Effect of Communication Style on Perceptions of Medication Side Effect Risk among Pharmacy Students.
Sawant, Ruta V; Beatty, Collin R; Sansgiry, Sujit S
2016-10-25
Objective. To assess the effect of communication style, and frequency and severity of medication side-effects, on pharmacy students' perception of risk of experiencing side effects. Methods. One hundred responses from pharmacy students were obtained using an online survey. Participants were presented with a drug information box containing drug name, drug usage, and one side-effect associated with the drug. Information on side-effect for each drug was presented in one of eight experimental conditions, in a 2 (side-effect frequency: low, high), X2 (side-effect severity: mild, severe) X2 (communication style: verbal, verbal + natural frequency) factorial design. Risk perception of experiencing side effects was measured. Results. Communication style was found to have a significant impact on risk perception depending on the context of frequency and severity associated with the side effect. Conclusion. Communication style plays a significant role in formulating risk perceptions of medication side effects. Training in pharmaceutical counseling should include special emphasis on effective language use.
Friedman, Michael C.; McGillivray, Shannon; Murayama, Kou; Castel, Alan D.
2014-01-01
Older adults often experience memory impairments, but can sometimes use selective processing and schematic support to remember important information. The current experiments investigate to what degree younger and healthy older adults remember medication side effects that were subjectively or objectively important to remember. Participants studied a list of common side effects, and rated how negative these effects were if they were to experience them, and were then given a free recall test. In Experiment 1, the severity of the side effects ranged from mild (e.g., itching) to severe (e.g., stroke), and in Experiment 2, certain side effects were indicated as critical to remember (i.e., “contact your doctor if you experience this”). There were no age differences in terms of free recall of the side effects, and older adults remembered more severe side effects relative to mild effects. However, older adults were less likely to recognize critical side effects on a later recognition test, relative to younger adults. The findings suggest that older adults can selectively remember medication side effects, but have difficulty identifying familiar but potentially critical side effects, and this has implications for monitoring medication use in older age. PMID:25331278
Side effect burden of antipsychotic drugs in real life - Impact of gender and polypharmacy.
Iversen, Trude Seselie Jahr; Steen, Nils Eiel; Dieset, Ingrid; Hope, Sigrun; Mørch, Ragni; Gardsjord, Erlend Strand; Jørgensen, Kjetil Nordbø; Melle, Ingrid; Andreassen, Ole A; Molden, Espen; Jönsson, Erik G
2018-03-02
Antipsychotic-associated side effects are well known and represent a significant treatment challenge. Still, few large studies have investigated the overall side effect burden of antipsychotics in real-life settings. To describe the occurrence of side effects and perceived burden of antipsychotics in a large naturalistic sample, taking polypharmacy and patient characteristics into account. Patients (n=1087) with psychotic disorders were assessed for side effects using the Udvalg for Kliniske Undersøgelser (UKU) side effect rating scale in addition to assessment of clinical and pharmacological data. Statistical analyses were performed controlling for possible confounding factors. Use of antipsychotics showed significant associations to neurologic and sexual symptoms, sedation and weight gain, and >75% of antipsychotics-users reported side effects. More side effects were observed in patients using several antipsychotics (p=0.002), with increasing total dose (p=0.021) and with antipsychotics in combinations with other psychotropic drugs. Patients and investigators evaluated the side effect burden differently, particularly related to severity, gender and antipsychotics dose. Twice as many females described side effect burden as severe (p=0.004). Patients with psychotic disorders have a high occurrence of symptoms associated with use of antipsychotics, and polypharmacy and female gender are seemingly risk factors for reporting a severe side effect burden. Due to the cross-sectional design evaluation of causality is tentative, and these findings should be further investigated in prospective studies. Copyright © 2017 Elsevier Inc. All rights reserved.
Side effects associated with anti-HIV drugs.
Highleyman, L
1998-04-01
Many side effects are associated with the use of anti-HIV drugs, impacting the development of drug resistance and the quality of life for HIV-patients. Concern about side effects is a primary factor in deterring people from beginning HIV therapy. Frequency and severity of side effects vary greatly, but they are frequently more common and severe in people who are taking a new drug or who have advanced HIV disease. Information on side effects comes largely from clinical trials; however, many side effects are not discovered until the drug has been approved and used by larger numbers of people. Side effects vary from serious toxicities that require stopping treatment to uncomfortable or annoying side effects that interfere with daily life. A table categorizes the four major side effects (nausea, fever, skin rash, and fatigue) and divides them into grades that describe their intensity. A chart lists the side effects associated with specific anti-HIV drugs. Suggestions for managing side effects are included.
Goethe, John W; Woolley, Stephen B; Cardoni, Alex A; Woznicki, Brenda A; Piez, Deborah A
2007-10-01
Patients with major depression discontinue taking their antidepressants for many reasons. Although side effects are often cited as the reason for discontinuation, few prospective studies have addressed this question, and none has specifically examined discontinuation in patients with severe depression. Inpatients and outpatients treated with a selective serotonin reuptake inhibitor for major depressive disorder were identified after admission. Three months later, patients were contacted and interviewed to determine antidepressant usage and the side effects experienced, including when these were experienced and their severity. Between October 2001 and April 2003, 406 English- or Spanish-speaking patients aged 18 to 75 years were followed up. One in 4 patients discontinued the index antidepressant. Among specific side effects noted, only "change in weight" and "anxiety" were significant predictors of discontinuation after controlling for confounders. Experiencing 1 or more "extremely" bothersome side effects was associated with more than a doubling of the risk of discontinuation, but the presence of side effects and side effects less severe than "extremely" bothersome were not significant predictors. There were no differences among selective serotonin reuptake inhibitor antidepressants in either the presence/absence of side effects or in the discontinuation rates. The results suggest that the contribution of side effects to antidepressant discontinuation is more complex than previously suggested. Disparate findings from earlier studies may reflect aspects of study design, such as examining populations whose severity of depression varied widely or not controlling for important confounding factors. Future research should separately examine high-risk groups (or control for severity of depression) and carefully rule out other potential contributors to discontinuation.
Reirradiation on recurrent cervical cancer case: Treatment response and side effects
NASA Astrophysics Data System (ADS)
Siregar, M. F.; Supriana, N.; Nuranna, L.; Prihartono, J.
2017-08-01
Management of recurrent cervical cancer by reirradiation after radiation treatment remains controversial. In Indonesia, there is currently no data about reirradiation tumor response and side effects. This study aims to assess the tumor response to and side effects of reirradiation, the effect of time interval between first radiation treatment and cancer recurrence on the tumor response and side effects, and the effect of tumor size on tumor response. A cohort retrospective study with no comparison was done with the Radiotherapy Department at Cipto Mangunkusumo General Hospital, Jakarta. Participants were recurrent cervical cancer patients undergoing reirradiation. Data was collected from patients’ medical records and follow-up phone calls. Twenty-two patients participated in this study. Nine patients (40.9%) had complete responses, 10 patients (45.5%) had partial responses, 1 patient (4.5%) had a stable response, and 2 patients (9.1%) had tumor progressions. In general, 15 patients (68.2%) had no to light side effects (grade 0-2 RTOG) and 7 patients (31.8%) had severe side effects (grade 3-4 RTOG). Four patients (18.1%) had severe gastrointestinal acute side effects, 6 patients (27.3%) had severe gastrointestinal late side effects, 2 patients (9.1%) had severe urogenital side effects, and there were no patients had severe urogenital late side effects. There was no significant difference in tumor response between patients with time interval between first radiation treatment and recurrence of <12 months vs. ≥12 months. There was no significant difference in tumor response between patients with tumor size ≤4 cm vs. >4 cm. Reirradiation can be considered as a modality in recurrent cervical cancer management since good tumor response was achieved and the majority of patients had no to light side effects (grade 0-2 RTOG). This study found no correlation between tumor response, side effects, and time gap between first radiation treatment and recurrence of <12 months vs. ≥12 months. There was also no correlation between tumor response and tumor size of ≤4 cm vs. > 4 cm.
Steentjes, L; Siesling, S; Drummond, F J; van Manen, J G; Sharp, L; Gavin, A
2018-01-01
We identified patient and disease characteristics associated with (1) "current" physical side-effects of any severity; and (2) "severe" physical side-effects "ever" experienced by 3,348 (54%) prostate cancer (PCa) survivors in Ireland diagnosed 2-18 years previously. Postal questionnaires collected symptoms at diagnosis, post-biopsy complications, comorbidities, primary treatments and physical side-effects post-treatment (urinary incontinence, erectile dysfunction, libido loss, bowel problems, breast changes, hot flushes, and fatigue, "ever" and "current" at time of questionnaire completion). Men were grouped by "early" (localised) and "late" (locally advanced/advanced) disease at diagnosis. Multivariable logistic regression analysis identified patient and disease-related factors associated with post-treatment side-effects. Complications post-biopsy were associated with higher risk of "current" libido loss and impotence. Radical prostatectomy was associated with higher risk of "current" and "severe" incontinence, libido loss and impotence in both early and late disease. In early disease, brachytherapy was associated with lower risk of "current" fatigue and "severe" impotence. Comorbidities were associated with higher risk of "current" experience of four side-effects (incontinence, libido loss, bowel problems, fatigue). Men on active surveillance/watchful-waiting reported lower risk of sexual dysfunction. These findings could inform development of tailored information on side-effects, which, in turn, could inform treatment decision-making and post-treatment monitoring. © 2016 John Wiley & Sons Ltd.
Decalf, Veerle H; Huion, Anja M J; Benoit, Dries F; Denys, Marie-Astrid; Petrovic, Mirko; Everaert, Karel C M M
2017-08-01
Understanding the importance older people attribute to the different side effects associated with oral antimuscarinic treatments for overactive bladder (OAB) could help inform prescribers, healthcare policy makers and the drug industry. Our objective was to quantify the importance of the most prevalent cognitive and side effects of oral antimuscarinic treatments for OAB in older people. We conducted a discrete-choice experiment (DCE) with the assistance of an interviewer with community-dwelling and hospitalized older people aged >65 years. The DCE involved two hypothetical drugs for imaginary OAB, with three levels of four side effects for each drug, and the International Consultation on Incontinence Questionnaire-Overactive Bladder and EuroQol 5-Dimensions (EQ-5D) questionnaire were also administered. Data were analysed using a conditional logit model. In total, 276 older people participated in the study. The median age was 75 years (interquartile range [IQR] 69-80), 63% were women and 21% had OAB syndrome. The most unwanted side effect in the choice of antimuscarinics for OAB was severe cognitive effects, followed by severe constipation, severe blurred vision, severe dry mouth, moderate cognitive effects and moderate constipation. Severe cognitive effects were at least 1.7 times as important as severe constipation. Exploratory subgroup analysis showed that none of the attributes was found to be significant in people who scored as anxious or depressed on the EQ-5D, and preferences about cognitive effects, constipation and blurred vision were equal in people with and without OAB. Older people attribute more importance to loss of cognitive function as a possible side effect of antimuscarinic treatment than to the three most prevalent possible side effects of this treatment.
Zeidan, B; Anderson, K; Peiris, L; Rainsbury, D; Laws, S
2016-10-01
In 2006 Nolvadex was discontinued and replaced by a variety of alternative generic tamoxifen brands for the adjuvant treatment of breast cancer. Anecdotally, patients are switching brands and taking alternative medications to reduce treatment related symptoms. Nevertheless, more severe side effects may equate to better relapse prevention. This study evaluates generic tamoxifen adherence and its correlation with side effects and brand switch. Consecutive disease free ER positive patients (stage I-III) were invited to respond to a questionnaire. 165 of 327 questionnaires were returned (50% response). Pearson's Chi Square test was used for data analysis. 63 patients (38%) reported a switch between generic tamoxifen. 59% of all patients experienced side effects associated with tamoxifen treatment of which 53% were severe. Patients experiencing differential symptoms dependent on tamoxifen brand reported more severe side effects (p = 0.02). Non-prescribed supplements were taken by 42% of all patients with no significant improvement in climacteric symptoms (p = 0.05). The concomitant use of SSRIs appeared to have no effect on symptoms. A significant number of patients considered discontinuing tamoxifen because of the side effects (p = 0.001), yet this did not translate into discontinuation or non-adherence (p = 0.8 and 0.08 respectively). Severe tamoxifen side effects are commonly experienced by breast cancer patients and can be significantly altered by change in tamoxifen brand. Most patients will continue to take tamoxifen, despite side effects to avoid cancer relapse. Supplementation and antidepressants did not improve tamoxifen related side effects in our cohort. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.
Haas, Marion; Viney, Rosalie; Pearson, Sallie-Anne; Haywood, Philip; Brown, Chris; Ward, Robyn
2017-01-01
Aim Chemotherapy side effects are often reported in clinical trials; however, there is little evidence about their incidence in routine clinical care. The objective of this study was to describe the frequency and severity of patient-reported chemotherapy side effects in routine care across treatment centres in Australia. Methods We conducted a prospective cohort study of individuals with breast, lung or colorectal cancer undergoing chemotherapy. Side effects were identified by patient self-report. The frequency, prevalence and incidence rates of side effects were calculated by cancer type and grade, and cumulative incidence curves for each side effect computed. Frequencies of side effects were compared between demographic subgroups using chi-squared statistics. Results Side effect data were available for 449 eligible individuals, who had a median follow-up of 5.64 months. 86% of participants reported at least one side effect during the study period and 27% reported a grade IV side effect, most commonly fatigue or dyspnoea. Fatigue was the most common side effect overall (85%), followed by diarrhoea (74%) and constipation (74%). Prevalence and incidence rates were similar across side effects and cancer types. Age was the only demographic factor associated with the incidence of side effects, with older people less likely to report side effects. Conclusion This research has produced the first Australian estimates of self-reported incidence of chemotherapy side effects in routine clinical care. Chemotherapy side effects in routine care are common, continue throughout chemotherapy and can be serious. This work confirms the importance of observational data in providing clinical practice-relevant information to decision-makers. PMID:29016607
Pearce, Alison; Haas, Marion; Viney, Rosalie; Pearson, Sallie-Anne; Haywood, Philip; Brown, Chris; Ward, Robyn
2017-01-01
Chemotherapy side effects are often reported in clinical trials; however, there is little evidence about their incidence in routine clinical care. The objective of this study was to describe the frequency and severity of patient-reported chemotherapy side effects in routine care across treatment centres in Australia. We conducted a prospective cohort study of individuals with breast, lung or colorectal cancer undergoing chemotherapy. Side effects were identified by patient self-report. The frequency, prevalence and incidence rates of side effects were calculated by cancer type and grade, and cumulative incidence curves for each side effect computed. Frequencies of side effects were compared between demographic subgroups using chi-squared statistics. Side effect data were available for 449 eligible individuals, who had a median follow-up of 5.64 months. 86% of participants reported at least one side effect during the study period and 27% reported a grade IV side effect, most commonly fatigue or dyspnoea. Fatigue was the most common side effect overall (85%), followed by diarrhoea (74%) and constipation (74%). Prevalence and incidence rates were similar across side effects and cancer types. Age was the only demographic factor associated with the incidence of side effects, with older people less likely to report side effects. This research has produced the first Australian estimates of self-reported incidence of chemotherapy side effects in routine clinical care. Chemotherapy side effects in routine care are common, continue throughout chemotherapy and can be serious. This work confirms the importance of observational data in providing clinical practice-relevant information to decision-makers.
Wykes, T; Evans, J; Paton, C; Barnes, T R E; Taylor, D; Bentall, R; Dalton, B; Ruffell, T; Rose, D; Vitoratou, S
2017-10-01
Capturing service users' perspectives can highlight additional and different concerns to those of clinicians, but there are no up to date, self-report psychometrically sound measures of side effects of antipsychotic medications. Aim To develop a psychometrically sound measure to identify antipsychotic side effects important to service users, the Maudsley Side Effects (MSE) measure. An initial item bank was subjected to a Delphi exercise (n = 9) with psychiatrists and pharmacists, followed by service user focus groups and expert panels (n = 15) to determine item relevance and language. Feasibility and comprehensive psychometric properties were established in two samples (N43 and N50). We investigated whether we could predict the three most important side effects for individuals from their frequency, severity and life impact. MSE is a 53-item measure with good reliability and validity. Poorer mental and physical health, but not psychotic symptoms, was related to side-effect burden. Seventy-nine percent of items were chosen as one of the three most important effects. Severity, impact and distress only predicted 'putting on weight' which was more distressing, more severe and had more life impact in those for whom it was most important. MSE is a self-report questionnaire that identifies reliably the side-effect burden as experienced by patients. Identifying key side effects important to patients can act as a starting point for joint decision making on the type and the dose of medication.
[Treatment side effects and compliance in patients with depression].
Petrova, N N; Kucher, E O
2012-01-01
The impact of treatment side-effects on the compliance was studied in 85 depressive patients with different mental disorders - recurrent depressive disorder, postschizophrenic depression and organic affective disorder. The comparison of objective and subjective evaluations of compliance and a comparative analysis of the level of compliance, with its dependence on the treatment specifics, in different diseases were done. A significant role of efficacy and treatment side-effects was identified. The levels of "mental" and "autonomous" side-effects were highest in the treatment of depression: patients with postschizophrenic depression had the highest risk in respect of maintenance treatment; patients with recurrent depressive disorder and organic (affective) disorder were more tolerant to the treatment side-effects and their treatment, including the maintenance therapy, was rather effective. The compliance of all patients with depression was negatively correlated with the severity of side-effects of pharmacotherapy. The greatest side-effects and the lowest level of compliance were observed in the complex treatment with antidepressants and atypical neuroleptics. The effect of side-effects on the compliance was dependent on their severity and subjective tolerability and, to a lesser extent, on the amount of drugs.
Conklin, Heather M; Lawford, Joanne; Jasper, Bruce W; Morris, E Brannon; Howard, Scott C; Ogg, Susan W; Wu, Shengjie; Xiong, Xiaoping; Khan, Raja B
2009-07-01
To investigate the frequency and severity of side effects of methylphenidate among childhood survivors of acute lymphoblastic leukemia and brain tumors and identify predictors of higher adverse effect levels. Childhood cancer survivors (N = 103) identified as having attention and learning problems completed a randomized, double-blind, 3-week, home-crossover trial of placebo, low-dose methylphenidate (0.3 mg/kg; 10 mg twice daily maximum) and moderate-dose methylphenidate (0.6 mg/kg; 20 mg twice daily maximum). Caregivers completed the Barkley Side Effects Rating Scale (SERS) at baseline and each week during the medication trial. Siblings of cancer survivors (N = 49) were recruited as a healthy comparison group. There was a significantly higher number and severity of symptoms endorsed on the SERS when patients were taking moderate dose compared with placebo or low dose, but not low dose compared with placebo. The number of side effects endorsed on the SERS was significantly lower during all 3 home-crossover weeks (placebo, low dose, moderate dose) when compared with baseline symptom scores. The severity of side effects was also significantly lower, compared with baseline screening, during placebo and low-dose weeks but not moderate-dose weeks. Both the number and severity of symptoms endorsed at baseline were significantly higher for patients compared with siblings. Female gender and lower IQ were associated with higher adverse effect levels. Methylphenidate is generally well tolerated by childhood cancer survivors. There is a subgroup at increased risk for side effects that may need to be closely monitored or prescribed a lower medication dose. The seemingly paradoxical findings of increased "side effects" at baseline must be considered when monitoring side effects and designing clinical trials.
Adebahr, Sonja; Schimek-Jasch, Tanja; Nestle, Ursula; Brunner, Thomas B
2016-08-01
The oesophagus as a serial organ located in the central chest is frequent subject to "incidental" dose application in radiotherapy for several thoracic malignancies including oesophageal cancer itself. Especially due to the radiosensitive mucosa severe radiotherapy induced sequelae can occur, acute oesophagitis and strictures as late toxicity being the most frequent side-effects. In this review we focus on oesophageal side effects derived from treatment of gastrointestinal cancer and secondly provide an overview on oesophageal toxicity from conventional and stereotactic fractionated radiotherapy to the thoracic area in general. Available data on pathogenesis, frequency, onset, and severity of oesophageal side effects are summarized. Whereas for conventional radiotherapy the associations of applied doses to certain volumes of the oesophagus are well described, the tolerance dose to the mediastinal structures for hypofractionated therapy is unknown. The review provides available attempts to predict the risk of oesophageal side effects from dosimetric parameters of SBRT. Copyright © 2016 Elsevier Ltd. All rights reserved.
Almond-Roesler, B; Blume-Peytavi, U; Bisson, S; Krahn, M; Rohloff, E; Orfanos, C E
1998-01-01
Isotretinoin for oral therapy in severe acne conglobata and acne nodulocystica represents a significant achievement; however, the drug exerts several mucocutaneous and systemic adverse effects, besides its teratogenic potency. The aim of this study was to investigate the plasma levels of isotretinoin and of 4-oxo-isotretinoin over long-term treatment of severe acne and to assess any correlation with the given dose, the clinical improvement and the occurrence of side effects. Forty-one patients with severe acne and acne-related disorders were studied under long-term oral intake of isotretinoin. Therapeutic effects and side effects were evaluated prior, during and at the end of therapy. The plasma levels of isotretinoin and of its major metabolite 4-oxo-isotretinoin were measured by reversed-phase HPLC and were correlated with the administered oral dose and the number and frequency of side effects. Dose-dependent plasma levels of isotretinoin and its metabolite were observed. At a mean dosage of 0.75-1.0 mg/kg/day, 404 +/- 142 ng/ml were measured, whereas the plasma levels of 4-oxo-isotretinoin were 1-2x higher. The plasma levels correlated well with the orally administered dose of isotretinoin and the observed mucocutaneous side effects. The study demonstrates that measuring of the plasma levels may be a helpful tool to monitor the individual therapeutic dose regimen in patients with severe acne in order to minimize undesired side effects and to control oral intake.
Ignjatović Ristić, Dragana; Cohen, Dan; Obradović, Andrea; Nikić-Đuričić, Katarina; Drašković, Marija; Hinić, Darko
2018-02-01
The inconsistency in clinician and patient ratings of clozapine-induced side effects underscore the need to supplement clinician-based estimates of side effects with patient-reported ones. The main aims of the study are validation of the Glasgow antipsychotic side-effects scale for clozapine (GASS-C) in Serbian inpatients/outpatients with schizophrenia or schizo-affective disorder and recommendations for its future use, based on common and rare clozapine-associated side-effects. The GASS-C was administered to 95 outpatients/inpatients diagnosed with schizophrenia, schizoaffective, or chronic psychotic disorder. The scale showed good overall reliability, with an internal consistency coefficient of α = 0.84, an average retest coefficient of rho = 0.76, and a Spearman-Brown coefficient of validity of 0.81. Side effects were absent or mild in 64.2% of the patients, moderate in 31.6%, severe in 4.2%; 14% of the subjects considered their symptoms distressing. The most commonly reported side-effects were drowsiness, thirst, frequent urination, and dry mouth. Women reported more side effects than men, and patients not in a relationship reported significantly fewer side effects than patients in a relationship. Results indicate a weak positive correlation (rho = 0.231; p = .025) between severity of side effects and clozapine dose. The GASS-C showed good psychometric characteristics in clinical population of patients on clozapine. In future studies, clozapine serum concentrations should be measured when using the GASS-C to monitor side effects.
Gastrointestinal Side Effects of Antiarrhythmic Medications: A Review of Current Literature.
Amjad, Waseem; Qureshi, Waqas; Farooq, Ali; Sohail, Umair; Khatoon, Salma; Pervaiz, Sarah; Narra, Pratyusha; Hasan, Syeda M; Ali, Farman; Ullah, Aman; Guttmann, Steven
2017-09-03
Antiarrhythmic drugs are commonly prescribed cardiac drugs. Due to their receptor mimicry with several of the gastrointestinal tract receptors, they can frequently lead to gastrointestinal side effects. These side effects are the most common reasons for discontinuation of these drugs by the patients. Knowledge of these side effects is important for clinicians that manage antiarrhythmic drugs. This review focuses on the gastrointestinal side effects of these drugs and provides a detailed up-to-date literature review of the side effects of these drugs. The review provides case reports reported in the literature as well as possible mechanisms that lead to gastrointestinal side effects.
ERIC Educational Resources Information Center
Matson, Johnny L.; Fodstad, Jill C.; Rivet, Tessa T.; Rojahn, Johannes
2009-01-01
Participants were 109 adults with severe intellectual disabilities and long histories of psychotropic drug use. Side effect profiles were examined in the context of types of mental health disorders observed using the Diagnostic Assessment for the Severely Handicapped-Revised (DASH-II) and the Behavior Problems Inventory-Revised (BPI-01). The best…
Meijer, W J; Wensing, A M J; Bos, A A; Kuiphuis, J C F; Hagelen, E M M; Wilschut, J C; de Vries, M J T; Riezebos-Brilman, A
2017-03-13
To explore the nature and severity of side effects and future preference of intradermal versus intramuscular influenza vaccination in healthcare workers. Prospective cohort study. Two University Medical Centers in The Netherlands. Healthcare workers receiving an influenza vaccination. Healthcare workers that were vaccinated during the influenza vaccination season of 2012-2013 were approached for participation in a questionnaire study. The questionnaire was divided into two parts. The first part had to be answered directly after vaccination and the second part two weeks after vaccination. The motivation for vaccine uptake, whether or not the HCWs had direct contact with patients and the prevalence and severity of local and systemic side effects of influenza vaccination were explored. In addition, it was assessed how participants experienced the vaccination and which type of administration they preferred for future vaccination. Side effects of vaccination were more prevalent in the intradermal group versus the intramuscular group (56% versus 26%, p<0.001). Local side effects were perceived as more severe in healthcare workers receiving the intradermal vaccine. Directly after vaccination, healthcare workers preferred the intradermal vaccination. Two weeks after vaccination both types of vaccine were equally appreciated. This study shows that there are significant differences in the nature and severity of side effects upon intramuscular and intradermal influenza vaccination. This difference did not result in a preference among the vaccinated subjects for one type of vaccine. Copyright © 2017 Elsevier Ltd. All rights reserved.
Pedersen, O N
1996-01-01
In a prospective study lumbar iohexol myelography was performed in 107 consecutive patients, randomised for lumbar puncture with a Quincke or Whitacre spinal needle. All patients answered a questionnaire about possible side effects. Data from 100 patients (58 men, 42 women) were evaluated. In the Quincke group (n = 53), 23 (43%) reported no side effects. In the 30 patients who reported various side effects, post-dural puncture headache (PDPH) occurred in 22 (42%), of whom 9 had mild, 6 moderate and 7 (13%) severe cephalalgia, 18 (34%) reported increased low back pain/sciatica, 5 nausea and 7 dizziness. In the Whitacre group (n = 47), 33 (70%) had no side effects. PDPH was reported by 9 patients (19%), of whom 2 had mild, 6 moderate and only 1 (2%) severe cephalalgia, 4 (9%) reported increased low back pain/sciatica, 5 nausea and 4 dizziness. The conclusion drawn from this study is that lumbar myelography performed with the Whitacre spinal needle reduces postspinal side effects.
Safety of Adrenaline Use in Anaphylaxis: A Multicentre Register.
Cardona, Victòria; Ferré-Ybarz, Laia; Guilarte, Mar; Moreno-Pérez, Nuria; Gómez-Galán, Catalina; Alcoceba-Borràs, Eva; Delavalle, Maria Belén; Garriga-Baraut, Teresa
2017-01-01
The use of intramuscular adrenaline to treat anaphylaxis is suboptimal, despite being the first-line treatment recommended by national and international anaphylaxis guidelines. Fear of potentially severe side effects may be one of the underlying factors. The aim of this study was to assess the incidence and severity of adverse side effects after the use of adrenaline in anaphylaxis, as well as potential risk factors. Observational study based on a multicenter online registry of cases of adrenaline administration for suspected anaphylaxis. 277 registered valid cases were included: 138 (51.49%) female, median age 29 years (12-47), and 6 children under 2 years with a median age of 9 months (1-21). Side effects occurred in 58 cases (21.64%), with tremors, palpitations, and anxiety being the most frequent. There was a significant association of developing side effects with older age, higher dose of adrenaline, or use of the intravenous route. Potentially severe adverse effects (high blood pressure, chest discomfort, or ECG alterations) occurred only in 8 cases (2.99%); in these cases, no differences were found according to age or adrenaline dose, but again, intravenous administration was associated with more severe adverse events. This study shows that side effects affect less than 1 in 5 patients who receive adrenaline for an anaphylactic reaction, and are usually mild and transient. Therefore, in an emergency situation such as anaphylaxis, restricting adrenaline administration due to potential adverse effects would, in general, not be justified. © 2017 S. Karger AG, Basel.
Nwosu, Benjamin U.; Meltzer, Bruce; Maranda, Louise; Ciccarelli, Carol; Reynolds, Daniel; Curtis, Laura; King, Jean; Frazier, Jean A.; Lee, Mary M.
2014-01-01
Second-generation antipsychotic (SGA) medications introduced about 20 years ago are increasingly used to treat psychiatric illnesses in children and adolescents. There has been a five-fold increase in the use of these medications in U.S. children and adolescents in the past decade. However, there has also been a parallel rise in the incidence of side effects associated with these medications, such as obesity, dyslipidemia, insulin resistance, and diabetes mellitus. Despite the severity of these complications and their financial impact on the national healthcare budget, there is neither a clear understanding of the mechanisms contributing to these side effects nor the best ways to address them. Studies that examined lifestyle modification and pharmaceutical agents have yielded mixed results. Therefore, clinical studies using agents, such as vitamin D, which are inexpensive, readily available, with low side effects profile, and have mechanisms to counteract the metabolic side effects of SGA agents, are warranted. Vitamin D is a prohormone with skeletal and extraskeletal properties that could potentially reduce the severity of these metabolic side effects. Its role as an adjunctive therapy for the management of metabolic side effects of SGA agents has not been adequately studied. Effective strategies to curb these side effects will improve the overall health of youths with psychiatric illnesses who receive SGAs. Herein we present a pilot study on the use of vitamin D in patients on treatment with SGAs. PMID:22145446
Kuzman, Martina Rojnic; Andlauer, Olivier; Burmeister, Kai; Dvoracek, Boris; Lencer, Rebekka; Koelkebeck, Katja; Nawka, Alexander; Riese, Florian
2017-06-01
Mobile health interventions are regarded as affordable and accessible tools that can enhance standard psychiatric care. As part of the mHealth Psycho-Educational Intervention Versus Antipsychotic-Induced Side Effects (mPIVAS) project (www.psylog.eu), we developed the mobile application "PsyLOG" based on mobile "smartphone" technology to monitor antipsychotic-induced side effects. The aim of this paper is to describe the rationale and development of the PsyLOG and its clinical use. The PsyLOG application runs on smartphones with Android operating system. The application is currently available in seven languages (Croatian, Czech, English, French, German, Japanese and Serbian). It consists of several categories: "My Drug Effects", "My Life Styles", "My Charts", "My Medication", "My Strategies", "My Supporters", "Settings" and "About". The main category "My Drug Effects" includes a list of 30 side effects with the possibility to add three additional side effects. Side effects are each accompanied by an appropriate description and the possibility to rate its severity on a visual analogue scale from 0-100%. The PsyLOG application is intended to enhance the link between patients and mental health professionals, serving as a tool that more objectively monitors side-effects over certain periods of time. To the best of our knowledge, no such applications have so far been developed for patients taking antipsychotic medication or for their therapists.
Neural mechanisms associated with treatment decision making: An fMRI study.
Abidi, Malek; Bruce, Jared; Le Blanche, Alain; Bruce, Amanda; Jarmolowicz, David P; Csillik, Antonia; Thai, N Jade; Lim, Seung-Lark; Heinzlef, Olivier; de Marco, Giovanni
2018-04-23
Great progress has been made in understanding how people make financial decisions. However, there is little research on how people make health and treatment choices. Our study aimed to examine how participants weigh benefits (reduction in disease progression) and probability of risk (medications' side effects) when making hypothetical treatment decisions, and to identify the neural networks implicated in this process. Fourteen healthy participants were recruited to perform a treatment decision probability discounting task using MRI. Behavioral responses and skin conductance responses (SCRs) were measured. A whole brain analysis were performed to compare activity changes between "mild" and "severe" medications' side effects conditions. Then, orbitofrontal cortex (OFC), ventral striatum (VS), amygdala and insula were chosen for effective connectivity analysis. Behavioral data showed that participants are more likely to refuse medication when side effects are high and efficacy is low. SCRs values were significantly higher when people made medication decisions in the severe compared to mild condition. Functionally, OFC and VS were activated in the mild condition and were associated with increased likehood of choosing to take medication (higher area under the curve "AUC" side effects/efficacy). These regions also demonstrated an increased effective connectivity when participants valued treatment benefits. By contrast, the OFC, insula and amygdala were activated in the severe condition and were associated with and increased likelihood to refuse treatment. These regions showed enhanced effective connectivity when participants were confronted with increased side effects severity. This is the first study to examine the behavioral and neural bases of medical decision making. Copyright © 2018 Elsevier B.V. All rights reserved.
Sensorimotor dysfunction of grasping in schizophrenia: a side effect of antipsychotic treatment?
Nowak, D A; Connemann, B J; Alan, M; Spitzer, M
2006-01-01
Background Antipsychotic treatment in schizophrenia is frequently associated with extrapyramidal side effects. Objective behavioural measures to evaluate the severity of extrapyramidal side effects in the clinical setting do not exist. Objectives This study was designed to investigate grasping movements in five drug naive and 13 medicated subjects with schizophrenia and to compare their performance with that of 18 healthy control subjects. Deficits of grip force performance were correlated with clinical scores of both parkinson‐like motor disability and psychiatric symptom severity Methods Participants performed vertical arm movements with a handheld instrumented object and caught a weight that was dropped into a handheld cup either expectedly from the opposite hand or unexpectedly from the experimenter's hand. The scaling of grip force and the temporospatial coupling between grip and load force profiles was analysed. The psychiatric symptom severity was assessed by the positive and negative symptom score of schizophrenia and the brief psychiatric rating scale. Extrapyramidal symptoms were assessed by the unified Parkinson's disease rating scale. Results Drug naive subjects with schizophrenia performed similar to healthy controls. In contrast, medicated subjects with schizophrenia exhibited excessive grip force scaling and impaired coupling between grip and load force profiles. These performance deficits were strongly correlated with the severity of both extrapyramidal side effects related to antipsychotic therapy and negative symptoms related to the underlying pathology. Conclusions These data provide preliminary evidence that deficits of sensorimotor performance in schizophrenia are, at least in part, related to the side effects of antipsychotic treatment. The investigation of grasping movements may provide a sensitive measure to objectively evaluate extrapyramidal side effects related to antipsychotic therapy. PMID:16614027
... taking azithromycin unless you experience the severe side effects described in the SIDE EFFECTS section. If you stop taking azithromycin too soon ... to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in ...
Numerical analysis of urine flow through the side holes of a double J stent in a ureteral stenosis.
Kim, Hyoung-Ho; Choi, Young Ho; Lee, Seung Bae; Baba, Yasutaka; Kim, Kyung-Wuk; Suh, Sang-Ho
2017-07-20
Ureteral stenosis presents with a narrowing in the ureter, due to an intrinsic or extrinsic ureteral disease, such as ureter cancer or retroperitoneal fibrosis. The placement of a double J stent in the upper urinary system is one of the most common treatments of ureteral stenosis, along with the insertion of a percutaneous nephrostomy tube into the renal pelvis. The effect that the side holes in a double J stent have on urine flow has been evaluated in a few studies using straight ureter models. In this study, urine flow through a double J stent's side holes was analyzed in curved ureter models, which were based on human anatomy. In ureteral stenosis, especially in severe ureteral stenosis, a stent with side holes had a positive effect on the luminal and total flow rates, compared with the rates for a stent without side holes. The more side holes a stent has, the greater the luminal and total flow rates. However, the angular positions of the side holes did not affect flow rate. In conclusion, the side holes in a double J stent had a positive effect on ureteral stenosis, and the effect became greater as the ureteral stenosis became more severe.
Driver injury in near- and far-side impacts: Update on the effect of front passenger belt use.
Parenteau, Chantal S; Viano, David C
2018-04-03
This is a study that updates earlier research on the influence of a front passenger on the risk for severe driver injury in near-side and far-side impacts. It includes the effects of belt use by the driver and passenger, identifies body regions involved in driver injury, and identifies the sources for severe driver head injury. 1997-2015 NASS-CDS data were used to investigate the risk for Maximum Abbreviated Injury Scale (MAIS) 4 + F driver injury in near-side and far-side impacts by front passenger belt use and as a sole occupant in the driver seat. Side impacts were identified with GAD1 = L or R without rollover (rollover ≤ 0). Front-outboard occupants were included without ejection (ejection = 0). Injury severity was defined by MAIS and fatality (F) by TREATMNT = 1 or INJSEV = 4. Weighted data were determined. The risk for MAIS 4 + F was determined using the number of occupants with known injury status MAIS 0 + F. Standard errors were determined. Overall, belted drivers had greater risks for severe injury in near-side than far-side impacts. As a sole driver, the risk was 0.969 ± 0.212% for near-side and 0.313 ± 0.069% for far-side impacts (P < .005). The driver's risk was 0.933 ± 0.430% with an unbelted passenger and 0.596 ± 0.144% with a belted passenger in near-side impacts. The risk was 2.17 times greater with an unbelted passenger (NS). The driver's risk was 0.782 ± 0.431% with an unbelted passenger and 0.361% ± 0.114% with a belted passenger in far-side impacts. The risk was 1.57 times greater with an unbelted passenger (P < .10). Seat belt use was 66 to 95% effective in preventing MAIS 4 + F injury in the driver. For belted drivers, the head and thorax were the leading body regions for Abbreviated Injury Scale (AIS) 4+ injury. For near-side impacts, the leading sources for AIS 4+ head injury were the left B-pillar, roof, and other vehicle. For far-side impacts, the leading sources were the other occupant, right interior, and roof (8.5%). Seat belt use by a passenger lowered the risk of severe driver injury in side impacts. The reduction was 54% in near-side impacts and 36% in far-side impacts. Belted drivers experienced mostly head and thoracic AIS 4+ injuries. Head injuries in the belted drivers were from contact with the side interior and the other occupant, even with a belted passenger.
Antidepressants: Which Cause the Fewest Sexual Side Effects?
... problems Orgasm problems Problems with arousal, comfort and satisfaction The severity of sexual side effects depends on ... Impact of antidepressant drugs on sexual function and satisfaction. CNS Drugs. 2015;29:905. La Torre A, ...
Side effects during subcutaneous immunotherapy in children with allergic diseases.
Tophof, Max A; Hermanns, Anne; Adelt, Thomas; Eberle, Peter; Gronke, Christine; Friedrichs, Frank; Knecht, Roland; Mönter, Ernst; Schöpfer, Helmut; Schwerk, Nicolaus; Steinbach, Jörg; Umpfenbach, Hans-Ulrich; Weißhaar, Christian; Wilmsmeyer, Brigitte; Bufe, Albrecht
2018-05-01
Allergen-specific immunotherapy is the only causal form of therapy for IgE-mediated allergic diseases. Subcutaneous immunotherapy (SCIT) is considered safe and well tolerated in adults, yet there is less evidence of safety in the pediatric population. A non-interventional prospective observing longitudinal study was carried out to determine the incidence of local and systemic side effects by SCIT, routinely performed in pediatric patients. A total of 581 pediatric patients were observed in 18 study centers between March 2012 and October 2014, recording 8640 treatments and 10 015 injections. A total of 54.6% of the patients experienced immediate local side effects at least once; delayed local side effects were seen in 56.1%. Immediate systemic adverse reactions occurred in 2.2% of patients; 7.4% experienced delayed systemic side effects. However, severe systemic side effects (grade III in the classification of Ring and Messmer) were seen in 0.03% of all treatments, all appearing within 30 minutes after the injections. No grade IV reactions were observed. In addition, many potential risk factors were investigated, yet only a few were found to be associated with the occurrence of side effects. Subcutaneous immunotherapy is a safe form of therapy in pediatric patients, with similar rates of local side effects compared to adult patients and low rates of severe systemic side effects. However, local and systemic reactions occurring later than 30 minutes after injection were observed more often than expected, which makes it essential to be attentive on behalf of pediatricians, patients, and parents. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
3-D simulation of hanging wall effect at dam site
NASA Astrophysics Data System (ADS)
Zhang, L.; Xu, Y.
2017-12-01
Hanging wall effect is one of the near fault effects. This paper focuses on the difference of the ground motions on the hanging wall side between the footwall side of the fault at dam site considering the key factors, such as actual topography, the rupture process. For this purpose, 3-D ground motions are numerically simulated by the spectrum element method (SEM), which takes into account the physical mechanism of generation and propagation of seismic waves. With the SEM model of 548 million DOFs, excitation and propagation of seismic waves are simulated to compare the difference between the ground motion on the hanging wall side and that on the footwall side. Take Dagangshan region located in China as an example, several seismogenic finite faults with different dip angle are simulated to investigate the hanging wall effect. Furthermore, by comparing the ground motions of the receiving points, the influence of several factors on hanging wall effect is investigated, such as the dip of the fault and the fault type (strike slip fault or dip-slip fault). The peak acceleration on the hanging wall side is obviously larger than those on the footwall side, which numerically evidences the hanging wall effect. Besides, the simulation shows that only when the dip is less than 70° does the hanging wall effect deserve attention.
Montgomery, Guy H.; Schnur, Julie B.; Erblich, Joel; Diefenbach, Michael A.; Bovbjerg, Dana H.
2010-01-01
Prior to scheduled surgery, breast cancer surgical patients frequently experience high levels of distress and expect a variety of post-surgery symptoms. Previous literature has supported the view that pre-surgery distress and response expectancies are predictive of post-surgery outcomes. However, the contributions of distress and response expectancies to post-surgical side effect outcomes have rarely been examined together within the same study. Furthermore, studies on the effects of response expectancies in the surgical setting have typically focused on the immediate post-surgical setting rather than the longer term. The purpose of the present study was to test the contribution of pre-surgery distress and response expectancies to common post-surgery side effects (pain, nausea, fatigue). Female patients (n=101) undergoing breast cancer surgery were recruited to a prospective study. Results indicated that pre-surgery distress uniquely contributed to patients’ post-surgery pain severity (P<0.05) and fatigue (P<0.003) one week following surgery. Response expectancies uniquely contributed to pain severity (P<0.001), nausea (P<0.012) and fatigue (P<0.010) one week following surgery. Sobel tests indicated that response expectancies partially mediated the effects of distress on pain severity (P<0.03) and fatigue (P<0.03). Response expectancies also mediated the effects of age on pain severity, nausea and fatigue. Results highlight the contribution of pre-surgery psychological factors to post-surgery side effects, the importance of including both emotional and cognitive factors within studies as predictors of post-surgery side effects, and suggest pre-surgical clinical targets for improving patients’ postoperative experiences of side effects. PMID:20538186
Nicotine lozenges may cause side effects. Tell your doctor if either of these symptoms is severe or does not go away: heartburn ... doctor immediately: mouth problems irregular or fast heartbeat Nicotine lozenges may cause other side effects. Call your doctor if you have any unusual ...
Kaspar, Kai
2013-01-01
Peoples' perception of diseases and pharmaceutical drugs is a critical issue in health research. Beliefs about disease severity influence the compliance with recommendations for convalescence and the motivation to perform proper health-behavior. The estimated effectiveness of drugs and severity of side effects influence medication adherence and contribute to placebo effects. The present paper closes the gap between these effects and the concept of embodied cognition from a metaphor-enriched perspective. In five studies, we demonstrate that the bodily sensation of weight influences our evaluations of diseases and drugs. The experience of heaviness enhanced the estimated seriousness of diseases and the estimated effectiveness of drugs. The perceived seriousness of drug side effects was also affected by weight but only when drug effectiveness was not attended to. Moreover, the incidental sensation of weight shows a novel effect when evaluating weight-related drugs. The results are in line with the idea of embodied metaphors and reveal important boundary conditions which contribute to a better understanding of the underlying mechanisms. PMID:24244302
Side Effect Perceptions and Their Impact on Treatment Decisions in Women.
Waters, Erika A; Pachur, Thorsten; Colditz, Graham A
2017-04-01
Side effects prompt some patients to forego otherwise-beneficial therapies. This study explored which characteristics make side effects particularly aversive. We used a psychometric approach, originating from research on risk perception, to identify the factors (or components) underlying side effect perceptions. Women ( N = 149) aged 40 to 74 years were recruited from a patient registry to complete an online experiment. Participants were presented with hypothetical scenarios in which an effective and necessary medication conferred a small risk of a single side effect (e.g., nausea, dizziness). They rated a broad range of side effects on several characteristics (e.g., embarrassing, treatable). In addition, we collected 4 measures of aversiveness for each side effect: choosing to take the medication, willingness to pay to avoid the side effect (WTP), negative affective attitude associated with the side effect, and how each side effect ranks among others in terms of undesirability. A principal components analysis (PCA) was used to identify the components underlying side effect perceptions. Then, for each aversiveness measure separately, regression analyses were used to determine which components predicted differences in aversiveness among the side effects. The PCA revealed 4 components underlying side effect perceptions: affective challenge (e.g., frightening), social challenge (e.g., disfiguring), physical challenge (e.g., painful), and familiarity (e.g., common). Side effects perceived as affectively and physically challenging elicited the highest levels of aversiveness across all 4 measures. Understanding what side effect characteristics are most aversive may inform interventions to improve medical decisions and facilitate the translation of novel biomedical therapies into clinical practice.
Side Effect Perceptions and their Impact on Treatment Decisions in Women
Waters, Erika A.; Pachur, Thorsten; Colditz, Graham A.
2016-01-01
Background Side effects prompt some patients to forego otherwise-beneficial therapies. This study explored which characteristics make side effects particularly aversive. Methods We used a psychometric approach, originating from research on risk perception, to identify the factors (or components) underlying side effect perceptions. Women (N=149) aged 40–74 were recruited from a patient registry to complete an online experiment. Participants were presented with hypothetical scenarios in which an effective and necessary medication conferred a small risk of a single side effect (e.g., nausea, dizziness). They rated a broad range of side effects on several characteristics (e.g., embarrassing, treatable). In addition, we collected four measures of aversiveness for each side effect: choosing to take the medication, willingness to pay to avoid the side effect (WTP), negative affective attitude associated with the side effect, and how each side effect ranks among others in terms of undesirability. A principle-components analysis (PCA) was used to identify the components underlying side effect perceptions. Then, for each aversiveness measure separately, regression analyses were used to determine which components predicted differences in aversiveness among the side effects. Results The PCA revealed four components underlying side effect perceptions: affective challenge (e.g., frightening), social challenge (e.g., disfiguring), physical challenge (e.g., painful), and familiarity (e.g., common). Side effects perceived as affectively and physically challenging elicited the highest levels of aversiveness across all four measures. Conclusions Understanding what side effect characteristics are most aversive may inform interventions to improve medical decisions and facilitate the translation of novel biomedical therapies into clinical practice. PMID:27216581
Current perspectives in NSAID-induced gastropathy.
Sinha, Mau; Gautam, Lovely; Shukla, Prakash Kumar; Kaur, Punit; Sharma, Sujata; Singh, Tej P
2013-01-01
Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most highly prescribed drugs in the world. Their analgesic, anti-inflammatory, and antipyretic actions may be beneficial; however, they are associated with severe side effects including gastrointestinal injury and peptic ulceration. Though several approaches for limiting these side effects have been adopted, like the use of COX-2 specific drugs, comedication of acid suppressants like proton pump inhibitors and prostaglandin analogs, these alternatives have limitations in terms of efficacy and side effects. In this paper, the mechanism of action of NSAIDs and their critical gastrointestinal complications have been reviewed. This paper also provides the information on different preventive measures prescribed to minimize such adverse effects and analyses the new suggested strategies for development of novel drugs to maintain the anti-inflammatory functions of NSAIDs along with effective gastrointestinal protection.
Current Perspectives in NSAID-Induced Gastropathy
Sinha, Mau; Gautam, Lovely; Shukla, Prakash Kumar; Kaur, Punit; Sharma, Sujata; Singh, Tej P.
2013-01-01
Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most highly prescribed drugs in the world. Their analgesic, anti-inflammatory, and antipyretic actions may be beneficial; however, they are associated with severe side effects including gastrointestinal injury and peptic ulceration. Though several approaches for limiting these side effects have been adopted, like the use of COX-2 specific drugs, comedication of acid suppressants like proton pump inhibitors and prostaglandin analogs, these alternatives have limitations in terms of efficacy and side effects. In this paper, the mechanism of action of NSAIDs and their critical gastrointestinal complications have been reviewed. This paper also provides the information on different preventive measures prescribed to minimize such adverse effects and analyses the new suggested strategies for development of novel drugs to maintain the anti-inflammatory functions of NSAIDs along with effective gastrointestinal protection. PMID:23576851
[Adverse effects of non-steroidal anti-inflammatory drugs. A prevalence study in Austria].
Kolarz, Gernot; Mayrhofer, Franz; Neumann, Kurt; Singer, Franz
2003-01-31
Gastrointestinal side effects are the limiting factor in the prescription of non-steroidal antirheumatic drugs (NSAID). However, there are no recent data from Austria. The aim of this prevalence study was therefore to assess the gastrointestinal risk from NSAID in Austria. A total of 1347 patients were observed in an outpatient setting between March 2000 and February 2001. Side effects from NSAID were documented by questionnaire at two time points with a mean interval of 31 days. Documented data were analysed descriptively using an explorative strategy. The prevalence of side effects was compared to data from literature. Side effects were reported by 18.1% of the patients, severe gastro-intestinal complications (ulcer, bleeding, perforation) were diagnosed in 0.7%. Prescription of effective GI-protection (proton pump inhibitors, misoprostole, famotidin in high dose) was seen in only one third of the patients at risk. The prevalence of severe gastrointestinal side effects by NSAIDs assessed in our study was clearly lower than the prevalence reported in the Anglo-American literature. This may be due to a different prescription behaviour: about 75% of the patients took Diclofenac, lbuprofen or Meloxicam, drugs which have a very low potential of gastrointestinal complications. However, more information for general practitioners is needed yet to sufficiently protect patients at gastrointestinal risk from NSAID.
From clinically relevant outcome measures to quality of life in epilepsy: A time trade-off study.
de Kinderen, Reina J A; Wijnen, Ben F M; van Breukelen, Gerard; Postulart, Debby; Majoie, Marian H J M; Aldenkamp, Albert P; Evers, Silvia M A A
2016-09-01
A proposed method for bridging the gap between clinically relevant epilepsy outcome measures and quality-adjusted life years is to derive utility scores for epilepsy health states. The aim of this study is to develop such a utility-function and to investigate the impact of the epilepsy outcome measures on utility. Health states, based on clinically important epilepsy attributes (e.g. seizure frequency, seizure severity, side-effects), were valued by a sample of the Dutch population (N=525) based on the time trade-off method. In addition to standard demographics, every participant was asked to rate 10 or 11 different health state scenarios. A multilevel regression analysis was performed to account for the nested structure of the data. Results show that the best health state (no seizures and no side-effects) is estimated at 0.89 and the worst state (seizures type 5 twice a day plus severe side-effects) at 0.22 (scale: 0-1). An increase in seizure frequency, occurrence of side-effects, and seizure severity were all significantly associated with lower utility values. Furthermore, seizure severity has the largest impact on quality of life compared with seizure frequency and side-effects. This study provides a utility-function for transforming clinically relevant epilepsy outcome measures into utility estimates. We advise using our utility-function in economic evaluations, when quality of life is not directly measured in a study and hence, no health state utilities are available, or when there is convincing empirical evidence of the insensitivity of a generic quality-of-life-instrument within epilepsy. Copyright © 2016 Elsevier B.V. All rights reserved.
Horváth, Viktor József; Tabák, Gy Ádám; Szabó, Gergely; Putz, Zsuzsanna; Koós, Csaba Géza; Lakatos, Péter
2015-03-29
Among their beneficial effects, non-steroidal anti-inflammatory drugs may also exert several side effects which depend on the dosage and the type of these medications. The most frequent gastrointestinal side effects usually develop shortly after the beginning of their administration, but others such as cardiovascular interactions (which are present much less frequently than gastrointestinal side effects) can also occur after the beginning of drug administration without a latency period. For a long-term treatment, non-steroidal anti-inflammatory drugs are most frequently used in the elderly population where patients typically have high cardiovascular risk and take other medicines, e.g. low dose acetylsalicylic acid that can interact with non-steroidal anti-inflammatory drugs; in this aspect diclofenac may cause less side effects. In this review, the authors briefly review cardiovascular side effects of non-steroidal anti-inflammatory drugs, the processes which potentially influence them, therapeutic consequences and their interaction with acetylsalicylic acid.
Pharmacokinetics of Scopolamine Intranasal Gel Formulation (INSCOP) During Antiorthostatic Bedrest
NASA Technical Reports Server (NTRS)
Putcha, Lakshmi; Boyd, J. L.; Du, B.; Daniels, V.; Crady, C.
2011-01-01
Space Motion sickness (SMS) is an age old problem for space travelers on short and long duration space flight Oral antiemetics are not very effective in space due to poor bioavailability. Scopolamine (SCOP) is the most frequently used drug by recreational travelers V patch, tablets available on the market. Common side effects of antiemetics, in general, include drowsiness, sedation, dry mouth and reduced psychomotor performance. Severity and persistence of side effects are often dose related Side effects can be detrimental in high performance demanding settings, e.g. space flight, military.
Sunnevång, Cecilia; Rosén, Erik; Boström, Ola; Lechelt, Ulf
2010-01-01
Side airbags reduce the risk of fatal injury by approximately 30%. Due to limited real-life data the risk reducing effect for serious injury has not yet been established. Since side airbags are mainly designed and validated for crash severities used in available test procedures little is known regarding the protective effect when severity increases. The objective of this study was to understand for which crash severities AIS3+ thorax occupant protection in car-to-car nearside collisions need to and can be improved. The aim was fulfilled by means of real life data, for older cars without side airbag, and a series of car-to-car tests performed with the WorldSID 50%-ile in modern and older cars at different impact speeds. The real life data showed that the risk of AIS3+ injury was highest for the thorax followed by the pelvis and head. For both non-senior and senior occupants, most thorax injuries were sustained at lateral delta-v from 20 km/h to 40 km/h. In this severity range, senior occupants were found to have approximately four times higher risk of thoracic injury than non-senior occupants. The crash tests at lateral impact speed 55 km/h (delta-v 32 km/h) confirmed the improved performance at severities represented in current legal and rating tests. The structural integrity of the modern car impacted at 70 km/h showed a potential for improved side impact protection by interior countermeasures. PMID:21050600
Sunnevång, Cecilia; Rosén, Erik; Boström, Ola; Lechelt, Ulf
2010-01-01
Side airbags reduce the risk of fatal injury by approximately 30%. Due to limited real-life data the risk reducing effect for serious injury has not yet been established. Since side airbags are mainly designed and validated for crash severities used in available test procedures little is known regarding the protective effect when severity increases.The objective of this study was to understand for which crash severities AIS3+ thorax occupant protection in car-to-car nearside collisions need to and can be improved. The aim was fulfilled by means of real life data, for older cars without side airbag, and a series of car-to-car tests performed with the WorldSID 50%-ile in modern and older cars at different impact speeds.The real life data showed that the risk of AIS3+ injury was highest for the thorax followed by the pelvis and head. For both non-senior and senior occupants, most thorax injuries were sustained at lateral delta-v from 20 km/h to 40 km/h. In this severity range, senior occupants were found to have approximately four times higher risk of thoracic injury than non-senior occupants. The crash tests at lateral impact speed 55 km/h (delta-v 32 km/h) confirmed the improved performance at severities represented in current legal and rating tests. The structural integrity of the modern car impacted at 70 km/h showed a potential for improved side impact protection by interior countermeasures.
Wiggin, Timothy D.; Peck, Jack H.; Masino, Mark A.
2014-01-01
The cellular and network basis for most vertebrate locomotor central pattern generators (CPGs) is incompletely characterized, but organizational models based on known CPG architectures have been proposed. Segmental models propose that each spinal segment contains a circuit that controls local coordination and sends longer projections to coordinate activity between segments. Unsegmented/continuous models propose that patterned motor output is driven by gradients of neurons and synapses that do not have segmental boundaries. We tested these ideas in the larval zebrafish, an animal that swims in discrete episodes, each of which is composed of coordinated motor bursts that progress rostrocaudally and alternate from side to side. We perturbed the spinal cord using spinal transections or strychnine application and measured the effect on fictive motor output. Spinal transections eliminated episode structure, and reduced both rostrocaudal and side-to-side coordination. Preparations with fewer intact segments were more severely affected, and preparations consisting of midbody and caudal segments were more severely affected than those consisting of rostral segments. In reduced preparations with the same number of intact spinal segments, side-to-side coordination was more severely disrupted than rostrocaudal coordination. Reducing glycine receptor signaling with strychnine reversibly disrupted both rostrocaudal and side-to-side coordination in spinalized larvae without disrupting episodic structure. Both spinal transection and strychnine decreased the stability of the motor rhythm, but this effect was not causal in reducing coordination. These results are inconsistent with a segmented model of the spinal cord and are better explained by a continuous model in which motor neuron coordination is controlled by segment-spanning microcircuits. PMID:25275377
Metabolomics Based Profiling of Dexamethasone Side Effects in Rats
Malkawi, Abeer K.; Alzoubi, Karem H.; Jacob, Minnie; Matic, Goran; Ali, Asmaa; Al Faraj, Achraf; Almuhanna, Falah; Dasouki, Majed; Abdel Rahman, Anas M.
