Prevalence of clozapine-induced sialorrhea and its effect on quality of life.

RATIONALE: Clozapine has proven to be superior to other antipsychotic drugs in the treatment of schizophrenia but is under-prescribed due to its potentially severe side effects. Clozapine-induced sialorrhea (CIS) is a frequent and extremely uncomfortable side effect, which remains understudied. OBJECTIVES: To examine the prevalence of diurnal and nocturnal CIS in a sample of patients treated with clozapine, and to evaluate its impact on quality of life. METHODS: We conducted a cross-sectional, observational study of 130 patients with schizophrenia spectrum disorders treated with clozapine. The prevalence of CIS was evaluated via specific sialorrhea scales. None of the patients included in the study was receiving a specific treatment for hypersalivation during the study period. Possible associations between sialorrhea and clinical and quality of life variables were analyzed. RESULTS: Of 130 subjects, 120 (92.3%) suffered from CIS. Eighty-one (62.31%) suffered from diurnal CIS, 115 (88.56%) from nocturnal CIS, and 85 (65.38%) suffered from both. Significant positive associations between quality of life and diurnal CIS (B = 0.417; p = 2.1e - 6, R2 = 0.156) and nocturnal CIS (B = 0.411; p = 7.7e - 6, R2 = 0.139) were detected. Thirty per cent of the subjects reported a moderate to severe negative impact of sialorrhea on their quality of life. CONCLUSIONS: The present study suggests that CIS is highly prevalent in patients with schizophrenia and has an important impact on quality of life in one-third of our sample. Therefore, the inclusion of a systematic evaluation and treatment of CIS in standard clinical practice is highly recommended. TRIAL REGISTRATION: Clinical Trials ( https://clinicaltrials.gov ) under reference NCT04197037.

Long-term outcome predictors after functional remediation in patients with bipolar disorder.

BACKGROUND: Improving functioning in patients with bipolar disorder (BD) is one of the main objectives in clinical practice. Of the few psychosocial interventions that have been specifically developed to enhance the psychosocial outcome in BD, functional remediation (FR) is one which has demonstrated efficacy. The aim of this study was to examine which variables could predict improved functional outcome following the FR intervention in a sample of euthymic or subsyndromal patients with BD. METHODS: A total of 92 euthymic outpatients were included in this longitudinal study, with 62 completers. Partial correlations controlling for the functional outcome at baseline were calculated between demographic, clinical and neurocognitive variables, and functional outcome at endpoint was assessed by means of the Functioning Assessment Short Test scale. Next, a multiple regression analysis was run in order to identify potential predictors of functional outcome at 2-year follow-up, using the variables found to be statistically significant in the correlation analysis and other variables related to functioning as identified in the previous scientific literature. RESULTS: The regression model revealed that only two independent variables significantly contributed to the model (F(6,53): 4.003; p = 0.002), namely verbal memory and inhibitory control. The model accounted for 31.2% of the variance. No other demographic or clinical variable contributed to the model. CONCLUSIONS: Results suggest that patients with better cognitive performance at baseline, especially in terms of verbal memory and executive functions, may present better functional outcomes at long term follow-up after receiving functional remediation.

Augmentation of EMDR with multifocal transcranial current stimulation (MtCS) in the treatment of fibromyalgia: study protocol of a double-blind randomized controlled exploratory and pragmatic trial.

BACKGROUND: Fibromyalgia (FM) is a generalized, widespread chronic pain disorder affecting 2.7% of the general population. In recent years, different studies have observed a strong association between FM and psychological trauma. Therefore, a trauma-focused psychotherapy, such as eye movement desensitization and reprocessing (EMDR), combined with a non-invasive brain stimulation technique, such as multifocal transcranial current stimulation (MtCS), could be an innovative adjunctive treatment option. This double-blind randomized controlled trial (RCT) analyzes if EMDR therapy is effective in the reduction of pain symptoms in FM patients and if its potential is boosted with the addition of MtCS. METHODS: Forty-five patients with FM and a history of traumatic events will be randomly allocated to Waiting List, EMDR + active-MtCS, or EMDR + sham-MtCS. Therapists and patients will be kept blind to MtCS conditions, and raters will be kept blind to both EMDR and MtCS. All patients will be evaluated at baseline, post-treatment, and follow-up at 6 months after post-treatment. Evaluations will assess the following variables: sociodemographic data, pain, psychological trauma, sleep disturbance, anxiety and affective symptoms, and wellbeing. DISCUSSION: This study will provide evidence of whether EMDR therapy is effective in reducing pain symptoms in FM patients, and whether the effect of EMDR can be enhanced by MtCS. TRIAL REGISTRATION: ClinicalTrials.gov NCT04084795 . Registered on 2 August 2019.

