell distribution width in an internal medicine ward.

BACKGROUND: The prognostic significance of red cell distribution width (RDW) during hospitalization in internal medicine wards was not sufficiently investigated. METHODS: Demographic, clinical and laboratory characteristics were collected from 586 internal medicine inpatients. Following discharge, all-cause mortality was recorded. The data were compared according to ΔRDW during hospitalization (primary endpoint), and to normal (≤14.7%) vs. high (>14.7%) RDW values on admission/discharge (secondary endpoint). RESULTS: Group A (rise in RDW, ΔRDW +0.4%), group B (nonsignificant RDW changes, ΔRDW up to 0.4%) and group C (drop in RDW, ΔRDW -0.4%) comprised 20.3%, 60.6% and 19.1% of the patients, respectively. High RDW on admission and discharge was found in 31.7% and 31.4% of patients, respectively. In-hospital mortality rates were higher in group A than in groups B and C (14.3% vs. 2.8% and 4.5%, p<0.001), whereas increased long-term (median follow-up 43 months) mortality rates were observed in group C (35.7%), compared to groups A (17.6%) and B (23.4%), p=0.009. Mortality rates were significantly higher (p<0.001) in patients with high than normal RDW on admission (51.1% vs. 20.3%) and on discharge (50.5% vs. 20.6%). Every 1% increment of RDW on admission and discharge strongly predicted mortality (relative risks 1.21 and 1.21; 95% confidence intervals 1.12-1.31 and 1.13-1.32, respectively). CONCLUSIONS: High RDW on admission and discharge predicted poor prognosis. Rising RDW throughout hospitalization was associated with higher in-hospital mortality, while an elevated long-term mortality rate was observed in patients with declining RDW. Repeated RDW measurements may improve risk stratification for internal medicine inpatients.

Clinical characteristics and prognostic significance of changes in platelet count in an internal medicine ward.

BACKGROUND: The clinical characteristics and prognostic significance of changes in platelet count (PC) during hospitalization in internal medicine wards have not been well investigated. METHODS: Demographic, clinical and laboratory data were collected from 345 patients admitted to an internal medicine ward. Following discharge, all-cause mortality was recorded. These data were compared, according to deltaPC (PC on discharge minus PC on admission): group 1 (drop in PC, deltaPC -50×10(9)/l), group 2 (no significant PC changes, deltaPC up to 50×10(9)/l) and group 3 (rise in PC, deltaPC +50×10(9)/l). RESULTS: Groups 1, 2 and 3 comprised 64 (18.5%), 200 (58%) and 81 (23.5%) patients, respectively. Patients from group 3 were younger, more likely admitted for infection and less likely for cardiovascular disorder, and less often presenting with coronary artery disease, complex nursing care and thrombocytosis on admission or thrombocytopenia on discharge than patients from groups 1 and 2. Mean platelet volume was higher in group 2 on admission and lower in group 3 on discharge. During a median follow-up of 25 months, 146 (42.3%) of 345 patients died. The survival rate was higher for group 3 (65.4%) than for groups 1 (45.3%) and 2 (58.5%), p=0.003. In the entire cohort, each 100×10(9)/l increment of deltaPC was a powerful predictor of lower mortality (p=0.03, relative risk=0.83, 95% confidence interval=0.71-0.98). CONCLUSIONS: Increased PC throughout hospitalization was associated with better prognosis than a drop or blunted rise in PC. The assessment of PC changes in an internal medicine ward may provide useful prognostic information.

Clinical characteristics and prognostic significance of serum albumin changes in an internal medicine ward.

BACKGROUND: The prognostic significance of hypoalbuminemia and the dynamic changes in serum albumin during hospitalization in internal medicine wards has not been sufficiently investigated. METHODS: Demographic, clinical and laboratory data were collected from 276 patients admitted to our internal medicine ward for a variety of acute disorders. Following discharge, all-cause mortality was recorded. These data were compared between patient groups, according to levels of albumin: hypoalbuminemia or normoalbuminemia (serum albumin <34 g/l and ≥ 34 g/l, respectively), on admission and discharge. RESULTS: Hypoalbuminemia on admission and on discharge was found in 46% and 54% of patients, respectively. Anemia, renal dysfunction, malignant disease, hypocholesterolemia, lymphopenia and albuminuria were more prevalent in patients with hypoalbuminemia, compared to those with normoalbuminemia (p ≤ 0.03). During a median follow-up period of 23 months, 107 of 276 patients died. Mortality was significantly higher (p<0.001) in patients with hypoalbuminemia than normoalbuminemia on admission (52.0% vs. 27.5%) and on discharge (53.7% vs. 21.2%), including those admitted with normoalbuminemia and discharged with hypoalbuminemia (43.6%). Survival rate was higher for patients admitted with hypoalbuminemia and discharged with normoalbuminemia than for those remaining with hypoalbuminemia (82.4% vs. 42.8%, p=0.004). The level of albumin on discharge (each 10 g/l decrement) was the most powerful predictor of shortened survival (relative risk 2.79, 95% confidence interval 2.04-3.70). CONCLUSIONS: Hypoalbuminemia on admission, as well as persistence or development of hypoalbuminemia throughout hospitalization, was associated with poor prognosis. Treatment aimed at increasing low albumin or maintaining its normal level may improve survival.