2018-01-01
Dexamethasone (Dex) is a synthetic glucocorticoid that has anti-inflammatory and immunosuppressant effects and is used in several conditions such as asthma and severe allergy. Patients receiving Dex, either at a high dose or for a long time, might develop several side effects such as hyperglycemia, weight change, or osteoporosis due to its in vivo non-selectivity. Herein, we used liquid chromatography-tandem mass spectrometry-based comprehensive targeted metabolomic profiling as well as radiographic imaging techniques to study the side effects of Dex treatment in rats. The Dex-treated rats suffered from a ∼20% reduction in weight gain, hyperglycemia (145 mg/dL), changes in serum lipids, and reduction in total serum alkaline phosphatase (ALP) (∼600 IU/L). Also, compared to controls, Dex-treated rats showed a distinctive metabolomics profile. In particular, serum amino acids metabolism showed six-fold reduction in phenylalanine, lysine, and arginine levels and upregulation of tyrosine and hydroxyproline reflecting perturbations in gluconeogenesis and protein catabolism which together lead to weight loss and abnormal bone metabolism. Sorbitol level was markedly elevated secondary to hyperglycemia and reflecting activation of the polyol metabolism pathway causing a decrease in the availability of reducing molecules (glutathione, NADPH, NAD+). Overexpression of succinylacetone (4,6-dioxoheptanoic acid) suggests a novel inhibitory effect of Dex on hepatic fumarylacetoacetate hydrolase. The acylcarnitines, mainly the very long chain species (C12, C14:1, C18:1) were significantly increased after Dex treatment which reflects degradation of the adipose tissue. In conclusion, long-term Dex therapy in rats is associated with a distinctive metabolic profile which correlates with its side effects. Therefore, metabolomics based profiling may predict Dex treatment-related side effects and may offer possible novel therapeutic interventions. PMID:29503615
Metabolomics Based Profiling of Dexamethasone Side Effects in Rats.
Malkawi, Abeer K; Alzoubi, Karem H; Jacob, Minnie; Matic, Goran; Ali, Asmaa; Al Faraj, Achraf; Almuhanna, Falah; Dasouki, Majed; Abdel Rahman, Anas M
2018-01-01
Dexamethasone (Dex) is a synthetic glucocorticoid that has anti-inflammatory and immunosuppressant effects and is used in several conditions such as asthma and severe allergy. Patients receiving Dex, either at a high dose or for a long time, might develop several side effects such as hyperglycemia, weight change, or osteoporosis due to its in vivo non-selectivity. Herein, we used liquid chromatography-tandem mass spectrometry-based comprehensive targeted metabolomic profiling as well as radiographic imaging techniques to study the side effects of Dex treatment in rats. The Dex-treated rats suffered from a ∼20% reduction in weight gain, hyperglycemia (145 mg/dL), changes in serum lipids, and reduction in total serum alkaline phosphatase (ALP) (∼600 IU/L). Also, compared to controls, Dex-treated rats showed a distinctive metabolomics profile. In particular, serum amino acids metabolism showed six-fold reduction in phenylalanine, lysine, and arginine levels and upregulation of tyrosine and hydroxyproline reflecting perturbations in gluconeogenesis and protein catabolism which together lead to weight loss and abnormal bone metabolism. Sorbitol level was markedly elevated secondary to hyperglycemia and reflecting activation of the polyol metabolism pathway causing a decrease in the availability of reducing molecules (glutathione, NADPH, NAD + ). Overexpression of succinylacetone (4,6-dioxoheptanoic acid) suggests a novel inhibitory effect of Dex on hepatic fumarylacetoacetate hydrolase. The acylcarnitines, mainly the very long chain species (C12, C14:1, C18:1) were significantly increased after Dex treatment which reflects degradation of the adipose tissue. In conclusion, long-term Dex therapy in rats is associated with a distinctive metabolic profile which correlates with its side effects. Therefore, metabolomics based profiling may predict Dex treatment-related side effects and may offer possible novel therapeutic interventions.
Using a graphical risk tool to examine willingness to take migraine prophylactic medications.
Turner, Dana P; Golding, Adrienne N; Houle, Timothy T
2016-10-01
Many migraine sufferers use daily prophylactic therapy to reduce the frequency of their headache attacks. The Food and Drug Administration has approved several different medications for migraine prophylaxis, but it is not clear whether sufferers perceive these treatments to provide clinically significant benefits given their side effect profiles. Three hundred headache sufferers were recruited from the community and local headache clinics using print and television advertising. Participants reported experiencing problematic headache attacks with a median (IQR) frequency of 7.0 (4-13) headache days per month. These sufferers participated in a cross-sectional, single-site, study that used a specially designed computer assessment task. Participants were instructed on the probability of experiencing the 3 most commonly experienced side effects for several blinded medication profiles: divalproex sodium, venlafaxine, gabapentin, propranolol, and topiramate. After learning the likelihood of experiencing side effect profiles of each medication, participants were asked whether they would be willing to take the medication for a given headache reduction level, which ranged from 0 to 7 days per month. The side effect profile for divalproex sodium was associated with the smallest willingness to take, with gabapentin, propranolol, and topiramate perceived to be much more agreeable. However, <60% of participants reported willingness to take any of these medications even if they provided a 50% reduction in headache frequency. Several general predictors of willingness to take were observed including high headache-related disability, depressive symptoms, and pain medication concerns including fear of tolerance. These findings suggest that if properly informed of the side effect profiles of these medications, many patients might opt for other treatments.
Russo, Stefania; Cinausero, Marika; Gerratana, Lorenzo; Bozza, Claudia; Iacono, Donatella; Driol, Pamela; Deroma, Laura; Sottile, Roberta; Fasola, Gianpiero; Puglisi, Fabio
2014-02-01
Analysis of relative importance of side effects of anticancer therapy is extremely useful in the process of clinical decision making. There is evidence that patients' perception of the side effects of anticancer treatments changes over time. Aim of this study was to evaluate the cancer patients' perceptions of physical and non-physical side effects of contemporary anticancer therapy. Four hundred and sixty-four patients entered the study (153 men and 311 women). Participants were asked to rank their side effects in order of distress by using two sets of cards naming physical and non-physical effects, respectively. Influencing factors, including treatment and patient characteristics, were also analysed. Patients ranked the non-physical side effect 'Affects my family or partner' first. 'Constantly tired' and 'Loss of hair' were ranked second and third, respectively. Significant differences from previous studies on this topic emerged. In particular, 'Vomiting', a predominant concern in previous studies, almost disappeared, whereas 'Nausea' and 'Loss of hair' remained important side effects in the patients' perception. Interestingly, marital status was predominant in driving patients' perception, being associated with several side effects ('Constantly tired', 'Loss of appetite', 'Affects my work/Home duties', 'Affects my social activities', 'Infertility'). Other significant factors influencing patient's perception of side effects included age, disease characteristics and ongoing anticancer therapy. This study provided information on current status of patients' perceptions of side effects of anticancer treatment. These results could be used in pre-treatment patient education and counselling.
Rydén, Anna; Blackhall, Fiona; Kim, Hye Ryun; Pillai, Rathi N; Braam, Lauren; Martin, Mona L; Walding, Andrew
2017-10-01
Capturing the patient experience during treatment is important to both regulatory authorities and to patients starting treatment. We identified the symptoms and side effects experienced by patients with advanced non-small-cell lung cancer during osimertinib treatment, to understand treatment expectations, satisfaction, and the level of difficulty coping with the side effects experienced during treatment. Qualitative interviews (approximately 4-6 weeks after treatment initiation and again after approximately 4 months of treatment) were conducted during the phase I/II AURA clinical trial of osimertinib, a tyrosine kinase inhibitor of epidermal growth factor receptor-sensitizing and T790M resistance mutations. During the first interview (23 patients), the most commonly reported symptoms/side effects were coughing, itching, tiredness (each reported by 56.5% of patients), and rash (43.5%). During the second interview (21 patients), compared with the first interview, shortness of breath and diarrhea were reported by more patients (57.1 and 38.1%, respectively; both increased from 34.8%); tiredness remained predominant (42.9%); and itching (38.1%), coughing (38.1%), and rash (14.3%) were reported by fewer patients. At both interviews, the most frequently reported symptoms/side effects were also those most often rated by patients for bothersomeness and severity, and generally received mean scores in the low-to-moderate range. However, several rarely expressed symptoms/side effects (e.g., abdominal pain, frequent day time urination) received high bothersomeness ratings. At the second interview, patients were highly satisfied with osimertinib and had a low level of difficulty in coping with side effects during treatment. These data enhance our understanding of patients' experiences of symptoms/side effects, which could increase the accuracy of the osimertinib benefit-risk assessment, guide management of adverse events, and improve the information given to patients receiving the drug.
Littleton, Sheila Robertson; Heriza, Carolyn B; Mullens, Pamela A; Moerchen, Victoria A; Bjornson, Kristie
2011-01-01
To examine the effect of positioning on respiratory measurements in individuals with cerebral palsy and severe scoliosis. Five individuals aged 17 to 37 years participated in an alternating treatment, single-subject design. Oxygen saturation, respiratory rate, heart rate, and chest wall excursion measurements were obtained in supine, sitting, and sidelying positions. Level of support for hypotheses varied on the basis of the respiratory measurement and participants' status. Respiratory rate appeared to be most sensitive to change in the positions. Severity of respiratory compromise and age may be associated with less tolerance for supine position versus sitting and sidelying positions. The use of therapeutic positioning in sitting and sidelying positions should be considered as a noninvasive intervention for a population with respiratory compromise. Further research with a larger sample is needed to empirically link specific positions with improved respiratory efficiency.
New findings in pharmacogenetics of schizophrenia.
Zai, Clement C; Tiwari, Arun K; Zai, Gwyneth C; Maes, Miriam S; Kennedy, James L
2018-05-01
This review highlights recent advances in the investigation of genetic factors for antipsychotic response and side effects. Antipsychotics prescribed to treat psychotic symptoms are variable in efficacy and propensity for causing side effects. The major side effects include tardive dyskinesia, antipsychotic-induced weight gain (AIWG), and clozapine-induced agranulocytosis (CIA). Several promising associations of polymorphisms in genes including HSPG2, CNR1, and DPP6 with tardive dyskinesia have been reported. In particular, a functional genetic polymorphism in SLC18A2, which is a target of recently approved tardive dyskinesia medication valbenazine, was associated with tardive dyskinesia. Similarly, several consistent findings primarily from genes modulating energy homeostasis have also been reported (e.g. MC4R, HTR2C). CIA has been consistently associated with polymorphisms in the HLA genes (HLA-DQB1 and HLA-B). The association findings between glutamate system genes and antipsychotic response require additional replications. The findings to date are promising and provide us a better understanding of the development of side effects and response to antipsychotics. However, more comprehensive investigations in large, well characterized samples will bring us closer to clinically actionable findings.
Recommendations for the paracetamol treatment nomogram and side effects of N-acetylcysteine.
Koppen, A; van Riel, A; de Vries, I; Meulenbelt, J
2014-06-01
Treatment of paracetamol intoxication consists of administration of N-acetylcysteine, preferably shortly after paracetamol ingestion. In most countries, the decision to treat patients with N-acetylcysteine depends on the paracetamol plasma concentration. In the literature, different arguments are given regarding when to treat paracetamol overdose. Some authors do not recommend treatment with N-acetylcysteine at low paracetamol plasma concentrations since unnecessary adverse effects may be induced. But no treatment with N-acetylcysteine at higher paracetamol plasma concentrations may lead to unnecessary severe morbidity and mortality. In this review, we provide an overview on the severity and prevalence of adverse side effects after N-acetylcysteine administration and the consequences these side effects may have for the treatment of paracetamol intoxication. The final conclusion is to continue using the guidelines of the Dutch National Poisons Information Centre for N-acetylcysteine administration in paracetamol intoxication.
Sabbatini, F; Minieri, M; Manzi, G; Piai, G; D'Angelo, V; Mazzacca, G
1991-01-01
The clinical efficacy and the safety of chronic oral administration of cisapride, a new gastrointestinal prokinetic agent, (10 mg tid) and clebopride (0.5 mg tid) was assayed in 48 outpatients affected with functional dyspepsia, in a randomized double-blind study. Each of the drugs induced a significant reduction in dyspeptic symptoms after 2 and 4 weeks (p less than 0.001). Two patients, given clebopride, dropped out of the study because of severe side effects during the first week of treatment. Mild adverse reactions were reported in 6 out of 23 cisapride-treated patients and in 10 out of 20 clebopride-treated patients who completed the study. The most common side effect of cisapride was diarrhoea and that of clebopride was drowsiness. Cisapride appears to be as effective as clebopride in reducing dyspeptic symptoms and seems to induce less severe side effects.
Simultaneous confidence sets for several effective doses.
Tompsett, Daniel M; Biedermann, Stefanie; Liu, Wei
2018-04-03
Construction of simultaneous confidence sets for several effective doses currently relies on inverting the Scheffé type simultaneous confidence band, which is known to be conservative. We develop novel methodology to make the simultaneous coverage closer to its nominal level, for both two-sided and one-sided simultaneous confidence sets. Our approach is shown to be considerably less conservative than the current method, and is illustrated with an example on modeling the effect of smoking status and serum triglyceride level on the probability of the recurrence of a myocardial infarction. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Löbel, U; Trah, J; Escherich, G
2015-03-01
Systemic and intrathecal methotrexate is widely used in treatment protocols for childhood acute lymphoblastic leukemia. Its side effects vary in characteristics, intensity and time of onset, and depend on the administration route. Interactions with several drugs are known. Side effects of nitrous oxide sedation, often used for moderately painful procedures, typically occur after long time use and include neurological symptoms. We present a child who experienced a severe and long-lasting neurotoxicity after the third intrathecal application of methotrexate with short sedation by nitrous oxide during induction therapy for acute lymphoblastic leukemia. Symptoms completely resolved after 12 months. © 2014 Wiley Periodicals, Inc.
Haleem, Kirolos; Gan, Albert
2013-09-01
This study identifies geometric, traffic, environmental, vehicle-related, and driver-related predictors of crash injury severity on urban freeways. The study takes advantage of the mixed logit model's ability to account for unobserved effects that are difficult to quantify and may affect the model estimation, such as the driver's reaction at the time of crash. Crashes of 5 years occurring on 89 urban freeway segments throughout the state of Florida in the United States were used. Examples of severity predictors explored include traffic volume, distance of the crash to the nearest ramp, and detailed driver's age, vehicle types, and sides of impact. To show how the parameter estimates could vary, a binary logit model was compared with the mixed logit model. It was found that the at-fault driver's age, traffic volume, distance of the crash to the nearest ramp, vehicle type, side of impact, and percentage of trucks significantly influence severity on urban freeways. Additionally, young at-fault drivers were associated with a significant severity risk increase relative to other age groups. It was also observed that some variables in the binary logit model yielded illogic estimates due to ignoring the random variation of the estimation. Since the at-fault driver's age and side of impact were significant random parameters in the mixed logit model, an in-depth investigation was performed. It was noticed that back, left, and right impacts had the highest risk among middle-aged drivers, followed by young drivers, very young drivers, and finally, old and very old drivers. To reduce side impacts due to lane changing, two primary strategies can be recommended. The first strategy is to conduct campaigns to convey the hazardous effect of changing lanes at higher speeds. The second is to devise in-vehicle side crash avoidance systems to alert drivers of a potential crash risk. The study provided a promising approach to screening the predictors before fitting the mixed logit model using the random forest technique. Furthermore, potential countermeasures were proposed to reduce the severity of impacts. Copyright © 2013 National Safety Council and Elsevier Ltd. All rights reserved.
Fatemi Naeini, Farahnaz; Abtahi-Naeini, Bahareh; Pourazizi, Mohsen; Nilforoushzadeh, Mohammad Ali; Mirmohammadkhani, Majid
2015-11-01
Primary axillary hyperhidrosis (PAH) creates social stress in patients. Although there are several options for treating PAH, only surgical modalities have conferred a permanent solution. This study evaluated the clinical effectiveness of fractionated microneedle radiofrequency (FMR) treatment for PAH. This study is based on a single-blind, sham control comparative design. In all, 25 patients with severe PAH underwent three sessions of FMR at 3-week intervals. One side was treated with FMR while the other was sham controlled. Efficacy was evaluated using the hyperhidrosis disease severity scale (HDSS), sweating intensity visual analogue scale (VAS) and patient satisfaction at baseline, 3 weeks after each session and at 3 months after the last. Skin biopsies were obtained from two enrolled patients. The HDSS and VAS demonstrated significant improvement after treatment on the treated side in comparison with the control side. The mean ± SD of the HDSS after 21 weeks were 1.87 ± 0.61 and 3.38 ± 0.49 (P < 0.001) for the treated and the controlled side, respectively. The follow-up evaluation revealed that 79% of the patients showed a 1 or 2-score decrease in HDSS. In total, 80% of patients reported more than 50% satisfaction at the end of the study. Histopathological findings showed a decrease of the number of the sweat glands in the treated side, confirming the above findings. Treatment of PAH with FMR as a non-invasive modality can be a safe option with positive therapeutic effects on HDSS without any long-lasting side effects. © 2014 The Australasian College of Dermatologists.
Kumar, Amandeep; Suri, Ashish; Sharma, Bhawani S
2014-07-01
Valproic acid (VPA) is a commonly used drug for epilepsy, psychiatric disorders and migraine and is frequently used in neurosurgical intensive care units. Though most of its side-effects are mild and transient, certain idiosyncratic side-effects have been attributed to VPA. Valproate induced hyperammonemia (VIH) is one such side-effect. VIH can produce symptoms of encephalopathy known as valproate induced hyperammonemic encephalopathy (VHE). VIH and VHE usually respond to withdrawal of VPA. However, in some cases VHE can be unresponsive to supportive measures and severe enough to be life-threatening. In such cases, dialysis can be used to rapidly reverse hyperammonemia and VHE and can prove to be a lifesaving measure. We report such a case of VIH and life-threatening VHE in a postoperative neurosurgical patient that was managed successfully with peritoneal dialysis.
In Jae, Jeong; Dong Ju, Hyun; Dong Hyun, Kim; Yoon, Moon Soo; Lee, Hee Jung
2017-11-21
Superficial chemical peels are frequently used in acne vulgaris treatment. Although glycolic acid (GA) has been widely used in clinical practice, its pH ranges from 0.08-2.75 and thus should be neutralized after application to avoid burns. To evaluate treatment efficacy and safety of chemical peeling using buffered 50% GA (pH 3.0) + 0.5% salicylic acid (SA) solution that does not need to be neutralized in the treatment of acne vulgaris compared to the conventional peeling using Jessner's solution. We performed a prospective, randomized, evaluator-blind, split-face clinical trial. Twenty patients were randomized by assigning one side of each patient's face to receive a 50% GA (pH 3.0) + 0.5% SA peel (GA side) and the other side to receive the Jessner's solution (Jessner's solution side). All patients underwent 2 sessions of treatment spaced 2 weeks apart. Lesion count, acne severity, subjective efficacy assessment, and side effects were evaluated. The total lesion count was significantly reduced for the GA and Jessner's solution sides (P < .001). However, there was no significant difference in the total lesion count, acne severity, or subjective efficacy assessment between the 2 sides (P > .05). The GA side had fewer side effects than the Jessner's solution side. The results of this study suggest that chemical peeling using the 50% GA (pH 3.0) + 0.5% SA solution can be as effective and convenient as the conventional peeling using Jessner's solution in the treatment of acne vulgaris and may show fewer adverse events than the conventional peeling. © 2017 Wiley Periodicals, Inc.
Side Effects to Antidepressant Treatment in Patients With Depression and Comorbid Panic Disorder.
Shankman, Stewart A; Gorka, Stephanie M; Katz, Andrea C; Klein, Daniel N; Markowitz, John C; Arnow, Bruce A; Manber, Rachel; Rothbaum, Barbara O; Thase, Michael E; Schatzberg, Alan F; Keller, Martin B; Trivedi, Madhukar H; Kocsis, James H
2017-04-01
Side effects to antidepressant medication can affect the efficacy of treatment, but few predictors foretell who experiences side effects and which side effects they experience. This secondary data analysis examined whether depressed patients with comorbid panic disorder were more likely to experience side effects than those without panic disorder. The study also examined whether greater burden of side effects predicted a poorer treatment course for patients with panic disorder than those without panic disorder. To examine the specificity of these effects, analyses also examined 2 other anxiety disorders-social phobia and generalized anxiety disorder (GAD). Between 2002 and 2006, a large sample (N = 808) of chronically depressed individuals (assessed using the Structured Clinical Interview for DSM-IV-TR Axis I Disorders [SCID-IV]) received antidepressants according to a predetermined algorithm for 12 weeks. Every 2 weeks, depressive symptoms (per the Hamilton Depression Rating Scale) and side effects (specific side effects as well as several indicators of side effect burden) were assessed. Lifetime diagnosis of panic disorder (assessed using the SCID-IV) at baseline was associated with higher likelihood of gastrointestinal (OR = 1.6 [95% CI, 1.0-2.6]), cardiac (OR = 1.8 [95% CI, 1.1-3.1]), neurologic (OR = 2.6 [95% CI, 1.6-4.2]), and genitourinary side effects (OR = 3.0 [95% CI, 1.7-5.3]) during treatment. Increases in side effect frequency, intensity, and impairment over time were more strongly associated with increases in depressive symptoms for patients with panic disorder compared to those without panic disorder. Neither social phobia nor GAD was associated with these effects. Potentially due to heightened interoceptive awareness of changes in their body, chronically depressed individuals with panic disorder may be at greater risk than those without panic disorder for antidepressant side effects and to experience a worsening of depressive symptoms as a result of these side effects over time. ClinicalTrials.gov identifier: NCT00057551. © Copyright 2017 Physicians Postgraduate Press, Inc.
Risk factors for non-adherence to antidepressant treatment in patients with mood disorders.
De las Cuevas, Carlos; Peñate, Wenceslao; Sanz, Emilio J
2014-01-01
Adherence to antidepressant therapy by patients with depressive disorders is essential not only to achieve a positive patient outcome but also to prevent a relapse. The aim of this study was to identify potential modelling factors influencing adherence to antidepressant treatment by patients with mood disorders in the community mental health care setting A total of 160 consecutive psychiatric outpatients attending two Community Mental Health Centres on Tenerife Island between September 2011 and May 2012 were asked to participate in the study; of these, 145 accepted. The Morisky self-report scale was used to assess adherence. The potential predictors examined included socio-demographic, clinical and therapeutic variables. The Clinical Global Impression-Severity and -Improvement scales and the Beck Depression Inventory were used for clinical assessment. Drug treatment side-effects were assessed using the "Self-report Antidepressant Side-Effect Checklist." All participants were also asked to complete the "Drug Attitude Inventory" (DAI), "Beliefs about Medicine Questionnaire" (BMQ), and "Leeds Attitude towards concordance Scale". Discriminant analyses were performed to predict non-adherence. There was no clear correlation between adherence and the socio-demographic variables examined, but adherence was related to a positive attitude of the patients towards his/her treatment (DAI) and low scores in the BMQ-Harm and -Concern subscales. Non-adherence was also related to an increasing severity of depression and to the presence and severity of side-effects. Among our study cohort, the profiles of adherent patients to antidepressant treatment were more closely associated with each patient's attitudes and beliefs than to objective socio-demographic variables. The severity of depression played a relevant role in adherence, but whether this role is direct or an interaction with several concurrent factors is not yet clear. Side-effects were also closely related to adherence, as conditioned by frequent polypharmacy.
Factors effecting paint performance on wood siding
Christopher G. Hunt; R. Sam Williams; Mark Knaebe; Peter Sotos; Steven Lacher
2009-01-01
Several different studies are compared to assess the effectiveness of commercial water repellent preservatives (WRPâs) in the late 1990âs on vertical and horizontal siding. Besides WRP, variables included wood species, exposure location (Wisconsin or Mississippi), and solid color stain vs. primer + paint. Data on substrate checking and paint flaking are presented....
Wang, H; Gu, Q; Wei, J; Cao, Z; Liu, Q
2015-05-01
A novel recommendation-based drug repositioning strategy is presented to simultaneously determine novel drug indications and side effects in one integrated framework. This strategy provides a complementary method to medical genetics-based drug repositioning, which reduces the occurrence of false positives in medical genetics-based drug repositioning, resulting in a ranked list of new candidate indications and/or side effects with different confidence levels. Several new drug indications and side effects are reported with high prediction confidences. © 2015 American Society for Clinical Pharmacology and Therapeutics.
Nonlinear side effects of fs pulses inside corneal tissue during photodisruption
NASA Astrophysics Data System (ADS)
Heisterkamp, A.; Ripken, T.; Mamom, T.; Drommer, W.; Welling, H.; Ertmer, W.; Lubatschowski, H.
In order to evaluate the potential for refractive surgery, fs laser pulses of 150-fs pulse duration were used to process corneal tissue of dead and living animal eyes. By focusing the laser radiation down to spot sizes of several microns, very precise cuts could be achieved inside the treated cornea, accompanied with minimum collateral damage to the tissue by thermal or mechanical effects. During histo-pathological analysis by light and transmission electron microscopy considerable side effects of fs photodisruption were found. Due to the high intensities at the focal region several nonlinear effects occurred. Self-focusing, photodissociation, UV-light production were observed, leading to streak formation inside the cornea.
Song, Byong Han; Lee, Dong Hun; Kim, Byung Chul; Ku, Sang Hyeon; Park, Eun Joo; Kwon, In Ho; Kim, Kwang Ho; Kim, Kwang Joong
2014-10-01
Chlorophyll-a is a novel photosensitizer recently tested for the treatment of acne vulgaris. We sought to evaluate the clinical efficacy and safety of chlorophyll-a photodynamic therapy used for acne treatment. Subjects with acne on both sides of the face were included. Eight treatment sessions were performed over a 4-week duration. Half of the face was irradiated using a blue and red light-emitting diode after topical application of chlorophyll-lipoid complex. The other half underwent only light-emitting diode phototherapy. The lesion counts and acne severity were assessed by a blinded examiner. Sebum secretion, safety, and histologic changes were also evaluated. In total, 24 subjects completed the study. Facial acne improved on both treated sides. On the chlorophyll-a photodynamic therapy-treated side, there were significant reductions in acne lesion counts, acne severity grades, and sebum levels compared with the side treated with light-emitting diode phototherapy alone. The side effects were tolerable in all the cases. All the subjects were of Asian descent with darker skin types, which may limit the generalizability of the study. A chlorophyll-a arm alone is absent, as is a no-treatment arm. We suggest that chlorophyll-a photodynamic therapy for the treatment of acne vulgaris can be effective and safe with minimal side effects. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Side impact crashes--factors affecting incidence and severity: review of the literature.
Chipman, Mary L
2004-03-01
Many traffic crashes are side impact collisions resulting in significant death and injury. A review was conducted of the evidence of driver, road, and vehicle characteristics affecting either the risk of occurrence or the severity of injury in such crashes for papers published from 1996 to early 2003. For drivers, evidence was found of increased crash risk or injury severity only for age and age-related medical conditions (e.g., dementia). Traffic roundabouts and other traffic control devices--stop signs, traffic lights, and so on--had mixed results; traffic controls were better than no controls, but their effectiveness varied with circumstance. Most vehicle characteristics have had little or no effect on crash occurrence. Antilock braking systems (ABS) in the striking vehicle had been anticipated to reduce the risk of crashes, but so far have demonstrated little effect. The primary emphasis in vehicle design has been on protective devices to reduce the severity of injury. Disparity in the size of the two vehicles, especially when the struck vehicle is smaller and lighter, is almost a consistent risk factor for occupant injury. The occupants of light trucks, however, when struck by passengers cars on the opposite side, were at higher risk of injury. Wearing seat belts had a consistently protective effect; airbags did not, but there were few studies, and no field studies, of lateral airbags found. Of all the characteristics examined, vehicle design, including occupant restraints, is the most easily modified in the short term, although road design, traffic control, and the monitoring of older drivers may also prove effective in reducing side impact crashes in the longer term.
[Side Effects of Occupational Group Therapy].
Flöge, B; Fay, D; Jöbges, M; Linden, M; Muschalla, B
2016-12-01
Background: Occupational therapy is an important co-therapy in psychiatric therapy. It is a common belief that no risks are associated with occupational therapy. Negative effects caused by group therapy, especially occupational therapy, have not been in the focus of research yet. In this study we want to illustrate possible types and intensities of group side effects through occupational therapy. Patients and Methods: Patients of an inpatient rehabilitation facility filled out the Adverse Treatment Reaction Group Checklist. The checklist contains 47 items divided in six dimensions: group size, content, group participants, group outcome and global. The self-rating used a 5-point likert scale (0 = not at all; 4 = very much, extremely stressful) and gives information about types and intensities of the side effects. Results: 88.9 % of 45 patients reported negative effects of occupational group therapy. 28.9 % of the patients rated the side effect as at least severe. Discussion: Occupational therapy is associated with side effects as every other group therapy. Possible side effects caused by group therapy should be considered while planning and implementing occupational therapy. © Georg Thieme Verlag KG Stuttgart · New York.
Propofol interruption of ECT seizure to reduce side-effects: a pilot study.
Warnell, Ronald L; Swartz, Conrad M; Thomson, Alice
2010-01-30
Fifteen depressed subjects received six bitemporal electroconvulsive therapy (ECT) treatments under etomidate anesthesia. They were randomized to blindly either receive propofol 0.5mg/kg 15s post-stimulus or not. Propofol infusion significantly prevented long seizures, and prevented cognitive decrements in most neuropsychological tests, several significantly. Propofol interruption may clinically help reduce ECT side-effects.
Ocular side effects of biological agents in oncology: what should the clinician be aware of?
Hager, Tobias; Seitz, B
2014-01-01
During the last 20 years, biologicals have become increasingly relevant in oncologic therapy. Depending on the medication used, there are different profiles of ocular side effects. Although these can be present in up to 70% of patients, they are generally underreported in the literature. Therefore, the pathophysiological details of their development are often poorly understood. Herein we attempt to identify groups of biologicals to which a specific side effect profile can be assigned. We also tried to capture all relevant side effects and therefore conducted several database investigation including Medline, Cochrane library, and the drugs section of the US Food and Drug Administration (FDA), using the following search strings: “name of biological agent (both generic and commercial names)” AND “eye” OR “ocular”. If we found a side effect that has been associated with a drug, we researched Medline using the following search string: “name of biological agent” (both generic and commercial names) AND “term for the specific side effect”. Due to the wealth of material we report only the drugs that are approved by the FDA. PMID:24391443
Micallef-Trigona, Beppe
2014-01-01
Electroconvulsive therapy (ECT) is the longest standing psychiatric treatment available and has unequivocal benefit in severe depression. However this treatment comes with a number of side effects such as memory impairment. On the other hand, Repetitive Transcranial Magnetic Stimulation (rTMS) is a relatively new form of treatment which has been shown to be efficacious in patients suffering from a number of psychopathologies, including severe depression, with few reported side effects. Due to its potential therapeutic efficacy and lack of side effects, rTMS has gained traction in the treatment of depression, with a number of authors keen to see it take over from ECT. However, it is not clear whether rTMS represents a therapeutic alternative to ECT. This meta-analysis will therefore compare the "gold standard" treatment for severe depression, with the relatively new but promising rTMS. A literature search will be performed with the intention to include all randomised clinical trials. The null hypothesis is that there is no difference in the antidepressant efficacy between the two types of treatment modalities. Statistical analysis of Hamilton Depression Rating Scale (HDRS) scores will be performed.
Viani, Gustavo Arruda; Fendi, Ligia Issa de
2017-01-01
In this systematic review, we evaluated studies involving adjuvant and primary topical treatment for ocular surface squamous neoplasia (OSSN). The findings were: (i) adjuvant 5-fluorouracil (5-FU) reduces the risk of relapse after surgical excision with mild side effects [level Ib, grade of recommendation (GR) A]. (ii) Primary topical mitomycin (MMC) produces a high rate of complete response, low recurrence rate, and mild side effects (level Ib, GR A). (iii) Primary chemotherapy versus adjuvant chemotherapy produce similar rates of recurrence, with no significant difference (level IIb, GR B). (iv) Adjuvant 5-FU versus MMC showed no significant differences, with mild side effects in both groups and a better toxicity profile for MMC (level III, GR C). (v) Primary topical 5-FU versus MMC versus interferon (IFN) showed similar rates of tumor recurrence, mild side effects for all drugs, and more severe side effects in the 5-FU arm, followed successively by MMC and IFN (level III, GR C).
The treatment of Parkinson's disease with deep brain stimulation: current issues.
Moldovan, Alexia-Sabine; Groiss, Stefan Jun; Elben, Saskia; Südmeyer, Martin; Schnitzler, Alfons; Wojtecki, Lars
2015-07-01
Deep brain stimulation has become a well-established symptomatic treatment for Parkinson's disease during the last 25 years. Besides improving motor symptoms and long-term motor complications, positive effects on patients' mobility, activities of daily living, emotional well-being and health-related quality of life have been recognized. Apart from that, numerous clinical trials analyzed effects on non-motor symptoms and side effects of deep brain stimulation. Several technical issues and stimulation paradigms have been and are still being developed to optimize the therapeutic effects, minimize the side effects and facilitate handling. This review summarizes current therapeutic issues, i.e., patient and target selection, surgical procedure and programming paradigms. In addition it focuses on neuropsychological effects and side effects of deep brain stimulation.
The efficacy in melasma treatment using a 1410 nm fractional photothermolysis laser.
Wanitphakdeedecha, R; Keoprasom, N; Eimpunth, S; Manuskiatti, W
2014-03-01
Melasma treatment modalities including topical and procedural therapy have been employed with variable results and high recurrence rate. To quantitatively assess improvement in melasma and side effects after 1410 nm fractional photothermolysis laser treatments and to determine efficacy at 1-, 2- and 3-month follow-up after treatment. Thirty volunteers with melasma were treated with 1410 nm fractional photothermolysis for four passes on full face and additional four passes on melasma area. They were randomly treated on one side of their face with 20 mJ at 5% coverage and the other side of their face with 20 mJ at 20% coverage. All subjects were treated monthly for five times. Melanin index, Visual analogue scale and Melasma Area and Severity Index score were measured at baseline and 1-, 2- and 3-month follow-up after complete treatment protocol. There was statistically significant improvement of Melanin index at 2- and 3-month follow-up visits, but not at 1-month follow-up visit. Visual analogue scale and Melasma Area and Severity Index score improved significantly on both sides at 1-, 2- and 3-month follow-ups. The overall patients' satisfaction was significantly higher on the side treated with 20 mJ, 5% coverage. Adverse reactions included erythema, dryness and post-inflammatory hyperpigmentation on melasma area. Those side effects were significantly more intense on the side treated with 20 mJ, 20% coverage. 1410 nm fractional photothermolysis laser treatment is a safe and temporary effective procedure for melasma; however, long-term follow-up is still needed. Only 5% coverage should be used to minimize risks of adverse effects. © 2013 The Authors Journal of the European Academy of Dermatology and Venereology © 2013 European Academy of Dermatology and Venereology.
Mulders, Anne E P; Leentjens, Albert F G; Schruers, Koen; Duits, Annelien; Ackermans, Linda; Temel, Yasin
2017-08-01
Patients with treatment-resistant obsessive-compulsive disorder (OCD) are potential candidates for deep brain stimulation (DBS). The anteromedial subthalamic nucleus (STN) is among the most commonly used targets for DBS in OCD. We present a patient with a 30-year history of treatment-resistant OCD who underwent anteromedial STN-DBS. Despite a clear mood-enhancing effect, stimulation caused motor side effects, including bilateral hyperkinesia, dyskinesias, and sudden large amplitude choreatic movements of arms and legs when stimulating at voltages greater than approximately 1.5 V. DBS at lower amplitudes and at other contact points failed to result in a significant reduction of obsessions and compulsions without inducing motor side effects. Because of this limitation in programming options, we decided to reoperate and target the ventral capsule/ventral striatum (VC/VS), which resulted in a substantial reduction in key obsessive and compulsive symptoms without serious side effects. Choreatic movements and hemiballismus have previously been linked to STN dysfunction and have been incidentally reported as side effects of DBS of the dorsolateral STN in Parkinson disease (PD). However, in PD, these side effects were usually transient, and they rarely interfered with DBS programming. In our patient, the motor side effects were persistent, and they made optimal DBS programming impossible. To our knowledge, such severe and persistent motor side effects have not been described previously for anteromedial STN-DBS. Copyright © 2017 Elsevier Inc. All rights reserved.
Continuous prostaglandin-F 2 infusion for middle-trimester abortion.
Lauersen, N H; Wilson, K H
1973-05-26
Induction of midtrimester abortion with a continuous intravenous infusion of prostaglandin (PG) was described by Karim and Filshie and Roth-Brandel et al. in 1970, but the effective dose of PGF2alpha was associated with side effects severely limiting clinical usefulness. Karim and Sharma induced abortion by intravaginal PG, but again this route also seemed complicated by severe side effects. Independent reports followed of successful induction of midtrimester abortion by intraamniotic PGF2alpha and PGE2 with few side effects. Although we also successfully induced abortion in 20 patients with a single intraamniotic instillation of 40 mg PGF2alpha, there is a potential hazard in this method; i.e., PG may leak from the amniotic cavity around the catheter and pass in large quantity into the systemic circulation, resulting in undesirable, severe side effects. A more reasonable and effective method would be to inject the PGF2alpha directly at the target organ, the myometrium, by extraovular administration. Side effects could thus be minimized and effective doses of PG reduced. Such intrauterine extraovular administration of PG has been reported. The incidence of side effects was greatly reduced, although the instillation of PG was required every 1-3 hours and there were some incomplete abortions. The investigation of extraovular PGF2alpha administration for induction of abortion in gestations between 12 and 16 weeks has been especially interesting. The procedure outlined by Wiqvist and Bygdeman and Embrey and Hillier was the 1 that the authors followed initially. 250 mcg PGF2alpha was instilled initially and was followed by 750 mcg in 5 minutes and 1 mg in 30 minutes. 1 mg was then instilled at 6 hour intervals. However, the failure rate with this dosage schedule was quite high. There was a good initial uterine response, but during the administrationsat 12, 18, and 24 hours, the response diminished considerably . The frequency of administration was then increased to every 2-3 hours and the amount instilled was increased to 2-3 mg. Although somewhat more successful than the original dose schedule, this method was also unsatisfactory. It appeared from our results that the closer the injections, the higher the success rate. Thus, a brief case report is presented using continuous extraovular administration of PGF2alpha with a Harvard pump, and the results indicate it is quite satisfactory. The patients complained of very little pain and side effects have been slight. The mean abortion time for 15 patients was 14 hours. The mean time for multiparas, 11.7 hours, was faster than the 15.8 hours for primiparas.
Nakata, Mary; Goya, Seijirow; Fukayama, Toshiharu
2017-01-01
Background After thoracic surgery, adhesions between the pleura can cause substantial complications. This study investigated the effectiveness of a novel membrane utilizing surface water induction technology to prevent adhesions. Methods Eight beagles were divided into an experimental group (five males) and a control group (three females). The experimental group underwent thoracotomy on both the left and right sides of the chest. Both sides received the membrane, and the membrane on one side was glued to the pleura using tissue adhesive. The control group underwent thoracotomy only on the left side. Two weeks postoperatively, all dogs were sacrificed and adhesions were evaluated macroscopically and microscopically. Results Severe adhesion was seen between the parietal and visceral pleura in all control dogs, whereas the experimental group showed minor adhesion in only one dog on one side. Conclusions Our novel anti-adhesive membrane appeared highly effective in preventing postthoracotomy pleural adhesions. PMID:28654705
Analgesic Prodrugs for Combating their Side-Effects: Rational Approach.
Ruchita; Sucheta; Nanda, Sanju; Pathak, Dharampal
2017-01-01
Analgesics are the drugs which bring insensibility to pain without loosing consciousness. Treatment strategy is generally based on the type of pain. Most of the analgesics are associated with serious side effects, such as NSAIDS can cause severe GI disturbance and opioids can cause addiction. There are various ways to reduce their side effects The analgesic prodrug approach is one of the several strategies used to attain the required pharmacological response with a considerable decrease in side effects. The aim of this paper is to introduce in depth the rational behind the use of the analgesic prodrug approach from past to present. Data is collected from online as well as from extensive literature survey which have appeared on this subject during the last decades. This review will map the origins and development of the most important of the analgesic prodrugs to date. This review indicates that, designing analgesic prodrugs represent successful strategy to gain the required pharmacological activity with a considerable decrease in side effects. However thorough knowledge of diverse biological phenomena is needed which enables scientists to invent and design superior, nontoxic and better-targeted prodrugs. The newly synthesized chemical entity or prodrugs may or may not have intrinsic pharmacological activity and also synthesizing novel molecules consume a lot of time and money than developing prodrugs of existing clinically used analgesic drugs which is surely an attractive and promising area of research now a days. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Efficient hiding of confidential high-utility itemsets with minimal side effects
NASA Astrophysics Data System (ADS)
Lin, Jerry Chun-Wei; Hong, Tzung-Pei; Fournier-Viger, Philippe; Liu, Qiankun; Wong, Jia-Wei; Zhan, Justin
2017-11-01
Privacy preserving data mining (PPDM) is an emerging research problem that has become critical in the last decades. PPDM consists of hiding sensitive information to ensure that it cannot be discovered by data mining algorithms. Several PPDM algorithms have been developed. Most of them are designed for hiding sensitive frequent itemsets or association rules. Hiding sensitive information in a database can have several side effects such as hiding other non-sensitive information and introducing redundant information. Finding the set of itemsets or transactions to be sanitised that minimises side effects is an NP-hard problem. In this paper, a genetic algorithm (GA) using transaction deletion is designed to hide sensitive high-utility itemsets for PPUM. A flexible fitness function with three adjustable weights is used to evaluate the goodness of each chromosome for hiding sensitive high-utility itemsets. To speed up the evolution process, the pre-large concept is adopted in the designed algorithm. It reduces the number of database scans required for verifying the goodness of an evaluated chromosome. Substantial experiments are conducted to compare the performance of the designed GA approach (with/without the pre-large concept), with a GA-based approach relying on transaction insertion and a non-evolutionary algorithm, in terms of execution time, side effects, database integrity and utility integrity. Results demonstrate that the proposed algorithm hides sensitive high-utility itemsets with fewer side effects than previous studies, while preserving high database and utility integrity.
Treatment of gastro-esophageal reflux disease: the new kids to block.
Blondeau, K
2010-08-01
Refractory gastro-esophageal reflux disease (GERD), defined as persistent symptoms despite proton pump inhibitor (PPI) therapy, is an increasingly prevalent condition and is becoming a major challenge for the clinician. Since non-acidic reflux may be associated with symptoms persisting during PPI treatment, the lower esophageal sphincter (LES), the most important barrier protecting against reflux, has become an important target for the treatment of (refractory) GERD. Preclinical research has identified several receptors that are involved in the control of transient lower esophageal sphincter relaxations (TLESRs), the predominant mechanism of both acid and non-acidic reflux events, and several drugs have now been tested in humans. The GABA(B) agonist baclofen has demonstrated to effectively reduce the rate of TLESRs and the amount of reflux in both GERD patients and healthy volunteers. Nevertheless, the occurrence of central side effects limits its clinical use for the treatment of GERD. Several analogues are being developed to overcome this limitation and have shown promising results. Additionally, metabotropic glutamate receptor 5 (mGluR5) receptor antagonists have shown to reduce both acid and non-acidic reflux in GERD patients and several molecules are currently being evaluated. Although CB(1) antagonists have been shown to reduce TLESRs, they are also associated with central side effects, limiting their clinical applicability. Despite the identification of several potentially interesting drugs, the main challenge for the future remains the reduction of central side effects. Moreover, future studies will need to demonstrate the efficacy of these treatments in patients with refractory GERD.
Minoxidil for severe hypertension after failure of other hypotensive drugs.
Devine, B L; Fife, R; Trust, P M
1977-01-01
Forty-four patients with severe hypertension who were resistant to treatment with more conventional hypotensive drugs or could not tolerate the side effects were treated with minoxidil, a potent peripheral vasodilator. A beta-blocking drug and a diuretic were used routinely to control, respectively, the tachycardia and fluid retention caused by minoxidil. During treatment the outpatient supine blood pressure fell from a mean of 221/134 mm Hg to 162/98 mm Hg. Eleven patients required additional or alternative hypotensive agents before blood pressure was adequately controlled. Side effects were minor, although the invariable hirsuties caused by minoxidil was unacceptable to three women. The possibility of cardiotoxic effects, raised by early studies in dogs, has not been excluded, and therefore this drug should be used only in patients with severe hypertension. In such patients minoxidil appears to be most effective. PMID:902045
Side Effects of Virtual Environments: A Review of the Literature
2004-05-01
Cybersickness symptoms are the unintended psychophysiological side effects of participation in virtual environments. Symptoms can occur both during...induced motion sickness, cybersickness is believed to result from sensory and perceptual mismatches between the visual and vestibular systems, and can...and the task carried out, can affect either incidence or severity of cybersickness . Taking account of these factors may avoid or minimize symptoms. This
Medication Side Effects among People with Epilepsy Taking Phenobarbital in Zambia
Elafros, Melissa A.; Bui, Esther; Birbeck, Gretchen L.
2014-01-01
Phenobarbital remains one of the most widely used antiepileptic drugs worldwide, yet there are limited data regarding side effects associated with its use in routine clinical care settings in low-income countries. Available data suggests that phenobarbital is as effective as other first-line drugs for treating tonic-clonic seizures, but side effect reports differ widely between high and low-income settings. A better understanding of phenobarbital side effect profile and severity in low-income settings is warranted given its role in efforts to decrease the epilepsy treatment gap. We used the Liverpool Adverse Events Profile (LEAP) to assess side effects in consecutive patients with epilepsy on phenobarbital seeking care in rural Zambia. Data regarding age, gender, medication dose, and medication adherence were also collected. T-tests and Spearman’s correlation coefficient were used to assess predictors of LEAP score and medication adherence. Thirty-five patients receiving a mean dose of 2.1 mg/kg/day (SD: 2.78 mg/kg/day) of phenobarbital were assessed. All participants reported at least one side effect in the previous four weeks with a median of 6 symptoms (IQR: 4–8) and a mean side effects score of 28/76 (SD: 5.38). Over half reported sleepiness and dizziness. Memory problems and depression were also common (both 46%). Total LAEP score was not associated with age (p=0.88), gender (p=0.17), or phenobarbital dose (p=0.13). Medication adherence was not associated with side effects total score (p=0.56). Rural Zambian adults taking phenobarbital at doses recommended by the WHO report a significant number of side effects. The most common side effects reported were similar to those reported in high-income countries. The significant burden of phenobarbital-associated side effects in this African cohort is in contrast to data from non-randomized clinical trials in China that reported phenobarbital to be well-tolerated with few side effects. Additional investigations regarding phenobarbital side effects in routine care in low income settings is warranted. PMID:25219354
Medication side effects among people with epilepsy taking phenobarbital in Zambia.
Elafros, Melissa A; Bui, Esther; Birbeck, Gretchen L
2014-11-01
Phenobarbital remains one of the most widely used antiepileptic drugs worldwide, yet there are limited data regarding side effects associated with its use in routine clinical care settings in low-income countries. Available data suggests that phenobarbital is as effective as other first-line drugs for treating tonic-clonic seizures, but side effect reports differ widely between high and low-income settings. A better understanding of phenobarbital side effect profile and severity in low-income settings is warranted given its role in efforts to decrease the epilepsy treatment gap. We used the Liverpool adverse events profile (LEAP) to assess side effects in consecutive patients with epilepsy on phenobarbital seeking care in rural Zambia. Data regarding age, gender, medication dose, and medication adherence were also collected. T-tests and Spearman's correlation coefficient were used to assess predictors of LEAP score and medication adherence. Thirty-five patients receiving a mean dose of 2.1mg/kg/day (SD: 2.78 mg/kg/day) of phenobarbital were assessed. All participants reported at least one side effect in the previous four weeks with a median of 6 symptoms (IQR: 4-8) and a mean side effects score of 28/76 (SD: 5.38). Over half reported sleepiness and dizziness. Memory problems and depression were also common (both 46%). Total LAEP score was not associated with age (p=0.88), gender (p=0.17), or phenobarbital dose (p=0.13). Medication adherence was not associated with side effects total score (p=0.56). Rural Zambian adults taking phenobarbital at doses recommended by the World Health Organization report a significant number of side effects. The most common side effects reported were similar to those reported in high-income countries. The significant burden of phenobarbital-associated side effects in this African cohort is in contrast to data from non-randomized clinical trials in China that reported phenobarbital to be well-tolerated with few side effects. Additional investigations regarding phenobarbital side effects during routine care in low income settings is warranted. Copyright © 2014 Elsevier B.V. All rights reserved.
Evaluation of amino-oxyacetic acid as a palliative in tinnitus.
Guth, P S; Risey, J; Briner, W; Blair, P; Reed, H T; Bryant, G; Norris, C; Housley, G; Miller, R
1990-01-01
Amino-oxyacetic acid (AOAA) was evaluated as a palliative in tinnitus. Sixty-six patients with tinnitus presumed to be of cochlear origin were given either a placebo or 75 mg of AOAA four times a day for 1 week. Response was evaluated by both audiometric measurement of tinnitus loudness and subjective rating by patients of change or no change in tinnitus severity. Because loudness measurements and self-rating have not been shown to be independent, and since the aim of clinical treatment of tinnitus is the alleviation of subjective distress, greater weight was given to the patient's self-rating. A total of 21% of all patients reported a subjective decrease in tinnitus severity, usually within 3 to 4 days after the start of AOAA use. Patients with tinnitus caused by presbycusis or Meniere's disease were the most likely to respond to AOAA treatment with a reduction in tinnitus severity, whereas those with drug-induced tinnitus were the least likely to respond. Nausea and dysequilibrium were the most common side effects of AOAA use. Of the 21% of patients who responded to AOAA, 71% developed some type of side effect. Amino-oxyacetic acid produces a reduction in the severity of tinnitus in about 20% of patients; however, the incidence of side effects makes the drug unacceptable for clinical use.
Lambert, M; Conus, P; Eide, P; Mass, R; Karow, A; Moritz, S; Golks, D; Naber, D
2004-11-01
(1) determine which antipsychotic side effects (SE) schizophrenic patients consider the most distressing during treatment with typical antipsychotics, (2) measure the impact of actual and past SE on patients' attitude toward antipsychotics and (3) assess the influence of both on adherence. The 213 schizophrenics, treated with conventional antipsychotics, were recruited in two psychiatric hospitals in Hamburg. Subjects were assessed about type and severity of present and past side effects and their attitude and adherence to antipsychotic treatment. The 82 (39%) patients presented present SE while 131 (61%) did not. Sexual dysfunctions (P < 0.001), extrapyramidal (P < 0.05) and psychic side effects (P < 0.05) were rated as significantly subjectively more distressing than sedation or vegetative side effects. Patients presenting with present SE compared with patients without present SE had a significantly more negative general attitude toward antipsychotics (P < 0.05), were more doubtful about their efficacy (P < 0.01) and were less likely to encourage a relative to take such a medication in case of need (P < 0.001). A regression analysis indicated that nonadherence was mainly influenced by negative general and efficacy attitudes toward antipsychotics and the experience of past or present antipsychotic side effects. All antipsychotic side effects, present or past, can have a durable negative impact on patient's attitude toward antipsychotic treatment and adherence. Non-adherence is mainly determined, among other factors, by these negative attitudes, which are partly influenced by the experience of past or present antipsychotic-induced side effects.
Gray, Meeghan E; Cameron, Elissa Z
2010-01-01
The efficacy of contraceptive treatments has been extensively tested, and several formulations are effective at reducing fertility in a range of species. However, these formulations should minimally impact the behavior of individuals and populations before a contraceptive is used for population manipulation, but these effects have received less attention. Potential side effects have been identified theoretically and we reviewed published studies that have investigated side effects on behavior and physiology of individuals or population-level effects, which provided mixed results. Physiological side effects were most prevalent. Most studies reported a lack of secondary effects, but were usually based on qualitative data or anecdotes. A meta-analysis on quantitative studies of side effects showed that secondary effects consistently occur across all categories and all contraceptive types. This contrasts with the qualitative studies, suggesting that anecdotal reports are insufficient to investigate secondary impacts of contraceptive treatment. We conclude that more research is needed to address fundamental questions about secondary effects of contraceptive treatment and experiments are fundamental to conclusions. In addition, researchers are missing a vital opportunity to use contraceptives as an experimental tool to test the influence of reproduction, sex and fertility on the behavior of wildlife species.
Diagnosing the Causes and Severity of One-sided Message Contention
DOE Office of Scientific and Technical Information (OSTI.GOV)
Tallent, Nathan R.; Vishnu, Abhinav; van Dam, Hubertus
Two trends suggest network contention for one-sided messages is poised to become a performance problem that concerns application developers: an increased interest in one-sided programming models and a rising ratio of hardware threads to network injection bandwidth. Unfortunately, it is difficult to reason about network contention and one-sided messages because one-sided tasks can either decrease or increase contention. We present effective and portable techniques for diagnosing the causes and severity of one-sided message contention. To detect that a message is affected by contention, we maintain statistics representing instantaneous (non-local) network resource demand. Using lightweight measurement and modeling, we identify themore » portion of a message's latency that is due to contention and whether contention occurs at the initiator or target. We attribute these metrics to program statements in their full static and dynamic context. We characterize contention for an important computational chemistry benchmark on InfiniBand, Cray Aries, and IBM Blue Gene/Q interconnects. We pinpoint the sources of contention, estimate their severity, and show that when message delivery time deviates from an ideal model, there are other messages contending for the same network links. With a small change to the benchmark, we reduce contention up to 50% and improve total runtime as much as 20%.« less
Antipsychotics side effects' influence on stigma of mental illness: focus group study results.
Novak, Lan; Svab, Vesna
2009-03-01
Little research was done on the influence of antipsychotics' side effects on stigma of mental illness. An overview of studies shows that people with mental illness state that because of medication side effects they feel discriminated in the field of employment, observe worsening of family relations and tend to skip or discontinue their regular medication. It is difficult to discriminate between stigmatizing effects of antipsychotics and other stigma related factors such as illness symptoms. A focus group of ten patients with schizophrenia or schizoaffective disorder with severe and remitting mental illness treated with antipsychotic medication was conducted to obtain their personal views on how side effects of antipsychotic drugs affect their everyday lives and contribute to the stigmatization because of mental illness. The patients felt most stigmatized in areas of employment and occupation. They repeatedly skipped or discontinued regular medication due to side effects. Their families supported them throughout treatment and recovery despite problems associated with psychotropic medication. Medication induced stigma affects patients' lives in substantial ways and therefore merits further research, part of which is the patients' personal experience.
Aydin, Memduha; Ilhan, Bilge Cetin; Calisir, Saliha; Yildirim, Seda; Eren, Ibrahim
2016-01-01
Objective: Clozapine is a second-generation antipsychotic used for treatment-resistant schizophrenia. Despite its effectiveness, clozapine is largely underused due to serious side effects such as leukopenia or neutropenia. We aimed to review whether to continue, discontinue or rechallenge clozapine treatment after such haematological side effects. Methods: We reviewed and summarized the literature on the use of clozapine, how to deal with its side effects, and suitable options in case of any haematological problems. Then, we described several cases successfully treated with clozapine and lithium after development of neutropenia or leukopenia Results: We present three patients with treatment-resistant schizophrenia. While they had demonstrated poor response to multiple antipsychotic trials, clozapine was started. Clozapine induced neutropenia; or leukopenia developed in some cases that was successfully reversed after lithium onset. Increased serious side effects related with coprescription of lithium and clozapine were not observed. Conclusion: Lithium increases neutrophil and total white blood cell count as a side effect that may be useful in patients who develop neutropenia or leukopenia while being treated with clozapine. PMID:26913176
Aydin, Memduha; Ilhan, Bilge Cetin; Calisir, Saliha; Yildirim, Seda; Eren, Ibrahim
2016-02-01
Clozapine is a second-generation antipsychotic used for treatment-resistant schizophrenia. Despite its effectiveness, clozapine is largely underused due to serious side effects such as leukopenia or neutropenia. We aimed to review whether to continue, discontinue or rechallenge clozapine treatment after such haematological side effects. We reviewed and summarized the literature on the use of clozapine, how to deal with its side effects, and suitable options in case of any haematological problems. Then, we described several cases successfully treated with clozapine and lithium after development of neutropenia or leukopenia. We present three patients with treatment-resistant schizophrenia. While they had demonstrated poor response to multiple antipsychotic trials, clozapine was started. Clozapine induced neutropenia; or leukopenia developed in some cases that was successfully reversed after lithium onset. Increased serious side effects related with coprescription of lithium and clozapine were not observed. Lithium increases neutrophil and total white blood cell count as a side effect that may be useful in patients who develop neutropenia or leukopenia while being treated with clozapine.