The evolution of physical and technical performance parameters in the English Premier League.

This study examined the evolution of physical and technical soccer performance across a 7-season period in the English Premier League. Match performance observations (n=14 700) were analysed for emergent trends. Total distance covered during a match was ~2% lower in 2006-07 compared to 2012-13. Across 7 seasons, high-intensity running distance and actions increased by ~30% (890±299 vs. 1 151±337 m, p<0.001; ES: 0.82) and ~50% (118±36 vs. 176±46, p<0.001; ES: 1.41), respectively. Sprint distance and number of sprints increased by ~35% (232±114 vs. 350±139 m, p<0.001; ES: 0.93) and ~85% (31±14 vs. 57±20, p<0.001; ES: 1.46), respectively. Mean sprint distance was shorter in 2012-13 compared to 2006-07 (5.9±0.8 vs. 6.9±1.3 m, p<0.001; ES: 0.91), with the proportion of explosive sprints increasing (34±11 vs. 47±9%, p<0.001; ES: 1.31). Players performed more passes (35±17 vs. 25±13, p<0.001; ES: 0.66) and successful passes (83±10% vs. 76±13%, p<0.001; ES: 0.60) in 2012-13 compared to 2006-07. Whereas the number of short and medium passes increased across time (p<0.001; ES>0.6), the number of long passes varied little (p<0.001; ES: 0.11). This data demonstrates evolution of physical and technical parameters in the English Premier League, and could be used to aid talent identification, training and conditioning preparation.

Laminaria versus extra-amniotic saline solution infusion for cervical ripening in second-trimester labor inductions.

OBJECTIVE: The aim of this study was to determine which cervical ripening method, laminaria placement or extra-amniotic saline solution infusion, was associated with the shorter interval from induction to delivery in the second trimester. STUDY DESIGN: Women admitted for indicated second-trimester labor induction with an unfavorable cervix were randomly assigned to receive either intracervical placement of laminaria (n = 25) or extra-amniotic saline solution infusion (n = 25) with concurrent concentrated oxytocin and vaginally administered prostaglandin E2 (10 mg every 6 hours). Treatment success was defined as an interval from induction to delivery of < or =24 hours. RESULTS: Maternal age, race, parity, gestational age, and initial cervical dilatation were similar between the groups. Indications for uterine evacuation were also similar and included fetal death (n = 7), aneuploidy (n = 20), fetal structural anomaly (n = 18), and maternal indications (n = 4). There was no difference in the mean intervals from induction to delivery (laminaria, 16 +/- 8 hours, vs extra-amniotic saline solution infusion, 17 +/- 10 hours) or the number of treatment successes (laminaria, n = 23, vs extra-amniotic saline solution infusion, n = 21). Retained placenta, live birth, and hemorrhage occurred with similar frequencies in the two groups. CONCLUSION: Relative to laminaria, extra-amniotic saline solution infusion did not shorten the induction-to-delivery interval in women undergoing indicated second-trimester labor induction with concentrated oxytocin and low-dose vaginally administered prostaglandin E2.

Antiphospholipid antibodies in women at risk for preeclampsia.