The treatment of Parkinson's disease with deep brain stimulation: current issues
Moldovan, Alexia-Sabine; Groiss, Stefan Jun; Elben, Saskia; Südmeyer, Martin; Schnitzler, Alfons; Wojtecki, Lars
2015-01-01
Deep brain stimulation has become a well-established symptomatic treatment for Parkinson's disease during the last 25 years. Besides improving motor symptoms and long-term motor complications, positive effects on patients’ mobility, activities of daily living, emotional well-being and health-related quality of life have been recognized. Apart from that, numerous clinical trials analyzed effects on non-motor symptoms and side effects of deep brain stimulation. Several technical issues and stimulation paradigms have been and are still being developed to optimize the therapeutic effects, minimize the side effects and facilitate handling. This review summarizes current therapeutic issues, i.e., patient and target selection, surgical procedure and programming paradigms. In addition it focuses on neuropsychological effects and side effects of deep brain stimulation. PMID:26330809
Nilotinib Induced Recurrent Gastric Polyps: Case Report and Review of Literature.
Kassem, Nancy; Ismail, Omar M; Elomri, Halima; Yassin, Mohamad A
2017-07-14
BACKGROUND Tyrosine kinase inhibitors (TKIs) are currently an important targeted drug class in the treatment of chronic myeloid leukemia (CML). Imatinib was the first approved TKI for CML in 2001. Nilotinib is a second-generation TKI, approved in 2007; it inhibits BCR-ABL, PDGFR, and c-KIT, and is 30 times more potent than imatinib. Tyrosine kinase enzymes are expressed in multiple tissues and are involved in several signaling pathways; they have been shown to have several off-target side effects. CASE REPORT We report a case of an elderly male with CML and no history of gastrointestinal diseases, treated with nilotinib, and developed recurrent gastric polyps after three years of treatment. We excluded common causes of gastric polyps and therefore considered nilotinib as a probable cause of recurrent gastric polyps. CONCLUSIONS Recurrent gastric polyps could be a potential side effect of nilotinib treatment. Careful long-term monitoring of patients on TKI therapy is necessary and further long-term studies of TKI side effects are needed.
The Risks and Benefits of Cannabis in the Dermatology Clinic.
Dhadwal, Gurbir; Kirchhof, Mark G
Cannabis ( Cannabis sativa/indica), also known as marijuana, has been used for medicinal and recreational purposes for millennia. There has been a recent trend to legalize the use of cannabis, as illustrated by the recent legalization votes in numerous states in the United States and legislation in Canada to allow recreational cannabis use. With this increasing consumption of cannabis, dermatologists will see increased pressure to prescribe cannabis and will see the side effects of cannabis use with greater frequency. There are several approved medical indications for cannabis use, including psoriasis, lupus, nail-patella syndrome, and severe pain. In addition, very preliminary studies have suggested cannabis and its derivatives might have use in acne, dermatitis, pruritus, wound healing, and skin cancer. Further well-controlled studies are required to explore these potential uses. Conversely, the side effects of cannabis use are relatively well documented, and dermatologists should be aware of these presentations. Side effects of cannabis use include cannabis allergy manifesting as urticaria and pruritus, cannabis arteritis presenting with necrosis and ulcers, and oral cancers from cannabis smoke. In this review, we summarize some of the studies and reports regarding the medicinal uses of cannabis in the dermatology clinic and some of the side effects that might present more often to dermatologists as the use of cannabis increases.
Wang, Yu; Cao, Hai-yan; Xie, Ming-xing; He, Lin; Han, Wei; Hong, Liu; Peng, Yuan; Hu, Yun-fei; Song, Ben-cai; Wang, Jing; Wang, Bin; Deng, Cheng
2016-04-01
To investigate the application and effectiveness of vascular corrosion technique in preparing fetal cardiovascular cast models, 10 normal fetal heart specimens with other congenital disease (control group) and 18 specimens with severe congenital heart disease (case group) from induced abortions were enrolled in this study from March 2013 to June 2015 in our hospital. Cast models were prepared by injecting casting material into vascular lumen to demonstrate real geometries of fetal cardiovascular system. Casting effectiveness was analyzed in terms of local anatomic structures and different anatomical levels (including overall level, atrioventricular and great vascular system, left-sided and right-sided heart), as well as different trimesters of pregnancy. In our study, all specimens were successfully casted. Casting effectiveness analysis of local anatomic structures showed a mean score from 1.90±1.45 to 3.60±0.52, without significant differences between case and control groups in most local anatomic structures except left ventricle, which had a higher score in control group (P=0.027). Inter-group comparison of casting effectiveness in different anatomical levels showed no significant differences between the two groups. Intra-group comparison also revealed undifferentiated casting effectiveness between atrioventricular and great vascular system, or left-sided and right-sided heart in corresponding group. Third-trimester group had a significantly higher perfusion score in great vascular system than second-trimester group (P=0.046), while the other anatomical levels displayed no such difference. Vascular corrosion technique can be successfully used in fabrication of fetal cardiovascular cast model. It is also a reliable method to demonstrate three-dimensional anatomy of severe congenital heart disease and normal heart in fetus.
Hendriksen, Ruben G F; Lionarons, Judith M; Hendriksen, Jos G M; Vles, Johan S H; McAdam, Laura C; Biggar, W Douglas
There is no cure for Duchenne Muscular Dystrophy (DMD); treatment is symptomatic and corticosteroids slow the progression. Side effects of corticosteroids - especially the physical effects - have been described, however patients' and caregivers perception on chronic corticosteroid treatment and their side effects is less well known, in particular with regards to cognition, behaviour, and emotional functioning. The primary aim of this pilot study was to (i) construct a self-report questionnaire to assess the perceived benefits and side effects of corticosteroids for patients with DMD and their parents. Furthermore we aimed to (ii) investigate the psychometric qualities of this questionnaire, (iii) whether there was a difference between parents' and patient's perceptions, and finally (iv) to what extent reported side effects may alter over time. A 23-item questionnaire (SIDECORT: side effect of corticosteroids) was constructed to assess the perception of these benefits and side effects in a systematic manner. In total, 86 patients (aged 5 - 28 years) and 125 of their parents completed the questionnaire. Internal consistency was good. Using factor analyses on the side effect items as reported by parents, two underlying factors were found, with the first factor describing cognitive, behavioural and emotional functioning, and the second factor describing physical functioning. The potential benefits of corticosteroids were highly rated among both parents and patients, although parents rated the importance of the benefits higher than their sons (p = 0.002). Similarly, parents rated the severity of the side effects generally higher than their sons (p = 0.011), especially with regards to the physical side effects (p = 0.014). Based on the parent's perception, the neurodevelopmental side effects generally appeared to decline the longer corticosteroids were used. To our knowledge, this is the first explicit study on perceived cognitive-, behavioural-, and emotional side effects and the allocation of benefits to corticosteroids in DMD. On the basis of our research we suggest a short form questionnaire, which proves to be reliable and valid for research- and clinical practice. This questionnaire could provide useful insights for the care of boys and men with DMD.
NASA Technical Reports Server (NTRS)
Ribner, Herbert S
1945-01-01
It was realized as early as 1909 that a propeller in yaw develops a side force like that of a fin. In 1917, R. G. Harris expressed this force in terms of the torque coefficient for the unyawed propeller. Of several attempts to express the side force directly in terms of the shape of the blades, however, none has been completely satisfactory. An analysis that incorporates induction effects not adequately covered in previous work and that gives good agreement with experiment over a wide range of operating conditions is presented. The present analysis shows that the fin analogy may be extended to the form of the side-force expression and that the effective fin area may be taken as the projected side area of the propeller.
Lindsay, Julian N; Barras, Michael
2015-08-01
With the emergence of new oral therapies for metastatic melanoma to the market, as well as ongoing pre-marketing trials and special access schemes, it is important to keep up to date with the side effect profiles of these medications. A common side effect associated with the BRAF inhibitor dabrafenib is severe fever symptoms such as pyrexia and rigors/chills; however, treatment options are limited. We report a patient who was debilitated by severe pyrexia and rigors caused by dabrafenib used in combination with trametinib to treat metastatic melanoma, who was treated with low-dose steroids. To our knowledge, the use of prednisolone for the treatment and prevention of further dabrafenib-associated pyrexia is not published; however, it is a low risk and low cost option that was very effective in this case. © The Author(s) 2014.
[Drug eruptions caused by noncorticoid anti-inflammatory agents].
Roujeau, J C; Guillaume, J C; Revuz, J; Touraine, R
1984-01-01
Non-steroidal anti-inflammatory drugs (NSAI) may elicit various kinds of cutaneous side effects. The commonest ones are non-specific erythematous eruptions, sometimes with a phototoxic distribution, and urticaria. Vasculitis and severe bullous eruptions (Stevens-Johnson's syndrome and Toxic Epidermal Necrolysis) are rare but may have severe outcomes. The overall incidence of cutaneous reactions is about the same for all NSAI, 1 to 3 p. 100, during the clinical studies performed before marketing the drug, but this increases afterwards (up to 45 p. 100 for Benoxaprofen). Drugs with long half-lives may carry a higher risk for severe cutaneous reactions. NSAI are now the main cause of drug induced TEN. Urticarial reactions seem related to pharmacological phenomena while the pathogenic events leading to other kinds of skin reactions remain unknown. An hypersensitivity reaction is postulated. The therapeutic value of corticosteroids for the severe cutaneous side effects of drugs is still controversial.
Coolbrandt, Annemarie; Van den Heede, Koen; Vanhove, Ellen; De Bom, Ann; Milisen, Koen; Wildiers, Hans
2011-04-01
The aim of this study was to examine how patients recall symptoms at a delayed self-report. Accurate insight into toxicity symptoms during chemotherapy is essential so that nurses and doctors can assess therapeutic tolerance and adjust supportive care accordingly. A non-experimental, longitudinal design was employed. Using the Therapy-Related Symptoms Checklist (TRSC), respondents (n = 142) reported their initial symptoms during the first 7 days of the chemotherapy cycle at two different times: (1) each day of the first seven days after the chemotherapy administration (immediate self-report), and (2) at their next hospital visit for chemotherapy (delayed self-report). We compared the number and severity of symptoms and side effects reported in the immediate and delayed self-reports. Respondents reported significantly fewer symptoms and fewer severe symptoms in the delayed self-report. For 22 out of 25 symptoms the delayed-reported grade was significantly lower than the immediate-reported maximum grade. Compared to the immediate-reported median grade, significant differences occurred in only 10 out of the 25 symptoms. In all cases, except fatigue, the delayed-reported grade was significantly higher than the immediate-reported median grade. This study indicates that delayed self-report of chemotherapy side effects is not an appropriate measure of actual symptoms and side effects experienced by patients. Delayed self-report gives a weaker insight into actual symptom burden. Fatigue is at particular risk to be minimized at the delayed self-report. Therefore it is recommended to assess chemotherapy-related symptoms and side effects by means of immediate self-report. Copyright © 2010 Elsevier Ltd. All rights reserved.
Rodríguez, Américo David; Penilla, Rosa Patricia; Rodríguez, Mario Henry; Hemingway, Janet; Trejo, Antonio; Hernández-Avila, Juan Eugenio
2006-01-01
To assess household acceptability and perceived side effects of residual indoor pyrethroid (PYR), carbamate and organophosphate insecticides sprayed by annual rotation (ROT), spatial mosaic (MOS), and a single insecticide (DDT or PYR) in communities of the coastal plain of Chiapas, Mexico. A questionnaire to assess the acceptability and perceived side effects of indoor insecticides was administered to one member of 30% of the families in eight villages of Chiapas. The association of different insecticide treatments with their responses was evaluated (Chi-square). The intensity of side effects indicated under different treatments was compared in an ordered logistic model, using a severity index as the response variable. Insecticide spraying as a probable cause of symptoms was identified by 2.1% of interviewees. A significantly high percentage of persons with blurred vision, dizziness, sneezing, coughing, numbness, watery eyes, and itching lived in villages under MOS and ROT and a high severity index was significantly associated with ROT treatment. Reduction of mosquito bites and cockroaches were the perceived main benefits, and most villagers that perceived no benefits lived in DDT treated villages. Most of the interviewees welcomed spraying (83.7%), but the smell and having to remove furniture from houses were the main arguments against it. Acceptability correlated with insecticide spray coverage, although the most frequent suggestion for improvement was to increase the understanding of the objectives of spraying in the communities. The frequency of side effects was low, but higher in localities where a combination of insecticides was applied. This is a limitation for the use of this type of resistance management strategy in public health.
The differences in the assessments of side effects at an oncology outpatient clinic.
Bayraktar-Ekincioglu, A; Kucuk, E
2018-04-01
Background There is a growing interest in the use of targeted and immunotherapies in oncology. However, the assessment of side effects can be different due to interpretation of patients' health status by healthcare professionals in oncology outpatient clinics. Objective To demonstrate the differences in the assessments of side effects conducted independently by a clinical pharmacist and nurses in patients who receive targeted therapies at an oncology outpatient clinic. Setting The study was conducted at the University Oncology Hospital in an outpatient clinic from October 2015 to March 2016. Method Patients receiving ipilimumab, nivolumab, pembrolizumab, bevacizumab, panitumumab or cetuximab during study period were included. The assessment of side effects was conducted by a pharmacist and nurse independently using the NCI-CTCAE version-2. Main outcome measure To compare the severity assessments of side effects between a clinical pharmacist and nurses in an outpatient clinic. Results During the study, 204 visits for 43 patients with a total of 5508 side effect assessments were recorded where 1137 (20.64%) assessments were graded differently. Out of 1137 assessments, 473 of them were graded higher by a clinical pharmacist whereas 664 were graded higher by nurses. Statistically significant differences were detected in the assessment of vomiting, taste changes, sense changes, alopecia, fatigue, mood changes, anxiety, hearing impairment, and allergic reactions. Conclusion An assessment of side effects by healthcare providers in patients with cancer may be challenging due to an increased workload in clinics and undistinguishable symptoms of side effects and cancer itself. Therefore, a new care model which increases an interprofessional communication may improve pharmaceutical care in oncology outpatient clinics.
Prediction of large negative shaded-side spacecraft potentials
NASA Technical Reports Server (NTRS)
Prokopenko, S. M. L.; Laframboise, J. G.
1977-01-01
A calculation by Knott, for the floating potential of a spherically symmetric synchronous-altitude satellite in eclipse, was adapted to provide simple calculations of upper bounds on negative potentials which may be achieved by electrically isolated shaded surfaces on spacecraft in sunlight. Large (approximately 60 percent) increases in predicted negative shaded-side potentials are obtained. To investigate effective potential barrier or angular momentum selection effects due to the presence of less negative sunlit-side or adjacent surface potentials, these expressions were replaced by the ion random current, which is a lower bound for convex surfaces when such effects become very severe. Further large increases in predicted negative potentials were obtained, amounting to a doubling in some cases.
[Side effects of psychotropic medication: Suggestions for clinical practice].
Grunze, Anna; Mago, Rajnish; Grunze, Heinz
2017-11-01
Psychotropics are highly effective medications that, however, have adverse drug reactions attached to them. They are indispensable for many patients. How to cope with side effects - watchful waiting, dose reduction, change of medication, addition of an "antidote" and behavioural modifications - depends on their nature, severity and finally the patients wish. This review is meant to aid clinician's and patient's decisions in case of the occurrence of compromising, frequent adverse drug reactions. © Georg Thieme Verlag KG Stuttgart · New York.
Santos, Kleber; Palmini, Andre; Radziuk, Ana L; Rotert, Rosana; Bastos, Fernanda; Booij, Linda; Fernandes, Brisa S
2013-07-01
Difficult-to-treat epilepsies and attention-deficit-hyperactivity disorder (ADHD) often co-occur. Because of concerns about the use of stimulants in children with this comorbidity, the impact of ADHD treatment on seizure frequency and severity is not known. This pilot study evaluated the safety and efficacy of methylphenidate in this population. After a 3 month period in which antiepileptic drugs were adjusted, 22 patients recruited from a specialist outpatient clinic for severe epilepsy (16 males, six females; mean age 11 y 2 mo, SD 3 y 2 mo) received methylphenidate for 3 months in an open label, non-controlled trial; four with generalized or multifocal (symptomatic/cryptogenic) epilepsy, one with generalized (idiopathic) epilepsy, 17 with partial (symptomatic/cryptogenic) epilepsy; five with partial seizures only, 17 with primarily or secondarily generalized seizures). Epilepsy, ADHD symptoms, and side effects were assessed using the Swanson, Nolan, and Pelham Questionnaire, the Child Behavior Checklist, the Hague Seizure Severity Scale, and the Side Effects Rating Scale. Methylphenidate significantly improved ADHD. After 3 months of treatment, 73% of patients no longer had clinically significant symptoms. Methylphenidate also reduced seizure severity (9-point median decrease on the Hague Seizure Severity Scale). Seizure frequency increased in four out of 22 patients, but only one patient withdrew from the study for this reason. Most patients experienced no major side effects. These data are among the first showing that low doses of methylphenidate are safe and effective to treat ADHD symptoms in patients with difficult-to-treat epilepsies. Randomized controlled trials are needed to replicate the findings. © The Authors. Developmental Medicine & Child Neurology © 2013 Mac Keith Press.
Pharmacological Issues for Astronauts
NASA Technical Reports Server (NTRS)
Wotring, Virginia E.
2010-01-01
Medication-induced side effects, called untoward effects by pharmacologists, can be a problem with any medication. Few therapies are perfectly specific for the desired physiological activity; rather they act on multiple biological targets and result in multiple physiological effects. There are several strategies that are employed to prevent, alleviate or counteract medication-induced side effects. The administered dose may be optimized to the lowest possible amount that provides the desired therapeutic effect, with the expectation that untoward effects will be minimized by a lower dose. Empirical trials of different therapies for a particular medical problem may be used in the hopes of finding a drug with minimal side effects for a particular patient, or at least of finding a set of side effects that the patient considers tolerable. If these two strategies have been exhausted, it may be possible to administer another medication to block or ameliorate side effects. A recent search of published scientific literature has revealed that there are medications used in spaceflight that seem to be associated with a significant number of reports of untoward effects. To prevent future medical problems and to improve the well-being and productivity of crew members, it would be best to eliminate (or at least reduce) untoward effects. Reports from the literature will be examined, with the aim of identifying a strategy for reducing untoward effects.
Hayter, Mark
2007-05-01
This paper is a report of an analysis of the discourse about contraceptive efficacy and side effects used by nurses when prescribing contraception. All women seeking contraception should be informed of the efficacy and potential adverse effects of the particular method they are considering. This information facilitates an informed choice. Women also require this information in order to monitor for any side effects. Paradoxically, side effects are also a key factor in reducing adherence with contraceptive regimens. However, there is no literature that explores specifically how this issue is addressed in clinical consultations, or places these practices in a theoretical context. Forty-nine consultations between nurses and women in sexual health clinics were audio-recorded during 2002. Data were subject to a discourse analysis using Foucault's 'procedures of exclusion' to explore the discursive construction of contraceptive efficacy and side effects The nurses employed specific discursive strategies when discussing contraception. When addressing efficacy, discourse centred on medico-statistical facts, but side effects were described in lay terms that minimized their severity. Nurses contextualized contraceptive side effects within potential problems that women might experience in pregnancy, and also attempted to 'normalize' contraceptive-related problems. Discourse and its deployment play a key role in practitioner-client relationships that sexual health nurses need to become more aware of how they discuss clinical issues about contraception with women. Clinical data on contraceptive side-effects are present in the literature, and it is important that sexual health nurses use this to help women make truly informed decisions.
A model of the impact of reimbursement schemes on health plan choice.
Keeler, E B; Carter, G; Newhouse, J P
1998-06-01
Flat capitation (uniform prospective payments) makes enrolling healthy enrollees profitable to health plans. Plans with relatively generous benefits may attract the sick and fail through a premium spiral. We simulate a model of idealized managed competition to explore the effect on market performance of alternatives to flat capitation such as severity-adjusted capitation and reduced supply-side cost-sharing. In our model flat capitation causes severe market problems. Severity adjustment and to a lesser extent reduced supply-side cost-sharing improve market performance, but outcomes are efficient only in cases in which people bear the marginal costs of their choices.
Pycnogenol may alleviate adverse effects in oncologic treatment.
Belcaro, G; Cesarone, M R; Genovesi, D; Ledda, A; Vinciguerra, G; Ricci, A; Pellegrini, L; Gizzi, G; Ippolito, E; Dugall, M; Cacchio, M; Di Renzo, A; Stuard, S
2008-09-01
A large variety of adverse reactions are well known to frequently occur during chemotherapy and radiotherapy in oncology. Specific medications exist to target individual side effects. The aim of this study was to explore in a pilot trial whether supplementation with French maritime pine bark extract Pycnogenol could alleviate side effects and improve patient's quality of life. Cancer patients who previously underwent surgery and who were in view of their pathology in relatively good condition, both physically and psychologically, were recruited for this study and divided into two groups. These patients received their first cycle of radiotherapy or chemotherapy, which lasted from 10 days up to 1 month. Then one group of patients received 150 mg Pycnogenol, the control group comparable placebo in a single-blinded fashion. The authors studied the occurrence of side effects and made attempts to judge their severity on a semi-quantitative visual analogue scale over a 2 months period starting after patients completed their first cycle of chemo- or radiotherapy, respectively. Twenty five radiotherapy patients receiving Pycnogenol showed a decreased frequency of essentially all investigated side-effects as compared to 21 patients receiving placebo, though in many categories the difference was limited. The most apparent improvements of acute side effects related to decreased soreness and ulceration in the mouth and throat as well as less dryness of the mouth and the eyes. A decreased incidence of nausea /vomiting, diarrhoea, edema and weakness was noticed, which was reflected by semi-quantitative evaluation suggesting that severity was only half or even less pronounced than in the control group. Only one case of deep vein thrombosis occurred in the Pycnogenol group whereas 2 cases of superficial vein thromboses and one case of deep vein thrombosis occurred in the control group (2.9% vs 10%). Thirty four chemotherapy patients were supplemented with Pycnogenol and another 30 patients were in the control group. For all patients this was the first chemotherapy treatment period. The Pycnogenol group presented with a lowered incidence of all investigated side effects as compared to the control group, though in many cases to a limited extent. The most prominent improvements were found for nausea, vomiting, diarrhoea and weight loss. Semi-quantitative evaluation showed that here again symptom severity was half or less pronounced than in the control group. Various further symptoms improved such as cognitive impairment and also cardiotoxicity and neutropenia. Effects on anemia could not be investigated as several patients received erythrocyte transfusion. In the Pycnogenol group one case of superficial vein thrombosis was indentified while 3 cases of superficial vein thromboses and one deep vein thrombosis were detected in the control group (4% vs 19%). In both chemotherapy and radiotherapy patients Pycnogenol lowered the requirement for medication to address side effects. This was reflected by less days of hospitalisation the patients required. The authors did not investigate a possible interference with the anti-neoplastic efficacy of chemo- and radiotherapy. This possibility requires attention in future studies with Pycnogenol. From their previous clinical experience the authors suggest that alleviation of side effects described in this study results from Pycnogenol activities related to endothelial protection, and anti-inflammatory anti-edema activities. The results of this pilot trial warrant further prospective studies with larger number of patients to validate benefits more specifically with regard to type of malignancy and treatment regimen.
Abadi, Shaivad Shabee Hulhasan; Moin, Afrasim; Veerabhadrappa, Gangadharappa Hosahalli
2016-01-01
Microparticles are polymeric bodies ranging 1-1000 µm that constitute a variety of forms such as microcapsules, microspheres, microcages, microshells, microrods, biosensors microparticles, radiolabeled microparticles, and so forth. This review focuses on general microparticles, mainly microcapsules and microspheres. Nonsteriodal anti-inflammatory drugs (NSAIDs) are one of the mostcommonly prescribed medications in the world. Most of the NSAIDs available have severe side effects. With increased awareness of NSAID-induced gastrointestinal (GI) side effects, safety has become a priority in treatment of arthritis and other inflammatory diseases with NSAIDs. A trend in NSAID development has been to improve therapeutic efficacy while reducing the severity of GI side effects by altering dosage through modified release to optimize drug delivery. One such approach is the use of fabricated microparticles such as microcapsules and microspheres as carriers of drugs. Microparticles provide delivery of macromolecules and micromolecules via different routes and effectively control the release profile of such drugs. Microcapsules and microspheres are compatible with most natural and synthetic polymers and can be used for several routes of administration, including parenteral, oral, nasal, intra-ocular, topical, and the like. Because of greater stability and multiple manufacturing techniques, microspheres and microcapsules are preferred as drug carriers over other colloidal drug delivery systems. Microparticles provide effective protection of the encapsulated agent against degradation by enzymatic activities, controlled and confined delivery of drugs from a few hours to months, and ingenious administration compared to alternative forms of controlled-release parenteral dosages, such as macro-sized implants. This comprehensive overview of fabricated microparticles describes microencapsulation technologies to produce microparticles for targeted therapy of arthritis and other inflammatory diseases which provide constant and prolonged therapeutic effects that reduce dosing frequency and thereby minimize potential adverse effects of NSAIDs such as GI irritation and insufficient patient compliance. The present review describes the latest developments in microparticulate drug delivery systems and the best alternatives for safe and effective microcapsular systems in a controlled manner for the delivery of NSAIDs.
Ombitasvir, Paritaprevir, and Ritonavir
... so that the medication will have a greater effect. It is not known if ombitasvir, paritaprevir, or ... the medication and whether you experience severe side effects. Do not stop taking ombitasvir, paritaprevir, and ritonavir ...
Sunnevang, Cecilia; Rosén, Erik; Bostrom, Ola
2009-04-01
Recent studies have shown that current side airbags, protecting head and chest, are saving lives in near-side impacts (Kahane 2007; McCartt and Kyrychenko 2007). The aim of this study was to analyze NASS/CDS real-life data on fatal trauma in near-side car-to-car crashes, stratified by age into non-senior and senior occupants. Furthermore, a hypothetical model explaining side airbag effectiveness as a function of lateral delta-v was presented. The model together with the field data was then used to demonstrate further enhancement of side airbag restraint performance. Weighted NASS/CDS data from 1994 to 2006 for front seat occupants in near-side car-to-car impacts was used to calculate the exposure, incidence, and risk of fatal trauma with respect to lateral delta-v. The dataset was also divided into non-senior (10-59 years) and senior (age > or = 60 years) occupants. The hypothetical model was created to adjust the NASS/CDS data to represent a car fleet fully equipped with current side airbag protection. The model was then used to evaluate the increase in effectiveness of improved side airbag protection achieved by increasing the lateral delta-v in the range where the airbag have most mitigating effect, increasing the airbag protection level within the delta-v range currently tested, and a combination of the two approaches. From the NASS/CDS data, the median delta-v for fatal injury was 37 km/h for the total sample. When stratified with respect to age, the median delta-v for fatal injury was 41 km/h for non-seniors and 28 km/h for senior occupants. The exposures for both age groups were similar. However, the fatal incidence showed a difference in delta-v range between non-senior and senior occupants. Applying the airbag model increased the median delta-v to 40 km/h for the total sample and 47 and 30 km/h for non-seniors and seniors, respectively. Current side airbag systems offer very good protection for non-senior occupants up to delta-v 40 km/h. Though still high, the protection for senior occupants is lower. To enhance side airbag protection, the side airbag performance should be maximized where the fatal incidence is high. Therefore, to further reduce non-senior fatalities, the test speed should be increased. To further reduce senior fatalities, the protection level within severities currently tested should be increased. A combination of the two approaches would result in about a 40 percent increase of the side airbag effectiveness.
Chaves, Katarina Melo; Serrano-Blanco, Antoni; Ribeiro, Susana Barbosa; Soares, Luiz Alberto Lira; Guerra, Gerlane Coelho Bernardo; do Socorro Costa Feitosa Alves, Maria; de Araújo Júnior, Raimundo Fernandes; de Paula Soares Rachetti, Vanessa; Filgueira Júnior, Antônio; de Araújo, Aurigena Antunes
2013-03-01
This cross-sectional study aimed to compare the effects of treatment with an atypical antipsychotic drug (olanzapine or risperidone) on quality of life (QoL) and to document adverse effects in 115 patients diagnosed with schizophrenia who attended the ambulatory service of Hospital Dr. João Machado, Natal, Rio Grande do Norte, Brazil. Socioeconomic, sociodemographic, and clinical variables were compared. The QoL Scale validated for Brazil (QLS-BR) was used to evaluate QoL, and adverse effects were assessed using the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale. Data were analyzed using the χ(2) test and Student's t test, with a significance level of 5 %. Patients in both drug groups showed severe impairment in the occupational domain of the QLS-BR. Global QLS-BR scores indicated impairment among risperidone users and severe impairment among olanzapine users. The most significant side effects were associated with risperidone, including asthenia/lassitude/fatigue, somnolence/sedation, paresthesia, change in visual accommodation, increased salivation, diarrhea, orthostatic posture, palpitations/tachycardia, erythema, photosensitivity, weight loss, galactorrhea, decreased sexual desire, erectile/orgasmic dysfunction, vaginal dryness, headache, and physical dependence. QoL was impaired in patients using olanzapine and in those using risperidone. Risperidone use was associated with psychic, neurological, and autonomous adverse effects and other side effects.
Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir
... so that the medication will have a greater effect. Dasabuvir is a non-nucleoside NS5B polymerase inhibitor. ... the medication, and whether you experience severe side effects. Do not stop taking ombitasvir, paritaprevir, ritonavir, and ...
Quantitative prediction of drug side effects based on drug-related features.
Niu, Yanqing; Zhang, Wen
2017-09-01
Unexpected side effects of drugs are great concern in the drug development, and the identification of side effects is an important task. Recently, machine learning methods are proposed to predict the presence or absence of interested side effects for drugs, but it is difficult to make the accurate prediction for all of them. In this paper, we transform side effect profiles of drugs as their quantitative scores, by summing up their side effects with weights. The quantitative scores may measure the dangers of drugs, and thus help to compare the risk of different drugs. Here, we attempt to predict quantitative scores of drugs, namely the quantitative prediction. Specifically, we explore a variety of drug-related features and evaluate their discriminative powers for the quantitative prediction. Then, we consider several feature combination strategies (direct combination, average scoring ensemble combination) to integrate three informative features: chemical substructures, targets, and treatment indications. Finally, the average scoring ensemble model which produces the better performances is used as the final quantitative prediction model. Since weights for side effects are empirical values, we randomly generate different weights in the simulation experiments. The experimental results show that the quantitative method is robust to different weights, and produces satisfying results. Although other state-of-the-art methods cannot make the quantitative prediction directly, the prediction results can be transformed as the quantitative scores. By indirect comparison, the proposed method produces much better results than benchmark methods in the quantitative prediction. In conclusion, the proposed method is promising for the quantitative prediction of side effects, which may work cooperatively with existing state-of-the-art methods to reveal dangers of drugs.
He, Haiyan; An, Ran; Hou, Jian; Fu, Weijun
2017-06-01
Arsenic trioxide (ATO), a component of the traditional Chinese medicine arsenic sublimate, promotes apoptosis and induces leukemic cell differentiation. Combined with all-trans-retinotic acid (ATRA), ATO has become the first-line induction therapy in treating acute promyelocytic leukemia (APL). The most common side effects of ATO include hepatotoxicity, gastrointestinal symptoms, water-sodium retention, and nervous system damage. In this report, we present a rare side effect, rhabdomyolysis, in a 68-year-old female APL patient who was treated with ATO. After taking 10 mg ATO daily for 6 days, she presented shortness of breath, myodynia, elevated creatine kinase, and acute renal insufficiency. This report describes the first case of ATO-induced rhabdomyolysis.
Improving Adherence to Endocrine Therapy in Women With HR-Positive Breast Cancer.
Brockway, Julia P; Shapiro, Charles L
2018-05-15
Aromatase inhibitors (AIs) are the standard treatment for postmenopausal women with hormone receptor-positive breast cancers. One of the most common side effects of AIs is joint pain; it is also the most frequently cited reason for nonadherence and discontinuation before completion of the prescribed treatment course. Nonadherence and, in particular, discontinuation, can lead to increased rates of breast cancer mortality. The prevalence of AI-induced arthralgias is about 50%, and there are several interventions, including switching to a different AI, that can increase adherence. The healthcare professional plays a part in fostering adherence by communicating the side effects of AIs to patients before the initiation of treatment, as well as explaining the strategies for addressing these side effects, should they occur.
Otero, M E; van den Reek, J M; Seyger, M M; van de Kerkhof, P C; Kievit, W; de Jong, E M
2017-08-01
As methotrexate (MTX) is a widely used treatment for psoriasis, it is important to gain insight into the reasons for the discontinuation of MTX and to understand the determinants for drug survival. To describe 5-year drug survival for MTX in patients with psoriasis, split according to different reasons for discontinuation, and to identify the determinants for drug survival. Data were extracted from a prospective psoriasis registry of patients treated with MTX (MTX-CAPTURE). Drug survival was analysed using Kaplan-Meier estimates and the determinants for discontinuation were analysed using Cox regression analysis. Analyses were split according to the reason for discontinuation: side-effects or ineffectiveness. We included 85 patients treated with MTX, with a maximum treatment duration of 5·2 years. The overall drug survival rates were 63%, 30% and 15% after 1, 3 and 5 years, respectively. The median survival was 1·8 years. Overall, 55 patients (65%) discontinued MTX for the following reasons: side-effects (35%), ineffectiveness (26%), combination of side-effects and ineffectiveness (13%), other reasons (16%) and 11% were lost to follow-up. The most reported side-effects were gastrointestinal symptoms, despite the use of folic acid in 99% of patients. Based on univariate analysis, a high Psoriasis Area and Severity Index score and a high score on the visual analogue scale for disease severity at baseline were possible determinants for a short drug survival. Drug survival of MTX was low with 15% of patients 'on drug' after 5 years. Side-effects alone or in combination with inadequate disease control were more important in the context of treatment discontinuation than inadequate disease control alone. © 2017 British Association of Dermatologists.
Li, Xiuze; Liu, Jun; Zhou, Mengjun; Zhou, Chaojing
2017-07-01
Myoclonus induced by etomidate during induction of general anesthesia is a common phenomenon. This prospective, randomized, saline-controlled clinical study was performed to evaluate the effect of parecoxib sodium pretreatment on the incidence and severity of etomidate-induced myoclonus. 60 patients, American Society of Anesthesiologists (ASA) physical status I or II, aged 20 to 60 years, who were scheduled to undergo elective laparoscopic cholecystectomy under general anesthesia, were allocated randomly into one of two groups to receive parecoxib sodium 40 mg intravenous (group P, n = 30) or the same volume of saline (group S, n = 30) 30 minutes before administration of etomidate (0.3 mg/kg). Myoclonus was assessed on a scale of 0 - 3. Postoperative side effects were recorded. The two groups were comparable with regard to baseline characteristics. The incidence of myoclonus was significantly lower in the parecoxib sodium group (11/30; 37%) than in the saline group (21/30; 70%) (p < 0.05). The severity of myoclonic movements was also significantly reduced by parecoxib sodium (p < 0.05). There were no significant differences between the two groups with respect to postoperative side effects. Pretreatment with intravenous injection of parecoxib sodium 40 mg significantly reduced the incidence and severity of etomidate-induced myoclonus without significant side effects. .
Evaluation of an immunosuppressant side effect instrument.
Winsett, Rebecca P; Arheart, Kris; Stratta, Robert J; Alloway, Rita; Wicks, Mona N; Gaber, A Osama; Hathaway, Donna K
2004-09-01
Clinicians continue to be compelled to evaluate the impact of immunosuppressive medication side effects on the quality of life of transplant recipients. We Were asked to develop an instrument to measure side effects in immunosuppressed transplant recipients. To construct an instrument that measures the impact and severity of side effects of immunosuppressive medications used in transplantation and to assess the reliability and validity of the newly developed instrument called the Memphis Survey. The instrument was constructed by a panel of physicians, nurses, and pharmacists with experience in treating transplant recipients. A small group of kidney transplant recipients (n= 13) provided pilot data for refining and testing the instrument. A national sample of kidney, liver, and heart transplant recipients (n = 505) provided data that were used to further develop the instrument. Factor analysis was used to determine the psychological dimensions underlying the instrument and to guide the construction of scales from the survey items. The instrument scales were then computed from the dataset of 505 transplant recipients to quantify the impact of immunosuppressant side effects on the quality of life of transplant recipients. Analyses showed the final instrument scales to be valid and reliable. Exploratory analysis suggests the need for further testing of the instrument to determine gender differences.
Blanch, Jordi; Rousaud, Araceli; Martinez, Esteban; De Lazzari, Elisa; Milinkovic, Ana; Peri, Josep-Maria; Blanco, José-Luis; Jaen, Jesús; Navarro, Victor; Massana, Guillem; Gatell, Josep-Maria
2004-05-15
A standardized questionnaire was used to assess the impact of lipodystrophy (LD) on quality of life (QoL). Eighty-four consecutive asymptomatic human immunodeficiency virus type 1 (HIV-1)-infected outpatients with clinical LD completed a modified version of the Dermatology Life Quality Index (DLQI) survey to measure the impact of body fat changes on their QoL. Body changes influenced dressing for 55 patients (65%), produced feelings of shame for 41 (49%), and disrupted sexual life for 23 (27%). There was a greater impact on the DLQI due to body changes among women, injection drug users, patients with abdominal or breast lipoaccumulation, and patients with a high number of non-LD side effects. Multivariate proportional odds model analysis showed that the severity of non-LD-associated side effects and the presence of breast lipoaccumulation were associated with impaired psychosocial functioning. Specific characteristics of patients, antiretroviral-based side effects, and breast lipoaccumulation exert a greater impact on QoL in HIV-1-infected patients with LD.
Kähler, Katharina C; Blome, Christine; Forschner, Andrea; Gutzmer, Ralf; Hauschild, Axel; Heinzerling, Lucie; Livingstone, Elisabeth; Loquai, Carmen; Müller-Brenne, Tina; Schadendorf, Dirk; Utikal, Jochen; Wagner, Tobias; Augustin, Matthias
2018-05-25
After more than two decades with interferon alfa-2a and 2b (IFN) as the only approved drugs in the adjuvant setting for melanoma, new treatment approaches like immune checkpoint inhibitors and BRAF-MEK inhibitors improve the progression free survival (PFS) and also the overall survival (OS). We compared physicians' preferences ("utilities") for health states associated with IFN therapy to their patients' preferences. Utilities describe a preference for a specific health state on a scale of 0 (as bad as death) to 1.0 (perfect health). We assessed utilities for health states associated with adjuvant IFN using the standard gamble technique in 108 physicians and 130 melanoma patients. Four IFN toxicity scenarios and three outcome scenarios were given to the participants. Both groups were asked for the 5-year disease free survival (DFS) they would need to accept the described IFN-related side effects. In both groups, utilities for melanoma relapse were significantly lower than for IFN side effects, showing that toxicity was more acceptable than relapse. Physicians indicated higher utilities for each scenario and needed lower 5-year DFS both in case of mild-to-moderate and severe side effects. Patients were willing to tolerate mild-to-moderate and severe toxicity for a 50% and 75% chance of 5-year DFS, while physicians only required a chance of 40% and 50%, respectively. Both physicians and patients rated melanoma recurrence much lower than even severe IFN side effects. In direct comparison, physicians rated cancer-related scenarios more positively and accepted IFN toxicity for an even lower treatment benefit.
Brumbelow, Matthew L; Mueller, Becky C; Arbelaez, Raul A
2015-01-01
The Insurance Institute for Highway Safety (IIHS) introduced its side impact consumer information test program in 2003. Since that time, side airbags and structural improvements have been implemented across the fleet and the proportion of good ratings has increased to 93% of 2012-2014 model year vehicles. Research has shown that drivers of good-rated vehicles are 70% less likely to die in a left-side crash than drivers of poor-rated vehicles. Despite these improvements, side impact fatalities accounted for about one quarter of passenger vehicle occupant fatalities in 2012. This study is a detailed analysis of real-world cases with serious injury resulting from side crashes of vehicles with good ratings in the IIHS side impact test. NASS-CDS and Crash Injury Research and Engineering Network (CIREN) were queried for occupants of good-rated vehicles who sustained an Abbreviated Injury Scale (AIS) ≥ 3 injury in a side-impact crash. The resulting 110 cases were categorized by impact configuration and other factors that contributed to injury. Patterns of impact configuration, restraint performance, and occupant injury were identified and discussed in the context of potential upgrades to the current IIHS side impact test. Three quarters of the injured occupants were involved in near-side impacts. For these occupants, the most common factors contributing to injury were crash severities greater than the IIHS test, inadequate side-airbag performance, and lack of side-airbag coverage for the injured body region. In the cases where an airbag was present but did not prevent the injury, occupants were often exposed to loading centered farther forward on the vehicle than in the IIHS test. Around 40% of the far-side occupants were injured from contact with the struck-side interior structure, and almost all of these cases were more severe than the IIHS test. The remaining far-side occupants were mostly elderly and sustained injury from the center console, instrument panel, or seat belt. In addition, many far-side occupants were likely out of position due to events preceding the side impact and/or being unbelted. Individual changes to the IIHS side impact test have the potential to reduce the number of serious injuries in real-world crashes. These include impacting the vehicle farther forward (relevant to 28% of all cases studied), greater test severity (17%), the inclusion of far-side occupants (9%), and more restrictive injury criteria (9%). Combinations of these changes could be more effective.
Adverse reactions and interactions with beta-adrenoceptor blocking drugs.
Lewis, R V; McDevitt, D G
1986-01-01
beta-Blocking drugs are widely used throughout the world and serious adverse reactions are relatively uncommon. Most of those which do occur are pharmacologically predictable and may be avoided by ensuring that patients who are to be given beta-blockers do not have a predisposition to the development of bronchospasm, cardiac failure or peripheral ischaemia. In some situations, the use of a beta 1-selective blocking drug may reduce the risk of a severe adverse reaction, but there is little evidence that other ancillary properties such as partial agonist activity are of relevance in this context. Long term experience with many of the beta-blockers in current use suggests that unpredictable major adverse reactions such as the practolol oculomucocutaneous syndrome are unlikely to be repeated, although some of these drugs may be associated with immunological disturbances and some have been implicated in the development of retroperitoneal fibrosis. beta-Blocking drugs appear to be associated with a number of subjective side effects including muscle fatigue, peripheral coldness and some neurological symptoms. These side effects are highly subjective and are therefore difficult to quantify and it is not known whether they are of major importance in terms of their effect upon patients' overall well-being. It cannot be assumed that simply because such side effects can be elicited that they do, in fact, matter. However, because beta-blockers are often prescribed for patients who have no symptoms and for whom the benefits of therapy are generally small, such side effects would be of considerable importance if they had an overall effect upon quality of life. There are theoretical reasons to suppose that the incidence and severity of such side effects may be related to the ancillary properties of the individual drugs, but there is little evidence that parameters such as beta 1-selectivity, or partial agonist activity are clinically important determinants of the severity of these side effects. Lipophilicity, however, may be associated with an increased incidence of neurological symptoms. beta-Blocking drugs may cause a variety of metabolic disturbances including an increase in serum VLDL-cholesterol concentrations. However, long term studies have not shown that such disturbances are associated with an increased risk of cardiovascular disease, indicating that such metabolic changes may not be of major importance in practice. beta-Blocking drugs may be involved in a number of interactions with other drugs, but few of these have been shown to be of clinical significance.(ABSTRACT TRUNCATED AT 400 WORDS)
Kuijpers, Dirkjan; Janssen, Caroline H C; van Dijkman, Paul R M; Oudkerk, Matthijs
2004-10-01
The aim of the study was to evaluate safety and feasibility of dobutamine cardiovascular magnetic resonance (CMR) in patients with proven or suspected coronary artery disease. Dobutamine CMR was evaluated retrospectively in 400 consecutive patients with suspicion of myocardial ischemia. Dobutamine was infused using an incremental protocol up to 40 microg/kg body weight per minute. All anti-anginal medication was stopped 4 days before the CMR study and infusion time of dobutamine was 6 min per stage. Hemodynamic data, CMR findings and side effects were reported. Patients with contraindications to CMR (metallic implants and claustrophobia) were excluded from analysis. Dobutamine CMR was successfully performed in 355 (89%) patients. Forty-five (11%) patients could not be investigated adequately because of non-cardiac side effects in 29 (7%) and cardiac side effects in 16 (4%) patients. Hypotension (1.5%) and arrhythmias (1%) were the most frequent cardiac side effects. One patient developed a severe complication (ventricular fibrillation) at the end of the study. There were no myocardial infarctions or fatal complications of the stress test. The most frequent non-cardiac side effects were nausea, vomiting and claustrophobia. Age >70 years, prior myocardial infarction and rest wall motion abnormalities showed no significant differences with side effects (P>0.05). Dobutamine CMR is safe and feasible in patients with suspicion of myocardial ischemia. Copyright 2004 Springer-Verlag
Effects of electroconvulsive therapy and magnetic seizure therapy on acute memory retrieval.
Polster, Julia D; Kayser, Sarah; Bewernick, Bettina H; Hurlemann, René; Schlaepfer, Thomas E
2015-03-01
Electroconvulsive therapy (ECT) is currently the most effective treatment for severe depression. However, it is frequently associated with negative cognitive side effects. Magnetic seizure therapy (MST) depicts an alternative, although experimental, convulsive treatment for major depression. Initial results suggest comparable antidepressant effects accompanied by a better side effect profile. However, no studies up to now have addressed acute retrieval disruption after MST in comparison to ECT. Therefore, we intended to broaden insight into the side effect profile of MST compared to ECT by examining the disruption of acute verbal memory processes after treatment. Twenty depressed patients were randomly assigned to either MST (10 patients) or ECT (10 patients) treatment. On 2 treatment days and 2 treatment-free days, the patients memorized words using a controlled learning paradigm derived from the Batchelder and Riefer storage retrieval model. Four hours after memorization, the patients were asked to retrieve words freely (delayed recall) and a second time with the help of an additional cue constructed out of a hypernymic category (cued recall). By comparing memory performance on treatment days to control days, treatment-induced memory disruption was evaluated. After ECT, delayed recall was disturbed, whereas after MST, it was not. However, this difference in performance was no longer apparent upon cue application (cued recall). This study demonstrates that ECT-induced acute memory disruption measured by delayed recall is absent after MST, confirming its superior side effect profile. We hope that confirming advantages of MST over ECT will improve therapy options for patients with severe depression.
Krawczel, Peter D.
2017-01-01
Simple Summary Dairy cattle may experience discomfort in a myriad of ways throughout their life cycle, particularly when sustaining hock injuries or suboptimal locomotion. Lactating dairy cattle divide their lying time equally between left and right sides; however, discomfort experienced during pregnancy or following cannulation can cause a shift in the normal lying laterality. The objective of this study was to determine the effect of hock injuries and lameness on the lying behaviors of dairy cattle, particularly lying laterality. Lying laterality did not differ from the expected 50% (left side lying time) in cattle with hock injuries, lameness, or both. The current results suggest that lying laterality does not differ between varying levels of hock injury or lameness severity. Going forward, further research could determine if lying laterality shifts over the course of the animal developing a hock injury or lameness. Abstract Lactating dairy cattle divide their lying equally between their left side and their right side. However, discomfort, such as pregnancy and cannulation, can cause a cow to shift lying side preference. The objective of this study was to determine the effect of lameness and hock injuries on lying behaviors, particularly lying laterality, of lactating dairy cows. Cows from four commercial farms in eastern Croatia that had lying behavior data, health score data, and production records were used in the study. Health scores including hock injuries and locomotion were collected once per cow. Severely lame cows had greater daily lying time compared to sound cows and moderately lame cows. Overall, cows spent 51.3 ± 1.2% of their daily lying time on the left side. Maximum hock score, locomotion score, hock injury laterality, or parity did not result in lying laterality differing from 50%. PMID:29149044
Novel Molecular Strategies and Targets for Opioid Drug Discovery for the Treatment of Chronic Pain
Olson, Keith M.; Lei, Wei; Keresztes, Attila; LaVigne, Justin; Streicher, John M.
2017-01-01
Opioid drugs like morphine and fentanyl are the gold standard for treating moderate to severe acute and chronic pain. However, opioid drug use can be limited by serious side effects, including constipation, tolerance, respiratory suppression, and addiction. For more than 100 years, we have tried to develop opioids that decrease or eliminate these liabilities, with little success. Recent advances in understanding opioid receptor signal transduction have suggested new possibilities to activate the opioid receptors to cause analgesia, while reducing or eliminating unwanted side effects. These new approaches include designing functionally selective ligands, which activate desired signaling cascades while avoiding signaling cascades that are thought to provoke side effects. It may also be possible to directly modulate downstream signaling through the use of selective activators and inhibitors. Separate from downstream signal transduction, it has also been found that when the opioid system is stimulated, various negative feedback systems are upregulated to compensate, which can drive side effects. This has led to the development of multi-functional molecules that simultaneously activate the opioid receptor while blocking various negative feedback receptor systems including cholecystokinin and neurokinin-1. Other novel approaches include targeting heterodimers of the opioid and other receptor systems which may drive side effects, and making endogenous opioid peptides druggable, which may also reduce opioid mediated side effects. Taken together, these advances in our molecular understanding provide a path forward to break the barrier in producing an opioid with reduced or eliminated side effects, especially addiction, which may provide relief for millions of patients. PMID:28356897
The evolution of spinal/epidural neostigmine in clinical application: Thoughts after two decades
Lauretti, Gabriela Rocha
2015-01-01
Since the first clinical application of analgesia following spinal anticholinesterase by 1940's, several clinical double-blind studies have been conducted to date, where intrathecal doses of neostigmine in humans ranged from 750 to 1 μg, due to side-effects. Conversely, epidural neostigmine has been evaluated in proportionally higher doses and represents an alternative, but still deserves more investigation concerning both acute and chronic pain, as it seems devoid of important side-effects. PMID:25558203
Bain, J; Rachlis, V; Robert, E; Khait, Z
1980-04-01
A male contraceptive trial was undertaken in 23 men using a combination of oral medroxyprogesterone acetate (MPA) and oral methyltestosterone (MeT). The men were divided into four groups according to varying drug dosages and were followed for 15 months (control - 3 months, treatment - 6 months, follow-up - 6 months). The parameters assessed included sperm count and motility, serum gonadotropins and sex steroids, and several biochemical and hematological tests. A questionnaire dealing with side-effects and changes in sexual function was administered intermittently. Although sperm count was suppressed (most dramatically at the highest drug doses, MPA 20mg,MeT 20mg), it was not suppressed to infertile levels. Sperm motility was unaltered; LH was modestly suppressed, FSH was not suppressed; testosterone was suppressed even at low doses; dihydrotestosterone responses were inconsistent. No significant biochemical abnormalities or side-effects occurred although some men experienced mild transient acne, gynecomastia and decreased testicular size. We conclude that in the doses used in this trial, the combination of MPA and MeT is not effective for male contraceptive, purposes and that higher doses may induce severe and undesirable side-effects.
Wananukul, Siriwan; Limpongsanuruk, Wanida; Singalavanija, Srisupalak; Wisuthsarewong, Wanee
2006-10-01
Severity of irritant diaper dermatitis (IDD) from diarrhea varies from patient to patient depending on the nature of feces and the number of bowel movements. The purpose of the present study was to compare the effectiveness of dexpanthenol and zinc oxide ointment with ointment base in the treatment of irritant diaper dermatitis from acute diarrhea in children by measuring transepidermal water loss (TEWL). Forty-six children with diarrhea were prospectively, block randomized, investigator-blinded to receive dexpanthenol and zinc oxide ointment on one side and ointment base on the other side. TEWL was measured before and on days 1, 3, and 7 of treatment together with the assessment of severity score. The efficacy of treatment was defined by complete clearance of the lesion. TEWL in the treated and control side was not different before the application of the topical medication. In the present study, the efficacy of 5% dexpanthenol and zinc oxide ointment on D3 was 39% (18from 46 patients) compared to 32% in the ointment base side. On D7, the efficacy of the treated side was 58.7% and the ointment base side was 56%. The patients who still had skin lesions were those who had prolonged diarrhea. On the treated side, the mean of TEWL was lower than the control side on DI (p = 0.18) and had significant improvement on D3 (p = 0. 002). At the end of the present study, TEWL on the treated side was less than TEWL of the control side but it did not have statistical significance (p = 0.07). There was no rash or sign of abnormality on the treated side at the end of D7. In the treatment of lDD from acute diarrhea, 5% dexpanthenol and zinc oxide ointment significantly decreased TEWL in the treated side more than the ointment base on day 3 but the severity score was not significantly different on days 1, 3 and 7.
Treatment of sinusoidal obstruction syndrome with defibrotide: a single-center experience.
Sucak, G T; Aki, Z S; Yagcí, M; Yegin, Z A; Ozkurt, Z N; Haznedar, R
2007-06-01
Sinusoidal obstruction syndrome (SOS) is a frequent, troubling, and potentially fatal complication of hematopoietic stem cell transplantation. Despite promising results with defibrotide (DF), no treatment has been established as standard. DF is a single-stranded polydeoxyribonucleotide, obtained from controlled depolymerization of porcine intestinal mucosal cells. It has antithrombotic, antiischemic, antiinflammatory, and thrombolytic properties without significant side effects. We retrospectively evaluated the charts of 80 consecutive patients, with 89 hematopoietic stem cell transplants for hematologic malignancies. The results of early initiation of DF treatment in 14 patients with SOS are presented in this study. Fourteen patients, 8 males and 6 females % median age 40.5 years (range, 16-46 years) were diagnosed to have SOS. Disease severity was classified as severe in 6 (42.85%), moderate in 4 (28.57%), and mild in 4 (28.57%) patients. We treated 14 patients with DF for a median of 21.5 days (range, 4-39 days). All 14 patients received DF after the diagnosis of SOS. Three patients with severe and all of the patients with mild to moderate SOS responded to treatment with complete resolution of SOS-related signs and symptoms. All patients responding to DF were alive at 100 days posttransplantation. There was no significant drug-related side effect among patients treated with DF. With an overall response rate of 78.56% and a 50% complete response rate in severe SOS cases and minimal side effects, we suggest that DF is the best available agent to treat SOS.
Low-fluence Q-switched Nd: YAG 1064-nm laser and intense pulsed light for the treatment of melasma.
Vachiramon, V; Sirithanabadeekul, P; Sahawatwong, S
2015-07-01
Low-fluence Q-switched Nd:YAG 1064 nm laser (LFQS) and intense pulsed light (IPL) have been shown to be effective in the treatment of melasma. LFQS can target deeper pigment, while IPL can target a wide range of cutaneous structures. However, there is limited information on efficacy and side-effects of the combined treatment. To compare the efficacy and safety of combined LFQS and IPL therapy with LFQS monotherapy in the treatment of melasma. Twenty female patients with mixed-type melasma on both cheeks were treated with LFQS on full face for five sessions at 1-week intervals. One side of the face was randomly assigned to receive additional three sessions of IPL treatments at 2-week intervals. Patients were evaluated 12 weeks after the last treatment. Outcome measures include the assessment by colorimeter and calculated as relative lightness index (R*LI), modified Melasma Area and Severity Index (mMASI), patient satisfaction and adverse effects. Eighteen patients completed the study. Both sides of the face showed significant improvement of R*LI and mMASI. A more rapid improvement of R*LI and mMASI was observed on combined side. At the end of treatment, 55% improvement and 37% improvement of R*LI was observed on combined side and monotherapy side respectively. The overall patients' satisfaction was in favour of the combined side. Recurrence occurred on both sides but there was still a significant decrease compared to baseline. No serious side effect was noted. The combination of LFQS and IPL results in faster clearance of melasma and is more effective than LFQS alone for melasma treatment. However, recurrence is still inevitable. © 2014 European Academy of Dermatology and Venereology.
Faghihi, Gita; Mokhtari, Fatemeh; Fard, Nasrin Motamedi; Motamedi, Narges; Hosseini, Sayed Mohsen
2017-01-01
This study was conducted to compare the effect of low-dose isotretinoin with its conventional dose in patients with moderate and severe acne. This was a clinical trial conducted on 60 male and female patients with moderate and severe acne vulgaris. The patients were divided into two treatment groups: 0.5 mg/kg/day isotretinoin capsule and low-dose isotretinoin capsule (0.25 mg/kg/day). Patients in both groups received 6-month treatment. At the end of the 6 th month and 12 th month (6 months after the end of the treatment), they were examined again, and their improvement was determined and compared. The average severity of acne in the two treatment groups did not differ significantly within any of the study periods. The most common side effects were nose dryness in the low-dose group (17%) and hair thinning and loss in the conventional-dose group (33.2%), although all the patients had dry lips. According to the same severity of the acne in two groups in different study periods, as well as fewer side effects and more patients' satisfaction, the low-dose isotretinoin can be considered in the treatment of acne.