OBJECTIVE: The aim of this study was to determine whether positive results of tests for any of 5 antiphospholipid antibodies are associated with recurrent preeclampsia among women with a history of preeclampsia in a previous pregnancy. STUDY DESIGN: Second-trimester serum samples were obtained from 317 women with preeclampsia in a previous pregnancy who were being followed up in a prospective treatment trial. The serum samples were measured by enzyme-linked immunoassay for immunoglobulin G and immunoglobulin M antibodies against 5 phospholipids. Positive results were analyzed with regard to preeclampsia, severe preeclampsia, intrauterine growth restriction, and preterm delivery. RESULTS: Sixty-two of the 317 women (20%) had recurrent preeclampsia develop, 19 (6%) had severe preeclampsia, and 18 (5.8%) were delivered of infants with growth restriction. Positive results of tests for immunoglobulin G or immunoglobulin M antiphospholipid antibodies were not associated with recurrent preeclampsia. Positive results for immunoglobulin G or immunoglobulin M antibodies at the 99th percentile were also not associated with preterm delivery. Positive results at the 99th percentile for immunoglobulin G antiphosphatidylserine antibody were associated with severe preeclampsia, and positive results at the 99th percentile for immunoglobulin G anticardiolipin, antiphosphatidylinositol, and antiphosphatidylglycerol antibodies were associated with intrauterine growth restriction. The positive predictive values for these outcomes all were approximately 30%. CONCLUSION: Positive results of testing for antiphospholipid antibodies in the second trimester were not associated with recurrent preeclampsia among women at risk because of a history of preeclampsia. Positive results for immunoglobulin G antiphosphatidylserine antibody were associated with severe preeclampsia, and positive results for immunoglobulin G anticardiolipin, antiphosphatidylinositol, and antiphosphatidylglycerol antibodies were associated with intrauterine growth restriction. However, the positive predictive values for all these associations were modest. Testing for antiphospholipid antibodies during pregnancy is of little prognostic value in the assessment of the risk for recurrent preeclampsia among women with a history of preeclampsia.

Cardiovascular effects of intravaginal misoprostol in the mid trimester of pregnancy.

OBJECTIVE: Our aim was to evaluate the cardiovascular effects of high-dose intravaginal misoprostol administration by means of transthoracic electrical bioimpedance monitoring. STUDY DESIGN: Healthy women undergoing mid trimester pregnancy interruption with intravaginal misoprostol were eligible for this prospective observational study. Baseline blood pressure was obtained for 1 hour and transthoracic electrical bioimpedance monitoring was performed before misoprostol administration, 600 microg vaginally. Posttreatment assessments were made every 15 minutes for a total of 4 hours, with patients in a left lateral recumbent position. Heart rate, mean arterial pressure, cardiac index, stroke index, systemic vascular resistance index, and end-diastolic volume index were determined. Measurements were averaged for 30-minute intervals and reported as mean +/- SD. Statistical analyses included the paired t test and repeated-measures analysis of variance. RESULTS: Nine women consented to have transthoracic electrical bioimpedance monitoring, and no statistically significant changes in any of the measured cardiac parameters for the 4-hour monitoring interval were noted. Direct comparisons between the pretreatment and 2-hour posttreatment intervals (reported time peak of blood misoprostol levels) also revealed no significant differences in the cardiovascular index values. CONCLUSION: High-dose intravaginal misoprostol in the mid trimester does not alter maternal cardiac function as measured by transthoracic electrical bioimpedance.

Second-trimester plasma homocysteine levels and pregnancy-induced hypertension, preeclampsia, and intrauterine growth restriction.

OBJECTIVE: The purpose of this study was to determine whether second-trimester plasma homocysteine levels are elevated among women whose pregnancies are subsequently complicated by pregnancy-induced hypertension, preeclampsia, or intrauterine growth restriction. STUDY DESIGN: Women with normal but relatively low plasma zinc levels were randomly assigned to receive zinc supplementation or placebo from 19 weeks' gestation until delivery. Plasma homocysteine concentration and plasma and erythrocyte folate levels were determined for all available stored samples (zinc group, 231/294; placebo group, 206/286) at 26 and 37 weeks' gestation. Among all women with available samples, pregnancy-induced hypertension (n = 12) or preeclampsia (n = 4) developed in 16 women, and 22 pregnancies were complicated by intrauterine growth restriction. RESULTS: Mean homocysteine levels in women with pregnancy-induced hypertension and preeclampsia were similar to those of control subjects at 26 weeks' gestation but were significantly higher at 37 weeks' gestation. Homocysteine levels were similar between women with pregnancies complicated by intrauterine growth restriction and control subjects at both time points. CONCLUSION: Second-trimester plasma homocysteine concentrations do not predict the subsequent development of pregnancy-induced hypertension, preeclampsia, and intrauterine growth restriction.