Ahlstrom, Logan S.; Vorontsov, Ivan I.; Shi, Jun; Miyashita, Osamu
2017-01-01
Side chains in protein crystal structures are essential for understanding biochemical processes such as catalysis and molecular recognition. However, crystal packing could influence side-chain conformation and dynamics, thus complicating functional interpretations of available experimental structures. Here we investigate the effect of crystal packing on side-chain conformational dynamics with crystal and solution molecular dynamics simulations using Cyanovirin-N as a model system. Side-chain ensembles for solvent-exposed residues obtained from simulation largely reflect the conformations observed in the X-ray structure. This agreement is most striking for crystal-contacting residues during crystal simulation. Given the high level of correspondence between our simulations and the X-ray data, we compare side-chain ensembles in solution and crystal simulations. We observe large decreases in conformational entropy in the crystal for several long, polar and contacting residues on the protein surface. Such cases agree well with the average loss in conformational entropy per residue upon protein folding and are accompanied by a change in side-chain conformation. This finding supports the application of surface engineering to facilitate crystallization. Our simulation-based approach demonstrated here with Cyanovirin-N establishes a framework for quantitatively comparing side-chain ensembles in solution and in the crystal across a larger set of proteins to elucidate the effect of the crystal environment on protein conformations. PMID:28107510
Ahlstrom, Logan S; Vorontsov, Ivan I; Shi, Jun; Miyashita, Osamu
2017-01-01
Side chains in protein crystal structures are essential for understanding biochemical processes such as catalysis and molecular recognition. However, crystal packing could influence side-chain conformation and dynamics, thus complicating functional interpretations of available experimental structures. Here we investigate the effect of crystal packing on side-chain conformational dynamics with crystal and solution molecular dynamics simulations using Cyanovirin-N as a model system. Side-chain ensembles for solvent-exposed residues obtained from simulation largely reflect the conformations observed in the X-ray structure. This agreement is most striking for crystal-contacting residues during crystal simulation. Given the high level of correspondence between our simulations and the X-ray data, we compare side-chain ensembles in solution and crystal simulations. We observe large decreases in conformational entropy in the crystal for several long, polar and contacting residues on the protein surface. Such cases agree well with the average loss in conformational entropy per residue upon protein folding and are accompanied by a change in side-chain conformation. This finding supports the application of surface engineering to facilitate crystallization. Our simulation-based approach demonstrated here with Cyanovirin-N establishes a framework for quantitatively comparing side-chain ensembles in solution and in the crystal across a larger set of proteins to elucidate the effect of the crystal environment on protein conformations.
NASA Technical Reports Server (NTRS)
Espley, Jared R.; Dibraccio, Gina A.; Connerney, John E. P.; Brain, David; Gruesbeck, Jacob; Soobiah, Yasir; Halekas, Jasper S.; Combi, Michael; Luhmann, Janet; Ma, Yingjuan
2015-01-01
The nucleus of comet C/2013 A1 (Siding Spring) passed within 141,000?km of Mars on 19 October 2014. Thus, the cometary coma and the plasma it produces washed over Mars for several hours producing significant effects in the Martian magnetosphere and upper atmosphere. We present observations from Mars Atmosphere and Volatile EvolutioN's (MAVEN's) particles and field's instruments that show the Martian magnetosphere was severely distorted during the comet's passage. We note four specific major effects: (1) a variable induced magnetospheric boundary, (2) a strong rotation of the magnetic field as the comet approached, (3) severely distorted and disordered ionospheric magnetic fields during the comet's closest approach, and (4) unusually strong magnetosheath turbulence lasting hours after the comet left. We argue that the comet produced effects comparable to that of a large solar storm (in terms of incident energy) and that our results are therefore important for future studies of atmospheric escape, MAVEN's primary science objective.
Chemotherapeutic approaches to protozoa: kinetoplastida--current level of knowledge and outlook.
Harder, A; Greif, G; Haberkorn, A
2001-09-01
The possibilities for treating haemoflagellate infections (African trypanosomiasis) are very limited (Table 1; Mehlhorn and Schrevel 1995; Croft 1997; Hunter 1997; Wang 1997; Trouiller and Olliaro 1998). All the available drugs have severe side-effects in humans and animals. Vaccination is not really an option, in view of the wide antigen variability. At present, there are several drug combinations in clinical trials: suramin/eflornithine, suramin/metronidazole, suramin/pentamidine, melarsoprol/pentamidine, melarsoprol/nifurtimox and nifurtimox/eflornithine. Some of these combinations were successful in treating resistant Trypanosoma brucei rhodesiense and/or T. b. gambiense infections (Keiser et al. 2001). In leishmaniasis, the tendency is still to resort to the old antimony compounds, with their severe side effects. At present, miltefosine is in clinical phase and is the first oral drug against visceral leishmaniasis (Jha et al. 1999). Two drugs are currently used against Chagas' disease, although these do not cure chronic effects. There is no prospect of novel drugs in this indication either (Pecoul et al. 1999; Morel 2000).
Long-term treatment of severe hypertension with minoxidil.
Nawar, T.; Nolin, L.; Plante, G. E.; Caron, C.; Montambault, P.
1977-01-01
Minoxidil, a new potent hypotensive agent, was used as the primary antihypertensive agent in 11 patients--10 men and 1 woman aged 35 to 54 years with severe hypertension that was refractory to treatment with maximal (or maximally tolerated) doses of conventional antihypertensive agents. Six patients had severely impaired renal function and three of them were undergoing long-term hemodialysis. The patients were given 2.5 to 40 mg/d of minoxidil for periods of 2 to 29 months. All except one who was almost anuric received propranolol and diuretics. Blood pressure was controlled satisfactorily in all patients. In two patients the hypertension became partially resistant after 1 year of treatment. The main side effects were sodium retention, tachycardia and hirsutism. Renal function remained stable or improved and hemodialysis was discontinued in two patients. Minoxidil is a remarkably potent hypotensive with relatively few side effects and seems particularly advantageous in patients with chronic renal failure. PMID:603847
Acute myositis: an unusual and severe side effect of docetaxel: a case report and literature review.
Rochigneux, Philippe; Schleinitz, Nicolas; Ebbo, Mikael; Aymonier, Marie; Pourroy, Bertrand; Boissier, Romain; Salas, Sébastien; Deville, Jean-Laurent
2018-06-01
Docetaxel is an antimicrotubules cytotoxic agent prescribed widely by medical oncologists in multiple tumor types (breast, lung, prostate, stomach, head, and neck). However, the side effects of docetaxel are numerous (cytopenia, peripheral edema, myalgia, arthralgia, alopecia, and sensitive neuropathy) and recent concerns have been raised about neutropenic enterocolitis in France. Here, we report the case of a 57-year-old patient with metastatic prostatic cancer, who developed a severe myositis and fasciitis grade IV 1 week after his second docetaxel infusion. We reviewed the five cases of docetaxel-related myositis described in the literature, and found that most of them occurred in patients with diabetes (n=5/5) or hypertension (n=4/5). A vascular toxicity may explain this severe complication, and patients with diabetes or hypertension should be monitored closely in the context of a docetaxel chemotherapy.
A systematic review of the psychiatric side-effects of efavirenz.
Kenedi, Christopher A; Goforth, Harold W
2011-11-01
Concerns regarding the use of efavirenz in patients with a history of mental illness may predispose clinicians to not offer this agent to psychiatrically ill populations in spite of the convenience of once daily dosing, which can result in improved adherence in these at-risk populations. This systematic review examines the current data regarding the neuropsychiatric effects of efavirenz, and also attempts to provide guidance to clinicians using efavirenz to treat patients with mental illness. The review identified high rates of neuropsychiatric side effects including vivid dreams, insomnia and mood changes in approximately 50% of patients who initiate efavirenz. The effects begin quickly, commonly peak in the first 2 weeks, and are generally mild and transient in nature. Isolated case reports and uncontrolled data suggest higher rates of severe side effects; however, there is no clear evidence of a broadly increased risk of suicide or dangerous behavior for patients taking efavirenz as part of their antiretroviral regimen.
Psychopharmacology of Attention-Deficit Hyperactivity Disorder: Effects and Side Effects.
Golmirzaei, Javad; Mahboobi, Hamidreza; Yazdanparast, Maryam; Mushtaq, Gohar; Kamal, Mohammad A; Hamzei, Enayatollah
2016-01-01
Attention-deficit hyperactivity disorder (ADHD) is a common psychiatric disorder in children which manifests with hyperactivity, impulsivity, and/or inattention. Several drugs are used in treatment of ADHD. Stimulants, atomoxetine, anti-depressants, and bupropion are common medications used in the treatment of ADHD. Stimulants are widely used as the first line treatment in children with ADHD. Their mechanism of action is the release of dopamine and norepinephrine in central nervous system. Methylphenidate is the most common stimulant used for the treatment of ADHD. Methylphenidate significantly reduces ADHD symptoms in children both at home and school and improves their social skills. Methylphenidate is safe in healthy children and has shown to have no cardiac side effects in these patients. Other medications include: Atomoxetine, Amphetamines, Clonidine, Melatonin, and anti-depressants. Effects, side effects, and mechanism of action these drugs have been discussed in this paper.
Kaeser, H E
1986-06-14
The problems of long term treatment with antiparkinson drugs are numerous, involving increased involuntary movements, painful dystonic cramps, decrease or loss of therapeutic benefit, wearing-off, episodes of akinesia (on-off) and long periods of "freezing". Important side effects are also mental changes with heavy dreams, hallucinations, nocturnal confusional states and paranoid psychosis. As most of these side effects are dose-related, they are postponed and lessened by small daily doses of L-dopa and decarboxylase inhibitor. Frequent small doses may decrease the wearing-off effect but may cause unpredictable episodes of on-off. The addition of or partial replacement by bromocriptine may decrease fluctuations and dyskinesias in many patients. To reduce the side effects such as nausea, orthostatic hypotension and mental disturbances, daily doses of 15-30 mg should be built up very slowly. Painful dystonias are related to the off period and respond well to baclofen. For the treatment of severe psychic disturbances tranquilizers with little or no extrapyramidal side effects, such as clomethiazole, benzodiazepine derivatives and (if necessary) thioridazine, are recommended. Bromocriptine may also be useful in occasional cases which do not, or no longer, respond to L-dopa.
To brake or to accelerate? Safety effects of combined speed and red light cameras.
De Pauw, Ellen; Daniels, Stijn; Brijs, Tom; Hermans, Elke; Wets, Geert
2014-09-01
The present study evaluates the traffic safety effect of combined speed and red light cameras at 253 signalized intersections in Flanders, Belgium that were installed between 2002 and 2007. The adopted approach is a before-and-after study with control for the trend. The analyses showed a non-significant increase of 5% in the number of injury crashes. An almost significant decrease of 14% was found for the more severe crashes. The number of rear-end crashes turned out to have increased significantly (+44%), whereas a non-significant decrease (-6%) was found in the number of side crashes. The decrease for the severe crashes was mainly attributable to the effect on side crashes, for which a significant decrease of 24% was found. It is concluded that combined speed and red light cameras have a favorable effect on traffic safety, in particular on severe crashes. However, future research should examine the circumstances of rear-end crashes and how this increase can be managed. Copyright © 2014 National Safety Council and Elsevier Ltd. All rights reserved.
... that the oral suspension contains aspartame that forms phenylalanine. ... Linezolid may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away: diarrhea headache nausea vomiting ...
... powder for solution contains aspartame, a source of phenylalanine. ... Diclofenac may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away: diarrhea constipation gas or ...
Yıldırım Poyraz, Nilüfer; Özdemir, Elif; Poyraz, Barış Mustafa; Kandemir, Zuhal; Keskin, Mutlay; Türkölmez, Şeyda
2014-01-01
Objective: The aim of this study was to investigate the relationship between patient characteristics and adenosine-related side-effects during stress myocard perfusion imaging (MPI). The effect of presence of adenosine-related side-effects on the diagnostic value of MPI with integrated SPECT/CT system for coronary artery disease (CAD), was also assessed in this study. Methods: Total of 281 patients (109 M, 172 F; mean age:62.6±10) who underwent standard adenosine stress protocol for MPI, were included in this study. All symptoms during adenosine infusion were scored according to the severity and duration. For the estimation of diagnostic value of adenosine MPI with integrated SPECT/CT system, coronary angiography (CAG) or clinical follow-up were used as gold standard. Results: Total of 173 patients (61.6%) experienced adenosine-related side-effects (group 1); flushing, dyspnea, and chest pain were the most common. Other 108 patients completed pharmacologic stress (PS) test without any side-effects (group 2). Test tolerability were similar in the patients with cardiovascular or airway disease to others, however dyspnea were observed significantly more common in patients with mild airway disease. Body mass index (BMI) ≥30 kg/m2 and age ≤45 years were independent predictors of side-effects. The diagnostic value of MPI was similar in both groups. Sensitivity of adenosine MPI SPECT/CT was calculated to be 86%, specificity was 94% and diagnostic accuracy was 92% for diagnosis of CAD. Conclusion: Adenosine MPI is a feasible and well tolerated method in patients who are not suitable for exercise stress test as well as patients with cardiopulmonary disease. However age ≤45 years and BMI ≥30 kg/m2 are the positive predictors of adenosine-related side-effects, the diagnostic value of adenosine MPI SPECT/CT is not affected by the presence of adenosine related side-effects. PMID:25541932
Acute Intracranial and Spinal Subdural Hematoma Associated with Vardenafil.
Nakamura, Takaaki; Watanabe, Genya; Harada, Ryuhei; Kawasaki, Emiko; Tsukita, Kenichi; Suzuki, Yasushi
2018-05-02
A 28-year-old healthy man was admitted to our hospital because of right-sided headache, vomiting, and lower back pain after the administration of vardenafil. Computed tomography and magnetic resonance imaging of the brain showed a small, right-sided, subdural hematoma. A lumbar magnetic resonance imaging showed a longitudinally extended subdural hematoma. He had no history of trauma. We speculated that vardenafil might have had an association with the bleeding. Several reports have suggested a relationship between phosphodiesterase-5 inhibitors and intracerebral or subarachnoid hemorrhage. Our case suggested that there may also be risks of bleeding into the subdural space. Although headache and nausea are common side effects of vardenafil, hemorrhagic diseases should also be considered when symptoms are severe or prolonged. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.
The evil of the unknown--risk-benefit evaluation of new synthetic drugs in the 19th century.
Schneider, A; Helmstädter, A
2015-01-01
In the 19th century, synthetic chemistry discovered completely new chemical entities for medicinal use, which dramatically enriched the therapeutic armamentarium. However, no information was available regarding the safety of these new drugs, which were unrelated to most of the medicinal agents formerly known. Therefore, the question arises, if and how far, considerations regarding the relationship between benefit and risks were made. In this study, chloroform, phenazone (antipyrine) and sulfonal, were investigated as examples for drugs newly introduced in the 19th century. The results revealed that these drugs were provided by the manufacturer, tested by the physicians in a multicentre pattern and side effects were published in the medical literature soon after. Within a few years, several hundred cases were reported but the data were rarely summarized statistically. Therefore, physicians needed to stay updated with the medical literature because neither systematic industrial research nor regulatory authorities existed. The number of case reports within the first years were sufficient to detect common (> 1/100 to < 1/10) side effects but rare events were also reported. An extraordinary example is the drug-induced toxic epidermal necrolysis, which is commonly known as the Lyell syndrome or its less severe form, the Stevens-Johnson syndrome. This reaction has been clearly described by Baruch Spitz (1854-1932) as a side effect of antipyrine in 1887, several decades before Stevens, Johnson and particularly Lyell.
Hallman, Jason J; Brasel, Karen J; Yoganandan, Narayan; Pintar, Frank A
2009-10-01
Injury mechanisms from frontal airbags, first identified in anecdotal reports, are now well documented for pediatric, small female, and out-of-position occupants. In contrast, torso side airbags have not yet been consistently associated with specific injury risks in field assessments. To determine possible torso side airbag-related injuries, the present study identified crashes involving side airbags from reports within the CIREN, NASS, and SCI databases. Injury patterns were compared to patterns from lateral crashes in absence of side airbag. Splenic trauma (AIS 3+) was found present in five cases of torso side airbag deployment at lower impact severity (as measured by velocity change and compartment intrusion) than cases of splenic trauma without side airbag. Five additional cases were found to contain similar injury patterns but occurred with greater crash severity. To supplement case analyses, full scale sled tests were conducted with a THOR-NT dummy and cadaveric specimen. Four THOR tests with door- and seat-mounted torso side airbags confirmed that out-of-position (early inflation stage) airbag contact elevated thoracic injury metrics compared to optimal (fully inflated) contact. Out-of-position seat-mounted airbag deployment also produced AIS 3 splenic trauma in the cadaveric specimen. Due to potentially sudden or delayed onset of intraperitoneal hemorrhage and hypovolemic shock following splenic trauma, further biomechanical investigation of this anecdotal evidence is essential to identify injury mechanisms, prevention techniques, and methods for early diagnosis.
Hallman, Jason J.; Brasel, Karen J.; Yoganandan, Narayan; Pintar, Frank A.
2009-01-01
Injury mechanisms from frontal airbags, first identified in anecdotal reports, are now well documented for pediatric, small female, and out-of-position occupants. In contrast, torso side airbags have not yet been consistently associated with specific injury risks in field assessments. To determine possible torso side airbag-related injuries, the present study identified crashes involving side airbags from reports within the CIREN, NASS, and SCI databases. Injury patterns were compared to patterns from lateral crashes in absence of side airbag. Splenic trauma (AIS 3+) was found present in five cases of torso side airbag deployment at lower impact severity (as measured by velocity change and compartment intrusion) than cases of splenic trauma without side airbag. Five additional cases were found to contain similar injury patterns but occurred with greater crash severity. To supplement case analyses, full scale sled tests were conducted with a THOR-NT dummy and cadaveric specimen. Four THOR tests with door- and seat-mounted torso side airbags confirmed that out-of-position (early inflation stage) airbag contact elevated thoracic injury metrics compared to optimal (fully inflated) contact. Out-of-position seat-mounted airbag deployment also produced AIS 3 splenic trauma in the cadaveric specimen. Due to potentially sudden or delayed onset of intraperitoneal hemorrhage and hypovolemic shock following splenic trauma, further biomechanical investigation of this anecdotal evidence is essential to identify injury mechanisms, prevention techniques, and methods for early diagnosis. PMID:20184829
Hojjat-Farsangi, Mohammad
2014-08-08
Chemotherapeutic and cytotoxic drugs are widely used in the treatment of cancer. In spite of the improvements in the life quality of patients, their effectiveness is compromised by several disadvantages. This represents a demand for developing new effective strategies with focusing on tumor cells and minimum side effects. Targeted cancer therapies and personalized medicine have been defined as a new type of emerging treatments. Small molecule inhibitors (SMIs) are among the most effective drugs for targeted cancer therapy. The growing number of approved SMIs of receptor tyrosine kinases (RTKs) i.e., tyrosine kinase inhibitors (TKIs) in the clinical oncology imply the increasing attention and application of these therapeutic tools. Most of the current approved RTK-TKIs in preclinical and clinical settings are multi-targeted inhibitors with several side effects. Only a few specific/selective RTK-TKIs have been developed for the treatment of cancer patients. Specific/selective RTK-TKIs have shown less deleterious effects compared to multi-targeted inhibitors. This review intends to highlight the importance of specific/selective TKIs for future development with less side effects and more manageable agents. This article provides an overview of: (1) the characteristics and function of RTKs and TKIs; (2) the recent advances in the improvement of specific/selective RTK-TKIs in preclinical or clinical settings; and (3) emerging RTKs for targeted cancer therapies by TKIs.
... ibuprofen (Advil), naproxen (Aleve), and acetaminophen (Tylenol). Prescription painkillers, if needed, for more severe pain. Regular exams ... or injections -- This treatment helps shrink growths. Side effects may include weight gain and depression. Gonadotropin-agonist ...
... is in a class of medications called proton pump inhibitors. It works by decreasing the amount of ... symptoms are severe or do not go away: gas nausea vomiting Some side effects can be serious. ...
... is in a class of medications called proton pump inhibitors. It works by decreasing the amount of ... severe or do not go away: headache nausea gas constipation dry mouth Some side effects can be ...
... been helped or who have experienced severe side effects. Thioridazine is in a group of medications called ... to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in ...
Cruz, Ricardo Alcántara-de la; Zanuncio, José Cola; Lacerda, Mabio Chrisley; Wilcken, Carlos Frederico; Fernandes, Flávio Lemes; Tavares, Wagner de Souza; Soares, Marcus Alvarenga; Sediyama, Carlos Sigueyuki
2017-08-30
New plant protection strategies focus on minimizing chemical pesticide use and increasing their compatibility with biological control agents. The objective was to evaluate the side-effects of glyphosate, diflubenzuron, malathion, tebuconazole and triflumuron (at 720, 45, 400, 150 and 20 g ai ha -1 , respectively), pesticides authorized for soybean crops in Brazil, on the parasitoid Palmistichus elaeisis (Hymenoptera: Eulophidae) reared on Anticarsia gemmatalis (Lepidoptera: Noctuidae). The emergence and female numbers produced per P. elaeisis female were higher in A. gemmatalis pupae from caterpillars fed an artificial diet treated with glyphosate. However, emergence was lower than 50% when the caterpillars were fed on soybean leaves treated with glyphosate offered ad libitum (3-5 times). Palmistichus elaeisis died before parasiting A. gemmatalis pupae treated with malathion. Diflubenzuron reduced the P. elaesis sex ratio in the second generation. Tebuconazole and triflumuron did not cause side-effects on this parasitoid. A continuous exposure to glyphosate by the host may lead to side-effects on P. elaeisis emergence, but its moderate use is acceptable for this parasitoid. Diflubenzuron had severe transgenerational side-effects. Tebuconazole fungicide and triflumuron insecticide are compatible with P. elaeisis in sustainable integrated pest management (IPM) programs, while malathion can not be included in them.
Safety and side effects of cannabidiol, a Cannabis sativa constituent.
Bergamaschi, Mateus Machado; Queiroz, Regina Helena Costa; Zuardi, Antonio Waldo; Crippa, José Alexandre S
2011-09-01
Cannabidiol (CBD), a major nonpsychotropic constituent of Cannabis, has multiple pharmacological actions, including anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties. However, little is known about its safety and side effect profile in animals and humans. This review describes in vivo and in vitro reports of CBD administration across a wide range of concentrations, based on reports retrieved from Web of Science, Scielo and Medline. The keywords searched were "cannabinoids", "cannabidiol" and "side effects". Several studies suggest that CBD is non-toxic in non-transformed cells and does not induce changes on food intake, does not induce catalepsy, does not affect physiological parameters (heart rate, blood pressure and body temperature), does not affect gastrointestinal transit and does not alter psychomotor or psychological functions. Also, chronic use and high doses up to 1,500 mg/day of CBD are reportedly well tolerated in humans. Conversely, some studies reported that this cannabinoid can induce some side effects, including inhibition of hepatic drug metabolism, alterations of in vitro cell viability, decreased fertilization capacity, and decreased activities of p-glycoprotein and other drug transporters. Based on recent advances in cannabinoid administration in humans, controlled CBD may be safe in humans and animals. However, further studies are needed to clarify these reported in vitro and in vivo side effects.
Blaszczyk, Izabela; Foumani, Nazli Poorsafar; Ljungberg, Christina; Wiberg, Mikael
2015-11-06
Botulinum toxin A (BoNT-A) injections for treatment of spasticity in patients with cerebral palsy (CP) have been used for about two decades. The treatment is considered safe but a low frequency of adverse events (AE) has been reported. A good method to report AEs is necessary to verify the safety of the treatment. We decided to use an active surveillance of treatment-induced harm using a questionnaire we created. We studied the incidence of reported AEs and side effects in patients with CP treated with BoNT-A. We investigated the relationship between the incidence of AEs or side effects and gender, age, weight, total dose, dose per body weight, Gross Motor Function Classification System (GMFCS) and number of treated body parts. Seventy-four patients with CP participated in our study. In 54 (51%) of 105 BoNT-A treatments performed in 45 (61%) patients, there were 95 AEs and side effects reported, out of which 50 were generalized and/or focal distant. Severe AEs occurred in three patients (4%), and their BoNT-A treatment was discontinued. Consecutive collection of the AE and side-effect incidence using our questionnaire can increase the safety of BoNT-A treatment in patients with CP.
The study of CD side to side error in line/space pattern caused by post-exposure bake effect
NASA Astrophysics Data System (ADS)
Huang, Jin; Guo, Eric; Ge, Haiming; Lu, Max; Wu, Yijun; Tian, Mingjing; Yan, Shichuan; Wang, Ran
2016-10-01
In semiconductor manufacturing, as the design rule has decreased, the ITRS roadmap requires crucial tighter critical dimension (CD) control. CD uniformity is one of the necessary parameters to assure good performance and reliable functionality of any integrated circuit (IC) [1] [2], and towards the advanced technology nodes, it is a challenge to control CD uniformity well. The study of corresponding CD Uniformity by tuning Post-Exposure bake (PEB) and develop process has some significant progress[3], but CD side to side error happening to some line/space pattern are still found in practical application, and the error has approached to over the uniformity tolerance. After details analysis, even though use several developer types, the CD side to side error has not been found significant relationship to the developing. In addition, it is impossible to correct the CD side to side error by electron beam correction as such error does not appear in all Line/Space pattern masks. In this paper the root cause of CD side to side error is analyzed and the PEB module process are optimized as a main factor for improvement of CD side to side error.
Yao, X; Yoshioka, Y; Morishige, T; Eto, Y; Watanabe, H; Okada, Y; Mizuguchi, H; Mukai, Y; Okada, N; Nakagawa, S
2009-12-01
Cancer gene therapy by adenovirus vectors (Advs) for metastatic cancer is limited because systemic administration of Adv produces low therapeutic effect and severe side effects. In this study, we generated a dual cancer-specific targeting vector system by using PEGylation and the telomere reverse transcriptase (TERT) promoter and attempted to treat experimental metastases through systemic administration of the vectors. We first optimized the molecular size of PEG and modification ratios used to create PEG-Ads. Systemic administration of PEG-Ad with 20-kDa PEG at a 45% modification ratio (PEG[20K/45%]-Ad) resulted in higher tumor-selective transgene expression than unmodified Adv. Next, we examined the effectiveness against metastases and side effects of a TERT promoter-driven PEG[20K/45%]-Ad containing the herpes simplex virus thymidine kinase (HSVtk) gene (PEG-Ad-TERT/HSVtk). Systemic administration of PEG-Ad-TERT/HSVtk showed superior antitumor effects against metastases with negligible side effects. A cytomegalovirus (CMV) promoter-driven PEG[20K/45%]-Ad also produced antimetastatic effects, but these were accompanied by side effects. Combining PEG-Ad-TERT/HSVtk with etoposide or 5-fluorouracil enhanced the therapeutic effects with negligible side effects. These results suggest that modification with 20-kDa PEG at a 45% modification ratio is the optimal condition for PEGylation of Adv, and PEG-Ad-TERT/HSVtk is a prototype Adv for systemic cancer gene therapy against metastases.
Advances in Pharmacotherapeutics of Space Motion Sickness
NASA Technical Reports Server (NTRS)
Putcha, Lakshmi
2006-01-01
Space Motion Sickness (SMS) is common occurrence in the U.S. manned space flight program and nearly 2/3 of Shuttle crewmembers experience SMS. Several drugs have been prescribed for therapeutic management of SMS. Typically, orally-administered SMS medications (scopolamine, promethazine) have poor bioavailability and often have detrimental neurocognitive side effects at recommended doses. Intramuscularly administered promethazine (PMZ) is perceived to have optimal efficacy with minimal side effects in space. However, intramuscular injections are painful and the sedating neurocognitive side effects of promethazine, significant in controlled ground testing, may be masked in orbit because injections are usually given prior to crew sleep. Currently, EVAs cannot be performed by symptomatic crew or prior to flight day three due to the lack of a consistently efficacious drug, concern about neurocognitive side effects, and because an in-suit vomiting episode is potentially fatal. NASA has long sought a fast acting, consistently effective anti-motion sickness medication which has only minor neurocognitive side effects. Development of intranasal formulations of scopolamine and promethazine, the two commonly used SMS drugs at NASA for both space and reduced gravity environment medical operations, appears to be a logical alternative to current treatment modalities for SMS. The advantages are expected to be fast absorption, reliable and high bioavailability, and probably reduced neurocognitive side effects owing to dose reduction. Results from clinical trials with intranasal scopolamine gel formulation and pre-clinical testing of a prototype microcapsule intranasal gel dosage form of PMZ (INPMZ) will be discussed. These formulations are expected to offer a dependable and effective noninvasive treatment option for SMS.
Diffuse alveolar haemorrhage secondary to propylthiouracil-induced vasculitis
Ferreira, Catarina; Costa, Teresa; Marques, Ana Vieira
2015-01-01
Propylthiouracil is a drug used to treat hyperthyroidism. It can cause several side effects including pulmonary disorders that, although rare, can be severe. The authors describe the case of a woman treated with propylthiouracil who developed diffuse alveolar haemorrhage with severe respiratory failure and anaemia, which improved with discontinuation of the antithyroid drug and on starting systemic corticosteroid therapy. PMID:25661751
Intranasal corticosteroids topical characteristics: side effects, formulation, and volume.
Petty, David A; Blaiss, Michael S
2013-01-01
Guidelines from throughout the world recommend intranasal corticosteroids (INSs) as first-line treatment for most patients with moderate to severe allergic rhinitis. In general, limited comparative studies between different INSs have not indicated that one particular steroid moiety is more effective than another in controlling symptoms of allergic rhinitis. However, there are numerous formulations available with different ingredients that may influence a patient's adherence to treatment. This article looks at topical features with these agents, specifically, formulations, vehicles (aqueous vs aerosol), and side effects such as epistaxis and nasal septal perforation. Topical side effects are minimal with INSs with the exception of epistaxis. There are major differences in formulations, volumes, and vehicles between INSs, which could affect adherence. Physicians need to be aware of the different INS attributes to try to match patients' preferences in order to achieve better adherence and improve outcomes in sufferers of allergic rhinitis.
... phenylalanine. If PKU is not detected early, increasing phenylalanine levels in the baby will cause intellectual disability. When discovered early, changes in the diet can help prevent the severe side effects of PKU.
McGwin, Gerald; Metzger, Jesse; Porterfield, John R; Moran, Stephan G; Rue, Loring W
2003-09-01
Side air bags (SABs) have been introduced in an attempt to reduce the risk of injury in near-side-impact motor vehicle collisions (MVCs). The impact of SABs on MVC-related mortality and morbidity has yet to be evaluated with a large population-based study. The objective of this study was to assess the effectiveness of SABs in reducing the risk of injury or death in near-side-impact MVCs. A retrospective study investigated outboard front seat occupants involved in police-reported, near-side-impact MVCs using data from the General Estimates System (1997-2000). The risk of MVC-related nonfatal and fatal injury for occupants of vehicles with and without SABs was compared. Front seat occupants of vehicles with SABs had a risk of injury similar to that of occupants of vehicles without SABs (risk ratio [RR], 0.96; 95% CI confidence interval [CI], 0.79-1.15). Adjustment for the potentially confounding effects of age, gender, seat belt use, seating position, damage severity and location, and vehicle body type did not meaningfully affect the association (RR, 0.90; 95% CICI, 0.76-1.08). There is no association between the availability of SABs and overall injury risk in near-side-impact MVCs. Future research is necessary to determine the effectiveness of SABs in preventing the injuries for which they were specifically designed.
BANERJI, JULIAN
2015-01-01
The present treatment of childhood T-cell leukemias involves the systemic administration of prokary-otic L-asparaginase (ASNase), which depletes plasma Asparagine (Asn) and inhibits protein synthesis. The mechanism of therapeutic action of ASNase is poorly understood, as are the etiologies of the side-effects incurred by treatment. Protein expression from genes bearing Asn homopolymeric coding regions (N-hCR) may be particularly susceptible to Asn level fluctuation. In mammals, N-hCR are rare, short and conserved. In humans, misfunctions of genes encoding N-hCR are associated with a cluster of disorders that mimic ASNase therapy side-effects which include impaired glycemic control, dislipidemia, pancreatitis, compromised vascular integrity, and neurological dysfunction. This paper proposes that dysregulation of Asn homeostasis, potentially even by ASNase produced by the microbiome, may contribute to several clinically important syndromes by altering expression of N-hCR bearing genes. By altering amino acid abundance and modulating ribosome translocation rates at codon repeats, the microbiomic environment may contribute to genome decoding and to shaping the proteome. We suggest that impaired translation at poly Asn codons elevates diabetes risk and severity. PMID:26178806
Banerji, Julian
2015-09-01
The present treatment of childhood T-cell leukemias involves the systemic administration of prokaryotic L-asparaginase (ASNase), which depletes plasma Asparagine (Asn) and inhibits protein synthesis. The mechanism of therapeutic action of ASNase is poorly understood, as are the etiologies of the side-effects incurred by treatment. Protein expression from genes bearing Asn homopolymeric coding regions (N-hCR) may be particularly susceptible to Asn level fluctuation. In mammals, N-hCR are rare, short and conserved. In humans, misfunctions of genes encoding N-hCR are associated with a cluster of disorders that mimic ASNase therapy side-effects which include impaired glycemic control, dislipidemia, pancreatitis, compromised vascular integrity, and neurological dysfunction. This paper proposes that dysregulation of Asn homeostasis, potentially even by ASNase produced by the microbiome, may contribute to several clinically important syndromes by altering expression of N-hCR bearing genes. By altering amino acid abundance and modulating ribosome translocation rates at codon repeats, the microbiomic environment may contribute to genome decoding and to shaping the proteome. We suggest that impaired translation at poly Asn codons elevates diabetes risk and severity.
Calcium channel blockers: spectrum of side effects and drug interactions.
Hedner, T
1986-01-01
Calcium antagonists are a chemically heterogenous group of agents with potent cardiovascular effects which are beneficial in the treatment of angina pectoris, arterial hypertension and cardiac arrhythmias. The main side effects for the group are dose-dependent and the result of the main action or actions of the calcium antagonists, i.e. vasodilatation, negative inotropic effects and antiarrhythmic effects. Pronounced hypotension is reported for the main calcium antagonist drugs; verapamil, diltiazem and nifedipine. While conduction disturbances and bradycardia are seen more often after verapamil and diltiazem, tachycardia, headache and flush are more frequent after nifedipine. Constipation is relatively frequent after verapamil while nifedipine is reported to induce diarrhea in som patients. Idiosyncratic side effects are rare but have been reported from the skin, mouth, musculoskeletal system, the liver and the central nervous system. These side effects include urticarial rashes, gingival hyperplasia, arthralgia, hepathotoxicity and transistory mental confusion or akathisia. Verapamil, diltiazem and possibly also nifedipine have been reported to increase serum digoxin concentrations but the clinical relevance of these drug interactions are not clear. Furthermore, verapamil and diltiazem may potentiate the effects of beta-adrenergic blocking drugs and verapamil may also potentiate the effects of neuromuscular blocking drugs. It is concluded that side effects after calcium antagonist drugs are mostly trivial and transient although they may sometimes be relatively common. Clinically relevant drug interactions are few. Judged from the point of efficacy and safety, calcium antagonists will have a major place in the future pharmacotherapy of several cardiovascular disorders.
Objective Analysis of Poly-L-Lactic Acid Injection Efficacy in Different Settings.
Byun, Sang-Young; Seo, Koo-Il; Shin, Jung-Won; Kwon, Soon-Hyo; Park, Mi-Sook; Lee, Joshua; Park, Kyoung-Chan; Na, Jung-Im; Huh, Chang-Hun
2015-12-01
Poly-L-lactic acid (PLLA) filler is known to have continuous volume effect. The objective of this study is to analyze objective volume effect of PLLA in different settings of injection schedule on the cheek. A split-face, evaluator-blind randomized study in 24 volunteers was conducted. One side was injected 3 times with 4 cc dose and the other side was injected 2 times with 6 cc dose per visit. Facial volume loss scale (FVLS) and Vectra were evaluated. Measured average FVLS showed statistically significant improvement both in 3 and 2 times injection sides and maintained efficacy until 12 months. Vectra showed volume difference (cc) between before and after injection. In 3 times injection side, it was increased 2.12 (after 1 month) to 3.17 (after 12 months). In 2 times injection side, it was increased 2.26 (after 1 month) to 3.19 (after 12 months). Gradual volume improvement over 12 months was statistically significant in both sides. There was no statistically significant difference between 3 and 2 times injection in FVLS and Vectra. There was no severe adverse event. Poly-L-lactic acid has continuous volume effect and there was no significant difference by injection times at the same total injection volume.
Sediment sorting at a side channel bifurcation
NASA Astrophysics Data System (ADS)
van Denderen, Pepijn; Schielen, Ralph; Hulscher, Suzanne
2017-04-01
Side channels have been constructed to reduce the flood risk and to increase the ecological value of the river. In various Dutch side channels large aggradation in these channels occurred after construction. Measurements show that the grain size of the deposited sediment in the side channel is smaller than the grain size found on the bed of the main channel. This suggest that sorting occurs at the bifurcation of the side channel. The objective is to reproduce with a 2D morphological model the fining of the bed in the side channel and to study the effect of the sediment sorting on morphodynamic development of the side channel. We use a 2D Delft3D model with two sediment fractions. The first fraction corresponds with the grain size that can be found on the bed of the main channel and the second fraction corresponds with the grain size found in the side channel. With the numerical model we compute several side channel configurations in which we vary the length and the width of the side channel, and the curvature of the upstream channel. From these computations we can derive the equilibrium state and the time scale of the morphodynamic development of the side channel. Preliminary results show that even when a simple sediment transport relation is used, like Engelund & Hansen, more fine sediment enters the side channel than coarse sediment. This is as expected, and is probably related to the bed slope effects which are a function of the Shields parameter. It is expected that by adding a sill at the entrance of the side channel the slope effect increases. This might reduce the amount of coarse sediment which enters the side channel even more. It is unclear whether the model used is able to reproduce the effect of such a sill correctly as modelling a sill and reproducing the correct hydrodynamic and morphodynamic behaviour is not straightforward in a 2D model. Acknowledgements: This research is funded by STW, part of the Dutch Organization for Scientific Research under grant number P12-P14 (RiverCare Perspective Programme) project number 13516.
Continuous subcutaneous infusion of lidocaine for persistent hiccup in advanced cancer.
Kaneishi, Keisuke; Kawabata, Masahiro
2013-03-01
Persistent hiccup can cause anorexia, weight loss, disabling sleep deprivation, anxiety, and depression. Therefore, relief of persistent hiccup is important for advanced cancer patients and their family. Most reports on this condition are case series reports advocating the use of baclofen, haloperidol, gabapentin, and midazolam. However, these medications are occasionally ineffective or accompanied by intolerable side effects. The sodium channel blocker lidocaine has been shown to be effective in treating a variety of disorders thought to involve neuropathic mechanisms. Intravenous administration of lidocaine is common but efficacy has also been reported for subcutaneous infusion. In advanced cancer patients, subcutaneous infusion is easy, advantageous, and accompanied by less discomfort. We report a case of severe and sustained hiccup caused by gastric cancer that was successfully treated with a continuous subcutaneous infusion of lidocaine (480 mg (24 ml)/day) without severe side effects.
Cognitive context detection in UAS operators using eye-gaze patterns on computer screens
NASA Astrophysics Data System (ADS)
Mannaru, Pujitha; Balasingam, Balakumar; Pattipati, Krishna; Sibley, Ciara; Coyne, Joseph
2016-05-01
In this paper, we demonstrate the use of eye-gaze metrics of unmanned aerial systems (UAS) operators as effective indices of their cognitive workload. Our analyses are based on an experiment where twenty participants performed pre-scripted UAS missions of three different difficulty levels by interacting with two custom designed graphical user interfaces (GUIs) that are displayed side by side. First, we compute several eye-gaze metrics, traditional eye movement metrics as well as newly proposed ones, and analyze their effectiveness as cognitive classifiers. Most of the eye-gaze metrics are computed by dividing the computer screen into "cells". Then, we perform several analyses in order to select metrics for effective cognitive context classification related to our specific application; the objective of these analyses are to (i) identify appropriate ways to divide the screen into cells; (ii) select appropriate metrics for training and classification of cognitive features; and (iii) identify a suitable classification method.
Liu, X-J; Li, M; Su, J-Z; Wang, Z; Xie, Z; Yu, G-Y
2016-10-01
Poor secretion of transplanted submandibular glands (SMGs) during the latent period may cause duct obstruction and affects the surgical outcome. The objective of this study was to investigate the efficacy and systemic side effects of carbachol on transplanted SMG secretion. Twenty-seven patients who underwent SMG transplantation for severe keratoconjunctivitis sicca were treated with subcutaneous injections of 0.2mg/2ml carbachol at 10 days, 1 month, and/or 3 months after surgery. The effect on secretion was evaluated by Schirmer test and technetium 99m ((99m)Tc) scintigraphy. Systemic side effects were evaluated subjectively using a questionnaire. The results showed that the time to onset varied from 4 to 9min and the duration of action from 50 to 110min after carbachol administration. The secretion at each time point after drug administration was significantly higher than the pre-administration value (all P<0.01). (99m)Tc scintigraphy showed a decline in the dynamic time-activity curve in 26 patients, demonstrating a stimulatory effect on the secretion of carbachol. No serious systemic side effects were experienced. In conclusion, the intermittent administration of carbachol could be an effective and safe strategy to promote secretion from transplanted SMGs in the latent period to prevent duct obstruction. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Bohn, Laura M.
2016-01-01
Pain is a complex disorder with neurochemical and psychological components contributing to the severity, the persistence, and the difficulty in adequately treating the condition. Opioid and cannabinoids are two classes of analgesics that have been used to treat pain for centuries and are arguably the oldest of “pharmacological” interventions used by man. Unfortunately, they also produce several adverse side effects that can complicate pain management. Opioids and cannabinoids act at G protein-coupled receptors (GPCRs), and much of their effects are mediated by the mu-opioid receptor (MOR) and cannabinoid CB1 receptor (CB1R), respectively. These receptors couple to intracellular second messengers and regulatory proteins to impart their biological effects. In this chapter, we review the role of the intracellular regulatory proteins, β-arrestins, in modulating MOR and CB1R and how they influence the analgesic and side-effect profiles of opioid and cannabinoid drugs in vivo. This review of the literature suggests that the development of opioid and cannabinoid agonists that bias MOR and CB1R toward G protein signaling cascades and away from β-arrestin interactions may provide a novel mechanism by which to produce analgesia with less severe adverse effects. PMID:24292843
Clattenburg, Eben J; Hailozian, Christian; Haro, Daniel; Yoo, Tina; Flores, Stefan; Louie, Derex; Herring, Andrew A
2018-04-12
We compared the analgesic efficacy and incidence of side effects when low{\\hyphen}dose (0.3 mg{\\sol}kg) ketamine (LDK) is administered as a slow infusion (SI) over 15 minutes versus an intravenous push (IVP) over one minute. This was a prospective, randomized, double blind, double dummy, placebo{\\hyphen}controlled trial of adult ED patients presenting with moderate to severe pain (numerical rating score ≥ 5). Patients received ketamine 0.3mg{\\sol}kg administered either as a SI or IVP. Our primary outcome was the proportion of patients experiencing any psychoperceptual side effect over 60 minutes. A secondary outcome was incidence of moderate or greater psychoperceptual side effects. Additional outcomes included reduction in pain NRS scores at 60 minutes and percent maximum summed pain intensity difference ({\\percnt}SPID). Fifty{\\hyphen}nine participants completed the study. 86.2{\\percnt} of the IVP arm and 70.0{\\percnt} of the SI arm experienced any side effect (difference 16.2{\\percnt}, 95{\\percnt}CI {\\hyphen}5.4 - 37.8). We found a large reduction in moderate or greater psychoperceptual side effects with SI administration-75.9{\\percnt} reported moderate or greater side effects versus 43.4{\\percnt} in the SI arm (difference 32.5{\\percnt}, 95{\\percnt}CI 7.9 - 57.1). Additionally, the IVP arm experienced more hallucinations (n{\\equal}8, 27.6{\\percnt}) than the SI arm (SI n{\\equal}2, 6.7{\\percnt}; difference 20.9{\\percnt}, 95{\\percnt}CI 1.8 - 43.4). We found no significant differences in analgesic efficacy. At 60 minutes, the mean {\\percnt}SPID in the IVP and SI arms was 39.9{\\percnt} and 33.5{\\percnt}, respectively, with a difference of 6.5{\\percnt} (95{\\percnt}CI {\\hyphen}5.8 - 18.7). Most patients who are administered LDK experience a psychoperceptual side effect regardless of administration via SI or IVP. However, patients receiving LDK as a SI reported significantly fewer moderate or greater psychoperceptual side effects and hallucinations with equivalent analgesia. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Mastocytosis and insect venom allergy.
Bonadonna, Patrizia; Zanotti, Roberta; Müller, Ulrich
2010-08-01
To analyse the association of systemic allergic hymenoptera sting reactions with mastocytosis and elevated baseline serum tryptase and to discuss diagnosis and treatment in patients with both diseases. In recent large studies on patients with mastocytosis a much higher incidence of severe anaphylaxis following hymenoptera stings than in the normal population was documented. In patients with hymenoptera venom allergy, elevated baseline tryptase is strongly associated with severe anaphylaxis. Fatal sting reactions were reported in patients with mastocytosis, notably after stopping venom immunotherapy. During venom immunotherapy most patients with mastocytosis are protected from further sting reactions. Based on these observations immunotherapy for life is recommended for patients with mastocytosis and venom allergy. The incidence of allergic side-effects is increased in patients with mastocytosis and elevated baseline tryptase, especially in those allergic to Vespula venom. Premedication with antihistamines, or omalizumab in cases with recurrent severe side-effects, can be helpful. In all patients with anaphylaxis following hymenoptera stings, baseline serum tryptase should be determined. A value above 11.4 microg/l is often due to mastocytosis and indicates a high risk of very severe anaphylaxis following re-stings. Venom immunotherapy is safe and effective in this situation.
Bijlsma, Elisabeth Y; Chan, Johnny S W; Olivier, Berend; Veening, Jan G; Millan, Mark J; Waldinger, Marcel D; Oosting, Ronald S
2014-06-01
Antidepressant-induced sexual dysfunction adversely affects the quality of life of antidepressant users and reduces compliance with treatment. Animal models provide an instructive approach for examining potential sexual side effects of novel drugs. This review discusses the stability and reproducibility of our standardized test procedure that assesses the acute, subchronic and chronic effects of psychoactive compounds in a 30 minute mating test. In addition, we present an overview of the effects of several different (putative) antidepressants on male rat sexual behavior, as tested in our standardized test procedure. By comparing the effects of these mechanistically distinct antidepressants (paroxetine, venlafaxine, bupropion, buspirone, DOV 216,303 and S32006), this review discusses the putative mechanism underlying sexual side effects of antidepressants and their normalization. This review shows that sexual behavior is mainly inhibited by antidepressants that increase serotonin neurotransmission via blockade of serotonin transporters, while those that mainly increase the levels of dopamine and noradrenaline are devoid of sexual side effects. Those sexual disturbances cannot be normalized by simultaneously increasing noradrenaline neurotransmission, but are normalized by increasing both noradrenaline and dopamine neurotransmission. Therefore, it is hypothesized that the sexual side effects of selective serotonin reuptake inhibitors may be mediated by their inhibitory effects on dopamine signaling in sex brain circuits. Clinical development of novel antidepressants should therefore focus on compounds that simultaneously increase both serotonin and dopamine signaling. © 2013 Elsevier Inc. All rights reserved.
Russel, M G; Zeijen, R N; Brummer, R J; de Bruine, A P; van Kroonenburgh, M J; Stockbrügger, R W
1994-01-01
A patient with a 15 year history of diarrhoea of unknown origin is described. Scintigraphy with technetium-99m labelled albumin suggested albumin loss at the terminal ileum and caecum; subsequent colonoscopic biopsies of these macroscopically normal looking areas showed abundant infiltration with eosinophils. A diagnosis of eosinophilic enterocolitis was made. Treatment with prednisolone had good results, but had to be stopped because of severe side effects. Oral cromoglycate and mesalazine were not effective. Budesonide (CIR), a new topically active corticosteroid with very little systemic effects, was at least as effective as prednisolone without producing side effects. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7959211
Faghihi, Gita; Mokhtari, Fatemeh; Fard, Nasrin Motamedi; Motamedi, Narges; Hosseini, Sayed Mohsen
2017-01-01
Objective: This study was conducted to compare the effect of low-dose isotretinoin with its conventional dose in patients with moderate and severe acne. Methods: This was a clinical trial conducted on 60 male and female patients with moderate and severe acne vulgaris. The patients were divided into two treatment groups: 0.5 mg/kg/day isotretinoin capsule and low-dose isotretinoin capsule (0.25 mg/kg/day). Patients in both groups received 6-month treatment. At the end of the 6th month and 12th month (6 months after the end of the treatment), they were examined again, and their improvement was determined and compared. Findings: The average severity of acne in the two treatment groups did not differ significantly within any of the study periods. The most common side effects were nose dryness in the low-dose group (17%) and hair thinning and loss in the conventional-dose group (33.2%), although all the patients had dry lips. Conclusion: According to the same severity of the acne in two groups in different study periods, as well as fewer side effects and more patients' satisfaction, the low-dose isotretinoin can be considered in the treatment of acne. PMID:29417084
Keller, David P.; Feng, Ellias Y.; Oschlies, Andreas
2014-01-01
The realization that mitigation efforts to reduce carbon dioxide emissions have, until now, been relatively ineffective has led to an increasing interest in climate engineering as a possible means of preventing the potentially catastrophic consequences of climate change. While many studies have addressed the potential effectiveness of individual methods there have been few attempts to compare them. Here we use an Earth system model to compare the effectiveness and side effects of afforestation, artificial ocean upwelling, ocean iron fertilization, ocean alkalinization and solar radiation management during a high carbon dioxide-emission scenario. We find that even when applied continuously and at scales as large as currently deemed possible, all methods are, individually, either relatively ineffective with limited (<8%) warming reductions, or they have potentially severe side effects and cannot be stopped without causing rapid climate change. Our simulations suggest that the potential for these types of climate engineering to make up for failed mitigation may be very limited. PMID:24569320
Faculty Retirement and Recruitment in the Community Colleges
ERIC Educational Resources Information Center
Kisker, Carrie B.
2004-01-01
Several recent studies have shown that a large-scale turnover is likely to occur among community college instructors over the next several years, as veteran faculty retire in large numbers. As colleges begin to experience this mass retirement, researchers and administrators must consider the side effects of a faculty turnover, especially in…
Henstra, Marieke J; Jansma, Elise P; van der Velde, Nathalie; Swart, Eleonora L; Stek, Max L; Rhebergen, Didi
2017-05-01
Electroconvulsive therapy (ECT) is an effective treatment for severe late-life depression; however, ECT-induced cognitive side effects frequently occur. The cholinergic system is thought to play an important role in the pathogenesis. We systematically reviewed the evidence for acetylcholinesterase inhibitors (Ache-I) to prevent or reduce ECT-induced cognitive side effects. A systematic search was performed in Pubmed, EMBASE, PsychINFO, and the Cochrane database to identify clinical trials investigating the effect of Ache-I on ECT-induced cognitive side effects. Key search terms included all synonyms for ECT and Ache-I. Risk of bias assessment was conducted by using the Cochrane Collaboration's tool. Five clinical trials were eligible for inclusion. All studies focused on cognitive functioning as primary endpoint, but assessment of cognitive functioning varied widely in time point of assessment and in cognitive tests that were used. There was also great variety in study medication, route and time of administration and dosages, duration of drug administration, and ECT techniques. Finally, only two out of five studies were considered at low risk of bias. Despite the aforementioned shortcomings, without exception, all studies demonstrated significantly better cognitive performance in individuals treated with Ache-I. Despite large heterogeneity in studies, Ache-I appear to have beneficial effects on ECT-induced cognitive side effects, supporting an association with the cholinergic system in ECT-induced cognitive impairment. Methodological sound studies controlling for putative confounders are warranted. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.
2011-01-01
Background Antipsychotic are the cornerstone in the treatment of schizophrenia. They also have a number of side-effects. Constipation is thought to be common, and a potential serious side-effect, which has received little attention in recent literature. Method We performed a retrospective study in consecutively admitted patients, between 2007 and 2009 and treated with antipsychotic medication, linking different electronic patient data to evaluate the prevalence and severity of constipation in patients with schizophrenia under routine treatment conditions. Results Over a period of 22 months 36.3% of patients (99) received at least once a pharmacological treatment for constipation. On average medication for constipation was prescribed for 273 days. Severe cases (N = 50), non-responsive to initial treatment, got a plain x-ray of the abdomen. In 68.4% fecal impaction was found. Conclusion A high prevalence of constipation, often severe and needing medical interventions, was confirmed during the study period. Early detection, monitoring over treatment and early intervention of constipation could prevent serious consequences such as ileus. PMID:21385443
Steroid fears in children with eczema.
Hon, Kam-Lun Ellis; Kam, Wai-Yan Christy; Leung, Ting-Fan; Lam, Man-Ching Adrian; Wong, Kin-Yee; Lee, Kwing-Chin Kenneth; Luk, Nai-Ming Tommy; Fok, Tai-Fai; Ng, Pak-Cheung
2006-11-01
Topical glucocorticoids (GCs) are the mainstay of treatment for eczema, but GC phobia and fears are very common among the parents of paediatric patients. To survey the nature and extent of "fears" of GC use, and to evaluate if disease severity is associated with such fears. Patients with eczema managed in the paediatric dermatology outpatient clinic of a university hospital were recruited in this survey. Disease severity and various aspects of belief and practices of GC use were assessed with the Nottingham Eczema Severity Score and a questionnaire. GC "fears" were present in two fifths of informants with non-eczematous skin disease and mild eczema, but three fifths in moderate-to-severe disease. Requests for steroid-sparing medications (such as tacrolimus or pimecrolimus) had been made in nearly 50% of cases with moderate-to-severe eczema, and many parents would wait until eczema had worsened or apply GC only as a last resort to avoid potential side effects. "Fears" were predominantly interpersonal and rarely iatrogenic in nature. Skin problems (in particular skin thinning) and adverse effects on growth were the side effects of GC of most concern. However, fewer than half of the informants had discussed their concerns with doctors. Our results suggest the importance of understanding the nature and extent to which GC fears, regardless of eczema severity, are prevalent so that sound advice can be offered in a timely manner to parents and patients.
Martin, Roy C; Kretzmer, Tracy; Palmer, Cheryl; Sawrie, Stephen; Knowlton, Robert; Faught, Edward; Morawetz, Richard; Kuzniecky, Ruben
2002-12-01
Previous investigations indicate low risk for memory loss following anterior temporal lobectomy (ATL) in patients with severe hippocampal sclerosis (HS) compared with patients with mild HS. However, these conclusions have been established primarily with group-level analyses. To investigate individual base rate risk for verbal memory loss following ATL in patients who have pathologically verified mild, moderate, or severe HS. One hundred fifteen patients with unilateral temporal lobe epilepsy (68 with left-sided and 47 with right-sided epilepsy) were included. Acquisition, retrieval, and recognition components of verbal memory, as measured by the California Verbal Learning Test, were assessed before and after ATL. Postoperatively, the degree of neuronal loss and reactive gliosis of the hippocampus was assessed via a 3-tiered rating system establishing mild, moderate, and severe pathologic features. Patients with preoperative magnetic resonance imaging-based evidence of lesions outside the mesial temporal area (side of surgical resection) were excluded. Neither seizure laterality nor severity of HS was associated with preoperative verbal memory performance. Postoperatively, the left-sided ATL group demonstrated significant decline across the acquisition (P<.01), retrival (P<.001), and recognition (P<.001) verbal memory components compared with the right-sided ATL group. Patients who underwent left-sided ATL and had mild HS displayed the largest magnitude and percentage proportion of postoperative decline across all verbal memory components. However, 28 (48%) of the 58 patients who underwent left-sided ATL and who had moderate and severe HS displayed statistically reliable declines on retrieval aspects of verbal memory. Most patients undergoing right-sided ATL, regardless of the extent of hippocampal pathologic features, displayed no postoperative memory change. Substantial individual heterogeneity of memory outcome exists across groups of patients undergoing ATL, with various degrees of pathologically verified HS. Patients undergoing left-sided ATL who have mild HS seem at greatest risk for broad-spectrum verbal memory decline. However, when examining outcome on a patient-by-patient basis, many patients undergoing left-sided ATL who have moderate to severe HS were also vulnerable to verbal memory loss. This risk seems selective to a retrieval-based aspect of verbal memory.
Beliefs about medications predict adherence to antidepressants in older adults.
Fawzi, Waleed; Abdel Mohsen, Mohamed Yousry; Hashem, Abdel Hamid; Moussa, Suaad; Coker, Elizabeth; Wilson, Kenneth C M
2012-01-01
Adherence to treatment is a complex and poorly understood phenomenon. This study investigates the relationship between older depressed patients' adherence to antidepressants and their beliefs about and knowledge of the medication. Assessment was undertaken of 108 outpatients over the age of 55 years diagnosed with depressive disorder and treated for at least four weeks with antidepressants. Adherence was assessed using two self-report measures: the Medication Adherence Rating Scale (MARS) and a Global Adherence Measure (GAM). Potential predictors of adherence investigated included sociodemographic, medication and illness variables. In addition, 33 carers were interviewed regarding general medication beliefs. 56% of patients reported 80% or higher adherence on the GAM. Sociodemographic variables were not associated with adherence on the MARS. Specific beliefs about medicines, such as "my health depends on antidepressants" (necessity) and being less worried about becoming dependant on antidepressants (concern) were highly correlated with adherence. General beliefs about medicines causing harm or being overprescribed, experiencing medication side-effects and severity of depression also correlated with poor adherence. Linear regression with the MARS as the dependent variable explained 44.3% of the variance and showed adherence to be higher in subjects with healthy specific beliefs who received more information about antidepressants and worse with depression severity and autonomic side-effects. Our findings strongly support a role for specific beliefs about medicines in adherence. Challenging patients' beliefs, providing information about treatment and discussing side-effects could improve adherence. Poor response to treatment and medication side-effects can indicate poor adherence and should be considered before switching medications.
Managing side effects of JAK inhibitors for myelofibrosis in clinical practice.
Saeed, Iram; McLornan, Donal; Harrison, Claire N
2017-07-01
Myelofibrosis (MF) is characterized by bone marrow fibrosis, abnormalities in peripheral counts, extramedullary hematopoiesis, splenomegaly and an increased risk of transformation to acute myeloid leukaemia. The disease course is often heterogeneous and management can range from observation alone through to allogeneic stem cell transplantation. As of 2017, the only approved medication for MF remains the JAK Inhibitor (JAKi), ruxolitinib (Novartis Pharmaceuticals, Basel, Switzerland; Incyte, Wilmington, Detroit, USA) although several others have reached advanced stages of clinical trials. Areas covered: In this review, we focus on the management of both common and uncommon side effects arising from the use of currently approved and clinical trial JAKi. Most of the discussion concerns ruxolitinib although we also cover both pacritinib (CTI BioPharma) and momelotinib (Gilead Sciences, Foster City, California) which have been in recent large, multinational phase III trials. The various approaches to management of JAKi-related side effects are discussed - with particular emphasis to anaemia, thrombocytopaenia and infection risk. Expert commentary: JAK inhibitors are effective in many individuals with MF and have revolutionized the current treatment paradigm. The side effect profile, in the most, is predictable and manageable with high degrees of clinical surveillance and dose modifications.
Migraine Headaches: Treatment & Research
... please turn JavaScript on. Feature: Migraine Headaches Treatment & Research Past Issues / Fall 2015 Table of Contents Nondrug ... since some drugs may cause side effects. What Research Is Being Done? Several studies either conducted or ...
Unified double- and single-sided homogeneous Green’s function representations
van der Neut, Joost; Slob, Evert
2016-01-01
In wave theory, the homogeneous Green’s function consists of the impulse response to a point source, minus its time-reversal. It can be represented by a closed boundary integral. In many practical situations, the closed boundary integral needs to be approximated by an open boundary integral because the medium of interest is often accessible from one side only. The inherent approximations are acceptable as long as the effects of multiple scattering are negligible. However, in case of strongly inhomogeneous media, the effects of multiple scattering can be severe. We derive double- and single-sided homogeneous Green’s function representations. The single-sided representation applies to situations where the medium can be accessed from one side only. It correctly handles multiple scattering. It employs a focusing function instead of the backward propagating Green’s function in the classical (double-sided) representation. When reflection measurements are available at the accessible boundary of the medium, the focusing function can be retrieved from these measurements. Throughout the paper, we use a unified notation which applies to acoustic, quantum-mechanical, electromagnetic and elastodynamic waves. We foresee many interesting applications of the unified single-sided homogeneous Green’s function representation in holographic imaging and inverse scattering, time-reversed wave field propagation and interferometric Green’s function retrieval. PMID:27436983
Unified double- and single-sided homogeneous Green's function representations
NASA Astrophysics Data System (ADS)
Wapenaar, Kees; van der Neut, Joost; Slob, Evert
2016-06-01
In wave theory, the homogeneous Green's function consists of the impulse response to a point source, minus its time-reversal. It can be represented by a closed boundary integral. In many practical situations, the closed boundary integral needs to be approximated by an open boundary integral because the medium of interest is often accessible from one side only. The inherent approximations are acceptable as long as the effects of multiple scattering are negligible. However, in case of strongly inhomogeneous media, the effects of multiple scattering can be severe. We derive double- and single-sided homogeneous Green's function representations. The single-sided representation applies to situations where the medium can be accessed from one side only. It correctly handles multiple scattering. It employs a focusing function instead of the backward propagating Green's function in the classical (double-sided) representation. When reflection measurements are available at the accessible boundary of the medium, the focusing function can be retrieved from these measurements. Throughout the paper, we use a unified notation which applies to acoustic, quantum-mechanical, electromagnetic and elastodynamic waves. We foresee many interesting applications of the unified single-sided homogeneous Green's function representation in holographic imaging and inverse scattering, time-reversed wave field propagation and interferometric Green's function retrieval.
Loftis, Kathryn L.; Weaver, Ashley A.; Stitzel, Joel D.
2011-01-01
The objective of this study was to investigate side airbag (SAB) deployment in near side crashes and compare injuries and contact points between occupants with and without SAB deployment. Using NASS 2000–2008 and selecting for near side cases, with PDOF ± 20 degrees from 90 or 270, for non-pregnant adult belted occupants, there were 20,253 (weighted) SAB deployments. NASS showed that SABs have been increasing within the fleet, comprising 2% of airbags in 2000 and increasing to 33% of airbags in 2008. To investigate deployed SABs, we developed a three-step methology to pair CIREN cases to study the effects of deployment on occupant outcome. The first step involved extracting near side impacts from CIREN with adult, non-pregnant occupants seated in row 1 (drivers or right front passengers). In the second step, each case was quantitatively compared to FMVSS 214 barrier test standards using a 6 point similarity scoring system. Cases scoring at least 3 points were then qualitatively analyzed and 33 pairs of cases of the same vehicle make/model but opposite SAB status were chosen. Occupants with deployed SAB had reduced occurrences and severity of head and face, neck and cervical spine, and thoracic injuries and fewer injurious contacts to side components including the door, a-pillar, and window sill. SAB deployment was statistically significant for reducing occupant MAIS and ISS and thorax airbags were statistically significant for reducing thoracic and neck/cervical spine injury severity. The average ISS with SAB deployment was 21, while the average ISS of those without was 33. This study establishes methods for performing comparisons between CIREN cases based on regulatory conditions and shows injury reduction in key body regions with SAB deployment. PMID:22105386
Amanat, Dariush; Ebrahimi, Hooman; Zahedani, Maryam Zahed; Zeini, Nasim; Pourshahidi, Sara; Ranjbar, Zahra
2014-01-01
Oral lichen planus (OLP) is a chronic inflammatory disease of the oral mucosa with treatment challenges for clinicians. The objective of this study is to compare the effects of cryotherapy as a new modality with topical corticosteroids as a conventional therapy in the treatment of OLP. Thirty patients with bilateral OLP lesions were selected. From each patient a lesion on one side was chosen randomly for a single session of cryotherapy with nitrous oxide gas and the lesion on the other side received triamcinolone acetonide 0.1% ointment in orabase. Treatment outcome was measured by means of an appearance score, pain score (visual analogue scale), and severity of lesions before treatment and after 2, 4 and 6 weeks of treatment. Paired samples t-test and Wilcoxon test. In both methods of treatment sign score, pain score and severity of lesions was significantly reduced in all follow-up sessions (P<0.05). But the treatment outcome and relapse was not significantly different between the two treatment methods (P>0.05). Cryotherapy with nitrous oxide gas is as effective as topical triamcinolone acetonide in the treatment of OLP with no systemic side effects and needs less patient compliance. It can be considered as an alternative or adjuvant therapy in OLP patients to reduce the use of treatments with adverse effects.
Arcand, M.; Hottin, P.
1993-01-01
Classical treatment of depression in the elderly is often complicated by side effects and delayed therapeutic effect. After reviewing the literature and their clinical experiences, the authors suggest several acceptable indications for the use of psychostimulants in the elderly, especially when the depression is associated with a serious physical illness. PMID:8268747
IN-VITRO METHODS FOR EVALUATING SIDE EFFECTS OF PESTICIDES AND TOXIC SUBSTANCES
Several skeletal muscle and smooth muscle preparations have been examined for their usefulness in evaluating the toxic effects of a variety of insecticides. The following preparations were found satisfactory for such test: guinea pig ileum for muscarinic receptors, guinea pig hea...
[Iron deficiency anemia and pregnancy. Prevention and treatment].
Beucher, G; Grossetti, E; Simonet, T; Leporrier, M; Dreyfus, M
2011-05-01
To assess the effectiveness and the safety of prevention and treatment of iron deficiency anemia during pregnancy. French and English publications were searched using PubMed and Cochrane library. Early screening of iron deficiency by systematic examination and blood analysis seemed essential. Maternal and perinatal complications were correlated to the severity and to the mode of appearance of anemia. Systematic intakes of iron supplements seemed not to be recommended. In case of anemia during pregnancy, iron supplementation was not associated with a significant reduction in substantive maternal and neonatal outcomes. Oral iron supplementation increased blood parameters but exposed to digestive side effects. Women who received parenteral supplementation were more likely to have better hematological response but also severe potential side effects during pregnancy and in post-partum. The maternal tolerance of anemia motivated the choice between parenteral supplementation and blood transfusion. Large and methodologically strong trials are necessary to evaluate the effects of iron supplementation on maternal health and pregnancy outcomes. Copyright © 2011 Elsevier Masson SAS. All rights reserved.
Grønborg, Pia; Liljegren, Jeanette; Jansen, Jette
2009-06-22
Methylphenidate is a central nervous system (CNS)-stimulating agent. During recent years methylphenidate has been shown to increase arousal in patients with traumatic brain injury. We describe a patient with a severe traumatic injury in whom arousal was increased when methylphenidate was given, and the level of arousal decreased when the amount was diminished after some months. Due to possible side effects, methylphenidate treatment was reduced over several weeks 2 years after the trauma. Surprisingly, the cognitive level was then dramatically improved. To our knowledge, such paradoxical effect of methylphenidate has not previously been described.
Cost-effectiveness of pharmacological and psychosocial interventions for schizophrenia.
Phanthunane, Pudtan; Vos, Theo; Whiteford, Harvey; Bertram, Melanie
2011-05-13
Information on cost-effectiveness of interventions to treat schizophrenia can assist health policy decision making, particularly given the lack of health resources in developing countries like Thailand. This study aims to determine the optimal treatment package, including drug and non-drug interventions, for schizophrenia in Thailand. A Markov model was used to evaluate the cost-effectiveness of typical antipsychotics, generic risperidone, olanzapine, clozapine and family interventions. Health outcomes were measured in disability adjusted life years. We evaluated intervention benefit by estimating a change in disease severity, taking into account potential side effects. Intervention costs included outpatient treatment costs, hospitalization costs as well as time and travel costs of patients and families. Uncertainty was evaluated using Monte Carlo simulation. A sensitivity analysis of the expected range cost of generic risperidone was undertaken. Generic risperidone is more cost-effective than typicals if it can be produced for less than 10 baht per 2 mg tablet. Risperidone was the cheapest treatment with higher drug costs offset by lower hospital costs in comparison to typicals. The most cost-effective combination of treatments was a combination of risperidone (dominant intervention). Adding family intervention has an incremental cost-effectiveness ratio of 1,900 baht/DALY with a 100% probability of a result less than a threshold for very cost-effective interventions of one times GDP or 110,000 baht per DALY. Treating the most severe one third of patients with clozapine instead of risperidone had an incremental cost-effectiveness ratio of 320,000 baht/DALY with just over 50% probability of a result below three times GDP per capita. There are good economic arguments to recommend generic risperidone as first line treatment in combination with family intervention. As the uncertainty interval indicates the addition of clozapine may be dominated and there are serious side effects, treating severe patients with clozapine is advisable only for patients who do not respond to risperidone and only in the presence of a stricter side effect monitoring system than currently exists.
Warfarin Side Effects: Watch for Interactions
... in treatment. Severe bleeding, including heavier than normal menstrual bleeding Red or brown urine Black or bloody ... gums after you brush your teeth Bleeding between menstrual periods Diarrhea, vomiting or inability to eat for ...
Qu, Yang; Xu, Jinyu; Zhou, Haohan; Dong, Rongpeng; Kang, Mingyang; Zhao, Jianwu
2017-03-14
Antibiotics are always considered for surgical site infection (SSI) in adolescent idiopathic scoliosis (AIS) surgery. However, the use of antibiotics often causes the antibiotic resistance of pathogens and side effects. Thus, it is necessary to explore natural products as drug candidates. Chitin Oligosaccharide (COS) has anti-inflammation and anti-bacteria functions. The effects of COS on surgical infection in AIS surgery were investigated. A total of 312 AIS patients were evenly and randomly assigned into control group (CG, each patient took one-gram alternative Azithromycin/Erythromycin/Cloxacillin/Aztreonam/Ceftazidime or combined daily), experiment group (EG, each patient took 20 mg COS and half-dose antibiotics daily), and placebo group (PG, each patient took 20 mg placebo and half-dose antibiotics daily). The average follow-up was one month, and infection severity and side effects were analyzed. The effects of COS on isolated pathogens were analyzed. SSI rates were 2%, 3% and 8% for spine wounds and 1%, 2% and 7% for iliac wound in CG, EG and PG ( p < 0.05), respectively. COS reduces the side effects caused by antibiotics ( p < 0.05). COS improved biochemical indexes and reduced the levels of interleukin (IL)-6 and tumor necrosis factor (TNF) alpha. COS reduced the antibiotics dose and antibiotics-caused side effects in AIS patients with spinal fusion surgery by improving antioxidant and anti-inflammatory activities. COS should be developed as potential adjuvant for antibiotics therapies.
Amiri Farahani, Ë Leila; Hasanpoor-Azghdy, Seyedeh Batool; Kasraei, Hengameh; Heidari, Tooba
2017-08-01
Primary dysmenorrhea starts simultaneously with menstruation or before it and usually continues for 48-72 h. As a prevalence disorder, it affects about 80-97% of women in the reproductive age. The conventional treatment modalities of primary dysmenorrhea are associated with complications and side effects. In addition, there is a lack of knowledge of the effect of honey on the treatment of primary dysmenorrhea. The objective of this study is to investigate the effect of honey on the severity of pain in women with dysmenorrhea. A randomized crossover clinical trial was conducted on 56 female students. Subjects were randomly assigned to two groups. Groups I and II received honey and mefenamic acid in the 'first treatment period', respectively. In the 'second treatment period', the intervention methods were reversed between the groups. Samples recorded the severity of pain during the first 3 days of menstruation. There were no significant differences in the most severe level of pain in the first and second months of the first treatment period, and the first and second months of the second treatment period between the groups. Honey and the mefenamic acid capsules led to the same amount of pain relief in women with primary dysmenorrhea. Honey is suggested to be used for pain relief due to its lower side effects and pharmacological complications.
A phase I study of human natural interferon-beta in cancer patients.
Liberati, A M; Biscottini, B; Fizzotti, M; Schippa, M; De Angelis, V; Senatore, M; Vittori, O; Teggia, L; Natali, R; Palmisano, L
1989-06-01
In this phase I study 15 patients with metastatic tumors were given interferon (IFN)-beta by i.v. bolus injections. Twelve individual doses of 1, 2, 3.3, 5, 7, 9, 12, 16, 21, 27, 35, and 46 x 10(6) IU were administered every other day. The single maximal tolerated dose ranged from 9 to 46 x 10(6) IU. Eight patients tolerated the dose of 46 x 10(6) IU without side effects. Disturbances of cardiac rhythm were observed, but were closely related temporally to severe chills and appeared to be the consequence of adrenergic stimulation associated with this side-effect. In addition, no significant variations in the left ventricular function as assessed by nuclear stethoscope were observed. Neurotoxicity was not a major side-effect. The toxicity of IFN-beta given as scheduled in this study was significant, but acceptable.
Lenz, Destin U; Crutcher, Effie L; Greene, Elisa M
2017-01-01
Sexual dysfunction is a bothersome side effect of several medications, though it has not yet been reported with the use of ledipasvir/sofosbuvir for the treatment of hepatitis C. However, sexual dysfunction is a potentially unrecognized side effect of ledipasvir/sofosbuvir that could result in nonadherence and treatment failure. We report a case of a 42-year-old man with a sudden onset of sexual dysfunction with the initiation of ledipasvir/sofosbuvir for the treatment of hepatitis C. The patient had no prior history or risk factors for the development of sexual dysfunction. His symptoms resolved upon discontinuation of ledipasvir/sofosbuvir after a successful 12-week course. Clinicians should be aware that sexual dysfunction is a possible side effect of ledipasvir/sofosbuvir and educate patients appropriately. Adherence should be emphasized as the risks of untreated hepatitis C virus far outweigh transient sexual dysfunction.
[Pharmaceutical services for patients receiving AC chemotherapy].
Higuchi, Minako; Matsuo, Koichi; Ureshino, Yuko; Ogata, Kentaro; Futagami, Koujiro; Kitamura, Kaoru; Nishino, Hiroaki
2009-02-01
General treatments for breast cancer patients, such as surgery, chemotherapy, radiotherapy and lymphatic edema drainage, are performed at the Department of Breast Surgery in Kyushu Central Hospital. In those treatments, pharmacists provide the pharmaceutical treatment. Combination chemotherapy of doxorubicin and cyclophosphamide (AC therapy) is one of the standard regimens for breast cancer. In breast cancer patients who received AC therapy, we carried out investigations on side effects, and prepared pamphlets to support patients' self-management in their daily lives. In the process of preparing pamphlets, we made check sheets to monitor the severity and incidence of side effects. Based on the results of analysis and patients' opinions as well as staff remarks, we prepared pamphlets. According to the evaluation survey, pamphlets are regarded as useful. To meet the needs of patients, we intend to periodically revise pamphlets by continuing investigations on side effects, and provide up-to-date information.
Navia, José L; Elgharably, Haytham; Javadikasgari, Hoda; Ibrahim, Ahmed; Koprivanac, Marijan; Lowry, Ashley M; Blackstone, Eugene H; Klein, Allan L; Gillinov, A Marc; Roselli, Eric E; Svensson, Lars G
2017-08-01
Tricuspid regurgitation (TR) often accompanies ischemic mitral regurgitation and is generally assumed to be a secondary consequence of altered hemodynamics of the left-sided regurgitation. We hypothesized that it may also be a direct consequence of right-sided ischemic disease. Therefore, our objectives were to (1) characterize the nature of this TR and (2) describe its time course after mitral valve surgery for ischemic mitral regurgitation, with or without concomitant tricuspid valve repair. From 2001 to 2011, 568 patients with ischemic mitral regurgitation underwent mitral valve surgery. They had varying degrees of TR and altered right-side heart morphology and function; 131 had concomitant tricuspid valve repair. Postoperatively, 1,395 echocardiograms were available to assess residual and recurrent TR. Greater severity of preoperative TR was accompanied by larger tricuspid valve diameter, greater leaflet tethering, worse right ventricular function, and higher right ventricular pressure (all p [trend] ≤ 0.002). Without tricuspid valve repair, 31% of patients with no preoperative TR had moderate or greater TR by 5 years, as did 62% with moderate TR. With tricuspid valve repair, 25% with moderate preoperative TR remained in that grade at 5 years, but 11% had severe TR. Tricuspid regurgitation accompanying ischemic mitral regurgitation is associated with right-side heart remodeling and dysfunction often mirroring that occurring in the left side of the heart-ischemic TR. Tricuspid valve repair is effective initially, but as with mitral valve repair, TR progressively returns. Therefore, when the severity of TR and right-sided remodeling reaches the point of irreversibility, it may be an indication to eliminate the TR by replacing the tricuspid valve. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Broström, Anders; Strömberg, Anna; Mårtensson, Jan; Ulander, Martin; Harder, Lena; Svanborg, Eva
2007-12-01
Continuous positive airway pressure (CPAP) is the treatment of choice for obstructive sleep apnoea syndrome (OSAS), but side effects are common and long-term adherence low. The Type D (distressed) personality is defined as a combination of negative affectivity and social inhibition. The association of Type D personality with adherence has not been studied in CPAP-treated patients with OSAS. This study aimed to describe the prevalence of Type D personality in OSAS patients with CPAP treatment longer than 6 months and the association with self-reported side effects and adherence. A cross-sectional descriptive design was used. A total of 247 OSAS patients with a mean use of CPAP treatment for 55 months (6-182 months) were included. Data collection was achieved by two questionnaires; the Type D scale 14 (DS14) (Type D personality), SECI (side effects of CPAP), as well as from medical records (clinical variables and objective adherence to CPAP treatment). Type D personality occurred in 30% of the patients with OSAS and significantly (P < 0.05-0.001) increased the perceived frequency and severity of a broad range of side effects. The objective adherence was significantly lower (P < 0.001) for OSAS patients with Type D compared to OSAS patients without Type D, both with regard to a mean use of 4 h per night and 85% of the self-rated sleep time per night. The additional effect of a Type D personality on perceived side effects and adherence to CPAP treatment found in this study could be used by healthcare personnel when evaluating patients waiting for treatment.
Histone deacetylase inhibitors reverse age-related increases in side effects of haloperidol in mice.
Montalvo-Ortiz, Janitza L; Fisher, Daniel W; Rodríguez, Guadalupe; Fang, Deyu; Csernansky, John G; Dong, Hongxin
2017-08-01
Older patients can be especially susceptible to antipsychotic-induced side effects, and the pharmacodynamic mechanism underlying this phenomenon remains unclear. We hypothesized that age-related epigenetic alterations lead to decreased expression and functionality of the dopamine D2 receptor (D2R), contributing to this susceptibility. In this study, we treated young (2-3 months old) and aged (22-24 months old) C57BL/6 mice with the D2R antagonist haloperidol (HAL) once a day for 14 days to evaluate HAL-induced motor side effects. In addition, we pretreated separate groups of young and aged mice with histone deacetylase (HDAC) inhibitors valproic acid (VPA) or entinostat (MS-275) and then administered HAL. Our results show that the motor side effects of HAL are exaggerated in aged mice as compared to young mice and that HDAC inhibitors are able to reverse the severity of these deficits. HAL-induced motor deficits in aged mice are associated with an age- and drug-dependent decrease in striatal D2R protein levels and functionality. Further, histone acetylation was reduced while histone tri-methylation was increased at specific lysine residues of H3 and H4 within the Drd2 promoter in the striatum of aged mice. HDAC inhibitors, particularly VPA, restored striatal D2R protein levels and functionality and reversed age- and drug-related histone modifications at the Drd2 promoter. These results suggest that epigenetic changes at the striatal Drd2 promoter drive age-related increases in antipsychotic side effect susceptibility, and HDAC inhibitors may be an effective adjunct treatment strategy to reduce side effects in aged populations.
The Unexpected Side-Effects of Dissonance
ERIC Educational Resources Information Center
Bodner, Ehud; Gilboa, Avi; Amir, Dorit
2007-01-01
The effects of dissonant and consonant music on cognitive performance were examined. Situational dissonance and consonance were also tested and determined as the state where one's opinion is contrasted or matched with the majority's opinion, respectively. Subjects performed several cognitive tasks while listening to a melody arranged dissonantly,…
Enzymatic Hydrolysis of Peanut Flour Produces Bioactive Peptides with Reduced Allergenicity
USDA-ARS?s Scientific Manuscript database
Peanut allergy is one of the most severe food allergies due to its life-threatening nature and persistency. Current immunotherapy methods, though effective, are often accompanied by allergic side-effects. Enzymatic hydrolysis of peanut flour has the potential to produce bioactive peptides with impro...
Konstantinidis, I; Tsakiropoulou, E; Vital, I; Triaridis, S; Vital, V; Constantinidis, J
2008-06-01
Obstruction of the osteomeatal complex is the commonest anatomic finding in revision endoscopic sinus surgery. This study assesses the efficacy of topical mitomycin C in the middle meatus, intra- and postoperatively in the prevention of adhesion formation and restenosis of the maxillary sinus antrostomy. At the end of endoscopic surgery for chronic rhinosinusitis and four weeks postoperatively 30 patients received a pledget soaked with 1 ml of mitomycin C (0.5 mg/ml) in the middle meatus for 5 minutes while a pledget soaked in saline was placed in the contralateral side. Patients were assessed at least 6 months postoperatively by a blinded observer for the presence of synechiae and antrostomy stenosis. Medical records were reviewed for episodes of recurrent sinusitis. Adhesions were observed in 8 patients. All adhesions rated as moderate to severe (4 patients) were observed in the control side (p = 0.043). Restenosis was observed in 2 sides treated with mitomycin C and in 9 control sides (p = 0.032). Recurrent symptoms of sinusitis occurred in three patients on the saline side. Mitomycin C is safe and effective in the prevention of severe adhesions and antrostomy stenosis when applied twice, during surgery and the early postoperative period.
Spinella, Giuseppe; Cinti, Filippo; Pietra, Marco; Capitani, Ombretta; Valentini, Simona
2014-12-01
A 6-year-old, large-breed, female dog was evaluated for gastric dilatation (GD). The dog was affected by GD volvulus, which had been surgically treated with gastric derotation and right incisional gastropexy. Recurrence of GD appeared 36 hours after surgery. The dilatation was immediately treated with an orogastric probe but still recurred 4 times. Therefore, a left-side gastropexy by percutaneous endoscopic gastrostomy (PEG) was performed to prevent intermittent GD. After PEG tube placement, the patient recovered rapidly without side effects. Several techniques of gastropexy have been described as a prophylactic method for gastric dilatation volvulus, but to the authors' knowledge, this is the first report of left-sided PEG gastropexy performed in a case of canine GD recurrence after an incisional right gastropexy. Copyright © 2015 Elsevier Inc. All rights reserved.
Kristofikova, Zdenka; Ricny, Jan; Soukup, Ondrej; Korabecny, Jan; Nepovimova, Eugenie; Kuca, Kamil; Ripova, Daniela
2017-01-01
Reversible acetylcholinesterase inhibitors are used in Alzheimer disease therapy. However, tacrine and its derivatives have severe side effects. Derivatives of the tacrine analogue 7-methoxytacrine (MEOTA) are less toxic. We evaluated new derivatives of 7-MEOTA (2 homodimers linked by 2 C4-C5 chains and 5 N-alkylated C4-C8 side chain derivatives) in vitro, using the rat hippocampal choline transporter CHT1. Some derivatives were effective inhibitors of rat acetylcholinesterase and comparable with 7-MEOTA. All derivatives were able to inhibit CHT1, probably via quaternary ammonium, and this interaction could be involved in the enhancement of their detrimental side effects and/or in the attenuation of their promising effects. Under conditions of disrupted lipid rafts, the unfavorable effects of some derivatives were weakened. Only tacrine was probably able to stereospecifically interact with the naturally occurring amyloid-β isoform and to simultaneously stimulate CHT1. Some derivatives, when coincubated with amyloid β, did not influence CHT1. All derivatives also increased the fluidity of the cortical membranes. The N-alkylated derivative of 7-MEOTA bearing from C4 side chains appears to be the most promising compound and should be evaluated in future in vivo research. © 2016 S. Karger AG, Basel.
... amount of potassium-rich foods such as artichokes, avocados, bananas, cantaloupe, grapefruit juice, milk, orange juice, potatoes, ... Patiromer may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away: constipation diarrhea gas stomach discomfort ...
... the orally disintegrating tablets contain aspartame that forms phenylalanine.you should know that mirtazapine may cause angle- ... Mirtazapine may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away: drowsiness dizziness anxiousness confusion ...
... long-acting chewable tablets contain aspartame that forms phenylalanine.you should know that methylphenidate should be used ... Methylphenidate may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away: nervousness difficulty falling asleep ...
... that the chewable tablets contain aspartame that forms phenylalanine.you should know that while you are taking ... Raltegravir may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away: diarrhea gas stomach pain ...
... oral powder is sweetened with aspartame that forms phenylalanine.you should know that while you are taking ... Nelfinavir may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away: diarrhea nausea gas stomach ...
... oral powder is sweetened with aspartame that forms phenylalanine.you should know that while you are taking ... Atazanavir may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away: nausea vomiting stomach pain ...
Side effects from balsalazide can occur. Tell your doctor if any of these symptoms are severe or do not go away: headache abdominal pain upset stomach diarrhea vomiting joint pain difficulty falling or staying asleep tiredness gas runny nose muscle or back ...
Domecq, Juan Pablo; Prutsky, Gabriela; Mullan, Rebecca J.; Sundaresh, Vishnu; Wang, Amy T.; Erwin, Patricia J.; Welt, Corrine; Ehrmann, David; Montori, Victor M.
2013-01-01
Context: Polycystic ovary syndrome (PCOS) is common among women of childbearing age and the available pharmacological therapies have different side-effect profiles. Objective: We summarized the evidence about the side effects of oral contraceptive pills, metformin, and anti-androgens in women with PCOS. Data Source: Sources included Ovid Medline, OVID EMBASE, OVID Cochrane Library, Web of Science, Scopus, PsycInfo, and CINAHL from inception through April 2011. Study Selection: We included comparative observational studies enrolling women with PCOS who received the agents of choice for at least 6 months and reported adverse effects. Data Extraction: Using a standardized, piloted, and Web-based data extraction form and working in duplicate, we abstracted data from each study and performed meta-analysis when possible. Data Synthesis: We found 22 eligible studies of which 20 were randomized. No study reported severe side effects (eg, lactic acidosis, thromboembolic episodes, liver toxicity, cancer incidence, or pregnancy loss). Meta-analysis demonstrated no significant change in weight in oral contraceptive pills or flutamide users. Indirect evidence from populations without PCOS demonstrated no increased risk of lactic acidosis with metformin, only case reports of liver toxicity with flutamide (no comparative evidence), and increased relative risk difference of venous thromboembolism with oral contraceptive pills but very low absolute risk. Evidence on mortality, cardiovascular mortality, and cancer was inconclusive. Conclusions: Drugs commonly used to treat PCOS appear to be associated with very low risk of severe adverse effects although data are extrapolated from other populations. PMID:24092830
Domecq, Juan Pablo; Prutsky, Gabriela; Mullan, Rebecca J; Sundaresh, Vishnu; Wang, Amy T; Erwin, Patricia J; Welt, Corrine; Ehrmann, David; Montori, Victor M; Murad, Mohammad Hassan
2013-12-01
Polycystic ovary syndrome (PCOS) is common among women of childbearing age and the available pharmacological therapies have different side-effect profiles. We summarized the evidence about the side effects of oral contraceptive pills, metformin, and anti-androgens in women with PCOS. Sources included Ovid Medline, OVID EMBASE, OVID Cochrane Library, Web of Science, Scopus, PsycInfo, and CINAHL from inception through April 2011. We included comparative observational studies enrolling women with PCOS who received the agents of choice for at least 6 months and reported adverse effects. Using a standardized, piloted, and Web-based data extraction form and working in duplicate, we abstracted data from each study and performed meta-analysis when possible. We found 22 eligible studies of which 20 were randomized. No study reported severe side effects (eg, lactic acidosis, thromboembolic episodes, liver toxicity, cancer incidence, or pregnancy loss). Meta-analysis demonstrated no significant change in weight in oral contraceptive pills or flutamide users. Indirect evidence from populations without PCOS demonstrated no increased risk of lactic acidosis with metformin, only case reports of liver toxicity with flutamide (no comparative evidence), and increased relative risk difference of venous thromboembolism with oral contraceptive pills but very low absolute risk. Evidence on mortality, cardiovascular mortality, and cancer was inconclusive. Drugs commonly used to treat PCOS appear to be associated with very low risk of severe adverse effects although data are extrapolated from other populations.
Psychological Consequences of Abortion among the Post Abortion Care Seeking Women in Tehran
Pourreza, Abolghasem
2011-01-01
Objective Abortion either medical or criminal has distinctive physical, social, and psychological side effects. Detecting types and frequent psychological side effects of abortion among post abortion care seeking women in Tehran was the main objective of the present study. Method 278 women of reproductive age (15-49) interviewed as study population. Response rate was 93/8. Data collected through a questionnaire with 2 parts meeting broad socio-economic characteristics of the respondents and health- related abortion consequences. Tehran hospitals were the site of study. Results The results revealed that at least one-third of the respondents have experienced psychological side effects. Depression, worrying about not being able to conceive again and abnormal eating behaviors were reported as dominant psychological consequences of abortion among the respondents. Decreased self-esteem, nightmare, guilt, and regret with 43.7%, 39.5%, 37.5%, and 33.3% prevalence rates have been placed in the lower status, respectively. Conclusion Psychological consequences of abortion have considerably been neglected. Several barriers made findings limited. Different types of psychological side effects, however, experienced by the study population require more intensive attention because of chronic characteristic of psychological disorders, and women's health impact on family and population health. PMID:22952518
Intranasal ipratropium bromide for the common cold.
Albalawi, Zaina H; Othman, Sahar S; Alfaleh, Khalid
2011-07-06
The common cold is one of the most common illnesses in humans and constitutes an economic burden both in terms of productivity and expenditure for treatment. There is no proven cure for the common cold and symptomatic relief is the mainstay of treatment. The use of intranasal ipratropium bromide (IB) has been addressed in several studies and might prove an effective treatment for the common cold. To determine the effect of IB versus placebo or no treatment on severity of rhinorrhoea and nasal congestion in children and adults with the common cold. Subjective overall improvement was another primary outcome and side effects were reported as a secondary outcome. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2011, Issue 1) which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1950 to January week 4, 2011), MEDLINE in-process and other non-indexed citations (February 2011), EMBASE (1974 to February 2011), AMED (1985 to February 2011), Biosis (1974 to February 2011) and LILACS (1985 to February 2011). Randomised controlled trials (RCTs) comparing IB to placebo or no treatment in children and adults with the common cold. Two review authors independently extracted data and assessed trial quality. We used a standardised form to extract relevant data and we contacted trial authors for additional information. Seven trials with a total of 2144 participants were included. Four studies (1959 participants) addressed subjective change in severity of rhinorrhoea. All studies were consistent in reporting statistically significant changes in favour of IB. Nasal congestion was reported in four studies and was found to have no significant change between the two groups. Two studies found a positive response in the IB group for the global assessment of overall improvement. Side effects were more frequent in the IB group, odds ratio (OR) 2.09 (95% confidence interval (CI) 1.40 to 3.11). Commonly encountered side effects included nasal dryness, blood tinged mucus and epistaxis. For people with the common cold, the existing evidence, which has some limitations, suggests that IB is likely to be effective in ameliorating rhinorrhoea. IB had no effect on nasal congestion and its use was associated with more side effects compared to placebo or no treatment although these appeared to be well-tolerated and self-limiting. There is a need for larger, high-quality trials to determine the effectiveness of IB in relieving common cold symptoms.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kapoor, A.; Gordon, S.; Goldston, W.
2013-07-08
This paper describes the operating experience and lessons learned at U.S. Department of Energy (DOE) sites as a result of an evaluation of potential trailer contamination and soft-sided packaging integrity issues related to the disposal of low-level and mixed low-level (LLW/MLLW) radioactive waste shipments. Nearly 4.3 million cubic meters of LLW/MLLW will have been generated and disposed of during fiscal year (FY) 2010 to FY 2015—either at commercial disposal sites or disposal sites owned by DOE. The LLW/MLLW is packaged in several different types of regulatory compliant packaging and transported via highway or rail to disposal sites safely and efficientlymore » in accordance with federal, state, and local regulations and DOE orders. In 1999, DOE supported the development of LLW containers that are more volumetrically efficient, more cost effective, and easier to use as compared to metal or wooden containers that existed at that time. The DOE Idaho National Engineering and Environmental Laboratory (INEEL), working in conjunction with the plastic industry, tested several types of soft-sided waste packaging systems that meet U.S. Department of Transportation requirements for transport of low specific activity and surface contaminated objects. Since then, soft-sided packaging of various capacities have been used successfully by the decontamination and decommissioning (D&D) projects to package, transport, and dispose D&D wastes throughout the DOE complex. The joint team of experts assembled by the Energy Facility Contractors Group from DOE waste generating sites, DOE and commercial waste disposal facilities, and soft-sided packaging suppliers conducted the review of soft-sided packaging operations and transportation of these packages to the disposal sites. As a result of this evaluation, the team developed several recommendations and best practices to prevent or minimize the recurrences of equipment contamination issues and proper use of soft-sided packaging for transport and disposal of waste.« less
Wu, Yan; Sun, Nan; Xu, Yue; Liu, Huixian; Zhong, Shaomin; Chen, Liyang; Li, Dong
2016-04-01
Hyaluronic acid fillers are used to improve the appearance of nasolabial folds (NLF). This study aimed to compare the efficacy, safety, and durability of a new hyaluronic acid gel (BioHyalux) versus Restylane for the correction of NLF. This was a multicenter, double-blinded, randomized, controlled, non-inferiority clinical trial involving 88 subjects with moderate to severe NLF. Subjects were randomized to BioHyalux and Restylane on either sides of the NLF. NLF was assessed before and right after injection, and at 1 week, 1, 3, and 6 months. Patients were followed up for 13-15 months to evaluate the durability and long-term safety. A clinically meaningful response was predefined as at least one-point improvement on the Wrinkle Severity Rating Scale, which is a five-point scale. At 6 months, the response rate of BioHyalux was not inferior to that of Restylane (P < 0.05). At the 13-15 months follow-up, the response rate by investigators was 58.0 % on the BioHyalux side versus 63.8 % on the Restylane side. The response rate by subjects showed similar results, which was 56.5 % on the BioHyalux side versus 60.9 % on the Restylane side at 13-15 months. The subjects' Global Aesthetic Improvement Scale (GAIS) showed that most subjects felt improvements on both sides of NLF (P > 0.05) at all time points. At 6 months, 100 % reported improvements on both side; at 13-15 months, 60 % of subjects reported improvements with BioHyalux versus 64 % with Restylane. Adverse events were transient and predominantly mild or moderate in severity including injection site swelling, pain, itching, bruising, and tenderness. BioHyalux had reliable safety and tolerance, and could be an effective injectable filler for correcting NLF.
Quintini, Cristiano; Miller, Charles M; Hashimoto, Koji; Philip, Ding; Uso, Teresa Diago; Aucejo, Federico; Kelly, Dympna; Winans, Charles; Eghtesad, Bijan; Vogt, David; Fung, John
2009-01-01
Venous outflow obstruction is a rare but potentially lethal complication after orthotopic liver transplantation (OLT) with the "piggyback" technique. Therapeutic options include angioplasty with or without stent placement, surgical reconstruction of the venous anastomosis, and retransplantation. Surgical options are technically very challenging and the outcomes discouraging. We describe here two cases of venous outflow obstruction in recipients of piggyback liver grafts, one involving both the vena cava and hepatic veins and the other affecting only hepatic vein outflow. Both patients were treated successfully with side-to-side cavo-cavostomy using an endovascular (endo-GIA) stapler. This novel technique is fast and effective in resolving the outflow obstruction. Copyright 2008 AASLD.
[Functional selectivity of opioid receptors ligands].
Audet, Nicolas; Archer-Lahlou, Elodie; Richard-Lalonde, Mélissa; Piñeyro-Filpo, Graciela
2010-01-01
Opiates are the most effective analgesics available for the treatment of severe pain. However, their clinical use is restricted by unwanted side effects such as tolerance, physical dependence and respiratory depression. The strategy to develop new opiates with reduced side effects has mainly focused on the study and production of ligands that specifically bind to different opiate receptors subtypes. However, this strategy has not allowed the production of novel therapeutic ligands with a better side effects profile. Thus, other research strategies need to be explored. One which is receiving increasing attention is the possibility of exploiting ligand ability to stabilize different receptor conformations with distinct signalling profiles. This newly described property, termed functional selectivity, provides a potential means of directing the stimulus generated by an activated receptor towards a specific cellular response. Here we summarize evidence supporting the existence of ligand-specific active conformations for two opioid receptors subtypes (delta and mu), and analyze how functional selectivity may contribute in the production of longer lasting, better tolerated opiate analgesics. double dagger.
Schmidt, Lejla Sjanic; Petersen, Jeff Zarp; Vinberg, Maj; Hageman, Ida; Olsen, Niels Vidiendal; Kessing, Lars Vedel; Jørgensen, Martin Balslev; Miskowiak, Kamilla Woznica
2018-04-19
Electroconvulsive therapy (ECT) is the most effective treatment for severe depression, but its use is impeded by its cognitive side effects. Novel treatments that can counteract these side effects may therefore improve current treatment strategies for depression. The present randomized trial investigates (1) whether short-term add-on treatment with erythropoietin (EPO) can reduce the cognitive side -effects of ECT and (2) whether such effects are long-lasting. Further, structural and functional magnetic resonance imaging (MRI) will be used to explore the neural underpinnings of such beneficial effects of EPO. Finally, the trial examines whether potential protective effects of EPO on cognition are accompanied by changes in markers of oxidative stress, inflammation, and neuroplasticity. The trial has a double-blind, randomized, placebo-controlled, parallel group design. Patients with unipolar or bipolar disorder with current moderate to severe depression referred to ECT (N = 52) are randomized to receive four high-dose infusions of EPO (40,000 IU/ml) or placebo (saline). The first EPO/saline infusion is administered within 24 h before the first ECT. The following three infusions are administered at weekly intervals immediately after ECT sessions 1, 4, and 7. Cognition assessments are conducted at baseline, after the final EPO/saline infusion (3 days after eight ECT sessions), and at a 3 months follow-up after ECT treatment completion. The neuronal substrates for potential cognitive benefits of EPO are investigated with structural and functional MRI after the final EPO/saline infusion. The primary outcome is change from baseline to after EPO treatment (3 days after eight ECT sessions) in a cognitive composite score spanning attention, psychomotor speed, and executive functions. With a sample size of N = 52 (n = 26 per group), we have ≥ 80% power to detect a clinically relevant between-group difference in the primary outcome measure at an alpha level of 5% (two-sided test). Behavioral, mood, and blood-biomarker data will be analyzed using repeated measures analysis of covariance. Functional MRI data will be preprocessed and analyzed using the FMRIB Software Library. If EPO is found to reduce the cognitive side effects of ECT, this could have important implications for future treatment strategies for depression and for the scientific understanding of the neurobiological etiology of cognitive dysfunction in patients treated with ECT. ClinicalTrials.gov, NCT03339596 . Registered on 10 November 2017.
A Survey of Caffeine Use and Associated Side Effects in a College Population.
ERIC Educational Resources Information Center
Johnson-Greene, Douglas; And Others
1988-01-01
Surveyed 270 college students concerning their caffeine consumption. Results suggest there is identifiable group using excessive amounts of caffeine. Identified several deleterious effects possibly related to caffeine use. Approximately 75 percent of caffeine users surveyed rarely sought information on caffeine content of products or avoided…
The Effects of Market Structure on Television News Pricing.
ERIC Educational Resources Information Center
Wirth, Michael O.; Wollert, James A.
Multiple regression techniques were used to examine the business side of local television news operations for November 1978. Research questions examined the effect of several variables on local television news prices (advertising rates), including type of ownership, network affiliation/signal type, market size, cable network penetration, market…
Basic pharmacology of NMDA receptors.
Gonda, Xenia
2012-01-01
NMDA receptors are ionotropic receptors mediating glutamatergic neurotransmission and play a role in several basic functions in the central nervous system, from regulating neurodevelopment and synaptic plasticity, learning and memory formation, cognitive processes, rhythm generation necessary for locomotor activity and breathing, and excitotoxicity. Due to their complex involvement in the above processes, NMDA receptors have been established to play a role in the etiopathology of several neuropsychiatric disorders such as ischaemia and traumatic brain injury, neurodegenerative disorders, pain syndromes, addiction, affective disorders and such neurodevelopmental disorders as autism or schizophrenia. NMDA receptors contain multiple types of subunits with distinct functional and pharmacological properties making the picture more complex. These receptors also offer multiple binding sites to be targeted with pharmacons, however, early broad-spectrum NMDA receptor antagonists had limited clinical use due to their intolerable adverse effect profile. The discovery of several types of subunit selective NMDA receptor antagonists may offer valuable therapeutic possibilities for several disorders, with improved clinical efficacy and decreased side effects. However, in spite of our increasing knowledge concerning the involvement of NMDA receptors in pathological processes, molecules with a selective action, tolerable side effect profile and good clinical efficacy are still only in clinical development in the majority of cases. Nevertheless, NMDA receptors offer a novel opportunity in the treatment of various neuropsychiatric conditions.
Sruamsiri, Kamphee; Chenthanakij, Boriboon; Wittayachamnankul, Borwon
2014-09-01
Management of patients with severe hypertension without progressive target organ damage remains controversial. Some guidelines mentioned oral anti-hypertensive medication as a treatment to reduce blood pressure in the emergency department, while others recommended against such treatment. To review the management ofpatients with severe hypertension without progressive target organ damage in the emergency department, Maharaj Nakorn Chiang Mai hospital. In a retrospective descriptive analysis study, medical records ofadult patients diagnosed with severe hypertension without progressive target organ damage between January 2011 and December 2012 were reviewed. Patient demographics, data on management including investigation sent and treatment given were collected. Statistical analysis was done by using descriptive statistics and Kruskal-Wallis one-way analysis of variance test. One hundred fifty one medical records were reviewed. Four oral anti-hypertensive medication were used to reduce blood pressure, Amlodipine, Captopril, Hydralazine, and Nifedipine. There were no significant diference between each medication in terms of their effect on bloodpressure reduction (p = 0.513). No side effect or other complications from the use of oral anti-hypertensive medication were recorded The choice of medication used for the treatment of hypertensive urgency ranged from Amlodipine, Captopril, Hydralazine, and Nifedipine, which varied in dosage. However their efficacies were the same when compared with each other and none produced any notable side effects.
Ertzgaard, Per; Campo, Claudia; Calabrese, Alessandra
2017-03-06
Oral baclofen has long been a mainstay in the management of spasticity. This review looks at the clinical evidence for the efficacy and safety of oral baclofen in patients with spasticity of any origin or severity, to determine whether there is a rationale for the use of intrathecal baclofen. Results suggest that oral baclofen may be effective in many patients with spasticity, regardless of the underlying disease or severity, and that it is at least comparable with other antispasmodic agents. However, adverse effects, such as muscle weakness, nausea, somnolence and paraesthesia, are common with oral baclofen, affecting between 25% and 75% of patients, and limiting its usefulness. Intrathecal baclofen may be an effective alternative as the drug is delivered directly into the cerebrospinal fluid, thus bypassing the blood-brain barrier and thereby optimizing the efficacy of baclofen while minimizing drug-related side-effects. Intrathecal baclofen is a viable option in patients who experience intolerable side-effects or who fail to respond to the maximum recommended dose of oral baclofen.
Gaida, Razia; Truter, Ilse; Grobler, Christoffel
2016-01-01
It is acknowledged that almost half of patients initiated on efavirenz will experience at least one neuropsychiatric side effect. The aim was to determine the incidence and severity of neuropsychiatric side effects associated with efavirenz use in five public-sector primary healthcare clinics in the Eastern Cape. The study was a prospective drug utilisation study. A total of 126 medical records were reviewed to obtain the required information. After baseline assessment, follow-up reviews were conducted at 4 weeks, 12 weeks and 24 weeks from 2014 to 2015. The participant group was 74.60% female ( n = 94), and the average age was 37.57±10.60 years. There were no neuropsychiatric side effects recorded for any patient. After the full follow-up period, there were a total of 49 non-adherent patients and one patient had demised. A non-adherent patient was defined as a patient who did not return to the clinic for follow-up assessment and medication refills 30 days or more after the appointed date. Some patients ( n = 11) had sent a third party to the clinic to collect their antiretroviral therapy (ART). The clinic pharmacy would at times dispense a two-month supply of medication resulting in the patient presenting only every two months. Further pharmacovigilance studies need to be conducted to determine the true incidence of these side effects. Healthcare staff must be encouraged to keep complete records to ensure meaningful patient assessments. Patients being initiated on ART need to personally attend the clinic monthly for at least the first 6 months of treatment. Clinic staff should receive regular training concerning ART, including changes made to guidelines as well as reminders of side effects experienced.
Veerman, S R T; Schulte, P F J; Smith, J D; de Haan, L
2016-07-01
Dysfunction of neuroplasticity due to N-methyl-d-aspartate (NMDA) receptor hypofunction may be a causal factor for memory and executive dysfunctioning in schizophrenia. Deregulation of NMDA transmission in the prefrontal cortex may also explain negative and positive symptoms. Clozapine augmentation with memantine targets altered NMDA receptor-mediated neurotransmission in schizophrenia and showed substantial beneficial effects on several symptom domains in a small proof-of-concept study. We evaluate effects of memantine add-on treatment to clozapine for memory and executive function, and negative and positive symptoms in schizophrenia. Clozapine-treated patients with refractory schizophrenia were randomly assigned to 12 weeks of double-blind adjunctive treatment with memantine (n = 26) or placebo (n = 26). Crossover occurred after a 2-week placebo wash-out period. Primary endpoints were change from baseline to 12 weeks treatment and 14 weeks to 26 weeks treatment on memory and executive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression Severity Scale (CGI-S). Side effects were assessed using the Liverpool University Neuroleptic Side-Effect Rating Scale. When compared with placebo, memantine improved a composite memory score comprising verbal recognition memory and paired associates learning task scores on the CANTAB (effect size = 0.30) and PANSS negative subscale score (effect size = 0.29). Side effects were mild and transient. In patients with clozapine-treated refractory schizophrenia, memantine addition significantly improved verbal and visual memory and negative symptoms without serious adverse effects. These results justify further investigations on long-term memantine augmentation to clozapine in treatment-resistant schizophrenia.
Systemic treatment for alopecia areata.
Otberg, Nina
2011-01-01
Of the world population, 1.7% is suffering from alopecia areata at some point in their lives. The exact etiology of this disease is still unknown, and the course of the disease is unpredictable. Effective treatments, especially for severe multifocal alopecia areata, alopecia areata totalis, and alopecia areata universalis, are lacking. The present article will discuss side effects and relapse rates of different systemic agents for treatment of severe and rapid progressive alopecia areata. © 2011 Wiley Periodicals, Inc.
Hu, Yuanyuan; Berdunov, Nikolai; Di, Chong-an; Nandhakumar, Iris; Zhang, Fengjiao; Gao, Xike; Zhu, Daoben; Sirringhaus, Henning
2014-07-22
We have investigated the influence of the symmetry of the side chain substituents in high-mobility, solution processable n-type molecular semiconductors on the performance of organic field-effect transistors (OFETs). We compare two molecules with the same conjugated core, but either symmetric or asymmetric side chain substituents, and investigate the transport properties and thin film growth mode using scanning Kelvin probe microscopy (SKPM) and atomic force microscopy (AFM). We find that asymmetric side chains can induce a favorable two-dimensional growth mode with a bilayer structure, which enables ultrathin films with a single bilayer to exhibit excellent transport properties, while the symmetric molecules adopt an unfavorable three-dimensional growth mode in which transport in the first monolayer at the interface is severely hindered by high-resistance grain boundaries.
[Local cyclosporin A therapy of nummuli after epidemic keratoconjunctivitis--case report].
Reinhard, T; Sundmacher, R
1997-03-01
Steroid therapy for persistent or recurrent nummular adenoviral keratoconjunctivitis (AK) has little benefit because of the frequent recurrences, and mostly "offers" only serious steroid side effects. Since January 1995, we have treated different patients with nummuli after AK with topical Ciclosporin A (CSA) in an attempt to achieve at least the same symptomatic effect as with steroids, however, without side effects. Here, we report about our experiences in a very severe case with longterm treatment. The patient was sent to our clinic 4 months after AK with confluent nummuli and Descemet folds, more severe in the right than in the left eye. Best corrected visual acuity was 0.05 in the right and 0.5 in the left eye. Topical CSA 2% 4 times daily was first administered only in the right eye. When after 6 weeks a reduction of nummuli was noted in the right eye, the left eye, which had not improved, was started on the same regime. Therapy was tapered and finally stopped after 12 months in the right and 10 months in the left eye, when only minor changes were left in the corneae. A prompt recurrence of nummuli in both eyes within 4 weeks forced us to resume CSA therapy. At present, both corneae are clear with full vision, and this result is stable with 1 drop of CSA daily. No side effects of CSA therapy have been noted. The disappearance of nummuli with topical CSA and even more the reappearance of nummuli after cessation of CSA therapy show that topical CSA is about as effective as topical steroids in the symptomatic treatment of non-scarred nummuli after KE without the serious steroid side effects. Topical CSA treatment of nummuli after KE is, therefore, a very recommendable alternative for the potentially dangerous steroid therapy. Generally valid data on risk of recurrences, dosage and general effectiveness could only be learned from prospective studies with large numbers of AK patients, which, however, are not available outside epidemics.
Anti-interleukin-6 receptor antibody (tocilizumab) treatment of multicentric Castleman's disease.
Matsuyama, Masashi; Suzuki, Takeshi; Tsuboi, Hiroto; Ito, Satoshi; Mamura, Mizuko; Goto, Daisuke; Matsumoto, Isao; Tsutsumi, Akito; Sumida, Takayuki
2007-01-01
We report three cases of multicentric Castleman's disease (MCD) successfully treated with anti-interleukin-6 receptor antibody (tocilizumab). Tocilizumab was administered intravenously at a dose of 8 mg/kg every 2 weeks. In each case, tocilizumab alleviated symptoms, including generalized fatigue, pyrexia, and alleviated biochemical abnormalities, including anemia, hypoalbuminemia, hypergammaglobulinemia, and increased C-reactive protein (CRP). Side effects included hypercholesterolemia, acute pyelonephritis, mild inflammation of the parotid glands, and upper respiratory system inflammation. Other severe side effects were not observed. These results indicate that tocilizumab is effective for the treatment of MCD. This is the first report on tocilizumab efficacy for Castleman's disease after approval for use for Castleman's disease.
Trazodone may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away: headache nausea vomiting bad taste in mouth diarrhea constipation changes in appetite or weight weakness or tiredness nervousness dizziness or lightheadedness feeling unsteady when ...
... mistakenly attacks part of the nervous system) Side effects of some medicines Severe head trauma and other brain injuries Subarachnoid hemorrhage (a form of brain bleeding) Use of illegal stimulant drugs such as cocaine and amphetamines Symptoms Symptoms can include any of ...
Patient-Derived Antibody Targets Tumor Cells
An NCI Cancer Currents blog on an antibody derived from patients that killed tumor cells in cell lines of several cancer types and slowed tumor growth in mouse models of brain and lung cancer without evidence of side effects.
Deep brain stimulation to reduce sexual drive.
Fuss, Johannes; Auer, Matthias K; Biedermann, Sarah V; Briken, Peer; Hacke, Werner
2015-11-01
To date there are few treatment options to reduce high sexual drive or sexual urges in paraphilic patients with a risk for sexual offending. Pharmacological therapy aims to reduce sexual drive by lowering testosterone at the cost of severe side effects. We hypothesize that high sexual drive could also be reduced with deep brain stimulation (DBS) of circuits that generate sexual drive. This approach would help to avoid systemic side effects of antiandrogenic drug therapies. So far the best investigated target to reduce sexual drive is the ventromedial hypothalamus, which was lesioned unilaterally and bilaterally by stereotaxic interventions in paraphilic patients in the 1970s. Here, we discuss DBS as a treatment strategy in patients with severe paraphilic disorders with a serious risk of sexual offending. There are profound ethical and practical issues associated with DBS treatment of paraphilic patients that must be solved before considering such a treatment approach.
Bamoulid, Jamal; Staeck, Oliver; Crépin, Thomas; Halleck, Fabian; Saas, Philippe; Brakemeier, Susanne; Ducloux, Didier; Budde, Klemens
2017-10-01
Antithymocyte globulins (ATGs) are part of the immunosuppression arsenal currently used by clinicians to prevent or treat acute rejection in solid organ transplantation. ATG is a mixture of non-specific anti-lymphocyte immunoglobulins targeting not only T cell subsets but also several other immune and non-immune cells, rendering its precise immunoglobulin composition difficult to appreciate or to compare from one preparation to another. Furthermore, several mechanisms of action have been described. Taken together, this probably explains the efficacy and the side effects associated with this drug. Recent data suggest a long-term negative impact on allograft and patient outcomes, pointing out the need to better characterize the potential toxicity and the benefit-risk balance associated to this immunosuppressive therapy within large clinical trials. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
HPV Vaccine Awareness, Barriers, Intentions, and Uptake in Latina Women.