The incidence of actinomyces-like organisms in Papanicolaou-stained smears of copper- and levonorgestrel-releasing intrauterine devices.

Actinomyces-like organisms (ALOs) are a common finding in Papanicolaou-stained cervico-vaginal smears (PAP smears) of women using an intrauterine device (IUD). The incidence of ALOs positive PAP smears depends on the type of IUD. Pelvic actinomycosis is a severe disease that may require hysterectomy and salpingo-oophorectomy. In a retrospective study we compared the incidence of ALOs positive PAP smears in users of the new levonorgestrel-releasing intrauterine device (LNG-IUD) (n = 52) with the incidence in Multiload Copper IUD (ML375) users (n = 104). All IUDs had been inserted from 1996-1998. Women with a follow-up period of more than 9 months were included into the final analysis (LNG-IUD: n = 34; ML375: n = 65). The incidence of ALOs in LNG-IUD users (2.9%) was significantly lower than in ML375 users (20%). Clinical consequences of ALOs positive PAP smears are discussed controversially. The low incidence in the LNG-IUD users probably leads to less IUD-removals, reinsertions and less pelvic-inflammatory-diseases.

Safety of labor epidural anesthesia for women with severe hypertensive disease. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: The aim of this study was to determine whether epidural anesthesia during labor increased the frequencies of cesarean delivery, pulmonary edema, and renal failure among women with severe hypertensive disease. STUDY DESIGN: We performed a secondary retrospective analysis of a subgroup population within a multicenter double-blind trial of low-dose aspirin therapy for women at high risk for development of preeclampsia. Subjects in whom severe hypertensive disease developed were selected. The primary outcomes were the overall frequencies of cesarean delivery among women with severe hypertensive disease who had labor with and without epidural anesthesia. Other maternal and neonatal outcomes were also compared between women who did and did not receive epidural anesthesia. RESULTS: Among the women with severe hypertensive disease (n = 444) 327 had labor. Among the women with severe disease who had labor there was no difference in either the overall cesarean delivery rate (32.1% vs 28.0%; P =.44) or the rate of cesarean delivery for fetal distress or failure to progress (27.8% vs 22.0%; P =.26) between women who did and did not receive epidural analgesia. Women with chronic hypertension were more likely to have a cesarean delivery overall if they received epidural anesthesia, but there was otherwise no difference in the frequencies of cesarean delivery for these indications between women with and without epidural anesthesia within each of the high-risk groups. Pulmonary edema was rare and acute renal failure did not develop in any women. CONCLUSION: Epidural anesthesia use did not increase the frequencies of cesarean delivery, pulmonary edema, and renal failure among women with severe hypertensive disease.

A randomized, double-blind, hemodynamic evaluation of nifedipine and labetalol in preeclamptic hypertensive emergencies.

OBJECTIVE: Our purpose was to compare the hemodynamic effects of orally administered nifedipine and intravenously administered labetalol in preeclamptic hypertensive emergencies. STUDY DESIGN: Our study was a randomized, double-blind evaluation of nifedipine and labetalol in women with preeclampsia and a systolic blood pressure >170 mm Hg or a diastolic blood pressure >105 mm Hg. Nifedipine or labetalol and placebo were given, so patients received both tablet and intravenous solution. Hemodynamic parameters at dosing and at 15, 30, 60, and 120 minutes were recorded. Outcome measures were cardiac index, systemic vascular resistance index, mean arterial pressure, and heart rate. Data were analyzed by repeated-measures analysis of variance (Friedman test) with Dunn posttests, the Mann-Whitney U test, and the chi(2) test with the Yates correction. Significance was set at P <.05. RESULTS: At dosing, the nifedipine group (n = 6) had a cardiac index of 3.08 +/- 0.51 L/min per square meter. There was a 43% increase in the cardiac index after nifedipine administration (P =.0008). There was no significant effect in the labetalol group (P =.697). There was a significant decrease in the systemic vascular resistance index after nifedipine dosing (P =.002) but no significant effect on this index after labetalol use (P =.479). The mean arterial pressure was significantly affected in both groups as follows: nifedipine, P =. 001; labetalol, P =.004. The postanalysis showed significance at 60 minutes for both. An insignificant increase in heart rate with nifedipine (P =.147) and a significant decrease with labetalol (P =. 034) were noted. CONCLUSIONS: Nifedipine increases cardiac index, whereas labetalol may not do so.

Are oral contraceptives masking symptoms of chlamydial cervicitis and pelvic inflammatory disease?

Tubal factor infertility is often diagnosed without any documented history of pelvic inflammatory disease. Chlamydial infection is one of the most common causes of pelvic inflammatory disease and likely also of infertility and ectopic pregnancy. Oral contraceptives may alter the course of chlamydial infections which may mask the clinical expression of the disease. This paper considers a number of unresolved matters related to oral contraceptive use and its possible influence on the epidemiology and course of chlamydial pelvic inflammatory disease.

Fluorescence imaging of reactive oxygen metabolites generated in single macrophage cells (NR8383) upon phagocytosis of natural zeolite (erionite) fibers.

In this paper we address the phenomenon of reactive oxygen metabolite generation subsequent to phagocytosis of mineral fibers by macrophages. Natural erionite fibers were chosen because of their established toxicity. Macrophages (cell line NR8383) were loaded with the dye 5-(and 6)-carboxy-2',7'-dichlorodihydrofluorescein diacetate and exposed to erionite particles by centrifuging cells and fibers together to effect adherence. Reactive oxygen metabolite generation was examined by monitoring the fluorescence of oxidized dye formed via the reaction with oxygen species produced during phagocytosis. Individual cells were repeatedly scanned for up to 2 hr to monitor the evolution of this fluorescence. It was found that erionite-exposed cells had a mean total fluorescence of three times that of controls during the first 35 min, declining to two times that of controls at 35-60 min and about the same level as that of controls at 60-80 min. Ultrastructural studies of similarly treated aliquots of cells showed marked variation in size and numbers of the phagocytized particles. This study demonstrates that intracellular oxidation can be monitored on a single cell basis over a period of time. Quantitative studies are in progress to establish the relationship between the phagocytized particulate load and the extent of fluorescence.

Hemodynamic effects of oral nifedipine in preeclamptic hypertensive emergencies.

OBJECTIVE: Our purpose was to evaluate the hemodynamic effects of oral nifedipine in preeclamptic hypertensive emergencies. STUDY DESIGN: A prospective observational study of the hemodynamic effects of oral nifedipine was conducted with severely preeclamptic patients receiving magnesium sulfate infusion during a hypertensive emergency. Patients were eligible for the study if systolic blood pressure was > or = 170 m Hg or the diastolic blood pressure was > or = 105 mm Hg on repeat measurements 15 minutes apart at > or = 24 weeks' gestation. Nifedipine was given with an initial dose of 10 mg orally followed by 20 mg orally every 20 minutes until systolic blood pressure was > 160 mm Hg and the diastolic blood pressure was < 100 mm Hg, or for a total of five doses. Patients were hemodynamically monitored in the lateral recumbent position by thoracic electrical bioimpedance before during, and after oral nifedipine dosing. Cardiac index, systemic vascular resistance index, mean arterial pressure, heart rate, and stroke index were all recorded at baseline and during treatment. Data were analyzed by analysis of variance for repeated measures (alpha 0.05) and paired t tests, baseline versus 15 minutes (alpha 0.01). RESULTS: Ten severely preeclamptic patients at 33.2 +/- 3.0 (mean +/- SD) weeks' gestation were enrolled in the study. Mean arterial pressure measurements taken at baseline, 0.25, 0.5, 1, and 4 hours were 133 +/- 10, 119 +/- 8, 109 +/- 8 89 +/- 12, and 100 +/- 13 mm Hg (mean +/- SD, p < 0.0001, analysis of variance repeated measures). Cardiac index increased over time (p = 0.0011, analysis of variance repeated measures). There was no significant effect on maternal heart rate or stroke index. No periodic fetal heart rate changes were noted. One patient had nausea. CONCLUSION: Oral nifedipine appears to be an effective antihypertensive agent in preeclamptic hypertensive emergencies. A steady decrease in mean arterial pressure, systemic vascular resistance, and a mirrored increase in cardiac index are noted.