Lechuga, Julia; Vera-Cala, Lina; Martinez-Donate, Ana
2016-02-01
Latina women are at heightened risk of cervical cancer incidence and mortality. The human papillomavirus (HPV) is the principal cause of the majority of cervical cancer cases. A vaccine that protects against HPV was licensed in 2006. Eight years post-licensure, mixed research findings exist regarding the factors that predict vaccine uptake in Latinas. We conducted a population-based phone survey with a random sample of 296 Latinas living in a Midwestern U.S. City. Intention to vaccinate was significantly associated with health care provider recommendations, worry about side effects, knowing other parents have vaccinated, perceived severity of HPV, and worry that daughter may become sexually active following vaccination. Worry that daughter may become sexually active was the only factor related to vaccine uptake. Findings suggest that training providers to discuss the low risk of severe side effects, consequences of persistent HPV, and sexuality related concerns with Latino women may encourage vaccination.
HPV Vaccine Awareness, Barriers, Intentions, and Uptake in Latina Women
Lechuga, Julia; Vera-Cala, Lina; Martinez-Donate, Ana
2014-01-01
Latina women are at heightened risk of cervical cancer incidence and mortality. The Human Papillomavirus (HPV) is the principal cause of the majority of cervical cancer cases. A vaccine that protects against HPV was licensed in 2006. Eight years post-licensure, mixed research findings exist regarding the factors that predict vaccine uptake in Latinas. We conducted a population-based phone survey with a random sample of 296 Latinas living in a Midwestern U.S. city. Intention to vaccinate was significantly associated with health care provider recommendations, worry about side effects, knowing other parents have vaccinated, perceived severity of HPV, and worry that daughter may become sexually active following vaccination. Worry that daughter may become sexually active was the only factor related to vaccine uptake. Findings suggest that training providers to discuss the low risk of severe side effects, consequences of persistent HPV, and sexuality related concerns with Latino women may encourage vaccination. PMID:25432149
Corticosteroid treatment in Sydenham's chorea.
Fusco, C; Spagnoli, C
2018-03-01
Sydenham's chorea (SC) is an immune-mediated hyperkinetic movement disorder, developing after group A Beta-hemolytic streptococcal (GABHS) infection. Aside from conventional symptomatic treatment (carbamazepine, valproate, neuroleptics), the use of steroids has also been advocated, mainly in severe, drug-resistant cases or if clinically disabling side effects develop with first line therapies. Based on the description of 5 cases followed in the Child Neurology Unit of Santa Maria Nuova Hospital in Reggio Emilia and on the available medical literature on this topic, we propose considering the use of corticosteroids therapy in children with SC, with the administration of IV methyl-prednisolone followed by oral deflazacort in severe cases and of oral deflazacort alone in mild and moderate degrees of involvement. In our experience this therapy is effective both in the short and long-term period, in different clinical presentations (chorea paralytica, distal chorea, hemichorea, "classic" chorea, association with mood disorder or dyspraxia) and very well tolerated (no significant side effects were recorded). Copyright © 2017. Published by Elsevier Ltd.
Lead Phytochemicals for Anticancer Drug Development
Singh, Sukhdev; Sharma, Bhupender; Kanwar, Shamsher S.; Kumar, Ashok
2016-01-01
Cancer is a serious concern at present. A large number of patients die each year due to cancer illnesses in spite of several interventions available. Development of an effective and side effects lacking anticancer therapy is the trending research direction in healthcare pharmacy. Chemical entities present in plants proved to be very potential in this regard. Bioactive phytochemicals are preferential as they pretend differentially on cancer cells only, without altering normal cells. Carcinogenesis is a complex process and includes multiple signaling events. Phytochemicals are pleiotropic in their function and target these events in multiple manners; hence they are most suitable candidate for anticancer drug development. Efforts are in progress to develop lead candidates from phytochemicals those can block or retard the growth of cancer without any side effect. Several phytochemicals manifest anticancer function in vitro and in vivo. This article deals with these lead phytomolecules with their action mechanisms on nuclear and cellular factors involved in carcinogenesis. Additionally, druggability parameters and clinical development of anticancer phytomolecules have also been discussed. PMID:27877185
Novel Opioid Analgesics and Side Effects.
Del Vecchio, Giovanna; Spahn, Viola; Stein, Christoph
2017-08-16
Conventional opioids mediate analgesia as well as severe adverse effects via G-protein coupled opioid receptors (OR) in both inflamed (peripheral injured tissue) and healthy (brain, intestinal wall) environments. To exclude side effects, OR activation can be selectively achieved in damaged tissue by lowering the pK a of an opioid ligand to the acidic pH of inflammation. As a result, protonation of the ligand and consequent OR binding and activation of G-proteins is pH- and injury-specific. A novel compound (NFEPP) demonstrates the feasibility of this approach and displays blockade of pain transmission only at the peripheral site of injury, but with lack of central and gastrointestinal adverse effects. These findings suggest disease-specific receptor activation as a new strategy in drug design.
Gassia, V
2009-05-01
Botulinum toxin serotype A injections used in treating dynamic wrinkles is one of the least invasive cosmetic procedures. High patient satisfaction and low onset of always moderate side effects contribute to the growing popularity of botulinum toxin injections in cosmetic treatment over the past few years. Years of experience and use, in therapeutics [1,2] and esthetics (20 years) have proven the efficacy and the safety of this wrinkle treatment. Today, no severe or long-term side effects have been reported in esthetics. This article discusses only the most frequent locoregional effects. They are rare, moderate, transitory, and totally reversible. Properly informing and selecting patients will contribute to successfully preventing and managing these effects.
The role of nitrates, beta blockers, and calcium antagonists in stable angina pectoris.
Chan, P K; Heo, J Y; Garibian, G; Askenase, A; Segal, B L; Iskandrian, A S
1988-09-01
Numerous controlled studies have shown that nitrates, beta blockers, and calcium antagonists are effective in the treatment of stable angina pectoris. The pharmacokinetics, pharmacodynamics, and hemodynamic effects of these agents are different, and thus combination therapy offers additive improvement and also counterbalancing of the undesirable side effects of each drug. The choice of therapy depends on the severity of symptoms, associated diseases, compliance, side effects, and status of left ventricular function. The main mechanism of improvement is a decrease in myocardial oxygen consumption, though an increase in coronary blood flow is another potential reason for the use of calcium blockers. This review considers the properties of these drugs, their mechanism of action, and the results of randomized studies.
Sabo, C E; Michael, S R
1996-08-01
The purpose of this pilot study was to evaluate the benefits of a message from a patient's physician audiotaped over music on reducing anxiety and side effects of patients receiving chemotherapy. A convenience sample of 97 adult patients receiving chemotherapy for the first time was assigned to either an experimental or control group. Before beginning the first chemotherapy treatment, all subjects completed a demographic questionnaire and the Spielberger State Anxiety Inventory (SSAI). Participants in the experimental group (n = 47) received taped music and a message from their physicians during the next four chemotherapy treatments. Participants in the control group (n = 50) received no intervention from the researchers and underwent their next four chemotherapy treatments as prescribed. After the fourth chemotherapy treatment, the SSAI and a side-effects self-assessment evaluation were completed by all subjects. A paired one-tailed t test found a significant difference between pre- and postintervention scores on the state anxiety scale (p < 0.001). In addition, anxiety remained the same over time in the control group. There was no significant difference in the severity of side effects experienced between control and experimental groups. These preliminary findings indicate that a simple and cost-effective intervention can decrease a patient's anxiety when receiving chemotherapy.
Ahmad, Hesham M
2015-01-01
Acne vulgaris is a debilitating disorder and requires proper treatment. This work evaluates the clinical efficacy, side effects, and laboratory changes of serum lipids and liver function during oral isotretinoin therapy for acne vulgaris, comparing single versus twice daily dose. Fifty-eight patients with acne vulgaris were included and randomized into group I (26 patients), who received once daily dose, and group II (32 patients), who received twice daily dose of oral isotretinoin. Global acne scoring system was used to evaluate acne severity and post-treatment improvement. Both regimens resulted in highly significant clinical improvement of acne with no significant difference. However, side effects were significantly more common among patients of group I. Both regimens caused mild rise of serum cholesterol, alanine transaminase (ALT), and aspartate aminotransferase (AST) with more prominent rise of triglycerides especially with twice daily dose. Oral isotretinoin is a very effective treatment for acne vulgaris with no statistically significant difference in clinical efficacy between once and twice daily doses. However, dividing dose to twice per day might cause fewer incidence of side effects without reducing clinical efficacy. The drug causes mild clinically insignificant rise of serum cholesterol, triglycerides, AST, and ALT. © 2015 Wiley Periodicals, Inc.
Dybedal, Gro Strømnes; Tanum, Lars; Sundet, Kjetil; Bjølseth, Tor Magne
2015-01-01
Electroconvulsive therapy (ECT) is an effective biological treatment option for severely depressed elderly patients; however, it can cause cognitive side effects, including anterograde and retrograde amnesia. Elderly patients with "cognitive impairment no dementia" (CIND) are reported as being more vulnerable to the cognitive side effects of ECT compared with patients with "no cognitive impairment" (NCI). The few studies that have reached this conclusion can be criticized for using insensitive outcome measures. The present study investigated cognitive side effects using standard neuropsychological tests before and after twice-weekly ECT. Patients were assessed at baseline (T1) and within one week after a course of ECT (consisting of a mean of 10 treatments) (T2), and were followed up for three months after T2 (T3). The sample included 54 patients with NCI (n = 36) or CIND (n = 18). For a control group, we recruited 17 healthy elderly persons. Tests of anterograde memory, information-processing speed, executive function, and retrograde memory were administered. We computed reliable change indices using simple regression methods. Short-term side effects were detected at T2 in a large minority of patients, with no significant differences between NCI and CIND patients. Considerable improvement in global cognitive function from T1 to T3 was observed in 44% of the CIND patients. At the group level, information-processing speed improved significantly in CIND vs. NCI patients. CIND patients were not more vulnerable to amnesia than were NCI patients. Long-term cognitive side effects of ECT were not detected.
Paclitaxel Nano-Delivery Systems: A Comprehensive Review
Ma, Ping; Mumper, Russell J.
2013-01-01
Paclitaxel is one of the most effective chemotherapeutic drugs ever developed and is active against a broad range of cancers, such as lung, ovarian, and breast cancers. Due to its low water solubility, paclitaxel is formulated in a mixture of Cremophor EL and dehydrated ethanol (50:50, v/v) a combination known as Taxol. However, Taxol has some severe side effects related to Cremophor EL and ethanol. Therefore, there is an urgent need for the development of alternative Taxol formulations. The encapsulation of paclitaxel in biodegradable and non-toxic nano-delivery systems can protect the drug from degradation during circulation and in-turn protect the body from toxic side effects of the drug thereby lowering its toxicity, increasing its circulation half-life, exhibiting improved pharmacokinetic profiles, and demonstrating better patient compliance. Also, nanoparticle-based delivery systems can take advantage of the enhanced permeability and retention (EPR) effect for passive tumor targeting, therefore, they are promising carriers to improve the therapeutic index and decrease the side effects of paclitaxel. To date, paclitaxel albumin-bound nanoparticles (Abraxane®) have been approved by the FDA for the treatment of metastatic breast cancer and non-small cell lung cancer (NSCLC). In addition, there are a number of novel paclitaxel nanoparticle formulations in clinical trials. In this comprehensive review, several types of developed paclitaxel nano-delivery systems will be covered and discussed, such as polymeric nanoparticles, lipid-based formulations, polymer conjugates, inorganic nanoparticles, carbon nanotubes, nanocrystals, and cyclodextrin nanoparticles. PMID:24163786
Treatment of testicular hydrocele with tetracycline sclerotherapy.
Ozkan, S; Bircan, K; Ozen, H
1990-01-01
Fifteen patients with primary hydrocele of the testis were treated by aspiration and injection of tetracycline. Only 5 patients (33.3%) were cured by a single injection of tetracycline. Furthermore, 46.6% of our patients experienced severe scrotal pain, three of whom required open surgery. We do not recommend single injection tetracycline therapy, and further injections were not performed due to severe side effects.
PIV Measurements on a Blowing Flap
NASA Technical Reports Server (NTRS)
Hutcheson, Florence V.; Stead, Daniel J.
2004-01-01
PIV measurements of the flow in the region of a flap side edge are presented for several blowing flap configurations. The test model is a NACA 63(sub 2)-215 Hicks Mod-B main-element airfoil with a half-span Fowler flap. Air is blown from small slots located along the flap side edge on either the top, bottom or side surfaces. The test set up is described and flow measurements for a baseline and three blowing flap configurations are presented. The effects that the flap tip jets have on the structure of the flap side edge flow are discussed for each of the flap configurations tested. The results indicate that blowing air from a slot located along the top surface of the flap greatly weakened the top vortex system and pushed it further off the top surface. Blowing from the bottom flap surface kept the strong side vortex further outboard while blowing from the side surface only strengthened the vortex system or accelerated the merging of the side vortex to the flap top surface. It is concluded that blowing from the top or bottom surfaces of the flap may lead to a reduction of flap side edge noise.
Effects of modified short-leg walkers on ground reaction force characteristics.
Keefer, Maria; King, Jon; Powell, Douglas; Krusenklaus, John H; Zhang, Songning
2008-11-01
Although short-leg walkers are often used in the treatment of lower extremity injuries (ankle and foot fractures and severe ankle sprains), little is known about the effect the short-leg walker on gait characteristics. The purpose was to examine how heel height modifications in different short-leg walkers and shoe side may affect ground reaction forces in walking. Force platforms were used to collect ground reaction force data on 10 healthy participants. Five trials were performed in each of six conditions: lab shoes, gait walker, gait walker with heel insert on shoe side, gait walker modified with insert on walker side, equalizer walker, and equalizer walker with heel insert on shoe side. Conditions were randomized and walking speed was standardized between conditions. A 2x6 (sidexcondition) repeated analysis of variance was used on selected ground reaction force variables (P<0.05). The application of a walker created peak vertical and anteroposterior ground reaction forces prior to the normal peaks associated with the loading response. Wearing a walker introduced an elevated minimum vertical ground reaction force in all conditions except the equalizer walker when compared to shoe on the shoe side. Peak propulsive anteroposterior ground reaction forces were smaller in all walker conditions compared to shoe on walker side. The application of heel insert in gait walker with heel insert (on shoe side) and gait walker modified (on walker side) does not diminish the minimum vertical ground reaction force as hypothesized. Wearing a walker decreases the peak propulsive anteroposterior ground reaction force on the walker side and induces asymmetrical loading.
Rantanen, Tuomo; Kiljander, Toni; Salminen, Paulina; Ranta, Arto; Oksala, Niku; Kellokumpu, Ilmo
2013-06-01
There are no prospective studies available on the behavior of extraesophageal and esophageal symptoms and treatment-related side effects in patients without effective antireflux medication, receiving the most effective antireflux medication, and after laparoscopic fundoplication. Extraesophageal and esophageal reflux symptoms and treatment-related side effects were assessed in 60 patients while they were on no effective antireflux medication (three-week washout period), after three month of treatment with double-dose esomeprazole, and 3 months after laparoscopic Nissen fundoplication. Esophageal and extraesophageal reflux symptoms, rectal flatulence, and bloating were analyzed with the visual analog scale. In addition, dysphagia, rectal flatulence, and bloating were recorded as none, mild, moderate, or severe. Both extraesophageal and esophageal reflux symptoms decreased after treatment with esomeprazole and were further reduced after fundoplication. Dysphagia and flatulence did not increase from baseline after surgery. Bloating decreased both after treatment with esomeprazole and after fundoplication. In contrast, dysphagia and increased flatus were found more often after surgery than during treatment with esomeprazole. Dysphagia and rectal flatulence were less common during treatment with esomeprazole than at baseline or after surgery. Both extraesophageal and esophageal reflux symptoms decreased after treatment with esomeprazole and were reduced further after fundoplication. Any treatment-related side effect was not increased after surgery when compared to baseline. However, compared to esomeprazole there was more dysphagia and flatulence after fundoplication.
Sleep Disturbance During Smoking Cessation: Withdrawal or Side Effect of Treatment?
Ashare, Rebecca L; Lerman, Caryn; Tyndale, Rachel F; Hawk, Larry W; George, Tony P; Cinciripini, Paul; Schnoll, Robert A
2017-06-01
The nicotine-metabolite ratio (NMR) predicts treatment response and is related to treatment side effect severity. Sleep disturbance may be one important side effect, but understanding sleep disturbance effects on smoking cessation is complicated by the fact that nicotine withdrawal also produces sleep disturbance. To evaluate the effects of withdrawal and treatment side effects on sleep disturbance. This is a secondary analysis of data from a clinical trial (Lerman et al., 2015) of 1,136 smokers randomised to placebo ( n = 363), transdermal nicotine (TN; n = 381), or varenicline ( n = 392) and stratified based on NMR (559 slow metabolisers; 577 normal metabolisers). Sleep disturbance was assessed at baseline and at 1-week following the target quit date (TQD). We also examined whether sleep disturbance predicted 7-day point-prevalence abstinence at end-of-treatment (EOT). The varenicline and TN groups exhibited greater increases in sleep disturbance (vs. placebo; treatment × time interaction; p = 0.005), particularly among those who quit smoking at 1-week post-TQD. There was a main effect of NMR ( p = 0.04), but no interactions with treatment. TN and varenicline attenuated withdrawal symptoms unrelated to sleep (vs. placebo). Greater baseline sleep disturbance predicted relapse at EOT ( p = 0.004). Existing treatments may not mitigate withdrawal-related sleep disturbance and adjunctive treatments that target sleep disturbance may improve abstinence rates.
Taheri, Jamile B; Azimi, Somayyeh; Rafieian, Nasrin; Zanjani, Hosein Akhavan
2011-12-01
Herbs have been used for centuries to prevent and control disease. Herbal extracts are effective because they interact with specific chemical receptors within the body and are in a pharmacodynamic sense, drugs themselves. By using herbal medicines, patients have averted the many side effects that generally come with traditional medicines, but this does not mean that side effects do not occur. Only knowledgeable practitioners can prescribe the right herb and its proper dosage. Herbal medicines had been considered in every culture, however, pharmaceutical companies overturned this type of thinking. Now, pharmaceuticals are called traditional and herbs are libeled as the 'alternative'. The biggest challenge and problem is lack of information about the effect of herbs in oral tissues, mechanism of effect, and side effects. Several popular conventional drugs on the market are derived from herbs. These include aspirin (from white willow bark), digitalis (from foxglove), and sudafed (modelled after a component in the plant ephedra). Herbal products can vary in their potency. Therefore, care must be taken in selecting herbs, even so, herbal medicines have dramatically fewer side effects and are safer to use than conventional medications. The herbs described in this article are Bloodroot, Caraway, Chamomile, Echinacea, Myrrh, Peppermint, Rosemary, Sage, Thyme, Aloe Vera, Propolis, and a summary of other herbs that are useful in dentistry. Herbs may be good alternatives to current treatments for oral health problems but it is clear that we need more research. © 2011 FDI World Dental Federation.
O'Dea, C J; Brookes, J H; Wattchow, D A
2010-06-01
Disorders of colonic motility, such as severe constipation and pseudo-obstruction, remain difficult to treat. The pathophysiology of these conditions is not completely understood, but previous studies suggest a deficiency of cholinergic innervation and an imbalance in autonomic regulation of colonic motor function as contributing factors. Therefore, increasing the availability of acetylcholine in the bowel wall with a cholinesterase inhibitor, such as pyridostigmine, may improve symptoms. We studied thirteen patients with severe constipation (slow transit type) or recurrent pseudo-obstruction. The six patients with slow transit constipation had mechanical obstruction and pelvic floor dysfunction excluded, and normal calibre colon and slow transit confirmed. These patients were offered pyridostigmine in an attempt to avoid surgery. The seven patients with pseudo-obstruction had dilated bowel on imaging, and mechanical obstruction was excluded. These patients received pyridostigmine when symptoms recurred, despite previous treatments. Pyridostigmine was initiated at 10 mg b.i.d. and increased if required. One of the six patients with slow transit constipation reported improvement of symptoms and had concurrently weaned anti-psychotic medications. Pyridostigmine was ceased in the remaining five patients due to lack of efficacy and/or side effects. Four patients proceeded to surgery for refractory symptoms. All seven patients with pseudo-obstruction had some improvement of symptoms with few side effects. Of these, two later had surgery for recurrent symptoms. In patients with slow transit constipation, treatment with pyridostigmine does not improve symptoms. However, it does improve symptoms in patients with recurrent pseudo-obstruction with few side effects, offering an extra treatment option for these patients.
Algorithm for Automatic Behavior Quantification of Laboratory Mice Using High-Frame-Rate Videos
NASA Astrophysics Data System (ADS)
Nie, Yuman; Takaki, Takeshi; Ishii, Idaku; Matsuda, Hiroshi
In this paper, we propose an algorithm for automatic behavior quantification in laboratory mice to quantify several model behaviors. The algorithm can detect repetitive motions of the fore- or hind-limbs at several or dozens of hertz, which are too rapid for the naked eye, from high-frame-rate video images. Multiple repetitive motions can always be identified from periodic frame-differential image features in four segmented regions — the head, left side, right side, and tail. Even when a mouse changes its posture and orientation relative to the camera, these features can still be extracted from the shift- and orientation-invariant shape of the mouse silhouette by using the polar coordinate system and adjusting the angle coordinate according to the head and tail positions. The effectiveness of the algorithm is evaluated by analyzing long-term 240-fps videos of four laboratory mice for six typical model behaviors: moving, rearing, immobility, head grooming, left-side scratching, and right-side scratching. The time durations for the model behaviors determined by the algorithm have detection/correction ratios greater than 80% for all the model behaviors. This shows good quantification results for actual animal testing.
... adulthood. Patients experience severe throbbing, claw-like, or boring pain usually on one side of the face; ... adulthood. Patients experience severe throbbing, claw-like, or boring pain usually on one side of the face; ...
Severe injury in multiple impacts: Analysis of 1997-2015 NASS-CDS.
Viano, David C; Parenteau, Chantal S
2018-07-04
This is a descriptive study of the incidence and risk for severe injury in single-impact and multi-impact crashes by belt use and crash type using NASS-CDS. 1997-2015 NASS-CDS data were used to determine the distribution of crashes by the number of impacts and severe injury (Maximum Abbreviated Injury Score [MAIS] 4+F) to >15-year-old nonejected drivers by seat belt use in 1997+ MY vehicles. It compares the risk for severe injury in a single impact and in crashes involving 2, 3, or 4+ impacts in the collision with a focus on a frontal crash followed by other impacts. Most vehicle crashes involve a single impact (75.4% of 44,889,518 vehicles), followed by 2-impact crashes (19.6%), 3-impact crashes (5.0%) and 4+ impacts (2.6%). For lap-shoulder-belted drivers, the distribution of severe injury was 42.1% in a single impact, 29.3% in 2 impacts, 13.4% in 3 impacts, and 15.1% in 4+ impact crashes. The risk for a belted driver was 0.256 ± 0.031% in a single impact, 0.564 ± 0.079% in 2 impacts, 0.880 ± 0.125% in 3 impacts, and 2.121 ± 0.646% in 4+ impact. The increase in risk from a single crash to multi-impact collisions was statistically significant (P < .001). In a single impact, 53.8% of belted drivers were in a frontal crashes, 22.4% in side crashes, 20% in rear crashes, and 1.7% in rollover crashes. The risk for severe injury was highest in a rollover at 0.677 ± 0.250%, followed by near-side impact at 0.467 ± 0.084% and far-side impact at 0.237 ± 0.071%. Seat belt use was 82.4% effective in preventing severe injury (MAIS 4+F) in a rollover, 47.9% in a near-side impact, and 74.8% in a far-side impact. In 2-impact crashes with a belted driver, the most common sequence was a rear impact followed by a frontal crash at 1,843,506 (21.5%) with a risk for severe injury of 0.100 ± 0.058%. The second most common was a frontal impact followed by another frontal crash at 1,257,264 (14.7%) with a risk of 0.401 ± 0.057%. The risk was 0.658 ± 0.271% in a frontal impact followed by a rear impact. A near-side impact followed by a rear crash had the highest risk for severe injury at 2.073 ± 1.322%. Restraint systems are generally developed for a single crash or sled test. The risk for severe injury was significantly higher in 2-, 3-, and 4+-impact crashes than a single impact. The majority (57.9%) of severe injuries occurred in multi-impact crashes with belted drivers. The evaluation of restraint performance warrants additional study in multi-impact crashes.
Sun, Yu; Narayan, Vaibhav A; Wittenberg, Gayle M
2016-10-21
Side effects, or the adverse effects of drugs, contain important clinical phenotypic information that may be useful in predicting novel or unknown targets of a drug. It has been suggested that drugs with similar side-effect profiles may share common targets. The diagnostic class, Major Depressive Disorder, is increasingly viewed as being comprised of multiple depression subtypes with different biological root causes. One 'type' of depression generating substantial interest today focuses on patients with high levels of inflammatory burden, indicated by elevated levels of C-reactive proteins (CRP) and pro-inflammatory cytokines such as interleukin 6 (IL-6). It has been suggested that drugs targeting the immune system may have beneficial effect on this subtype of depressed patients, and several studies are underway to test this hypothesis directly. However, patients have been treated with both anti-inflammatory and antidepressant compounds for decades. It may be possible to exploit similarities in clinical readouts to better understand the antidepressant effects of immune-related drugs. Here we explore the space of approved drugs by comparing the drug side effect profiles of known antidepressants and drugs targeting the immune system, and further examine the findings by comparing the human cell line expression profiles induced by them with those induced by antidepressants. We found 7 immune-modulators and 14 anti-inflammatory drugs sharing significant side effect profile similarities with antidepressants. Five of the 7 immune modulators share most similar side effect profiles with antidepressants that modulate dopamine release and/or uptake. In addition, the immunosuppressant rapamycin and the glucocorticoid alclometasone induces transcriptional changes similar to multiple antidepressants. These findings suggest that some antidepressants and some immune-related drugs may affect common molecular pathways. Our findings support the idea that certain medications aimed at the immune system may be helpful in relieving depressive symptoms, and suggest that it may be of value to test immune-modulators for antidepressant-like activity in future proof-of-concept studies.
Chen, Jing-Xu; Su, Yun-Ai; Bian, Qing-Tao; Wei, Li-He; Zhang, Rong-Zhen; Liu, Yan-Hong; Correll, Christoph; Soares, Jair C; Yang, Fu-De; Wang, Shao-Li; Zhang, Xiang-Yang
2015-08-01
Hyperprolactinemia is an unwanted adverse effect associated with several antipsychotics. The addition of partial dopamine receptor agonist aripiprazole may attenuate antipsychotic-induced hyperprolactinemia effectively. However, the ideal dosing regimen for this purpose is unknown. We aimed to evaluate the dose effects of adjunctive treatment with aripiprazole on prolactin levels and hyperprolactinemia in schizophrenia patients. Stable subjects 18-45 years old with schizophrenia and hyperprolactinemia (i.e., >24 ng/ml for females and >20 ng/ml for males) were randomly assigned to receive 8 weeks of placebo (n=30) or oral aripiprazole 5mg/day (n=30), 10mg/day (n=29), or 20mg/day (n=30) added on to fixed dose risperidone treatment. Serum prolactin levels were measured at baseline and after 2, 4 and 8 weeks; clinical symptoms and side effects were assessed at baseline and week 8 using the Positive and Negative Syndrome Scale, Clinical Global Impressions Severity scale, Barnes Akathisia Scale, Simpson-Angus Scale and UKU Side Effects Rating Scale. Of 119 randomized patients, 107 (89.9%) completed the 8-week study. At study end, all three aripiprazole doses resulted in significantly lower prolactin levels (beginning at week 2), higher response rates (≥30% prolactin reduction) and higher prolactin normalization rates than placebo. Effects were significantly greater in the 10 and 20mg/day groups than the 5mg/day group. No significant changes were observed in any treatment groups regarding psychopathology and adverse effect ratings. Adjunctive aripiprazole treatment was effective and safe for resolving risperidone-induced hyperprolactinemia, producing significant and almost maximal improvements by week 2 without significant effects on psychopathology and side effects. Copyright © 2015 Elsevier Ltd. All rights reserved.
[Clinical evaluation of cefmenoxime in severe infections in leukemia and related disorders].
Tsuda, S; Nishida, K; Maekawa, T; Abe, T; Takino, T; Fujii, H; Taniwaki, M; Yashige, H; Horiike, S; Yokota, S
1986-10-01
Ninety nine patients with leukemia and/or related disorders were treated with cefmenoxime (CMX). Among them, 77 patients had severe infections, while other 22 patients did not suffer from infection, but it was expected that they would fall into serious conditions if they were infected. Sixty of the 77 patients who had severe infection were used in the evaluation of effectiveness. The remaining 17 patients were not evaluated because they were subjected to combined treatments of CMX and other therapeutic agents such as other antibiotics, gamma-globulin or interferon. Excellent responses were found in 26 (43.3%) patients and good responses in 12 (20.0%) patients. In total, the rate of effectiveness was 63.3%. Nineteen of the 22 patients who were treated prophylactically with CMX were used in the evaluation of effectiveness, while 3 patients were excluded from the evaluation because peripheral neutrophils were counted to be more than 1,000/mm3 before CMX was administrated, although these 3 patients were used in the final evaluation to examine side effects. In the prophylactic treatment, the rate of effectiveness was 89.5%. The side effects were seen in 4 patients (4/82:4.9%). A different symptom was identified in each patient. These symptoms were skin rash, mild nausea, mild diarrhea and slight elevation of serum bilirubin. Prompt improvements of these symptoms occurred as soon as CMX administration was stopped. These results show that CMX is a therapeutically effective and safe antibiotics for the treatment of severe infections or for the prophylaxis of infections in patients associated with leukemia and/or related disorders.
Hair loss at injection sites of mesotherapy for alopecia.
El-Komy, Mohamed; Hassan, Akmal; Tawdy, Amira; Solimon, Mohamed; Hady, Mohamed Abdel
2017-12-01
The side effects of mesotherapy for treatment of various forms of alopecia are often underreported, while scientific data for its efficacy are severely lacking. To demonstrate the late onset side effects of mesotherapy for alopecia. Three patients with androgenetic alopecia showed hair loss after previously uneventful mesotherapy sessions up to 1 year. Clinical, dermoscopic, and histopathological findings suggested an inflammatory scaring process at sites of mesotherapy injections. Mesotherapy for androgenetic alopecia may paradoxically induce hair loss and scarring. Proper regulation and monitoring of the use of mesotherapy products for treating hair loss in women, needs to be addressed. © 2017 Wiley Periodicals, Inc.
Relapsed hydroxychloroquine induced thrombocytopenia in a systemic lupus erythematosus patient.
Antón Vázquez, Vanesa; Pascual, Luis; Corominas, Héctor; Giménez Torrecilla, Isabel
Hydroxychloroquine is used in the long-term therapy of systemic lupus erythematosus (SLE). Although considered to be a safe treatment, side effects have been documented. An uncommon side effect is thrombocytopenia. In order to establish the diagnosis of thrombocytopenia secondary to Hydroxychloroquine, non-pharmacological causes must be ruled out and it is necessary to determine a recurrence after re-exposure to the drug. We present one case of severe thrombocytopenia occurring in a patient with SLE undergoing treatment with Hydroxychloroquine. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.
Severe hypophosphataemia after intravenous iron administration.
Blazevic, A; Hunze, J; Boots, J M M
2014-01-01
Currently, in many centres, intravenous administration of iron is becoming increasingly popular because of higher efficacy and decreased side effects, mainly gastrointestinal, compared with oral iron therapy. Studies of intravenous ferric carboxymaltose administration in the postpartum setting and in patients with non-dialysis-dependent chronic kidney disease revealed a decrease in serum phosphate levels that was generally asymptomatic and transient. Here, we report four cases of severe and symptomatic hypophosphataemia after intravenous iron administration. All patients received this as therapy for iron deficiency anaemia due to heavy menstrual bleeding. In most cases, a pre-existent disorder in the phosphate homeostasis existed, such as a secondary (cases 3 and 4) or tertiary hyperparathyroidism (case 1). However, in the second case there were no risk factors for a dysregulation of the phosphate homeostasis. Based on these findings, we conclude that severe and symptomatic hypophosphatemia can occur as a side effect of intravenous iron administration and can persist for months after administration. Especially patients with low phosphate levels prior to therapy due to concomitant disorders in phosphate homeostasis (e.g. hyperparathyroidism, vitamin D deficiency) are at risk.
Salient concerns in using analgesia for cancer pain among outpatients: A cluster analysis study.
Meghani, Salimah H; Knafl, George J
2017-02-10
To identify unique clusters of patients based on their concerns in using analgesia for cancer pain and predictors of the cluster membership. This was a 3-mo prospective observational study ( n = 207). Patients were included if they were adults (≥ 18 years), diagnosed with solid tumors or multiple myelomas, and had at least one prescription of around-the-clock pain medication for cancer or cancer-treatment-related pain. Patients were recruited from two outpatient medical oncology clinics within a large health system in Philadelphia. A choice-based conjoint (CBC) analysis experiment was used to elicit analgesic treatment preferences (utilities). Patients employed trade-offs based on five analgesic attributes (percent relief from analgesics, type of analgesic, type of side-effects, severity of side-effects, out of pocket cost). Patients were clustered based on CBC utilities using novel adaptive statistical methods. Multiple logistic regression was used to identify predictors of cluster membership. The analyses found 4 unique clusters: Most patients made trade-offs based on the expectation of pain relief (cluster 1, 41%). For a subset, the main underlying concern was type of analgesic prescribed, i.e ., opioid vs non-opioid (cluster 2, 11%) and type of analgesic side effects (cluster 4, 21%), respectively. About one in four made trade-offs based on multiple concerns simultaneously including pain relief, type of side effects, and severity of side effects (cluster 3, 28%). In multivariable analysis, to identify predictors of cluster membership, clinical and socioeconomic factors (education, health literacy, income, social support) rather than analgesic attitudes and beliefs were found important; only the belief, i.e ., pain medications can mask changes in health or keep you from knowing what is going on in your body was found significant in predicting two of the four clusters [cluster 1 (-); cluster 4 (+)]. Most patients appear to be driven by a single salient concern in using analgesia for cancer pain. Addressing these concerns, perhaps through real time clinical assessments, may improve patients' analgesic adherence patterns and cancer pain outcomes.
Tziona, Paraskevi; Theodosis-Nobelos, Panagiotis; Rekka, Eleni A
2017-01-01
Non-steroidal anti-inflammatory drugs are the oldest and most widely used medicines. However, their untoward effects, especially gastrointestinal toxicity, remain the main obstacle to their application. Because of their mechanism of action, cycloxygenase (COX) inhibition, in combination with the weekly acidic character of most of them, major protective mechanisms of the gastrointestinal system are suppressed and deregulated. In this review, several compounds designed to retain anti-inflammatory activity, but devoid of gastrointestinal side effects, are presented. Thus, gastro-protective drugs, selective COX-2 inhibitors, nitric monoxide- and hydrogen sulphide-releasing agents, prodrugs, lipoxygenase (LOX) inhibitors and dual COX/LOX inhibitors are presented. Their mechanism of action, as well as their advantages and disadvantages are discussed. Efforts, aiming to the development of safe non-steroidal anti-inflammatory agents, are evolving, however there are still several problems concerning gastro-protection to be efficiently solved, thus, design of effective and safe agents for the treatment of inflammatory conditions still remains a major challenge. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
An Impulse-Momentum Method for Calculating Landing-Gear Contact Conditions in Eccentric Landings
NASA Technical Reports Server (NTRS)
Yntema, Robert T; Milwitzky, Benjamin
1952-01-01
An impulse-momentum method for determining impact conditions for landing gears in eccentric landings is presented. The analysis is primarily concerned with the determination of contact velocities for impacts subsequent to initial touchdown in eccentric landings and with the determination of the effective mass acting on each landing gear. These parameters determine the energy-absorption requirements for the landing gear and, in conjunction with the particular characteristics of the landing gear, govern the magnitude of the ground loads. Changes in airplane angular and linear velocities and the magnitude of landing-gear vertical, drag, and side impulses resulting from a landing impact are determined by means of impulse-momentum relationships without the necessity for considering detailed force-time variations. The effective mass acting on each gear is also determined from the calculated landing-gear impulses. General equations applicable to any type of eccentric landing are written and solutions are obtained for the particular cases of an impact on one gear, a simultaneous impact on any two gears, and a symmetrical impact. In addition a solution is presented for a simplified two-degree-of-freedom system which allows rapid qualitative evaluation of the effects of certain principal parameters. The general analysis permits evaluation of the importance of such initial conditions at ground contact as vertical, horizontal, and side drift velocities, wing lift, roll and pitch angles, and rolling and pitching velocities, as well as the effects of such factors as landing gear location, airplane inertia, landing-gear length, energy-absorption efficiency, and wheel angular inertia on the severity of landing impacts. -A brief supplementary study which permits a limited evaluation of variable aerodynamic effects neglected in the analysis is presented in the appendix. Application of the analysis indicates that landing-gear impacts in eccentric landings can be appreciably more severe than impacts in symmetrical landings with the same sinking speed. The results also indicate the effects of landing-gear location, airplane inertia, initial wing lift, side drift velocity, attitude, and initial rolling velocity on the severity of both initial and subsequent landing-gear impacts. A comparison of the severity of impacts on auxiliary gears for tricycle and quadricycle configurations is also presented.
Tsang, Hector W H; Fong, Mandy W M; Fung, Kelvin M T; Chung, Raymond C K
2010-03-01
Abstract Objectives. We compared the satisfaction level of psychiatrists and psychiatric patients towards conventional (CDA) and atypical (ADA) depot antipsychotics on symptom management, role functioning, and side effects. Method. Patients from an out-patient clinic of a public hospital and psychiatrists from public hospitals participated in the survey in 2007-2008. A total of 153 patients were interviewed by a tailor-made questionnaire and 72 psychiatrists self-administered a similar questionnaire. Results. Both groups shared similar attitudes towards clinical effectiveness and treatment efficacy of ADA and CDA. More patients were ambivalent towards relapse prevention of CDA than psychiatrists (30.7 vs. 16.7%, P<0.044) and three quarters of psychiatrists believed that ADA are associated with less side effects. More than half of the patients showed negative attitudes towards the effectiveness of CDA on improving quality of life (52.40%), work (57.50%), and recreation (55.50%). Psychiatrists were more aware of the limitation of CDA and severity of side effects of CDA. They did not, however, seem to incorporate patients' opinions and research findings into their clinical practice. Conclusion. Evidence-based practice and shared decision-making model between clinicians and mental patients should be advocated. More investigations should be devoted to examine the efficacy of ADA as the alternative to CDA.
Pharmacogenetics of clozapine treatment response and side-effects in schizophrenia: an update.
Sriretnakumar, Venuja; Huang, Eric; Müller, Daniel J
2015-01-01
Clozapine (CLZ) is the most effective treatment for treatment-resistant schizophrenia (SCZ) patients, with potential added benefits of reduction in suicide risk and aggression. However, CLZ is also mainly underused due to its high risk for the potentially lethal side-effect of agranulocytosis as well as weight gain and related metabolic dysregulation. Pharmacogenetics promises to enable the prediction of patient treatment response and risk of adverse effects based on patients' genetics, paving the way toward individualized treatment. This article reviews pharmacogenetics studies of CLZ response and side-effects with a focus on articles from January 2012 to February 2015, as an update to the previous reviews. Pharmacokinetic genes explored primarily include CYP1A2, while pharmacodynamic genes consisted of traditional pharmacogenetic targets such as brain-derived neurotrophic factor as well novel mitochondrial genes, NDUFS-1 and translocator protein. Pharmacogenetics is a promising avenue for individualized medication of CLZ in SCZ, with several consistently replicated gene variants predicting CLZ response and side-effects. However, a large proportion of studies have yielded mixed results. Large-scale Genome-wide association studies (e.g., CRESTAR) and targeted gene studies with standardized designs (response measurements, treatment durations, plasma level monitoring) are required for further progress toward clinical translation. Additionally, in order to improve study quality, we recommend accounting for important confounders, including polypharmacy, baseline measurements, treatment duration, gender, and age at onset.
Cholestatic hepatitis as a possible new side-effect of oxycodone: a case report
Ho, Vincent; Stewart, Maxwell; Boyd, Peter
2008-01-01
Introduction Oxycodone is a widely-used semisynthetic opioid analgesic that has been used for over eighty years. Oxycodone is known to cause side effects such as nausea, pruritus, dizziness, constipation and somnolence. As far as we are aware cholestatic hepatitis as a result of oxycodone use has not been reported so far in the world literature. Case presentation A 34-year-old male presented with cholestatic jaundice and severe pruritus after receiving oxycodone for analgesia post-T11 vertebrectomy. Extensive laboratory investigations and imaging studies did not reveal any other obvious cause for his jaundice and a liver biopsy confirmed canalicular cholestatis suggestive of drug-induced hepatotoxicity. The patient's symptoms and transaminases normalised on withdrawal of oxycodone confirming that oxycodone was the probable cause of the patient's hepatotoxicity. Conclusion We conclude that cholestatic hepatitis is possibly a rare side effect of oxycodone use. Physicians should be aware of the possibility of this potentially serious picture of drug-induced hepatotoxicity. PMID:18452597
Developmental neurotoxicity of succeeding generations of insecticides
Abreu-Villaça, Yael; Levin, Edward D.
2016-01-01
Insecticides are by design toxic. They must be toxic to effectively kill target species of insects. Unfortunately, they also have off-target toxic effects that can harm other species, including humans. Developmental neurotoxicity is one of the most prominent off-target toxic risks of insecticides. Over the past seven decades several classes of insecticides have been developed, each with their own mechanisms of effect and toxic side effects. This review covers the developmental neurotoxicity of the succeeding generations of insecticides including organochlorines, organophosphates, pyrethroids, carbamates and neonicotinoids. The goal of new insecticide development is to more effectively kill target species with fewer toxic side effects on non-target species. From the experience with the developmental neurotoxicity caused by the generations of insecticides developed in the past advice is offered how to proceed with future insecticide development to decrease neurotoxic risk. PMID:27908457
Dominant use of the left hand by athetotic cerebral palsied children.
Yokochi, K; Shimabukuro, S; Kodama, M; Hosoe, A
1990-01-01
Hand preference was studied in 57 children with athetotic cerebral palsy. A left-sided preference was seen in 61% of the subjects. In more severely affected children for whom the possible cause was asphyxia, the left-sided preference was especially common. The perinatal brain damage causing athetosis may affect a motor system controlling movement on the right side more severely.
Geng, A; Weinstock, M A; Hall, R; Eilers, D; Naylor, M; Kalivas, J
2009-10-01
Topical tretinoin is a medication commonly used for acne that has potential application in the long-term treatment of photodamaged skin. However, there are few published data regarding the tolerability of high-dose tretinoin with long-term use. To assess the long-term tolerability of tretinoin 0.1% cream. A randomized, multicentre, double-blind, controlled trial for chemoprevention of keratinocyte carcinomas (i.e. basal cell or squamous cell carcinomas) using topical tretinoin cream to the face and ears was conducted. All participants were veterans and had a history of two or more keratinocyte carcinomas over the previous 5 years. Participants were examined (by a study dermatologist) and interviewed every 6 months (for up to 5.5 years to May 2004). Treatment comprised tretinoin 0.1% cream or vehicle control cream once daily, then twice daily as tolerated. Participants were instructed to step down application frequency to once daily or less if twice daily was not tolerated. The main outcome measures were reported side-effects, frequency of cream application and attendance at study visits. Appropriate data were available for four of the six clinical sites of this trial. Data from 736 randomized participants (mean age 71 years; 97% men) from four clinical sites were analysed. The tretinoin group more commonly reported one or more side-effects at the 6-month follow-up than the control group (61% vs. 42%, P < 0.0001). Side-effects decreased over time in both groups, but to a greater extent in the tretinoin group, and the difference became nonsignificant at 30 months. Burning was the most common side-effect (39% tretinoin vs. 17% control, P < 0.0001). There was no difference in severity of side-effects among those affected. Of the participants who reported burning in either group, most reported mild burning; only 11% of those with burning in the tretinoin group reported it as severe (mild 62% tretinoin vs. 70% placebo; severe 11% vs. 5%; P = 0.4). Itching (24% vs. 16%, P = 0.01) and other local cutaneous reactions (12% vs. 6%, P = 0.01) were also more commonly reported by the tretinoin group at 6 months. There was no difference in numbness (2% vs. 2%, P = 0.9). Participants in the tretinoin group were less likely to apply cream twice daily at 6 months (29% vs. 43%, P = 0.0002). This difference persisted over the entire duration of follow-up. There was little difference between groups in attendance at study visits or completion of telephone interviews (92% vs. 95%, P = 0.06). No unexpected adverse events were reported. Overall, the tolerability level of topical tretinoin was high in this study population, with almost 40% of the tretinoin group reporting no side-effects, and the majority (67%) tolerating at least once-daily dosing at 6-month follow-up. High-dose topical tretinoin is feasible for long-term use in this population.
Classics in Chemical Neuroscience: Aripiprazole.
Casey, Austen B; Canal, Clinton E
2017-06-21
Aripiprazole was the first antipsychotic developed to possess agonist properties at dopamine D 2 autoreceptors, a groundbreaking strategy that presented a new vista for schizophrenia drug discovery. The dopamine D 2 receptor is the crucial target of all extant antipsychotics, and all developed prior to aripiprazole were D 2 receptor antagonists. Extensive blockade of these receptors, however, typically produces extrapyramidal (movement) side effects, which plagued first-generation antipsychotics, such as haloperidol. Second-generation antipsychotics, such as clozapine, with unique polypharmacology and D 2 receptor binding kinetics, have significantly lower risk of movement side effects but can cause myriad additional ones, such as severe weight gain and metabolic dysfunction. Aripiprazole's polypharmacology, characterized by its unique agonist activity at dopamine D 2 and D 3 and serotonin 5-HT 1A receptors, as well as antagonist activity at serotonin 5-HT 2A receptors, translates to successful reduction of positive, negative, and cognitive symptoms of schizophrenia, while also mitigating risk of weight gain and movement side effects. New observations, however, link aripiprazole to compulsive behaviors in a small group of patients, an unusual side effect for antipsychotics. In this review, we discuss the chemical synthesis, pharmacology, pharmacogenomics, drug metabolism, and adverse events of aripiprazole, and we present a current understanding of aripiprazole's neurotherapeutic mechanisms, as well as the history and importance of aripiprazole to neuroscience.
Bultijnck, Renée; Surcel, Cristian; Ploussard, Guillaume; Briganti, Alberto; De Visschere, Pieter; Fütterer, Jurgen; Ghadjar, Pirus; Giannarini, Gianluca; Isbarn, Hendrik; Massard, Christophe; Sooriakumaran, Prasanna; Valerio, Massimo; van den Bergh, Roderick; Ost, Piet
2016-12-01
Evidence-based recommendations are available for the management of androgen deprivation therapy (ADT)-induced side effects; however, there are no data on the implementation of the recommendations into daily practice patterns. To compare practice patterns in the management of ADT-induced side effects with evidence-based strategies. A European Web-based survey was conducted from January 16, 2015, to June 24, 2015. The 25-item questionnaire was designed with the aid of expert opinion and covered general respondent information, ADT preference per disease stage, patient communication on ADT-induced side effects, and strategies to mitigate side effects. All questions referred to patients with long-term ADT use. Reported practice patterns were compared with available evidence-based strategies. Following data collection, descriptive statistics were used for analysis. Frequency distributions were compiled and compared using a generalised chi-square test. In total, 489 eligible respondents completed the survey. Luteinising hormone-releasing hormone-agonist with or without an antiandrogen was the preferred method of ADT in different settings. Patients were well informed about loss of libido (90%), hot flushes (85%), fatigue (67%), and osteoporosis (63%). An osteoporotic and metabolic risk assessment prior to commencing ADT was done by one-quarter of physicians. The majority (85%) took preventive measures and applied at least one evidence-based strategy. Exercise was recommended by three-quarters of physicians who advocate its positive effects; however, only 25% of physicians had access to exercise programmes. Although the minimum sample size was set at 400 participants, the current survey remains susceptible to volunteer and nonresponder bias. Patients were well informed about several ADT-induced complications but uncommonly underwent an osteoporotic and metabolic risk assessment. Nevertheless, physicians partially provided evidence-based strategies for the management of the complications. Physicians often advised exercise to reduce ADT-induced side effects, but programmes were not widely available. Implementation of evidence-based strategies for androgen deprivation therapy-induced side effects in real-life practice patterns should be improved. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.
1979-07-01
44 a. One-sided level ................................. 44 b. Two-sided level .......................................... 44 H. Testing...successively higher levels of severity must be used until failure is obtained, as in the applications of successively greater loads until failure is...severe than that applied at comparable levels of severity in the laboratory. Further- _ . more, interactions among environments and among components
Intranasal ipratropium bromide for the common cold.
AlBalawi, Zaina H; Othman, Sahar S; Alfaleh, Khalid
2013-06-19
The common cold is one of the most common illnesses in humans and constitutes an economic burden both in terms of productivity and expenditure for treatment. There is no proven cure for the common cold and symptomatic relief is the mainstay of treatment. The use of intranasal ipratropium bromide (IB) has been addressed in several studies and might prove an effective treatment for the common cold. To determine the effect of IB versus placebo or no treatment on severity of rhinorrhoea and nasal congestion in children and adults with the common cold. Subjective overall improvement was another primary outcome and side effects (for example, dry mucous membranes, epistaxis and systemic anticholinergic effects) were reported as a secondary outcome. In this updated review we searched CENTRAL 2013, Issue 3, MEDLINE (1950 to March week 4, 2013), MEDLINE in-process and other non-indexed citations (8 April 2013), EMBASE (1974 to April 2013), AMED (1985 to April 2013), Biosis (1974 to February 2011) and LILACS (1985 to April 2013). Randomised controlled trials (RCTs) comparing IB to placebo or no treatment in children and adults with the common cold. Two review authors independently extracted data and assessed trial quality. We used a standardised form to extract relevant data and we contacted trial authors for additional information. Seven trials with a total of 2144 participants were included. Four studies (1959 participants) addressed subjective change in severity of rhinorrhoea. All studies were consistent in reporting statistically significant changes in favour of IB. Nasal congestion was reported in four studies and was found to have no significant change between the two groups. Two studies found a positive response in the IB group for the global assessment of overall improvement. Side effects were more frequent in the IB group, odds ratio (OR) 2.09 (95% confidence interval (CI) 1.40 to 3.11). Commonly encountered side effects included nasal dryness, blood tinged mucus and epistaxis. The overall risk of bias in the included studies was moderate. For people with the common cold, the existing evidence, which has some limitations, suggests that IB is likely to be effective in ameliorating rhinorrhoea. IB had no effect on nasal congestion and its use was associated with more side effects compared to placebo or no treatment although these appeared to be well tolerated and self limiting. There is a need for larger, high-quality trials to determine the effectiveness of IB in relieving common cold symptoms.
Rear Seat Occupant Thorax Protection in Near Side Impacts
Bohman, Katarina; Rosén, Erik; Sunnevang, Cecilia; Boström, Ola
2009-01-01
Thoracic side-airbags (SAB) have proven to protect front seat occupants in side impacts. This benefit has not been evaluated for rear seat occupants who are typically small statured. The objective was to analyze field data from rear seat occupants in near side impacts, and evaluate the effect of a SAB in the rear seat, through full scale vehicle tests. A field study using the NASS-CDS database was performed to review rear seat crash characteristics, occupant injuries (Abbreviated Injury Scale 3+, AIS3+) and injury sources. Full scale tests were performed with the side impact dummy SID-IIs at two different crash severities, with and without SAB in a midsize passenger car. Field data showed that of all AIS3+ injured restrained occupants 13 years and older, 59% had AIS3+ thoracic injuries and 38% had AIS3+ head injuries. The thoracic injuries were distributed to lungs (60%), skeletal fractures (38%) and injuries to arteries (1,26%) and heart (0,1%). For AIS3+ injured children, age 4–12, 51% had AIS3+ thoracic injuries and 54% had AIS3+ head injuries. Compared to adults, children sustained less fractures and more lung injuries. The rear side interior was the main injury source regardless of age group. In the full scale tests, the thoracic side-airbag reduced the average rib deflection by 50% and resulted in an AIS3+ injury risk reduction from 36% to 3%. At the higher impact speed, SAB reduced the injury risk from 93% to 24%. The full scale crash tests showed that SAB offer a significant potential for thoracic injury reduction in the crash severities causing the majority of serious injuries in real life crashes. PMID:20184828
Topical minoxidil in the treatment of alopecia areata.
Fenton, D A; Wilkinson, J D
1983-01-01
A modified double blind crossover study was performed to assess the effect of 1% topical minoxidil as compared with placebo in 30 patients with alopecia areata and alopecia totalis. The active preparation produced a highly significant incidence of hair regrowth. A cosmetically acceptable response was noted in 16 patients. No side effects were seen. The study confirmed that topical minoxidil will induce new hair growth in alopecia areata but that it is less likely to do so in more severe and extensive disease. Furthermore, patients with alopecia universalis and totalis may not respond at all. Nevertheless, as compared with other drugs minoxidil applied topically is relatively non-toxic, is easy to use, and has no systemic or local side effects. Images p1016-a PMID:6412929
[Therapy of intermediate uveitis].
Doycheva, D; Deuter, C; Zierhut, M
2014-12-01
Intermediate uveitis is a form of intraocular inflammation in which the vitreous body is the major site of inflammation. Intermediate uveitis is primarily treated medicinally and systemic corticosteroids are the mainstay of therapy. When recurrence of uveitis or side effects occur during corticosteroid therapy an immunosuppressive treatment is required. Cyclosporine A is the only immunosuppressive agent that is approved for therapy of uveitis in Germany; however, other immunosuppressive drugs have also been shown to be effective and well-tolerated in patients with intermediate uveitis. In severe therapy-refractory cases when conventional immunosuppressive therapy has failed, biologics can be used. In patients with unilateral uveitis or when the systemic therapy is contraindicated because of side effects, an intravitreal steroid treatment can be carried out. In certain cases a vitrectomy may be used.
Long-term risks of psoralen and UV-A therapy for psoriasis
DOE Office of Scientific and Technical Information (OSTI.GOV)
Farber, E.M.; Abel, E.A.; Cox, A.J.
1983-05-01
It has been more than eight years since photochemotherapy with methoxsalen and UV-A (psoralen and UV-A (PUVA)) was introduced for the treatment of psoriasis. This treatment remained under investigation until May 1982 because of concerns about possible chronic toxic effects. With recent Food and Drug Administration approval of PUVA therapy for severe psoriasis, strict drug labeling for administration and patient use and continued monitoring of side effects have become essential. The full effects of PUVA in regard to carcinogenicity, prematurelly induced aging of the skin, pigmentary changes, immunologic alterations, and ocular side effects are still unknown. A review of themore » risks of PUVA therapy is presented, with the aim of maintaining a proper perspective for its limited use in treating selected patients.« less
The effect of linear spring number at side load of McPherson suspension in electric city car
NASA Astrophysics Data System (ADS)
Budi, Sigit Setijo; Suprihadi, Agus; Makhrojan, Agus; Ismail, Rifky; Jamari, J.
2017-01-01
The function of the spring suspension on Mc Pherson type is to control vehicle stability and increase ride convenience although having tendencies of side load presence. The purpose of this study is to obtain simulation results of Mc Pherson suspension spring in the electric city car by using the finite element method and determining the side load that appears on the spring suspension. This research is conducted in several stages; they are linear spring designing models with various spring coil and spring suspension modeling using FEM software. Suspension spring is compressed in the vertical direction (z-axis) and at the upper part of the suspension springs will be seen the force that arises towards the x, y, and z-axis to simulate the side load arising on the upper part of the spring. The results of FEM simulation that the side load on the spring toward the x and y-axis which the value gets close to zero is the most stable spring.
Treatment of pseudofolliculitis barbae in very dark skin with a long pulse Nd:YAG laser.
Ross, E. Victor; Cooke, Linda M.; Overstreet, Kristen A.; Buttolph, Greg D.; Blair, Mark A.
2002-01-01
BACKGROUND: Pseudofolliculitis barbae affects some individuals with coarse curly hair. Currently available treatment modalities are often ineffective. In some studies, lasers have been shown to be potentially helpful in mitigating disease severity by reducing the number and/or thickness of hair shafts. METHODS: This was a side-by-side interventional study conducted at a military tertiary medical facility. The study group included 26 patients (skin types IV, V, and VI) referred from primary care physicians with a diagnosis of pseudofolliculitis barbae refractory to medical therapy. A neodymium YAG laser was used to treat one half of the neck. One month later, shaving bumps were counted and compared to their preoperative levels on both sides. RESULTS: Mean postoperative papule counts were 11.6 +/- 6 (SD) and 30.1 +/- 19 (SD) on the treated side and untreated sides, respectively. CONCLUSION: Neodymium YAG laser treatment represents a safe and effective option for reducing papule formation in patients with pseudofolliculitis barbae. Images Figure 1 PMID:12408693
On the significance of electroconvulsive therapy in the treatment of severe mental diseases.
Grözinger, Michael; Smith, Elke Stefanie; Conca, Andreas
2015-04-01
Quite a few patients with severe mental diseases do not respond sufficiently to psychopharmacology and psychotherapy. For some of these, electroconvulsive therapy (ECT) offers a promising alternative. Erroneously, the method is being perceived as old fashioned by the lay public, but also by many doctors. Therefore, this overview aims at all colleagues who in their role as multipliers, referring physicians or ECT specialists can reduce the likelihood of mental disease to become chronic. During the last decades, numerous international medical societies including the Austrian and the German Association for Psychiatry (ÖGPP and DGPPN) have pointed to the importance of ECT as a modern medical intervention. Our overview is based on these guidelines and statements. Additionally selective literature searches have been conducted concerning some key aspects. Due to its excellent efficacy, ECT is an important option in the treatment of severe mental disease. Technological innovations and continued development in the psychiatric environment determined the evolution from the electroshock of the 1930s to the ECT of today. This process led to reduced side effects and a stronger patient-oriented praxis. ECT is a modern, highly effective and safe treatment of severe mental diseases with comparatively few side effects. The method should not be used as a last resort but in an evidence-based way. Patients should be informed timely and adequately about the therapeutic option.
Mining adverse drug reactions from online healthcare forums using hidden Markov model.
Sampathkumar, Hariprasad; Chen, Xue-wen; Luo, Bo
2014-10-23
Adverse Drug Reactions are one of the leading causes of injury or death among patients undergoing medical treatments. Not all Adverse Drug Reactions are identified before a drug is made available in the market. Current post-marketing drug surveillance methods, which are based purely on voluntary spontaneous reports, are unable to provide the early indications necessary to prevent the occurrence of such injuries or fatalities. The objective of this research is to extract reports of adverse drug side-effects from messages in online healthcare forums and use them as early indicators to assist in post-marketing drug surveillance. We treat the task of extracting adverse side-effects of drugs from healthcare forum messages as a sequence labeling problem and present a Hidden Markov Model(HMM) based Text Mining system that can be used to classify a message as containing drug side-effect information and then extract the adverse side-effect mentions from it. A manually annotated dataset from http://www.medications.com is used in the training and validation of the HMM based Text Mining system. A 10-fold cross-validation on the manually annotated dataset yielded on average an F-Score of 0.76 from the HMM Classifier, in comparison to 0.575 from the Baseline classifier. Without the Plain Text Filter component as a part of the Text Processing module, the F-Score of the HMM Classifier was reduced to 0.378 on average, while absence of the HTML Filter component was found to have no impact. Reducing the Drug names dictionary size by half, on average reduced the F-Score of the HMM Classifier to 0.359, while a similar reduction to the side-effects dictionary yielded an F-Score of 0.651 on average. Adverse side-effects mined from http://www.medications.com and http://www.steadyhealth.com were found to match the Adverse Drug Reactions on the Drug Package Labels of several drugs. In addition, some novel adverse side-effects, which can be potential Adverse Drug Reactions, were also identified. The results from the HMM based Text Miner are encouraging to pursue further enhancements to this approach. The mined novel side-effects can act as early indicators for health authorities to help focus their efforts in post-marketing drug surveillance.
Noaiseh, Ghaith; Baker, Joshua F; Vivino, Frederick B
2014-01-01
There are currently no head-to-head comparisons of sialagogues for Primary Sjögren's syndrome (pSS). We compared the tolerability and side effect profile of pilocarpine and cevimeline in patients with pSS and determined clinical, laboratory and pathological variables associated with therapeutic failure. We retrospectively reviewed the use of pilocarpine and cevimeline in 118 patients with pSS who fulfilled the 2002 American European Consensus Group criteria in a University-based setting. Clinical, laboratory and pathological baseline variables were collected. Failure of therapy was defined as the clinician or patient's decision to stop treatment either due to lack of efficacy or side effects. Cevimeline was associated with lower failure rates compared to pilocarpine among first-time users: 27% vs. 47% (p=0.02), and all users: 32% vs. 61% (p<0.001). Severe sweating was the most frequent side effect leading to cessation of therapy and occurred more frequently in pilocarpine (25%) than cevimeline (11%) users (p=0.02). Patients who previously failed one secretagogue were less likely to discontinue treatment with the other agent, 52% of first-time users vs. 27% of second-time users (p=0.004). Only ANA positivity was associated with failure: [59% vs. 38%] (p=0.03). pSS patients were more likely to continue cevimeline than pilocarpine long-term due to fewer reported side effects with cevimeline. Therapeutic failure of one secretagogue did not predict similar results with the other since second time users were more likely to continue long-term treatment.
Oliveira, V M; Khalil, N M; Carraro, E
2018-02-01
Amphotericin B is a fungicidal substance that is treatment of choice for most systemic fungal infections affecting immunocompromised patients. However, severe side effects have limited the utility of this drug. The aim of this study was to evaluate the antifungal effect of the combination of amphotericin B with black tea or white tea and protective of citotoxic effect. The present study shows that white and black teas have additive effects with amphotericin B against some species Candida. In addition, the combination of white and black tea with amphotericin B may reduce the toxicity of amphotericin B to red blood cells. Our results suggest that white and black tea is a potential agent to combine with amphotericin for antifungal efficacy and to reduce the amphotericin dose to lessen side effects.
2014-10-01
procedures in the clinic. The doctor wll decide if you will be given a local anesthesia to lessen the pain before beginning the injection procedure...injection and, while usually temporary, they may last several months. Pain , tenderness, or bruising around the injection site may also occur. Local weakness...indigestion; nausea; runny nose; stomach pain or upset; trouble sleeping; weakness Severe Side Effects: Severe allergic reactions (rash; hives
Krech, Lisa; Belz, Michael; Besse, Matthias; Methfessel, Isabel; Wedekind, Dirk; Zilles, David
2017-09-22
Electroconvulsive therapy (ECT) is the most effective therapy for severe depressive disorders. Though there are known clinical predictors of response (e.g., higher age, presence of psychotic symptoms), there is a lack of knowledge concerning the impact of patients' expectations on treatment outcome and tolerability in terms of possible placebo/nocebo effects. In 31 patients with unipolar or bipolar depressive disorder, we used a questionnaire to investigate the patients' expectations of ECT effectiveness and tolerability prior to and in the course of the treatment. Additionally, the questionnaire was used after the ECT course for a final assessment. Depressive symptoms and putative side-effects were measured at each time point. General linear models were used to analyze the course of depressive symptoms and patients' expectation of ECT effectiveness and tolerability. ECT significantly reduced depressive symptoms with large effect sizes. Patients' rating of ECT effectiveness decreased in parallel: While responders' rating of ECT effectiveness remained stable on a high level, non-responders' rating decreased significantly. Group difference was significant after, but not prior to and during the treatment. Regarding tolerability, there was a (temporary) significant increase in the severity of self-rated symptoms such as headache and memory impairment. In contrast, patients' expectation and assessment of ECT tolerability remained unchanged, and their expectations prior to ECT had no impact on the occurrence of side-effects. These findings contradict the presence of relevant placebo/nocebo effects in the context of ECT when investigating a population of mostly chronic or treatment resistant patients with moderate to severe depressive disorder.
New insights in the use of immunoglobulins for the management of immune deficiency (PID) patients
Krivan, Gergely; Jolles, Stephen; Granados, Eduardo Lopes; Paolantonacci, Phillipe; Ouaja, Rabye; Cissé, Ousmane Alfa; Bernatowska, Ewa
2017-01-01
Immunoglobulin replacement therapy (IRT) is standard treatment for patients with primary immunodeficiency (PID). Because most of the patients with PID will require long life-time immunoglobulin replacement therapy, the quality of the prescribed products is of utmost importance. The IRT is generally administered either intravenously (abbreviated IVIG), or subcutaneously (abbreviated SCIG). Both routes have been demonstrated to be effective. The preferred route may vary at different times during a given patient’s life. Options are therefore not fixed and the choice of route for immunoglobulin therapy will depend on several factors, including patient characteristics, clinical indication, venous access, side effects, rural or remote location, treatment compliance and patient preference. Many years ago, immunoglobulin therapy was associated with side effects which may compromise patient’s compliance and quality of life of the patients. Most of the side effects were related to impurities. Recently, major advances in the manufacturing process have been made and new processes, such as the Quality by design (QbD) approach were added into the manufacturing steps to ensure patients tolerability and safety. Due to the improved purity of the immunoglobulin products obtained by these processes, the incidence of side effects is lower, while the ways of administration of Ig therapy and the choice of the regimen has widened to suit patient’s preference and needs. PMID:29181272
ERIC Educational Resources Information Center
Matson, Johnny L.; Taras, Marie E.
1989-01-01
Studies assessing treatments for severe behavior problems of developmentally delayed persons were reviewed. Procedures used in the 382 studies, published from 1967-1987, were analyzed in terms of problem behaviors, side effects, and treatment methods. Also examined were number of studies reported yearly, maintenance and generalization of effects,…
Acute hemifacial dystonia possibly induced by clebopride.
Bosco, Domenico; Plastino, Massimiliano; Marcello, Maria Giovanna; Mungari, Pasquale; Fava, Antonietta
2009-01-01
Dystonic reactions produce twisting and repetitive movements or abnormal posturing. Severe dystonic reactions have been shown to occur in concert with numerous medications. This report details the case of a patient who developed hemifacial dystonia as acute side reaction from administration of clebopride for dyspeptic prophylaxis. When the drug was immediately stopped, the dystonic posture disappeared completely within 2 weeks. The use of clebopride may be associated with not only a reversible or persistent parkinsonism syndrome but also hemifacial dystonia; therefore, attention must be drawn to this possible side effect.
Does creating a subperiosteal tunnel influence the periorbital edema and ecchymosis in rhinoplasty?
Kara, Cüneyt Orhan; Kara, Inci Gökalan; Topuz, Bülent
2005-08-01
The study goal was to determine whether creating a subperiosteal tunnel before lateral osteotomy had an effect on postoperative periorbital edema, ecchymosis, and subconjunctival ecchymosis. Eighteen consecutive patients who underwent septorhinoplasty were included in the study. In all patients lateral osteotomies were carried out bilaterally, after creating a subperiosteal tunnel on a randomly chosen side and without creating a subperiosteal tunnel on the other side. The patients were seen on the second postoperative day, and a different surgeon who was unaware of the side with the periosteal tunnel determined the side of the face with more edema and ecchymosis. Subconjunctival ecchymosis was evaluated and recorded, as well. Creating subperiosteal tunnels before lateral osteotomy statistically increased periorbital ecchymosis. Although there was no statistically significant difference, creating subperiosteal tunnels also increased development and severity of subconjunctival ecchymosis and edema. We suggest performing lateral osteotomy without creating subperiosteal tunnels.
Potential benefits of underride guards in large truck side crashes.
Brumbelow, Matthew L
2012-01-01
To evaluate the maximum potential for side underride guards (SUGs) to reduce passenger vehicle occupant fatalities and injuries in crashes with large trucks in the United States. Examination of the Large Truck Crash Causation Study (LTCCS) identified 206 crash events involving a passenger vehicle impact with the side of a large truck. Each case was evaluated to determine whether the most severe injury sustained by a passenger vehicle occupant was a result of the impact with the side of the truck and whether an SUG could have reduced the injury severity. Data from the 2006-2008 Fatality Analysis Reporting System (FARS) and Trucks Involved in Fatal Accidents (TIFA) survey were used to compare the types of trucks involved in all fatal side impacts with passenger vehicles with the truck types in the LTCCS cases that were studied. FARS and TIFA data also were used to estimate the total annual number of passenger vehicle occupants killed in truck side impacts. In 143 of the 206 cases, the truck side impact produced the most severe injury sustained by a passenger vehicle occupant. In the other cases, no passenger vehicle occupant was injured or the most severe injury was due to an event preceding or following the truck side impact. Forty-nine of these occupants sustained injuries coded as level 3 or higher on the abbreviated injury scale (AIS) or were killed. SUGs could have reduced injury severity in 76 of the 143 cases, including 38 of the 49 cases with an AIS ≥ 3 coded injury or fatality. Semi-trailers were the most common type of impacted truck unit, both overall and when considering only cases where an SUG could have mitigated injury severity. Crashes where the front of the passenger vehicle struck the side of the semi-trailer perpendicularly or obliquely from the oncoming direction were less common overall than side-to-side and oblique/same direction crashes but more often produced an AIS ≥ 3 injury or fatality. The distribution of truck types in the LTCCS sample was similar to that in the FARS and TIFA data. Overall, around 1600 passenger vehicle occupants were killed in 2-vehicle truck side impact crashes during 2006-2008, or 22 percent of all passenger vehicle occupants who died in 2-vehicle crashes with large trucks. Structural incompatibility was a common factor in LTCCS crashes between passenger vehicles and the sides of large trucks. SUGs could have reduced injury risk in around three fourths of the crashes that produced an AIS ≥ 3 injury or fatality. Most of these crashes involved semi-trailers. However, the necessary strength and location of these SUGs present technical challenges that need to be addressed.
Macrocytic anemia and thrombocytopenia induced by orlistat.
Palacios-Martinez, David; Garcia-Alvarez, Juan Carlos; Montero-Santamaria, Nieves; Villar-Ruiz, Olga Patricia; Ruiz-Garcia, Antonio; Diaz-Alonso, Raquel Asuncion
2013-10-01
The overall incidence of obesity and its prevalence is increasing continuously. The obesity is a cardiovascular risk factor whose importance is increasing too. It is associated with many chronic conditions such as type II diabetes mellitus or cardiovascular diseases. The obesity is also implicated as a risk factor for several kinds of cancer such as esophagus, pancreas, colon, rectum, breast cancer in menopausal women. The treatment of the obesity may reduce the incidence of these diseases. The mainstray of the treatment of obesity is changing the lifestyles, but obesity´s treatment may need drug therapy or even though surgical treatment. Orlistat is a specific inhibitor of gastrointestinal lipases, which stops fat absortion. It is used along with a hypocaloric diet, for obesity´s treatment. The beneficial effects of orlistat include weight loss, the improvement of blood pressure´s control, it may delay the development of diabetes mellitus, and it may reduce HbA1c. Besides the interaction with other drugs (mainly warfarin and amiodarone). Orlistat´s mainly side effects are gastrointestinal disorders such as the existence of oily spotting from the rectum, abdominal pain or discomfort, fecal urgency. There are also side effects at other levels, like flu symptoms, hypoglycemia, heathache or upper respiratory infections. There are other side effects with very low incidence but clinically relevant like pancreatitis, subacute liver failure, severe liver disease, myopathy, or tubular necrosis secondary to oxalate nephropathy induced by Orlistat. IN THIS CASE REPORT APPEARS A NEW ADVERSE EFFECT OF ORLISTAT THAT HAS NOT BEEN DESCRIBED ABOVE: thrombopenia and macrocytic anemia.
Disthaporn, Suteeta; Suri, Sunjay; Ross, Bruce; Tompson, Bryan; Baena, Diogenes; Fisher, David; Lou, Wendy
2017-07-01
To compare the mixed dentition incisor and molar overjet, severity of contraction of the dental arch, and the sagittal molar relationship on the cleft side vs the noncleft side in children with repaired complete unilateral cleft of the lip and palate (UCLP). Orthodontic records taken prior to orthodontic preparation for alveolar bone grafting were screened to select study casts from patients with nonsyndromic repaired complete UCLP who did not have mandibular skeletal or dental asymmetry. The study sample comprised dental casts from 74 children aged 8.9 ± 1 years. Standardized digital photographs were acquired at 1:1 magnification. A coordinate system was developed using digital image-processing software (Photoshop CS4 and Adobe Illustrator). Incisor and molar overjet, Angle's classification, and arch contraction were recorded. Descriptive statistics, paired t-tests, and kappa statistics were used to compare the cleft and noncleft sides. A negative overjet of -1 to -5 mm was often present at the incisors, with greater frequency and magnitude on the cleft side. Class II molar relation was more frequent on the cleft side (61.1%) than on the noncleft side (47.2%). Significantly greater contraction of the cleft side deciduous canine and deciduous first molar was noted, while the difference was very minor at the first permanent molar. Cleft side maxillary arch contraction was most severe in the deciduous canine and first deciduous molar region and progressively less severe in the posterior region of the arch. A greater frequency and severity of negative overjet and Class II molar relationship was seen on the cleft side.
Intravenous flurbiprofen axetil can increase analgesic effect in refractory cancer pain
Wu, Hongyang; Chen, Zhendong; Sun, Guoping; Gu, Kangsheng; Pan, Yueyin; Hao, Jiqing; Du, Yingying; Ning, Jie
2009-01-01
Background The aim of this study was to investigate the analgesic effects of intravenous flurbiprofen axetil for the refractory pain in cancer patients. Methods 2109 patients were screened from the department of medical oncology, the first affiliated hospital of Anhui medical university in China between October of 2007 and October of 2008. Thirty-seven cases of cancer patients who had bad effect from anaesthetic drugs were received administration of intravenous flurbiprofen axetil with dose of 50 mg/5 ml/day. The pain score was evaluated for pre- and post- treatment by Pain Faces Scale criteria, and the side effects were also observed. Results Intravenous flurbiprofen axetil increased the analgesic effects. The total effective rate was 92%. The side effects, such as abdominal pain, alimentary tract bleeding which were found in using NSAIDs or constipation, nausea, vomit, sleepiness which were found in using opioid drugs did not be found. Conclusion Intravenous flurbiprofen axetil could provide better analgesia effects and few side effects to patients with refractory cancer pain. It could also increase analgesia effects when combining with anesthetic drugs in treatment of moderate or severe pain, especially breakthrough pain, and suit to patients who can not take oral drugs for the reason of constipation and psychosomatic symptoms. PMID:19267934
Analgesics for orthopedic postoperative pain.
Bourne, Michael H
2004-03-01
Postoperative pain management is critical for optimal care of orthopedic surgery patients. Opioids, administered intramuscularly, as epidurals, or IV as patient-controlled analgesia, are effective for severe pain. Adjunctive therapy and preemptive analgesia such as nerve blocks, and methods of delivery such as infusion pumps, may be used after total knee arthroplasty and anterior cruciate ligament (ACL) reconstruction. Oral opioids are effective for moderate to severe pain, and tramadol, with efficacy comparable to morphine but with fewer severe side effects, is selected for moderate to moderately severe pain. Opioid-sparing NSAIDs, such as ketorolac, and COX-2-specific NSAIDS have use in pain management of hip, knee, and ACL procedures. An individualized regimen of appropriate analgesics, combined with nonpharmacologic treatments such as physical therapy or cryotherapy and patient education, can aid orthopedic surgery patients' recovery.
NASA Astrophysics Data System (ADS)
Tsai, Ming-Yen; Chang, Ting-Chang; Chu, Ann-Kuo; Hsieh, Tien-Yu; Chen, Te-Chih; Lin, Kun-Yao; Tsai, Wu-Wei; Chiang, Wen-Jen; Yan, Jing-Yi
2013-07-01
This letter investigates the effect of temperature on hot-carrier stress-induced degradation behavior in InGaZnO thin film transistors. After hot-carrier stress at 25 °C, serious on-current and subthreshold swing degradations are observed due to trap state generation near the drain side. For identical stress performed at elevated temperatures, current degradation in the I-V transfer curve under reverse mode is gradually suppressed and the anomalous hump in the gate-to-drain capacitance-voltage curve becomes more severe. These suppressed degradations and the more severe hump can be both attributed to hole-trapping near the drain side due to high drain bias at high temperature.
Venkataraman, Narayan; Ulfarsson, Gudmundur F; Shankar, Venky N
2013-10-01
A nine-year (1999-2007) continuous panel of crash histories on interstates in Washington State, USA, was used to estimate random parameter negative binomial (RPNB) models for various aggregations of crashes. A total of 21 different models were assessed in terms of four ways to aggregate crashes, by: (a) severity, (b) number of vehicles involved, (c) crash type, and by (d) location characteristics. The models within these aggregations include specifications for all severities (property damage only, possible injury, evident injury, disabling injury, and fatality), number of vehicles involved (one-vehicle to five-or-more-vehicle), crash type (sideswipe, same direction, overturn, head-on, fixed object, rear-end, and other), and location types (urban interchange, rural interchange, urban non-interchange, rural non-interchange). A total of 1153 directional road segments comprising of the seven Washington State interstates were analyzed, yielding statistical models of crash frequency based on 10,377 observations. These results suggest that in general there was a significant improvement in log-likelihood when using RPNB compared to a fixed parameter negative binomial baseline model. Heterogeneity effects are most noticeable for lighting type, road curvature, and traffic volume (ADT). Median lighting or right-side lighting are linked to increased crash frequencies in many models for more than half of the road segments compared to both-sides lighting. Both-sides lighting thereby appears to generally lead to a safety improvement. Traffic volume has a random parameter but the effect is always toward increasing crash frequencies as expected. However that the effect is random shows that the effect of traffic volume on crash frequency is complex and varies by road segment. The number of lanes has a random parameter effect only in the interchange type models. The results show that road segment-specific insights into crash frequency occurrence can lead to improved design policy and project prioritization. Copyright © 2013 Elsevier Ltd. All rights reserved.
Taurine protects against methotrexate-induced toxicity and inhibits leukocyte death
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cetiner, Mustafa; Sener, Goeksel; Sehirli, A. Ozer
2005-11-15
The efficacy of methotrexate (MTX), a widely used cytotoxic chemotherapeutic agent, is often limited by severe side effects and toxic sequelae. Regarding the mechanisms of these side effects, several hypotheses have been put forward, among which oxidative stress is noticeable. The present study was undertaken to determine whether taurine, a potent free radical scavenger, could ameliorate MTX-induced oxidative injury and modulate immune response. Following a single dose of methotrexate (20 mg/kg), either saline or taurine (50 mg/kg) was administered for 5 days. After decapitation of the rats, trunk blood was obtained and the ileum, liver, and kidney were removed tomore » measure malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and collagen content, as well as histological examination. Our results showed that MTX administration increased the MDA, MPO activity, and collagen contents and decreased GSH levels in all tissues (P < 0.001), while these alterations were reversed in taurine-treated group (P < 0.05-0.01). Elevated (P < 0.001) TNF-{alpha} level observed following MTX treatment was depressed with taurine (P < 0.01). Oxidative burst of neutrophils stimulated by phorbol myristate acetate was reduced in saline-treated MTX group (P < 0.001), while taurine abolished this effect. Similarly, flow cytometric measurements revealed that leukocyte apoptosis and cell death were increased in MTX-treated animals, while taurine reversed these effects (P < 0.05). Reduced cellularity in bone marrow samples of MTX-treated group (P < 0.01) was reversed back to control levels in taurine-treated rats. Severe degeneration of the intestinal mucosa, liver parenchyma, glomerular, and tubular epithelium observed in saline-treated group was improved by taurine treatment. In conclusion, it appears that taurine protects against methotrexate-induced oxidant organ injury and inhibits leukocyte apoptosis and may be of therapeutic potential in alleviating the systemic side effects of chemotherapeutics.« less
Preventive treatment of migraine.
Silberstein, Steven D
2005-01-01
Migraine preventive therapy, even in the absence of a headache, is given in an attempt to reduce the frequency, duration, or severity of attacks. Circumstances that might warrant preventive treatment include disabling migraine attacks, the overuse of acute medications or failure of or contraindication to acute medications, troublesome side effects from medication, hemiplegic migraine, or very frequent headaches (more than 2 a week). The major medication groups for preventive treatment include anticonvulsants, antidepressants, b-adrenergic blockers, calcium channel antagonists, serotonin antagonists, neurotoxins, nonsteroidal anti-inflammatory drugs, and others. If preventive medication is indicated, the agent preferentially should be chosen from one of the first-line categories, based on the drug's side-effect profile and the patient's coexistent and comorbid conditions.
Renal thrombotic microangiopathy caused by interferon beta-1a treatment for multiple sclerosis
Mahe, Julien; Meurette, Aurélie; Moreau, Anne; Vercel, Caroline; Jolliet, Pascale
2013-01-01
Interferon beta-1a is available as an immunomodulating agent for relapsing forms of multiple sclerosis. Common side effects include flu-like symptoms, asthenia, anorexia, and administration site reaction. Kidney disorders are rarely reported. In this study we describe the case of a woman who has been undergoing treatment with interferon beta-1a for multiple sclerosis for 5 years. She developed a hemolytic-uremic syndrome with intravascular hemolysis in a context of severe hypertension. A kidney biopsy showed a thrombotic microangiopathy. This observation highlights an uncommon side effect of long-term interferon beta-1a therapy. Pathophysiological mechanisms leading to this complication might be explained by the antiangiogenic activity of interferon. PMID:23950639
Metabolic Syndrome and Antipsychotics: The Role of Mitochondrial Fission/Fusion Imbalance.
Del Campo, Andrea; Bustos, Catalina; Mascayano, Carolina; Acuña-Castillo, Claudio; Troncoso, Rodrigo; Rojo, Leonel E
2018-01-01
Second-generation antipsychotics (SGAs) are known to increase cardiovascular risk through several physiological mechanisms, including insulin resistance, hepatic steatosis, hyperphagia, and accelerated weight gain. There are limited prophylactic interventions to prevent these side effects of SGAs, in part because the molecular mechanisms underlying SGAs toxicity are not yet completely elucidated. In this perspective article, we introduce an innovative approach to study the metabolic side effects of antipsychotics through the alterations of the mitochondrial dynamics, which leads to an imbalance in mitochondrial fusion/fission ratio and to an inefficient mitochondrial phenotype of muscle cells. We believe that this approach may offer a valuable path to explain SGAs-induced alterations in metabolic homeostasis.
Metabolic Syndrome and Antipsychotics: The Role of Mitochondrial Fission/Fusion Imbalance
del Campo, Andrea; Bustos, Catalina; Mascayano, Carolina; Acuña-Castillo, Claudio; Troncoso, Rodrigo; Rojo, Leonel E.
2018-01-01
Second-generation antipsychotics (SGAs) are known to increase cardiovascular risk through several physiological mechanisms, including insulin resistance, hepatic steatosis, hyperphagia, and accelerated weight gain. There are limited prophylactic interventions to prevent these side effects of SGAs, in part because the molecular mechanisms underlying SGAs toxicity are not yet completely elucidated. In this perspective article, we introduce an innovative approach to study the metabolic side effects of antipsychotics through the alterations of the mitochondrial dynamics, which leads to an imbalance in mitochondrial fusion/fission ratio and to an inefficient mitochondrial phenotype of muscle cells. We believe that this approach may offer a valuable path to explain SGAs-induced alterations in metabolic homeostasis. PMID:29740394
NASA Astrophysics Data System (ADS)
Porter, Stephen Christopher
1999-10-01
New segmented polyetherurethanes (PEUs) with low surface energy hydrocarbon and fluorocarbon side-chains attached to the polymer hard segments were synthesized. The surface chemistry of solvent cast polymer films was studied using X-ray photoelectron spectroscopy, time-of-flight secondary ion mass spectrometry, and dynamic contact angle (DCA) measurements. Increases in the overall density and length of the alkyl side-chains within the PEUs resulted in greater side-chain concentrations at the polymer surface. PEUs bearing long alkyl (> C10 ) and perfluorocarbon side-chains were found to posses surfaces with highly enriched side-chain concentrations relative to the bulk polymer. In PEUs with significant side-chain surface enrichment, the relatively polar hard segment blocks were shown to reside in high concentrations just below the side-chain enriched surface layer. Furthermore, DCA measurements demonstrated that the surface of the alkyl side-chain PEUs did not undergo significant rearrangement when placed into an aqueous environment, whereas the surface of a hard segment model polymer bearing C18 sidechains (PEU-C18-HS) did. Hydrogen bonding within the PEUs was examined using FTIR and was shown to be disrupted by the addition of side-chains; an effect dependent on the density but not on the length of the side-chains. Heteropolymer blends comprised of mixtures of high side-chain density and side-chain free PEUs were compared with homopolymers having the same overall side-chain concentration as the blends. Significantly more surface enrichment of side-chains was found in the heteropolymer blends whereas hydrogen bonding nearly the same as in the homopolymers. Adsorption of native and delipidized human serum albumin (HSA) from pure solution and blood plasma; the elutabilty of adsorbed HSA; and static platelet adhesion to plasma preadsorbed surfaces, were all examined on alkyl side-chain PEUs. Several polymers with high C18 side-chain densities displayed increased affinity for albumin, and reduced elutability. Among these, PEU-C18-HS demonstrated a significant reduction in platelet adhesion at low plasma pre-adsorption concentrations. However, competitive binary adsorption of fibrinogen in the presence of HSA demonstrated lower relative albumin affinity for PEU-C18-HS than other PEUs. The observed effects are thought to be mainly a result of increased surface hydrophobicity of the alkyl-side chain modified PEU, and not high specificity albumin binding.
De Cassan, Chiara; Fiorino, Gionata; Danese, Silvio
2012-01-01
Systemic corticosteroids are highly effective at inducing clinical remission in cases of acute exacerbation of Crohn's disease (CD) and ulcerative colitis (UC); however, their use is limited by their frequent and sometimes severe side effects. Thus, a second generation of corticosteroids with less systemic effects has been developed. This review analyzed all of the studies on the new formulations of steroids with limited absorption (budesonide, budesonide MMX®, beclomethasone dipropionate and erythrocyte-mediated delivery of dexamethasone) in patients with CD and UC. All relevant articles published in English between September 1960 and April 2011 were reviewed. Budesonide is superior to placebo, and as effective as systemic corticosteroids in inducing clinical remission in patients with ileo-colonic CD, but evidence of mucosal healing is limited. When administered as an MMX formula, budesonide can also effectively induce clinical remission in patients with UC, but budesonide alone is not effective in maintaining clinical remission in CD or UC. Beclomethasone dipropionate seems to be effective in patients with mild-to-moderate left-sided and extensive UC, while data on erythrocyte-mediated delivery of dexamethasone are encouraging but still limited. The safety profile for all these products is good but more studies are needed. Steroids remain the mainstay for the induction of clinical remission in cases of acute relapse of both CD and UC. Second-generation corticosteroids are an interesting alternative, with the advantage of high topical activity, less systemic toxicity and limited side effects. Copyright © 2012 S. Karger AG, Basel.
Severe neuropathy after high dose carboplatin in three patients receiving multidrug chemotherapy
Heinzlef, O.; Lotz, J.; Roullet, E.
1998-01-01
Three patients are described who developed a severe neuropathy after chemotherapy with high dose cis-diamine-(1,1-cyclobutane dicarboxylato) platinum (carboplatin). This toxic side effect, which is unusual at conventional doses, might become more frequent as increasing doses are administered to overcome drug resistance in cancer treatment, and might limit its use at very high doses before haematopoietic stem cell transplantation. PMID:9598687
Curtis, Gabrielle; Lewis, Amy C
2014-12-01
Toxidendron (poison ivy, oak, and sumac) contact dermatitis is a common complaint in the outpatient primary care setting with little evidence-based guidance on best treatment duration. This randomized, controlled trial examined the efficacy and side effects of a 5-day regimen of 40 mg oral prednisone daily (short course) compared to the same 5-day regimen followed by a prednisone taper of 30 mg daily for 2 days, 20 mg daily for 2 days, 10 mg daily for 2 days, and 5 mg daily for 4 days over a total of 15 days (long course) in patients with severe poison ivy dermatitis. In 49 patients with severe poison ivy, non-adherence rates, rash return, medication side effects, and time to improvement and complete healing of the rash were not significantly different between the two groups. Patients receiving the long course regimen were significantly less likely to utilize other medications (22.7% vs. 55.6%, P = 0.02, number needed to treat 3.05). This study suggests that a longer course prescription may save patients' time and exposure to excess medication in the treatment of severe poison ivy. Application of this information to clinical practice will save return visits and reduce excess non-prescription medication administration to individual patients.
Curtis, Gabrielle; Lewis, Amy C.
2014-01-01
Background Toxidendron (poison ivy, oak, and sumac) contact dermatitis is a common complaint in the outpatient primary care setting with little evidence-based guidance on best treatment duration. Methods This randomized, controlled trial examined the efficacy and side effects of a 5-day regimen of 40 mg oral prednisone daily (short course) compared to the same 5-day regimen followed by a prednisone taper of 30 mg daily for 2 days, 20 mg daily for 2 days, 10 mg daily for 2 days, and 5 mg daily for 4 days over a total of 15 days (long course) in patients with severe poison ivy dermatitis. Results In 49 patients with severe poison ivy, non-adherence rates, rash return, medication side effects, and time to improvement and complete healing of the rash were not significantly different between the two groups. Patients receiving the long course regimen were significantly less likely to utilize other medications (22.7% vs. 55.6%, P = 0.02, number needed to treat 3.05). Conclusions This study suggests that a longer course prescription may save patients’ time and exposure to excess medication in the treatment of severe poison ivy. Application of this information to clinical practice will save return visits and reduce excess non-prescription medication administration to individual patients. PMID:25247016
Large and Small Cars in Real-World Crashes -Patterns of Use, Collision Types and Injury Outcomes
Thomas, Pete; Frampton, Richard
1999-01-01
Previous work examining the effect of vehicle mass has demonstrated the link with occupant injury severity. The principal factor has been related to Newtonian mechanics. This paper analyses data from the UK Co-operative Crash Injury Study and identifies other factors associated with car size. The mass of the car is found to have a predominant effect on injury outcome in frontal collisions only where the effect is seen most in injuries to the head, face and chest. Most fatal casualties in small cars die when in collision with another car in front or side collisions while the key group for large cars is frontal collisions with road-side objects. There are several characteristics of small car occupants that differ from those in large cars including gender, age and vehicle occupancy. New information in the analysis concerns the priorities in casualty reduction between small and large car occupants and the paper argues that vehicle design should take account of this variation to produce vehicles optimised for the complete range of crashes and car occupants.
Kishi, Taro; Iwata, Nakao
2015-01-01
Background: We performed an updated meta-analysis of randomized controlled trials of combination therapy with cholinesterase inhibitors and memantine in patients with Alzheimer’s disease. Methods: We reviewed cognitive function, activities of daily living, behavioral disturbance, global assessment, discontinuation rate, and individual side effects. Results: Seven studies (total n=2182) were identified. Combination therapy significantly affected behavioral disturbance scores (standardized mean difference=−0.13), activity of daily living scores (standardized mean difference=−0.10), and global assessment scores (standardized mean difference=−0.15). In addition, cognitive function scores (standardized mean difference=−0.13, P=.06) exhibited favorable trends with combination therapy. The effects of combination therapy were more significant in the moderate-to-severe Alzheimer’s disease subgroup in terms of all efficacy outcome scores. The discontinuation rate was similar in both groups, and there were no significant differences in individual side effects. Conclusions: Combination therapy was beneficial for the treatment of moderate-to-severe Alzheimer’s disease in terms of cognition, behavioral disturbances, activities of daily living, and global assessment was well tolerated. PMID:25548104
Matsunaga, Shinji; Kishi, Taro; Iwata, Nakao
2014-12-28
We performed an updated meta-analysis of randomized controlled trials of combination therapy with cholinesterase inhibitors and memantine in patients with Alzheimer's disease. We reviewed cognitive function, activities of daily living, behavioral disturbance, global assessment, discontinuation rate, and individual side effects. Seven studies (total n=2182) were identified. Combination therapy significantly affected behavioral disturbance scores (standardized mean difference=-0.13), activity of daily living scores (standardized mean difference=-0.10), and global assessment scores (standardized mean difference=-0.15). In addition, cognitive function scores (standardized mean difference=-0.13, P=.06) exhibited favorable trends with combination therapy. The effects of combination therapy were more significant in the moderate-to-severe Alzheimer's disease subgroup in terms of all efficacy outcome scores. The discontinuation rate was similar in both groups, and there were no significant differences in individual side effects. Combination therapy was beneficial for the treatment of moderate-to-severe Alzheimer's disease in terms of cognition, behavioral disturbances, activities of daily living, and global assessment was well tolerated. © The Author 2015. Published by Oxford University Press on behalf of CINP.
LACTIC ACIDOSIS: A RARE MANIFESTATION OF SYNTHETIC MARIJUANA INTOXICATION.
Antill, T; Jakkoju, A; Dieguez, J; Laskhmiprasad, L
2015-01-01
Synthetic cannabinoids are designer drugs that mimic the effect of cannabis, which has become popular with young drug users. These drugs have a similar chemical structure and pharmacologic effects as marijuana, but seem to be more potent. These substances have been banned by the US Drug Enforcement Agency in 2010. Prior to 2010, these drugs were perceived as "safer" by the general population. Synthetic cannabinoids cause effects similar to marijuana making the subjects euphoric. However, they act as full, rather than partial, agonist at the receptor sites causing more severe side effects such as severe agitation, seizures, acute renal failure, and lactic acidosis.
... injected intravenously (into a vein) over a 4 hour period by a doctor or nurse. It is usually given on days 1, 8, and 15 of a 28 day cycle. This cycle may be repeated as long as the medication continues to work and does not cause severe side effects.Talk ...
Epidemiologic, socioeconomic and psychosocial aspects in lupus erythematosus.
Aberer, E
2010-08-01
Epidemiologic, socioeconomic, and psychosocial factors play an important role in health care and handling of patients with the various clinical forms of lupus erythematosus (LE). Patients with LE are mostly young women; adolescents and some ethnic groups are especially prone to a severe course of disease. The unpredictable and fluctuating flares of disease, the need for longterm treatment, and the side effects and damage caused by the disease itself severely reduce quality of life. Problems arise, involving family members, adherence to medical advice and therapy, communication and self management. Socioeconomically, patients are often unable to take regular employment and to pay for health insurance. Stress factors that arise have a negative impact on the course of disease, increasing both fatigue and the basic burden of illness. Healthcare professionals must pay careful attention to all these items, as they attempt to treat flares, minimize drug side effects, provide pain relief, arrange communication and exercise programs along with behavioral and psychosocial interventions in multidisciplinary cooperation, and also involve and support family members.
Profound Bradycardia After Intrathecal Baclofen Injection in a Patient With Hydranencephaly.
Sechrist, Catherine; Kinsman, Stephen; Cain, Nicole
2015-12-01
Intrathecal baclofen is often used to treat medically intractable spasticity of cerebral or spinal origin. Complications are rare but close monitoring is routinely performed with intrathecal test doses and before pump implantation. We describe a 6 year-old girl with hydranencephaly who underwent an intrathecal baclofen test dose and developed severe bradycardia. A 6 year-old girl with hydranencephaly, quadriplegic cerebral palsy, and severe spasticiityn was a candidate for an intrathecal baclofen pump. She underwent an intrathecal baclofen test dose and within 4 hours developed a heart rate between 30-40 beats per minute and mild hypotension without neurological side effects. Vital signs subsequently normalized, and she was discharged home within 48 hours of admission. Although neurological side effects such as drowsiness and weakness are commonly associated with intrathecal baclofen test doses, attention should also be focused on possible hemodynamic complications including significant bradycardia, especially in vulnerable patients such as those with possible or known hypothalamic dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.
Er Effect of Low Molecular Liquid Crystal on One-Sided Patterned Electrodes
NASA Astrophysics Data System (ADS)
Kikuchi, Takehito; Inoue, Akio; Furusho, Junji; Kawamuki, Ryohei
Several kinds of ER fluids (ERF) have been developed and have been applied to some mechatronics devices and processing technologies. In many conventional applications of ERFs, these devices consist of bilateral electrodes to apply electric field in ERF. However, the electric field of several kV/mm may be necessary to generate an ER effect sufficiently for practical purposes. The gap between a pair of electrodes should be, therefore, maintained narrowly and exactly for fears of short-circuit. At the same time, this electrode system also requires an interconnection on driving parts. To improve these disadvantages, we proposed "one-sided patterned electrode" (OSPE) systems in previous works. In this report, we confirmed the flow characteristics of low molecular liquid crystal (LMLC) on OSPE. Next, we also confirmed the different characteristics depending on the pattern type. Depending on results of electro-static analysis, we conclude that such a difference may results from the directors of LC molecules derived by electric field.
Managing atrial fibrillation in the elderly: critical appraisal of dronedarone.
Trigo, Paula; Fischer, Gregory W
2012-01-01
Atrial fibrillation is the most commonly seen arrhythmia in the geriatric population and is associated with increased cardiovascular morbidity and mortality. Treatment of the elderly with atrial fibrillation remains challenging for physicians, because this unique subpopulation is characterized by multiple comorbidities requiring chronic use of numerous medications, which can potentially lead to severe drug interactions. Furthermore, age-related changes in the cardiovascular system as well as other physiological changes result in altered drug pharmacokinetics. Dronedarone is a new drug recently approved for the treatment of arrhythmias, such as atrial fibrillation and/or atrial flutter. Dronedarone is a benzofuran amiodarone analog which lacks the iodine moiety and contains a methane sulfonyl group that decreases its lipophilicity. These differences in chemical structure are responsible for making dronedarone less toxic than amiodarone which, in turn, results in fewer side effects. Adverse events for dronedarone include gastrointestinal side effects and rash. No dosage adjustments are required for patients with renal impairment. However, the use of dronedarone is contraindicated in the presence of severe hepatic dysfunction.
Focus on ulcerative colitis: stable gastric pentadecapeptide BPC 157.
Sikiric, P; Seiwerth, S; Rucman, R; Turkovic, B; Rokotov, D S; Brcic, L; Sever, M; Klicek, R; Radic, B; Drmic, D; Ilic, S; Kolenc, D; Stambolija, V; Zoricic, Z; Vrcic, H; Sebecic, B
2012-01-01
Stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419) may be the new drug stable in human gastric juice, effective both in the upper and lower GI tract, and free of side effects. BPC 157, in addition to an antiulcer effect efficient in therapy of inflammatory bowel disease (IBD) (PL 14736) so far only tested in clinical phase II, has a very safe profile, and exhibited a particular wound healing effect. It also has shown to interact with the NO-system, providing endothelium protection and angiogenic effect, even in severely impaired conditions (i.e., it stimulated expression of early growth response 1 gene responsible for cytokine and growth factor generation and early extracellular matrix (collagen) formation (but also its repressor nerve growth factor 1-A binding protein-2)), important to counteract severe complications of advanced and poorly controlled IBD. Hopefully, the lessons from animal studies, particularly advanced intestinal anastomosis healing, reversed short bowel syndrome and fistula healing indicate BPC 157's high significance in further IBD therapy. Also, this supportive evidence (i.e., no toxic effect, limit test negative, LD1 not achieved, no side effect in trials) may counteract the problems commonly exercised in the use of peptidergic agents, particularly those used on a long-term basis.
[Pharmacological aspects of pain research in Germany].
Niederberger, E; Kuner, R; Geißlinger, G
2015-10-01
In spite of several approved analgesics, the therapy of pain still constitutes a challenge due to the fact that the drugs do not exert sufficient efficacy or are associated with severe side effects. Therefore, the development of new and improved painkillers is still of great importance. A number of highly qualified scientists in Germany are investigating signal transduction pathways in pain, effectivity of new drugs and the so far incompletely investigated mechanisms of well-known analgesics in preclinical and clinical studies. The highlights of pharmacological pain research in Germany are summarized in this article.
Effectiveness of medical treatment for Cushing's syndrome: a systematic review and meta-analysis.
Broersen, Leonie H A; Jha, Meghna; Biermasz, Nienke R; Pereira, Alberto M; Dekkers, Olaf M
2018-05-31
To systematically review the effectiveness of medical treatment for Cushing's syndrome in clinical practice, regarding cortisol secretion, clinical symptom improvement, and quality of life. To assess the occurrence of side effects of these medical therapies. Eight electronic databases were searched in March 2017 to identify potentially relevant articles. Randomized controlled trials and cohort studies assessing the effectiveness of medical treatment in patients with Cushing's syndrome, were eligible. Pooled proportions were reported including 95% confidence intervals. We included 35 articles with in total 1520 patients in this meta-analysis. Most included patients had Cushing's disease. Pooled reported percentage of patients with normalization of cortisol ranged from 35.7% for cabergoline to 81.8% for mitotane in Cushing's disease. Patients using medication monotherapy showed a lower percentage of cortisol normalization compared to use of multiple medical agents (49.4 vs. 65.7%); this was even higher for patients with concurrent or previous radiotherapy (83.6%). Mild side effects were reported in 39.9%, and severe side effects were seen in 15.2% of patients after medical treatment. No meta-analyses were performed for clinical symptom improvement or quality of life due to lack of sufficient data. This meta-analysis shows that medication induces cortisol normalization effectively in a large percentage of patients. Medical treatment for Cushing's disease patients is thus a reasonable option in case of a contraindication for surgery, a recurrence, or in patients choosing not to have surgery. When experiencing side effects or no treatment effect, an alternate medical therapy or combination therapy can be considered.
Glycation, carbonyl stress and AGEs inhibitors: a patent review.
Jahan, Humera; Choudhary, M Iqbal
2015-01-01
The glycation process, comprising a series of reactions, results in the formation of heterogeneous adducts, known as advanced glycation end products (AGEs). AGEs are involved in several pathologies, including diabetes-associated late complications, atherosclerosis, Alzheimer's disease and inflammatory arthritis. Several inhibitors of AGEs and/or reactive carbonyl species have been identified from various sources, including natural products and synthetic molecules, and have been investigated for their mechanism of action. This review covers the literature on AGEs inhibitors published as patents between 2001 and 2014. Initially, the earlier reported molecules with AGEs inhibitory properties, their mechanism of actions and reported adverse effects are discussed. The main focus has been on the chemical structures, methods for evaluation of the activity, modes of action, pharmacokinetics and therapeutic outcomes. The potential of these AGEs inhibitors in the treatment and management of a number of diseases are also discussed in this review. The reactive carbonyl species and AGEs have recently emerged as novel therapeutic targets for the prevention and treatment of several diseases. Currently, the major concerns with the use of AGEs inhibitors as therapeutic agents are low effectiveness, poor pharmacokinetics and undesirable side effects. Many of the AGEs inhibitors reviewed here possess potent antiglycation activity and are devoid of undesirable side effects. These small molecules inhibitors can, therefore, serve as scaffolds for the development and designing of new AGEs inhibitors as clinical agents.
Lekwuttikarn, Ramrada; Tempark, Therdpong; Chatproedprai, Susheera; Wananukul, Siriwan
2017-08-01
The high prevalence of acne vulgaris in teenagers has increased comorbidities. Lasers offer alternative options for acne treatment because they have rapid action, low systemic adverse effects, and do not require everyday treatment. To study the efficacy and patients' satisfaction of 595-nm pulse dye laser (PDL) treatment of acne vulgaris and acne erythema in adolescents and early adulthood, we designed a blocked-randomized, split-faced 595-nm PDL (fluence 8 J/cm 3 pulse duration 10 ms, spot size 7 mm, 2 session every 2 weeks) study in patients with mild to moderate acne by comparing the laser-treated and non-treated side. The acne lesion counts, acne erythema grading, and acne severity grading were evaluated at baseline and 2, 4, and 8 weeks. Thirty patients were recruited. The results showed no statistically significant difference except the papule count at week 4 which was -1.828 on the treated side and 0.103 on the non-treated side of the face, P-value 0.0018. There was no statistically significant difference of acne severity grading and acne erythema grading between both sides of the face. The mean scores of patients' satisfaction on the laser-treated side were 75, 81, and 81%, respectively. The PDL treatment in this study reveals no significant improvement in acne therapy; however, the patients were satisfied with this laser treatment. © 2017 The International Society of Dermatology.
Kolshus, E; Jelovac, A; McLoughlin, D M
2017-02-01
Brief-pulse electroconvulsive therapy (ECT) is the most acutely effective treatment for severe depression though concerns persist about cognitive side-effects. While bitemporal electrode placement is the most commonly used form worldwide, right unilateral ECT causes less cognitive side-effects though historically it has been deemed less effective. Several randomized trials have now compared high-dose (>5× seizure threshold) unilateral ECT with moderate-dose (1.0-2.5× seizure threshold) bitemporal ECT to investigate if it is as effective as bitemporal ECT but still has less cognitive side-effects. We aimed to systematically review these trials and meta-analyse clinical and cognitive outcomes where appropriate. We searched PubMed, PsycINFO, Web of Science, Cochrane Library and EMBASE for randomized trials comparing these forms of ECT using the terms 'electroconvulsive' OR 'electroshock' AND 'trial'. Seven trials (n = 792) met inclusion criteria. Bitemporal ECT did not differ from high-dose unilateral ECT on depression rating change scores [Hedges's g = -0.03, 95% confidence interval (CI) -0.17 to 0.11], remission (RR 1.06, 95% CI 0.93-1.20), or relapse at 12 months (RR 1.42, 95% CI 0.90-2.23). There was an advantage for unilateral ECT on reorientation time after individual ECT sessions (mean difference in minutes = -8.28, 95% CI -12.86 to -3.70) and retrograde autobiographical memory (Hedges's g = -0.46, 95% CI -0.87 to -0.04) after completing an ECT course. There were no differences for general cognition, category fluency and delayed visual and verbal memory. High-dose unilateral ECT does not differ from moderate-dose bitemporal ECT in antidepressant efficacy but has some cognitive advantages.
Cutaneous Side-effects of Immunomodulators in MS.
Lebrun, C; Bertagna, M; Cohen, M
2011-09-01
Local skin reactions to subcutaneous injections of interferon beta (IFNB) or glatiramer acetate (GA) in multiple sclerosis (MS) are frequent, while severe cutaneous toxicity is rare. Both IFNB and GA are immunomodulatory drugs that have excellent safety profiles and are currently used for treatment of MS. They are administered by SC injection every other day for IFNB-1b, three times a week for IFNB-1a or daily for 20 mg for GA. The most common adverse effects, which occur in approximately 20-60% of patients, include pain, inflammation and induration at the injection sites. Another adverse effect is frank panniculitis followed by localized lipoatrophy at the injection sites, which has been described in half of the patients receiving GA injections but is also described with Subcutaneous IFNB-1b. No guidelines have yet been established for the treatment of skin reactions, which is a frequent point for discussion between neurologists and dermatologists. In addition, no treatment has been found for established lipoatrophy. The prevention and management of cutaneous side-effects include patient education, regular examination and manual palpation of all injection sites. Non-steroid antiinflammatory gels, local corticosteroids or endermology can help patients to resolve side-effects and to continue immunomodulatory treatment.
Experimental treatment of antipsychotic-induced movement disorders
Shireen, Erum
2016-01-01
Antipsychotic drugs are extensively prescribed for the treatment of schizophrenia and other related psychiatric disorders. These drugs produced their action by blocking dopamine (DA) receptors, and these receptors are widely present throughout the brain. Therefore, extended antipsychotic use also leads to severe extrapyramidal side effects. The short-term effects include parkinsonism and the later appearing tardive dyskinesia. Currently available treatments for these disorders are mostly symptomatic and insufficient, and are often linked with a number of detrimental side effects. Antipsychotic-drug-induced tardive dyskinesia prompted researchers to explore novel drugs with fewer undesirable extrapyramidal side effects. Preclinical studies suggest a role of 5-hydroxytryptamine (serotonin)-1A and 2A/2C receptors in the modulation of dopaminergic neurotransmission and motivating a search for better therapeutic strategies for schizophrenia and related disorders. In addition, adjunctive treatment with antioxidants such as vitamin E, red rice bran oil, and curcumin in the early phases of illness may prevent additional oxidative injury, and thus improve and prevent further possible worsening of related neurological and behavioral deficits in schizophrenia. This review explains the role of serotonergic receptors and oxidative stress, with the aim of providing principles for prospect development of compounds to improve therapeutic effects of antischizophrenic drugs. PMID:27540314
Burgdorf, Jeffrey; Zhang, Xiao-lei; Nicholson, Katherine L; Balster, Robert L; David Leander, J; Stanton, Patric K; Gross, Amanda L; Kroes, Roger A; Moskal, Joseph R
2013-01-01
Recent human clinical studies with the NMDA receptor (NMDAR) antagonist ketamine have revealed profound and long-lasting antidepressant effects with rapid onset in several clinical trials, but antidepressant effects were preceded by dissociative side effects. Here we show that GLYX-13, a novel NMDAR glycine-site functional partial agonist, produces an antidepressant-like effect in the Porsolt, novelty induced hypophagia, and learned helplessness tests in rats without exhibiting substance abuse-related, gating, and sedative side effects of ketamine in the drug discrimination, conditioned place preference, pre-pulse inhibition and open-field tests. Like ketamine, the GLYX-13-induced antidepressant-like effects required AMPA/kainate receptor activation, as evidenced by the ability of NBQX to abolish the antidepressant-like effect. Both GLYX-13 and ketamine persistently (24 h) enhanced the induction of long-term potentiation of synaptic transmission and the magnitude of NMDAR-NR2B conductance at rat Schaffer collateral-CA1 synapses in vitro. Cell surface biotinylation studies showed that both GLYX-13 and ketamine led to increases in both NR2B and GluR1 protein levels, as measured by Western analysis, whereas no changes were seen in mRNA expression (microarray and qRT-PCR). GLYX-13, unlike ketamine, produced its antidepressant-like effect when injected directly into the medial prefrontal cortex (MPFC). These results suggest that GLYX-13 produces an antidepressant-like effect without the side effects seen with ketamine at least in part by directly modulating NR2B-containing NMDARs in the MPFC. Furthermore, the enhancement of ‘metaplasticity' by both GLYX-13 and ketamine may help explain the long-lasting antidepressant effects of these NMDAR modulators. GLYX-13 is currently in a Phase II clinical development program for treatment-resistant depression. PMID:23303054
[Special characteristics of antibiotic therapy in the elderly].
Stock, Ingo
2012-03-01
The ever-increasing proportion of elderly people in the general population represents physicians and pharmacists with new challenges. Older people suffer more frequently than younger persons from bacterial diseases, and they have a higher tendency to develop more severe or progressive forms of these illnesses. Bacterial diseases of the urinary tract, respiratory tract, skin and soft tissues are especially common in old age. In general, most antibacterial agents are also promising agents for the therapy of bacterial diseases in the elderly. Prior to initiating therapy, however, the modified organ functions of the elderly have to be considered carefully. Depending on the individual and the antibacterial agent, a dose adjustment may be necessary. To reduce the high mortality rate characteristic for many infectious diseases in the elderly, antibacterial therapy ought to be carefully calculated and initiated as quickly as possible. It has to be born in mind that some side effects of antibiotics are more common and more severe in old age. Since older people often take several drugs simultaneously, the probability for the occurrence of side effects and drug interactions in this population is greatly increased. Significant compliance problems may also arise.
Yamasue, Hidenori; Fukui, Tsunehiro; Fukuda, Rin; Kasai, Kiyoto; Iwanami, Akira; Kato, Nobumasa; Kato, Tadafumi
2003-12-01
Extrapyramidal side-effects (EPS), the most frequent and severe side-effects of antipsychotics, sometimes become irreversible and cause severe psychosocial disturbance in patients with schizophrenia. However, the neurobiological basis of EPS has not yet been elucidated. In this study, neurochemical correlates of EPS were examined by 1H-MR spectroscopy (1H-MRS). Sixteen medicated patients with schizophrenia and 15 age-, gender- and parental-socioeconomic-status-matched normal controls were examined using single-voxel 1H-MRS. Absolute concentrations of N-acetyl aspartate (NAA), choline-containing compounds (Cho), creatine/phosphocreatine, myo-inositol, and Glx (glutamate and glutamine) in the left putamen were evaluated. The patient group showed mild EPS and no significant metabolic abnormalities in this region. The more severe drug-induced parkinsonism assessed by the Simpson-Angus Scale, however, significantly correlated with the higher Cho concentration and tended to be correlated with the higher NAA concentration in the patient group. These results suggest a potential of 1H-MRS as a non-invasive monitoring method of neurobiological correlates of EPS associated with neuroleptic treatments in patients with schizophrenia.