In vitro interaction of zeolite fibers with individual cells (macrophages NR8383): measurement of intracellular oxidative burst.

Inhalation of fibrous minerals such as asbestos and erionite can cause various lung diseases, including cancer. The mechanism by which these fibers induce disease is an area of active research. Interaction of fibers with lung macrophages leads to release of many substances. Among these, reactive oxygen metabolites (which include hydrogen peroxide, superoxide, and possibly hydroxyl radicals) are proposed to cause cellular damage. In this paper, we report a method for observing intracellular hydrogen peroxide release as rat lung-derived macrophages (NR-8383) phagocytize erionite fibers. This is possible by observing the fluorescence of 2',7'-dichlorofluorescein-the intracellular, oxidized form of 5 (and 6)-carboxy-2', 7'-dichlorodihydrofluorescin formed in the presence of newly released hydrogen peroxide. We are able to image the fluorescence within a single cell, thereby allowing us to get information on the spatial distribution of the metabolites.

Autologous blood donation with placenta previa: is it feasible?

Autologous blood donation has been recommended for patients with placenta previa. We hypothesized that premature delivery, preexisting anemia, and bleeding would limit its utilization. We reviewed the charts of all patients admitted with placenta previa between July 1, 1989, and April 30, 1992. To be eligible for autologous donation we assumed that the patient would need to be asymptomatic with a hematocrit 34% or higher at 32 weeks' gestation. Eighty-eight patients were admitted with placenta previa, 12 (14%) of whom were eligible for autologous donation. Two eligible patients required transfusion at delivery and four delivered prior to 34 weeks. Few patients with placenta previa are eligible for autologous donation and although two would have used their autologous units, twice as many may have been compromised by recent autologous donation. We conclude that autologous donation is not feasible in a majority of patients with placenta previa and is of limited usefulness in its management.

Favorable hemodynamic effects of magnesium sulfate in preeclampsia.

OBJECTIVE: Our purpose was to evaluate the hemodynamic effects of magnesium sulfate in preeclamptic and preterm labor patients. STUDY DESIGN: Fifteen preeclamptic patients at 32.4 +/- 3.3 (mean +/- SD) weeks' gestation and 11 preterm labor patients (31.3 +/- 2.8 weeks) were hemodynamically monitored in the lateral recumbent position by thoracic electrical bioimpedance (BoMed, Irvine, Calif.) before and during high-dose magnesium sulfate bolus and infusion. Cardiac index, systemic vascular resistance index, mean arterial pressure, heart rate, and stroke index were all recorded at baseline and during magnesium sulfate infusion. All patients received a standard crystalloid infusion. Data analysis continued until the patient received epidural placement or other antihypertensive therapy or was delivered. RESULTS: At baseline the systemic vascular resistance index was 2465 +/- 718 F.ohm/m2 and the cardiac index was 3.6 +/- 1.0 L/min/m2 for the preeclamptic patients. These were significantly different compared with the preterm labor patients, who had a systemic vascular resistance index of 1377 +/- 563 F.ohm/m2 and 4.6 +/- 1.2 L/min/m2. Magnesium sulfate infusion resulted in a rapid, sustained fall in systemic vascular resistance and a rise in cardiac index in the preeclamptic patient. This effect was evident at least 4 hours after initiation of the bolus and infusion. In the preterm labor patients the hemodynamic effects of magnesium sulfate were minimal and were noted only during the magnesium sulfate bolus. CONCLUSION: Magnesium sulfate infusion appears to have a prolonged hemodynamic effect in the preeclamptic patient. Sustained reduction in systemic vascular resistance and an increase in cardiac index is found in patients with preeclampsia but not in preterm labor.