Gau, Susan Shur-Fen; Chen, Shin-Jaw; Chou, Wen-Jiun; Cheng, Helen; Tang, Ching-Shu; Chang, Hsueh-Ling; Tzang, Ruu-Fen; Wu, Yu-Yu; Huang, Ya-Fen; Chou, Miao-Chun; Liang, Hsin-Yi; Hsu, Ya-Chen; Lu, Hui-Hua; Huang, Yu-Shu
2008-01-01
To identify the determinants of adherence to immediate-release (IR) methylphenidate in children and adolescents with attention-deficit/hyperactivity disorder (ADHD); to examine the impact of adherence on ADHD-related symptoms; and to compare the efficacy, adherence, and side effects of IR methylphenidate and osmotic release oral system (OROS) methylphenidate. This national survey, involving 12 hospitals, consisted of 2 phases of assessment. Treatment adherence in 240 (39.5%) of the 607 children aged 5 to 16 years with a clinical diagnosis of DSM-IV ADHD enrolled in the study was poor (defined as missing >or= 1 dose of ADHD medication a day and on 2 days or more during school days). Children with poor adherence at phase 1 were able to switch to OROS methylphenidate, while adherents remained on the IR variant. We reassessed 124 poor adherents who switched to OROS methylphenidate. The global ADHD severity, parent-child interaction, classroom behavior, academic performance, and side effects of the child subjects were evaluated by investigators. Parents completed the rating scales about the ADHD-related symptoms. The study began in April 2005 and was completed in February 2006. Determinants for poor adherence included older age, later onset of ADHD, family history of ADHD, higher paternal education level, and multi-dose administration. Mental retardation and treatment at medical centers were inversely related to poor adherence. Overall, poor adherence was associated with more severe ADHD-related symptoms by comparison to good adherence. Similar side effect profile, superior adherence, and improved efficacy were demonstrated in intra-individual comparison of the OROS and IR methylphenidate forms. Given that poor adherence to medication may be an important reason for suboptimal outcome in ADHD treatment, physicians should ensure adherence with therapy before adjusting dosage or switching medication. clinicaltrials.gov Identifier NCT00460720.
Desalu, Olufemi Olumuyiwa; Onyedum, Cajetan Chigozie; Adeoti, Adekunle Olatayo; Ozoh, Obianuju Beatrice; Fadare, Joseph Olusesan; Salawu, Fatai Kunle; Danburam, Ali; Fawibe, Ademola Emmanuel; Adewole, Olanisun Olufemi
2013-01-01
The prevalence of asthma in our society is rising and there is need for better understanding of the asthma patients' perception and treatment practice of physicians. The study was aimed at determining asthma attitudes and treatment practices among adult physicians and patients in Nigeria, with the goal of identifying barriers to optimal management. To assess asthma attitudes, treatment practices and limitations among adult physicians and patients in Nigeria, a questionnaire survey was conducted among 150 patients and 70 physicians. Majority (66.7%) of the patients reported their asthma as moderate to severe, 42.7% had emergency room visit and 32% had admission due to asthma in the previous 12 months. Physicians and patients perceptions significantly differed in the time devoted to educational issues (31.4% vs.18.7%) and its contents: individual management plan (64.3% vs.33.3%), correct inhaler technique (84.0% vs.71.0%), medication side effects (80.0% vs.60.0%) and compliance 100% of time (5.7% vs. 18.7%). Patients reported that non-compliance with medication causes increased symptoms (67.0%), exacerbations (60.0%), bronchodilator use (56.0%), urgent physician visit (52.0%) and hospitalizations /ER visits (38.7%). Asthma medication in patients caused short term (10.7%) and long term side effects (20.0%). Due to side effects, 28.0% skipped and stopped their medications. Most physicians (85.7%) and patients (56.0%) agreed on the need for new medication options. The need for new medication in patients was strongly related to asthma severity, limitation of activities, side effects, cost and lack of satisfaction with current medication. With the exception of pulmonologists, physicians did not readily prescribe ICS and their prescriptions were not in line with treatment guidelines. This study has highlighted the gaps and barriers to asthma treatment which need to be addressed to improve the quality of care in Nigeria.
Minoxidil: an underused vasodilator for resistant or severe hypertension.
Sica, Domenic A
2004-05-01
Minoxidil is a direct vasodilator introduced in the early 1970s for the treatment of hypertension. It is capable of reducing blood pressure in most persons with resistant hypertension where therapy has failed with multidrug regimens. Minoxidil's effect can be limited because of an increase in pulse rate and/or sodium (and water) retention. The latter may prove quite debilitating in some patients. Thus, minoxidil is generally administered with both a diuretic and an agent that can keep pulse rate in check, such as a beta blocker or a combined alpha-beta blocker. The prominent tachycardia with minoxidil can aggravate myocardial ischemia and, if long-standing, leads to left ventricular hypertrophy. Minoxidil has a particularly annoying side effect of hypertrichosis that may limit its use, particularly among women. Minoxidil use is infrequently associated with the idiosyncratic onset of a pericardial effusion. If a patient's hypertension is severe enough to warrant minoxidil therapy, a hypertension specialist should probably become involved in the patient's care. The use of this medication should be limited in view of the availability of effective agents with fewer side effects. There is, however, a place for minoxidil in the treatment of resistant hypertension especially in patients with advanced renal disease.
Kieninger, Martin; Flessa, Julia; Lindenberg, Nicole; Bele, Sylvia; Redel, Andreas; Schneiker, André; Schuierer, Gerhard; Wendl, Christina; Graf, Bernhard; Silbereisen, Vera
2018-02-01
Long-term continuous intra-arterial nimodipine infusion (CIAN) is a rescue therapy option in cases of severe refractory cerebral vasospasm (CV) following acute non-traumatic subarachnoid hemorrhage (SAH). However, CIAN therapy can be associated with relevant side effects. Available studies focus on intracerebral complications, whereas extracerebral side effects are rarely examined. Aim of the present study was to generate descriptive data on the clinical course during CIAN therapy and expectable extracerebral side effects. All patients treated with CIAN therapy for at least 5 days between May 2011 and December 2015 were included. We retrospectively extracted data from the patient data management system regarding the period between 2 days before the beginning and 5 days after the termination of CIAN therapy to analyze the course of ventilation parameters and pulmonary gas exchange, hemodynamic support, renal and liver function, integrity of the gastrointestinal tract, and the occurrence of infectious complications. In addition, we recorded the mean daily values of intracranial pressure (ICP) and intracerebral problems associated with CIAN therapy. Data from 28 patients meeting inclusion criteria were analyzed. The mean duration of long-term CIAN therapy was 10.5 ± 4.5 days. Seventeen patients (60.7%) reached a good outcome level (Glasgow Outcome Scale [GOS] 4-5) 6 months after SAH. An impairment of the pulmonary gas exchange occurred only at the very beginning of CIAN therapy. The required vasopressor support with norepinephrine was significantly higher on all days during and the first day after CIAN therapy compared to the situation before starting CIAN therapy. Two patients required short-time resuscitation due to cardiac arrest during CIAN therapy. Acute kidney injury was observed in four patients, and one of them required renal replacement therapy with sustained low-efficiency daily dialysis. During CIAN therapy, 23 patients (82.1%) needed the escalation of a previous antiinfective therapy or the onset of antibiotics which was in line with a significant increase of C-reactive protein and white blood cell count. Obstipation was observed in 22 patients (78.6%). Ten patients (35.7%) even showed insufficient defecation on at least seven consecutive days. Compared to the situation before, ICP was significantly higher during the whole period of CIAN therapy. Long-term CIAN therapy is associated with diverse side effects. The leading problems are an impairment of the hemodynamic situation and cardiac problems, an increase in infectious complications, a worsening of the motility of the gastrointestinal tract, and rising ICP values. Teams on neurointensive care units must be aware of these side effects to avoid that the beneficial effects of CIAN therapy on CV reported elsewhere are foiled by the problems this technique can be associated with.
Numerical Approach for Goaf-Side Entry Layout and Yield Pillar Design in Fractured Ground Conditions
NASA Astrophysics Data System (ADS)
Jiang, Lishuai; Zhang, Peipeng; Chen, Lianjun; Hao, Zhen; Sainoki, Atsushi; Mitri, Hani S.; Wang, Qingbiao
2017-11-01
Entry driven along goaf-side (EDG), which is the development of an entry of the next longwall panel along the goaf-side and the isolation of the entry from the goaf with a small-width yield pillar, has been widely employed in China over the past several decades . The width of such a yield pillar has a crucial effect on EDG layout in terms of the ground control, isolation effect and resource recovery rate. Based on a case study, this paper presents an approach for evaluating, designing and optimizing EDG and yield pillar by considering the results from numerical simulations and field practice. To rigorously analyze the ground stability, the numerical study begins with the simulation of goaf-side stress and ground conditions. Four global models with identical conditions, except for the width of the yield pillar, are built, and the effect of pillar width on ground stability is investigated by comparing aspects of stress distribution, failure propagation, and displacement evolution during the entire service life of the entry. Based on simulation results, the isolation effect of the pillar acquired from field practice is also considered. The suggested optimal yield pillar design is validated using a field test in the same mine. Thus, the presented numerical approach provides references and can be utilized for the evaluation, design and optimization of EDG and yield pillars under similar geological and geotechnical circumstances.
Sung, Kang Hoon; Lee, Moon J
2015-01-01
The authors investigated the effects of reading different types of online comments about a company on people's attitude change based on individual's prior attitude toward the company. Based on Social Judgment Theory, several hypotheses were tested. The results showed that the effects of online comments interact with individuals' prior attitudes toward a corporation. People with a strong negative attitude toward a corporation were less influenced by other's online comments than people with a neutral attitude in general. However, people with a prior negative attitude were more affected by refutational two-sided comments than one-sided comments. The results suggest that the effects of user generated content should be studied in a holistic manner, not only by investigating the effects of online content itself, but also by examining how others' responses to the content shape or change individuals' attitudes based on their prior attitudes.
Influence of fungicides on gas exchange of pecan foliage
USDA-ARS?s Scientific Manuscript database
There are several fungicide chemistries used for disease control on pecan (Carya illinoinensis), but there is little or no knowledge of subtle short- or long-term side-effects of these chemistries on host physiological processes, including photosynthesis (Pn). This study quantifies the impact of se...
RU-486: Abortion Controversy in U.S. Clouds Future of Promising Drug.
ERIC Educational Resources Information Center
Baum, Rudy M.
1991-01-01
Reviewed is the debate over research and approval of the use of this drug in the United States. Potential benefits and side effects of the drug are discussed. The points of view of several government officials, scientists, and social activists are presented. (CW)
Truchuelo, Maria Teresa; Jiménez, Natalia; Jaén, Pedro
2014-12-01
Melasma is a dermatosis with significant repercussions on patients' quality of life, and there is currently no standard treatment. Hydroquinone is deemed the treatment of choice, but its safety has been questioned in certain cases. To determine the efficacy and safety of a new combination of retinoids in the improvement of melasma. Prospective, double-blind, vehicle-controlled, and randomized study in 30 patients with melasma. The product was applied on one side of the face and the vehicle on the other, twice daily during 3 months. Standardized photographs were taken using RBX technology on the three visits (basal, at one and a half months and at 3 months). The main variable to determine the efficacy was the improvement of the hemifacial Melasma Area Severity Index (MASI). Other variables were determined such as improvement perceived by the investigator, improvement perceived by the patient, impact on quality of life or side effects. The MASI improvement at 3 months of treatment was significant on the treated side vs. the vehicle side, reaching an improvement of 70%, which is comparable to the percentage of improvement described with hydroquinone. No notable side effects were detected, in spite of a significant percentage of patients included in the study citing a history that could be compatible with sensitive skin. This new combination of retinoids and depigmenting agents proved to be effective and safe in the treatment of melasma. © 2014 Wiley Periodicals, Inc.
Banihashemi, Mahnaz; Zabolinejad, Naghmeh; Jaafari, Mahmoud Reza; Salehi, Maryam; Jabari, Asma
2015-09-01
Melasma is one of the most common cosmetic disorders with skin darkening. Although several treatment modalities are available, none is satisfactorily used in management of this condition. Tranexamic acid (TA), a plasmin inhibitor, is reported to improve melasma when injected locally or used as oral and topical forms. The aim of this study was to compare therapeutic effects of liposomal tranexamic acid and conventional hydroquinone on melasma. Thirty women with bilateral melasma were enrolled in a split-face trial lasting 12 weeks. Patients blindly applied 5% topical liposomal TA and 4% hydroquinone cream, to the designated sides of the face twice daily in addition to the assigned sunscreen in the morning. Skin pigmentation was measured using MASI (Melasma Area and Severity Index) at each visit separately for each side at the base line and every month until one month after treatment course. Data were obtained from patients file and were analyzed statistically using SPSS software, paired samples t-test, and repeated measured ANOVA. Twenty-three patients completed the study. The mean MASI scores significantly reduced in both treated sides (P < P = 0.001) after 12 week. A greater decrease was observed with 5% liposomal TA, although this difference was not statistically significant. Irritation occurred in three patients with hydroquinone, while no serious adverse events occurred with TA. On the basis of these results, topical liposomal TA can be used as a new, effective, safe, and promising therapeutic agent in melasma. © 2015 Wiley Periodicals, Inc.
Reichert, Christoph; Wenghoefer, Matthias; Kutschera, Eric; Götz, Werner; Jäger, Andreas
2014-01-01
Gingival invaginations develop after tooth extraction and subsequent orthodontic space closure. Aetiological factors and long-term effects of gingival invaginations on oral health are nearly unknown. In addition, preventive or therapeutic strategies are rare. This prospective clinical study employing the split mouth technique was performed to investigate the effect of extraction socket augmentation with a synthetic nanocrystalline hydroxyapatite (NanoBone(®) Artoss, Rostock, Germany) on the incidence and degree of gingival invaginations. A total of 10 orthodontic patients with need for symmetric premolar extractions offering a total of 28 extractions were included in this trial. The study plan provided one extraction site to be augmented with synthetic nanocrystalline hydroxyapatite (NanoBone(®)), the other served as control. After primary wound healing, space closure was performed under defined biomechanical conditions. After space closure was accomplished, occurrence and degree of gingival invaginations as well as probing depths of the adjacent teeth mesial and distal to the extractions were determined and dental radiographs were taken. The degree of gingival invaginations and probing depths mesial and distal of the extraction were significantly reduced on NanoBone(®) augmented extraction sites. In addition, 70% of the radiographs revealed translucent and hyperdense areas on the intervention side after space closure. Apical root resorption was found in 2 patients on both the NanoBone(®) side and the control side. Ridge preservation with NanoBone(®) appeared to reduce the severity of gingival invaginations. Further investigation on long-term effects is mandatory to eliminate the appearance of adverse effects.
Changes in the Severity and Injury Sources of Thoracic Aorta Injuries due to Vehicular Crashes.
Ryb, Gabriel; Dischinger, Patricia; Kerns, Timothy; Burch, Cynthia; Rabin, Joseph; Ho, Shiu
Research using the National Automotive Sampling System-Crashworthiness Data System (NASS-CDS) suggested a decreased adjusted risk of thoracic aorta injuries (TAI) for newer vehicles during near-side crashes and an increased adjusted TAI risk during frontal crashes. This study attempted to explore possible explanations of these findings. Adult front seat occupants in the Crash Injury Research and Engineering Network (CIREN) database through June 2012 were studied. TAI cases were compared with remaining cases in relation to crash and vehicular characteristics. TAI cases of later crash year (CY) (2004-2012) were compared to those in earlier CY (1996-2003) in relation to TAI severity (minor, moderate, severe and non-survivable). TAI cases in newer model year (MY) vehicles (1999-2012) were compared to those in older vehicles (1988-98) in relation to injury source (steering wheel, front, left, seat belt, air bag and other or unknown). Analysis was stratified by direction of impact (frontal and near-side) and the use of restraints. The similar TAI severity of earlier and later CY among frontal crashes suggests that the observed changes in the adjusted odds of injury seen in NASS-CDS are not due to an increase in injury detection. The decrease in TAI severity among newer vehicles in near-side crashes of later CY is consistent with a beneficial effect of crashworthiness improvements for this crash configuration. A shift of injury source in frontal crashes from the steering wheel in older vehicles to "front of vehicle structures", "seat belts" and "unknown and other" in newer vehicles should suggest potential sites for crashworthiness improvements.
The differential effects of acute right- vs. left-sided vestibular failure on brain metabolism.
Becker-Bense, Sandra; Dieterich, Marianne; Buchholz, Hans-Georg; Bartenstein, Peter; Schreckenberger, Mathias; Brandt, Thomas
2014-07-01
The human vestibular system is represented in the brain bilaterally, but it has functional asymmetries, i.e., a dominance of ipsilateral pathways and of the right hemisphere in right-handers. To determine if acute right- or left-sided unilateral vestibular neuritis (VN) is associated with differential patterns of brain metabolism in areas representing the vestibular network and the visual-vestibular interaction, patients with acute VN (right n = 9; left n = 13) underwent resting state (18)F-FDG PET once in the acute phase and once 3 months later after central vestibular compensation. The contrast acute vs. chronic phase showed signal differences in contralateral vestibular areas and the inverse contrast in visual cortex areas, both more pronounced in VN right. In VN left additional regions were found in the cerebellar hemispheres and vermis bilaterally, accentuated in severe cases. In general, signal changes appeared more pronounced in patients with more severe vestibular deficits. Acute phase PET data of patients compared to that of age-matched healthy controls disclosed similarities to these patterns, thus permitting the interpretation that the signal changes in vestibular temporo-parietal areas reflect signal increases, and in visual areas, signal decreases. These data imply that brain activity in the acute phase of right- and left-sided VN exhibits different compensatory patterns, i.e., the dominant ascending input is shifted from the ipsilateral to the contralateral pathways, presumably due to the missing ipsilateral vestibular input. The visual-vestibular interaction patterns were preserved, but were of different prominence in each hemisphere and more pronounced in patients with right-sided failure and more severe vestibular deficits.
Rieken, Stefan; Habermehl, Daniel; Nikoghosyan, Anna; Jensen, Alexandra; Haberer, Thomas; Jäkel, Oliver; Münter, Marc W; Welzel, Thomas; Debus, Jürgen; Combs, Stephanie E
2011-12-01
PUROPOSE: To asses early toxicity and response in 118 patients treated with scanned ion beams to validate the safety of intensity-controlled raster scanning at the Heidelberg Ion Therapy Center. Between November 2009 and June 2010, we treated 118 patients with proton and carbon ion radiotherapy (RT) using active beam delivery. The main indications included skull base chordomas and chondrosarcomas, salivary gland tumors, and gliomas. We evaluated early toxicity within 6 weeks after RT and the initial clinical and radiologic response for quality assurance in our new facility. In all 118 patients, few side effects were observed, in particular, no high numbers of severe acute toxicity were found. In general, the patients treated with particle therapy alone showed only a few single side effects, mainly Radiation Therapy Oncology Group/Common Terminology Criteria grade 1. The most frequent side effects and cumulative incidence of single side effects were observed in the head-and-neck patients treated with particle therapy as a boost and photon intensity-modulated RT. The toxicities included common radiation-attributed reactions known from photon RT, including mucositis, dysphagia, and skin erythema. The most predominant imaging responses were observed in patients with high-grade gliomas and those with salivary gland tumors. For skull base tumors, imaging showed a stable tumor outline in most patients. Thirteen patients showed improvement of pre-existing clinical symptoms. Side effects related to particle treatment were rare, and the overall tolerability of the treatment was shown. The initial response was promising. The data have confirmed the safe delivery of carbon ions and protons at the newly opened Heidelberg facility. Copyright © 2011 Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rieken, Stefan; Habermehl, Daniel; Nikoghosyan, Anna
2011-12-01
Puropose: To asses early toxicity and response in 118 patients treated with scanned ion beams to validate the safety of intensity-controlled raster scanning at the Heidelberg Ion Therapy Center. Patients and Methods: Between November 2009 and June 2010, we treated 118 patients with proton and carbon ion radiotherapy (RT) using active beam delivery. The main indications included skull base chordomas and chondrosarcomas, salivary gland tumors, and gliomas. We evaluated early toxicity within 6 weeks after RT and the initial clinical and radiologic response for quality assurance in our new facility. Results: In all 118 patients, few side effects were observed,more » in particular, no high numbers of severe acute toxicity were found. In general, the patients treated with particle therapy alone showed only a few single side effects, mainly Radiation Therapy Oncology Group/Common Terminology Criteria grade 1. The most frequent side effects and cumulative incidence of single side effects were observed in the head-and-neck patients treated with particle therapy as a boost and photon intensity-modulated RT. The toxicities included common radiation-attributed reactions known from photon RT, including mucositis, dysphagia, and skin erythema. The most predominant imaging responses were observed in patients with high-grade gliomas and those with salivary gland tumors. For skull base tumors, imaging showed a stable tumor outline in most patients. Thirteen patients showed improvement of pre-existing clinical symptoms. Conclusions: Side effects related to particle treatment were rare, and the overall tolerability of the treatment was shown. The initial response was promising. The data have confirmed the safe delivery of carbon ions and protons at the newly opened Heidelberg facility.« less
Mankowski, Colette; Ikenwilo, Divine; Heidenreich, Sebastian; Ryan, Mandy; Nazir, Jameel; Newman, Cathy; Watson, Verity
2016-01-01
To explore and quantify men's preferences and willingness to pay (WTP) for attributes of medications for lower urinary tract symptoms associated with benign prostatic hyperplasia using a discrete choice experiment. Men in the UK aged ≥45 years with moderate-to-severe lower urinary tract symptoms/benign prostatic hyperplasia (based on self-reported International Prostate Symptom Score ≥8) were recruited. An online discrete choice experiment survey was administered. Eligible men were asked to consider different medication scenarios and select their preferred medication according to seven attributes: daytime and nighttime (nocturia) urinary frequency, urinary urgency, sexual and nonsexual side effects, number of tablets/day, and cost/month. A mixed-logit model was used to estimate preferences and WTP for medication attributes. In all, 247 men completed the survey. Men were willing to trade-off symptom improvements and treatment side effects. Men preferred medications that reduced urinary urgency and reduced day- and nighttime urinary frequency. Men preferred medications without side effects (base-case level), but did not care about the number of tablets per day. WTP for symptomatic improvement was £25.33/month for reduced urgency (urge incontinence to mild urgency), and £6.65/month and £1.39/month for each unit reduction in night- and daytime urination frequency, respectively. The sexual and nonsexual side effects reduced WTP by up to £30.07/month. There was significant heterogeneity in preferences for most attributes, except for reduced urinary urgency from urge incontinence to mild urgency and no fluid during ejaculation (dry orgasm). To compensate for side effects, a medicine for lower urinary tract symptoms/benign prostatic hyperplasia must provide a combination of benefits, such as reduced urgency of urination plus reduced nighttime and/or reduced daytime urination.
Faghihi, Gita; Nouraei, Saeid; Asilian, Ali; Keyvan, Shima; Abtahi-Naeini, Bahareh; Rakhshanpour, Mehrdad; Nilforoushzadeh, Mohammad Ali; Hosseini, Sayed Mohsen
2015-01-01
Background: A number of treatments for reducing the appearance of acne scars are available, but general guidelines for optimizing acne scar treatment do not exist. The aim of this study was to compare the clinical effectiveness and side effects of fractional carbon dioxide (CO2) laser resurfacing combined with punch elevation with fractional CO2 laser resurfacing alone in the treatment of atrophic acne scars. Materials and Methods: Forty-two Iranian subjects (age range 18–55) with Fitzpatrick skin types III to IV and moderate to severe atrophic acne scars on both cheeks received randomized split-face treatments: One side received fractional CO2 laser treatment and the other received one session of punch elevation combined with two sessions of laser fractional CO2 laser treatment, separated by an interval of 1 month. Two dermatologists independently evaluated improvement in acne scars 4 and 16 weeks after the last treatment. Side effects were also recorded after each treatment. Results: The mean ± SD age of patients was 23.4 ± 2.6 years. Clinical improvement of facial acne scarring was assessed by two dermatologists blinded to treatment conditions. No significant difference in evaluation was observed 1 month after treatment (P = 0.56). Their evaluation found that fractional CO2 laser treatment combined with punch elevation had greater efficacy than that with fractional CO2 laser treatment alone, assessed 4 months after treatment (P = 0.02). Among all side effects, coagulated crust formation and pruritus at day 3 after fractional CO2 laser treatment was significant on both treatment sides (P < 0.05). Conclusion: Concurrent use of fractional laser skin resurfacing with punch elevation offers a safe and effective approach for the treatment of acne scarring. PMID:26538695
The toxicology of cannabis and cannabis prohibition.
Grotenhermen, Franjo
2007-08-01
The acute side effects caused by cannabis use are mainly related to psyche and cognition, and to circulation. Euphoria, anxiety, changes in sensory perception, impairment of memory and psychomotor performance are common effects after a dose is taken that exceeds an individually variable threshold. Cannabis consumption may increase heart rate and change blood pressure, which may have serious consequences in people with heart disease. Effects of chronic use may be induction of psychosis and development of dependency to the drug. Effects on cognitive abilities seem to be reversible after abstinence, except possibly in very heavy users. Cannabis exposure in utero may have negative consequences on brain development with subtle impairment of cognitive abilities in later life. Consequences of cannabis smoking may be similar to those of tobacco smoking and should be avoided. Use by young people has more detrimental effects than use by adults. There appear to be promising therapeutic uses of cannabis for a range of indications. Use of moderate doses in a therapeutic context is usually not associated with severe side effects. Current prohibition on cannabis use may also have harmful side effects for the individual and the society, while having little influence on prevalence of use. Harm is greatest for seriously ill people who may benefit from a treatment with cannabis. This makes it difficult to justify criminal penalties against patients.
Rahamathulla, Mohamudha Parveen
2017-01-01
Objective: To evaluate the consumption, prevalence, side effects and awareness of energy drinks among female university students in Saudi Arabia. Methods: A quantitative research design was implied with sample size of 358 female students, recruited from Prince Sattam bin Abdulaziz University. The data, gathered through self-administered questionnaire, was analyzed through SPSS version 20.0 with p value <0.005 deemed statistically significant. Results: From the sample of 358 female students, 337 attempted the questionnaire from which 274 students were identified as energy drink consumers. The reasons for increased consumption of energy drinks mainly include giving company to friends (59.4%), better performance in exams (41.2%), and better concentration in studies (39.4%). The most common side effect was headache (32.3%), and the least was identified as allergy (2%). Only 39.4% and 29.9% of students acquired awareness regarding the harmful effects of energy drink consumption during pregnancy and breast feeding respectively. Conclusion: A significant proportion of female students at Prince Sattam bin Abdulaziz have reported to consume energy drinks regularly with several adverse effects. The government of Saudi Arabia should take serious initiatives towards organizing effective awareness programs specifically in universities and colleges to control the consumption of energy drinks and educate on the adverse effects. PMID:28523035
Rahamathulla, Mohamudha Parveen
2017-01-01
To evaluate the consumption, prevalence, side effects and awareness of energy drinks among female university students in Saudi Arabia. A quantitative research design was implied with sample size of 358 female students, recruited from Prince Sattam bin Abdulaziz University. The data, gathered through self-administered questionnaire, was analyzed through SPSS version 20.0 with p value <0.005 deemed statistically significant. From the sample of 358 female students, 337 attempted the questionnaire from which 274 students were identified as energy drink consumers. The reasons for increased consumption of energy drinks mainly include giving company to friends (59.4%), better performance in exams (41.2%), and better concentration in studies (39.4%). The most common side effect was headache (32.3%), and the least was identified as allergy (2%). Only 39.4% and 29.9% of students acquired awareness regarding the harmful effects of energy drink consumption during pregnancy and breast feeding respectively. A significant proportion of female students at Prince Sattam bin Abdulaziz have reported to consume energy drinks regularly with several adverse effects. The government of Saudi Arabia should take serious initiatives towards organizing effective awareness programs specifically in universities and colleges to control the consumption of energy drinks and educate on the adverse effects.
A side-effect free method for identifying cancer drug targets.
Ashraf, Md Izhar; Ong, Seng-Kai; Mujawar, Shama; Pawar, Shrikant; More, Pallavi; Paul, Somnath; Lahiri, Chandrajit
2018-04-27
Identifying effective drug targets, with little or no side effects, remains an ever challenging task. A potential pitfall of failing to uncover the correct drug targets, due to side effect of pleiotropic genes, might lead the potential drugs to be illicit and withdrawn. Simplifying disease complexity, for the investigation of the mechanistic aspects and identification of effective drug targets, have been done through several approaches of protein interactome analysis. Of these, centrality measures have always gained importance in identifying candidate drug targets. Here, we put forward an integrated method of analysing a complex network of cancer and depict the importance of k-core, functional connectivity and centrality (KFC) for identifying effective drug targets. Essentially, we have extracted the proteins involved in the pathways leading to cancer from the pathway databases which enlist real experimental datasets. The interactions between these proteins were mapped to build an interactome. Integrative analyses of the interactome enabled us to unearth plausible reasons for drugs being rendered withdrawn, thereby giving future scope to pharmaceutical industries to potentially avoid them (e.g. ESR1, HDAC2, F2, PLG, PPARA, RXRA, etc). Based upon our KFC criteria, we have shortlisted ten proteins (GRB2, FYN, PIK3R1, CBL, JAK2, LCK, LYN, SYK, JAK1 and SOCS3) as effective candidates for drug development.
Popoff, Alexandre; Fichou, Denis
2008-05-01
We show here by means of scanning tunneling microscopy (STM) at the liquid/solid interface that paracetamol and benzocaine molecules bearing a long aliphatic chain can be immobilized on highly oriented pyrolitic graphite (HOPG) as perfectly ordered two-dimensional domains extending over several hundreds of nanometers. In both cases, high-resolution STM images reveal that compounds 1 and 2 self-assemble into parallel lamellae having a head-to-head arrangement. The paracetamol heads of 1 are in a zigzag position with entangled n-dodecyloxy side chains while benzocaine heads of compound 2 are perfectly aligned as a double row and have their palmitic side chains on either sides of the head alignment. We attribute the very long-range ordering of these two pro-drug derivatives on HOPG to the combined effects of intermolecular H-bonding on one side and Van der Waals interactions between aliphatic side chains and graphite on the other side. The 2D immobilization of pro-drug derivatives via a non-destructive physisorption mechanism could prove to be useful for applications such as drug delivery if it can be realized on a biocompatible substrate.
No blank slates: Pre-existing schemas about pharmaceuticals predict memory for side effects.
Heller, Monika K; Chapman, Sarah C E; Horne, Rob
2017-04-01
Attribution of symptoms as medication side effects is informed by pre-existing beliefs about medicines and perceptions of personal sensitivity to their effects (pharmaceutical schemas). We tested whether (1) pharmaceutical schemas were associated with memory (recall/recognition) for side effect information (2) memory explained the attribution of a common unrelated symptom as a side effect. In this analogue study participants saw the patient leaflet of a fictitious asthma drug listing eight side effects. We measured recall and recognition memory for side effects and used a vignette to test whether participants attributed an unlisted common symptom (headache) as a side effect. Participants who perceived pharmaceuticals as more harmful in general recalled fewer side effects correctly (r Correct Recall = -.273), were less able to differentiate between listed and unlisted side effects (r Recognition Sensitivity = -.256) and were more likely to attribute the unlisted headache symptom as a side effect (r side effect attribution = .381, ps < .01). The effect of harm beliefs on side effect attribution was partially mediated by correct recall of side effects. Pharmaceutical schemas are associated with memory for side effect information. Memory may explain part of the association between pharmaceutical schemas and the attribution of unrelated symptoms as side effects.
Fernandez, F; Levy, J K
1993-01-01
Four patients with HIV infection and psychosis from various etiologies, refractory to standard treatments, and suffering from severe extrapyramidal symptoms (EPS), had a marked beneficial response to molindone. There was significant control of neuropsychiatric dysfunction without major adverse side effects. The results suggest that further evaluation is warranted of the use of molindone in treating severely ill, psychotic, or delirious HIV-infected patients.
Ueda, Nao; Yokouchi, Ryoki; Onoda, Taro; Ogihara, Atsushi
2017-12-19
Media coverage and reports have a major influence on individual vaccination and other health-related activities. People use the media to seek information and knowledge on health-related behaviors. They obtain health-related information from media such as television and newspapers, and they trust such information. While several studies have examined the relation between media coverage and individual health, there is a lack of studies that have analyzed media reports of health information. In particular, we have found no analyses related to cervical cancer (human papillomavirus [HPV]) vaccine. This study aimed to identify mentions of cervical cancer vaccine in Japan's printed news media and to determine their characteristics. We used the archival databases of 2 Japanese newspapers, Yomiuri Shimbun (Yomidasu Rekishikan) and Asahi Shimbun (Kikuzo II Visual), for text mining. First, we created a database by extracting articles published between January 1, 2007, and December 31, 2014, that matched the terms "cervical cancer" AND "vaccination" in a keyword search. Then, we tallied the extracted articles based on the month of publication and number of characters in order to conduct a time-series analysis. We extracted a total of 219 articles. Of these, 154 (70.3%) were positive and 51 (23.3%) were negative toward HPV vaccination. Of the 51 negative articles, 4 (7.8%) were published before June 2013, when routine vaccination was temporarily discontinued due to concerns regarding side effects, and 47 (92.2%) were published since then. The negative reports commonly cited side effects, although prior to June 2013, these issues were hardly mentioned. Although foreign media reports mentioned side effects before routine vaccination was temporarily discontinued, fewer articles mentioned side effects than recommendations for vaccination. Furthermore, on June 13, 2013, the World Health Organization's advisory body Global Advisory Committee on Vaccine Safety issued a statement regarding the safety of HPV vaccines, but hardly any articles reported this statement. Rather, several articles were published about the side effects after June 2013. Since we consider media coverage to be a factor affecting human health behavior, the media should extensively report on the cost of not receiving cervical cancer vaccination, global trends concerning cervical cancer vaccination, and statements released by various agencies on the subject. ©Nao Ueda, Ryoki Yokouchi, Taro Onoda, Atsushi Ogihara. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 19.12.2017.
Comparison of two humidification systems for long-term noninvasive mechanical ventilation.
Nava, S; Cirio, S; Fanfulla, F; Carlucci, A; Navarra, A; Negri, A; Ceriana, P
2008-08-01
There is no consensus concerning the best system of humidification during long-term noninvasive mechanical ventilation (NIMV). In a technical pilot randomised crossover 12-month study, 16 patients with stable chronic hypercapnic respiratory failure received either heated humidification or heat and moisture exchanger. Compliance with long-term NIMV, airway symptoms, side-effects and number of severe acute pulmonary exacerbations requiring hospitalisation were recorded. Two patients died. Intention-to-treat statistical analysis was performed on 14 patients. No significant differences were observed in compliance with long-term NIMV, but 10 out of 14 patients decided to continue long-term NIMV with heated humidification at the end of the trial. The incidence of side-effects, except for dry throat (significantly more often present using heat and moisture exchanger), hospitalisations and pneumonia were not significantly different. In the present pilot study, the use heated humidification and heat and moisture exchanger showed similar tolerance and side-effects, but a higher number of patients decided to continue long-term noninvasive mechanical ventilation with heated humidification. Further larger studies are required in order to confirm these findings.
Zhang, L L; Gong, J P; Xu, Y W; Liu, B
2016-06-21
To investigate the nodal properties and reorganization of whole-brain functional network in subjects with severe right-sided SNHL. From June 2012 to June 2013, a total of 19 patients with severe right-sided SNHL were collected from Zhongda Hospital or the recruitment advertising along with 31 healthy controls.Based on the graph-theoretical analysis, the whole-brain functional networks were constructed using the BOLD-fMRI data of all subjects.Two sample two-tailed t-tests were used to investigate the differences between two groups in nodal metrics, such as node degree, node betweenness, node global efficiency and node local efficiency.All metrics were corrected by multiple comparisons.Partial correlation analysis was used to estimate the relationship between the significant metrics and the duration or severity of hearing loss. The right-sided SNHL showed significantly increased betweenness centrality in left supramarginal gyrus and right fusiform.However, other nodal parameters showed no statistical difference.Besides, patients exhibited no significant association between the altered metrics and clinical variables. Alterations of local topological properties may underlie cerebral cross-modal plastic reorganization in visual or speech-related regions in severe right-sided SNHL patients.
Coadjuvant treatment with surgery and pirfenidone in severe facial trauma due to dog bite.
Cantú-Cantú, María Zulema; Lyra-González, Iván; Armendáriz-Borunda, Juan
2013-03-01
This case report assesses the effectiveness of surgery plus pirfenidone (PFD) as a concomitant therapy in the management of facial trauma after severe dog bite. A 16-month-old female patient who suffered a severe attack by a big-sized dog (Rottweiler) in the midface area was managed with surgery/PFD combination and followed up for 20 months to evaluate the efficacy to control, prevent, and improve injury sequels. Surgery/PFD combination offered a good complementary therapy downregulating inflammatory activity, improving blood supply, and activating cytokine modulation and collagen synthesis/biosynthesis (scar control). No side effects were reported in this case report. Surgery/PFD management for severe facial dog bites represents a safe and effective therapeutic option to protect and improve a patient's quality of life, minimizing long-time sequels.
Badawi, Ashraf M; Osman, Mai Abdelraouf
2018-01-01
Background Melasma is a difficult-to-treat hyperpigmentary disorder. Ablative fractional laser (AFL)-assisted delivery of topically applied drugs to varied targets in the skin has been an area of ongoing study and research. Objective The objective of this study was to evaluate the efficacy and safety of fractional erbium-doped yttrium aluminum garnet (Er:YAG) laser as an assisted drug delivery for enhancing topical hydroquinone (HQ) permeation into the skin of melasma patients. Patients and methods Thirty female patients with bilateral melasma were randomly treated in a split-face controlled manner with a fractional Er:YAG laser followed by 4% HQ cream on one side and 4% HQ cream alone on the other side. All patients received six laser sessions with a 2-week interval. The efficacy of treatments was determined through photographs, dermoscopic photomicrographs and Melasma Area Severity Index (MASI) score, all performed at baseline and at 12 weeks of starting therapy. The patient’s level of satisfaction was also recorded. Results Er:YAG laser + HQ showed significantly better results (p<0.005) with regard to decrease in the degree of pigmentation as assessed on the 4-point scale than HQ alone. There was a significant decrease in MASI scores on Er:YAG laser + HQ side vs HQ side. Minor reversible side effects were observed on both sides. Conclusion AFL-assisted delivery of HQ is a safe and effective method for the treatment of melasma. PMID:29379308
Tacrolimus Improves Symptoms of Children With Myasthenia Gravis Refractory to Prednisone.
Liu, Chanchan; Gui, Mengcui; Cao, Yayun; Lin, Jing; Li, Yue; Ji, Suqiong; Bu, Bitao
2017-12-01
Myasthenia gravis tends to affect children in China. Oral pyridostigmine and prednisone could effectively improve the symptoms, but multiple side effects become a major concern after long-term oral prednisone. To avoid the long-term complications of prednisone therapy and to obtain more satisfactory improvement, we tested the efficacy and safety of tacrolimus in children with myasthenia gravis. Children with myasthenia gravis who had not achieved satisfactory improvement or who experienced severe side effects after prednisone therapy were recruited between January 2015 and December 2016 at Tongji Hospital. All the children were treated with tacrolimus 1 mg to 2 mg daily and the dose was adjusted on the basis of the clinical response and the serum concentration. The dosage of prednisone, the severity of symptoms, blood samples, the serum concentration of tacrolimus, and titers of antiacetylcholine receptor antibodies were evaluated every four weeks. Fourteen children were enrolled. One child withdrew two weeks after the enrollment. Thirteen children have completed the therapy for one year. At the end point, the dosage of prednisone was significantly decreased (P < 0.05), the symptoms were evaluated by the quantitative myasthenia gravis score, and myasthenia gravis-specific manual muscle testing and myasthenia gravis-activities of daily living scores were significantly improved (P < 0.05, P < 0.05, and P < 0.01, respectively). More importantly, ten (76.9%) patients had completely discontinued prednisone, and the major side effects were nearly reversed. The mean titer of antiacetylcholine receptor antibodies significantly dropped from 1.96±2.62 nmol/L to 0.70±1.04 nmol/L (P < 0.05). No severe adverse events were reported. Our results suggest that tacrolimus is a promising agent for children with refractory myasthenia gravis. Randomized clinical trials are needed to confirm the observation. Copyright © 2017 Elsevier Inc. All rights reserved.
Performance of Gout Impact Scale in a longitudinal observational study of patients with gout
Wallace, Beth; Khanna, Dinesh; Aquino-Beaton, Cleopatra; Singh, Jasvinder A.; Duffy, Erin; Elashoff, David
2016-01-01
Abstract Objective. The aim was to evaluate the reliability, validity and responsiveness to change of the Gout Impact Scale (GIS), a disease-specific measure of patient-reported outcomes, in a multicentre longitudinal prospective cohort of gout patients. Methods. Subjects completed the GIS, a 24-item instrument with five scales: Concern Overall, Medication Side Effects, Unmet Treatment Need, Well-Being during Attack, and Concern Over Attack. The total GIS score was calculated by averaging the GIS scale scores. HAQ-Disability Index (HAQ-DI), Short Form (SF)-36 physical and mental component summaries (PCS and MCS) and physician and patient gout severity assessments were also completed. Reliability was assessed with Cronbach’s α. Baseline GIS scores were compared in subjects with and without gout attacks in the past 3 months using Wilcoxon rank sum tests. Multivariate linear regression was used to evaluate predictors of total GIS. Pearson’s correlation coefficients 0.24–0.36 were considered moderate and >0.37 considered large. The effect size for responsiveness to change was interpreted as follows: 0.20–0.49 small, 0.50–0.79 medium and >0.79 large. Results. In 147 subjects, reliability was acceptable for total GIS (0.93) and all GIS scales (0.82–0.94) except Medication Side Effects and Unmet Treatment Need. Total GIS and all scales except Medication Side Effects discriminated between subjects with and without recent gout attacks (P < 0.05). Total GIS showed moderate-to-large correlations with HAQ-DI, SF-36 PCS and MCS (0.33–0.46). Improvement in total GIS tracked with improved physician and patient severity scores. Worsening physician severity score and recent gout attack predicted worsening total GIS. Conclusion. Total GIS score is reliable, valid and responsive to change in patients with gout, and differentiates between subjects with and without recent gout attacks. PMID:26888852
Adler, U. C.; Paiva, N. M. P.; Cesar, A. T.; Adler, M. S.; Molina, A.; Padula, A. E.; Calil, H. M.
2011-01-01
Homeopathy is a complementary and integrative medicine used in depression, The aim of this study is to investigate the non-inferiority and tolerability of individualized homeopathic medicines [Quinquagintamillesmial (Q-potencies)] in acute depression, using fluoxetine as active control. Ninety-one outpatients with moderate to severe depression were assigned to receive an individualized homeopathic medicine or fluoxetine 20 mg day−1 (up to 40 mg day−1) in a prospective, randomized, double-blind double-dummy 8-week, single-center trial. Primary efficacy measure was the analysis of the mean change in the Montgomery & Åsberg Depression Rating Scale (MADRS) depression scores, using a non-inferiority test with margin of 1.45. Secondary efficacy outcomes were response and remission rates. Tolerability was assessed with the side effect rating scale of the Scandinavian Society of Psychopharmacology. Mean MADRS scores differences were not significant at the 4th (P = .654) and 8th weeks (P = .965) of treatment. Non-inferiority of homeopathy was indicated because the upper limit of the confidence interval (CI) for mean difference in MADRS change was less than the non-inferiority margin: mean differences (homeopathy-fluoxetine) were −3.04 (95% CI −6.95, 0.86) and −2.4 (95% CI −6.05, 0.77) at 4th and 8th week, respectively. There were no significant differences between the percentages of response or remission rates in both groups. Tolerability: there were no significant differences between the side effects rates, although a higher percentage of patients treated with fluoxetine reported troublesome side effects and there was a trend toward greater treatment interruption for adverse effects in the fluoxetine group. This study illustrates the feasibility of randomized controlled double-blind trials of homeopathy in depression and indicates the non-inferiority of individualized homeopathic Q-potencies as compared to fluoxetine in acute treatment of outpatients with moderate to severe depression. PMID:19687192
Mouzakes, J; Koltai, P J; Kuhar, S; Bernstein, D S; Wing, P; Salsberg, E
2001-10-01
To evaluate the effect driver-side and passenger-side airbags have had on the incidence and severity of maxillofacial trauma in victims of automobile accidents. Retrospective analysis of all automobile (passenger cars and light trucks) accidents reported in 1994. New York State. Of the 595910 individuals involved in motor vehicle accidents in New York in 1994, 377054 individuals were initially selected from accidents involving cars and light trucks. Of this subset, 164238 drivers and 62755 right front passengers were selected for analysis. Each case is described in a single record with approximately 100 variables describing the accident, eg, vehicle, safety equipment installed and utilized or deployed, occupant position, patient demographics, International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnoses, and procedural treatments rendered. A maxillofacial trauma severity scale was devised, based on the ICD-9-CM diagnoses. Individuals using airbags and seat belts sustained facial injuries at a rate of 1 in 449, compared with a rate of 1 in 40 for individuals who did not use seat belts or airbags (P<.001). Those using airbags alone sustained facial injuries at the intermediate rate of 1 in 148, and victims using seat belts without airbags demonstrated an injury rate of 1 in 217 (P<.001). Use of driver-side airbags, when combined with use of seat belts, has resulted in a decrease in the incidence and severity of maxillofacial trauma.
Free Energy Perturbation Calculations of the Thermodynamics of Protein Side-Chain Mutations.
Steinbrecher, Thomas; Abel, Robert; Clark, Anthony; Friesner, Richard
2017-04-07
Protein side-chain mutation is fundamental both to natural evolutionary processes and to the engineering of protein therapeutics, which constitute an increasing fraction of important medications. Molecular simulation enables the prediction of the effects of mutation on properties such as binding affinity, secondary and tertiary structure, conformational dynamics, and thermal stability. A number of widely differing approaches have been applied to these predictions, including sequence-based algorithms, knowledge-based potential functions, and all-atom molecular mechanics calculations. Free energy perturbation theory, employing all-atom and explicit-solvent molecular dynamics simulations, is a rigorous physics-based approach for calculating thermodynamic effects of, for example, protein side-chain mutations. Over the past several years, we have initiated an investigation of the ability of our most recent free energy perturbation methodology to model the thermodynamics of protein mutation for two specific problems: protein-protein binding affinities and protein thermal stability. We highlight recent advances in the field and outline current and future challenges. Copyright © 2017 Elsevier Ltd. All rights reserved.
Effects of microstructure and mechanical properties of alloy 600 and 690 on secondary side SCC
DOE Office of Scientific and Technical Information (OSTI.GOV)
Vaillant, F.; Buisine, D.; Prieux, B.
1996-12-31
Modeling for secondary side cracking is needed to understand the behavior of alloy 600 in plants. They require a comprehensive understanding of the various influences of the material properties on Stress Corrosion Cracking (SCC), based on field experience and laboratory data. In an attempt to predict the materials effects on SCC behavior of new steam generators, laboratory corrosion data of alloy 690 were overviewed. French field experience with steam generators equipped with drilled tube support plates (TSPS) has demonstrated that the lower the yield stress (YS) and the carbon content, the higher the susceptibility to secondary side cracking of mill-annealedmore » (MA) alloy 600. Also heat treated (700 C x 16 h) tubing has been shown to have a much better resistance, but this excellent resistance could not be attributed only to the material properties. In laboratory environments, particularly in caustics, results have confirmed several of the above mentioned key findings on alloy 600.« less
Wang, Yilun; Zhu, Min; Bao, Yunqi; Li, Li; Zhu, Liping; Li, Feng; Xu, Jinhua; Liang, Jun
2018-06-01
Cutaneous mucormycosis is an uncommon disease and occurs rarely in immunocompetent patients. We reported the case of a 37-year-old man presenting with a skin lesion on the left side of the chest wall with no history of trauma or primary diseases. He was firstly misdiagnosed as tuberculosis and the proper treatment was thus delayed. Histopathological examination and fungal culture of the lesion confirmed cutaneous mucormycosis. The isolate was identified as Rhizopus microspores by ITS sequencing. The patient was treated with oral posaconazole 400 mg bid for 150 days. The patient recovered satisfactorily. No recurrence was found during the follow-up and no side effect of liver function was found. This case helps doctors to consider the possibility of serious fungal infection in immunocompetent patients. It also suggested that posaconazole could be an alternative choice for the treatment of mucormycosis considering the severe side effect of Amphotericin B.
The Structure Of Intact Side Tissue Loss Based On FTIR Spectroscopic Measurements
NASA Astrophysics Data System (ADS)
Hussain, N.; Al-Hadithi, K. O.; Jaafar, M. S.
2009-09-01
Laser applications in dentistry were strongly evolved during the last three decades. Among those applications are laser ablation of dental hard tissue, caries inhibition treatments by localized surface heating, and surface conditioning for bonding. In addition, infra-red lasers are ideally suited for the selective and precise removal of carious dental hard tissue while minimizing the healthy tissue loss. In the present study we applied laser spectroscopy technique FTIR for the study of the structure of intact side tissue of teeth. The aim of the recent work is to study the effect of race and sex (genealogy) on the structure of intact side tissue loss. Our sample consists of twenty Malay females' teeth where the FTIR has been applied. The data show a decrease in the amounts of main substances (like Hydroxyapatite crystals ([Ca5(PO4)3(OH)4], CaF2) than those in healthy teeth. The measured spectra represent the enamel with the characteristic peaks due to the phosphate group in carbonated, hydroxyapatite at 1000 cm-1 and two small peaks near 1500 cm-1 due to the carbonate group. The data explains the effect of the several factors on the intact side tissue loss.
Probiotics and Antibiotic-Associated Diarrhea and Clostridium difficile Infection
NASA Astrophysics Data System (ADS)
Surawicz, Christina M.
Diarrhea is a common side effect of antibiotics. Antibiotics can cause diarrhea in 5-25% of individuals who take them but its occurrence is unpredictable. Diarrhea due to antibiotics is called antibiotic-associated diarrhea (AAD). Diarrhea may be mild and resolve when antibiotics are discontinued, or it may be more severe. The most severe form of AAD is caused by overgrowth of Clostridium difficile which can cause severe diarrhea, colitis, pseudomembranous colitis, or even fatal toxic megacolon. Rates of diarrhea vary with the specific antibiotic as well as with the individual susceptibility.
Moltzahn, Felix; Haeni, Katharina; Birkhäuser, Frédéric D; Roth, Beat; Thalmann, George N; Zehnder, Pascal
2013-02-01
To evaluate the antibiotic treatment regime in patients with indwelling JJ stents, the benefits and disadvantages of a peri-interventional antibiotic prophylaxis were compared with those of a continuous low-dose antibiotic treatment in a prospective randomised trial. In all, 95 patients were randomised to either receive peri-interventional antibiotic prophylaxis during stent insertion only (group A, 44 patients) or to additionally receive a continuous low-dose antibiotic treatment until stent removal (group B, 51). Evaluations for urinary tract infections (UTI), stent-related symptoms (SRSs) and drug side-effects were performed before stent insertion and consecutively after 1, 2 and 4 weeks and/or at stent withdrawal. All patients received a peri-interventional antibiotic prophylaxis with 1.2 g amoxicillin/clavulanic acid. Amoxicillin/clavulanic acid (625 mg) once daily was administered for continuous low-dose treatment (group B). Primary endpoints were the overall rates of UTIs and SRSs. Secondary endpoints were the rates and severity of drug side-effects. Neither the overall UTI rates (group A: 9% vs group B: 10%), nor the rates of febrile UTIs (group A: 7% vs group B: 6%) were different between the groups. Similarly, SRS rates did not differ (group A: 98% vs group B: 96%). Antibiotic side-effect symptoms were to be increased in patients treated with low-dose antibiotics. A continuous antibiotic low-dose treatment during the entire JJ stent-indwelling time does not reduce the quantity or severity of UTIs and has no effect on SRSs either compared with a peri-interventional antibiotic prophylaxis only. © 2012 BJU International.
Emergency contraception: which is the best?
Mittal, Suneeta
2016-12-01
Emergency contraception is a safe and effective method to prevent an unwanted pregnancy after an unprotected or inadequately protected sexual intercourse. Several methods for emergency contraception (EC) are currently registered in many countries for use in an emergency to prevent a pregnancy following an unprotected, possibly fertile intercourse or after a contraceptive accident like condom rupture. Different methods have varying modes of action, time frame of efficacy, dosage schedule and unwanted effects. Since several methods are available it is important to decide the best method. In this article the available literature on emergency contraception has been reviewed and an attempt has been made to discuss the need for emergency contraception and compare different options for emergency contraception in terms of their efficacy in pregnancy prevention, their safety profile and unwanted side effects. EC repeated use and initiating a regular method after EC use are also discussed. Emergency contraceptive methods include copper Intra-uterine devices (IUD) and different types of pills like estrogen progestin combination pill (Yuzpe Regimen), Progestin only pill (LNG), antiprogestin pill (Mifepristone), and progesterone modulator Uripristal Acetate (UPA). There is a marginal difference in the mechanism of action, efficacy including time frame and ability to protect from pregnancy with regular doses in obese women, drug interactions and side effects. These are discussed in detail. Copper IUD is the most effective emergency contraceptive with advantage of providing continued contraception. However, it cannot be used universally due to lack of infrastructure and a trained provider as well as not being suitable option for women at risk of sexually transmitted infections. Amongst different pills LNG is more effective with fewer side effects than Yuzpe regimen. LNG and UPA are comparable with similar efficacy and side effect profile. UPA has a wider window of efficacy, in LNG efficacy declines after 72 hours. UPA is more suitable for obese women. Mifepristone is effective but is registered as EC pill only in few countries and use is limited as it is also used as an abortion pill. Yuzpe regimen is the least effective of all contraceptive pills as EC, and works only till 72 hours of unprotected sex, but is useful in places where dedicated methods are not available, as it is easily accessible. Any combined pill can be used in this regimen except triphasic pill.
Adenosine-Associated Delivery Systems
Kazemzadeh-Narbat, Mehdi; Annabi, Nasim; Tamayol, Ali; Oklu, Rahmi; Ghanem, Amyl; Khademhosseini, Ali
2016-01-01
Adenosine is a naturally occurring purine nucleoside in every cell. Many critical treatments such as modulating irregular heartbeat (arrhythmias), regulation of central nervous system (CNS) activity, and inhibiting seizural episodes can be carried out using adenosine. Despite the significant potential therapeutic impact of adenosine and its derivatives, the severe side effects caused by their systemic administration have significantly limited their clinical use. In addition, due to adenosine’s extremely short half-life in human blood (less than 10 s), there is an unmet need for sustained delivery systems to enhance efficacy and reduce side effects. In this paper, various adenosine delivery techniques, including encapsulation into biodegradable polymers, cell-based delivery, implantable biomaterials, and mechanical-based delivery systems, are critically reviewed and the existing challenges are highlighted. PMID:26453156
Hydroxyurea-induced oral ulceration.
Badawi, Maha; Almazrooa, Soulafa; Azher, Fatima; Alsayes, Fatin
2015-12-01
Hydroxyurea is an antimetabolite that is widely used in the treatment of many benign and malignant conditions. This drug is usually well tolerated but has a number of side effects that vary in incidence. In cases of clinically significant adverse events, hydroxyurea is usually discontinued either temporarily or permanently, depending on treatment need versus harm caused by side effects. Here, we report a case of oral ulceration associated with hydroxyurea treatment in a patient who had chronic myelogenous leukemia. The patient rapidly developed an oral ulcer 12 days after administration of the drug. Hydroxyurea was discontinued, and the oral lesion appreciably decreased in size and severity. Physicians and dentists should be aware of the association between hydroxyurea and oral lesions. Copyright © 2015 Elsevier Inc. All rights reserved.
Fatal necrotising enterocolitis due to mydriatic eye drops.
Ozgun, Uygur; Demet, Terek; Ozge, Koroglu A; Zafer, Dokumcu; Murat, Sezak; Mehmet, Yalaz; Nilgun, Kultursay
2014-05-01
Retinopathy of prematurity (ROP) is a serious problem of preterm infants which may lead to impairment of vision and even to blindness if untreated. Routine eye examination is necessary for early diagnosis and treatment of ROP in preterm infants. Mydriatic eye drops (cyclopentolate, tropicamide and phenylephrine) are applied before the ophthalmic examination. These agents are rarely absorbed to systemic circulation and in some cases result with serious side effects like skin rash, tachycardia, feeding intolerance, discomfort, apnea, gastric dilatation and ileus, despite different treatment models and dosage reducing strategies. We report here a preterm patient who died because of severe diffuse necrotizing enterocolitis (NEC) after topical application of 0.5% cyclopentolate and 1.25% phenylephrine during ROP screening to emphasise the serious side effects of these agents.
A Teacher's Guide to Using Extinction in School Settings
ERIC Educational Resources Information Center
Burt, Jonathan L.; Pennington, Robert C.
2017-01-01
The use of extinction procedures or the discontinuation of reinforcement following a behavior targeted for reduction is often used to enhance the efficacy of behavioral interventions. Unfortunately, the application of extinction procedures is associated with several side effects that can produce potentially harmful and counterproductive outcomes.…
Flagellate dermatitis after consumption of Shiitake mushrooms
Kreft, Burkhard; Marsch, Wolfgang Ch.
2014-01-01
Flagellate dermatitis occurs in patients who have eaten Shiitake mushrooms. We are reporting on a 55-year-old man, who developed whiplash-striped, severely itching efflorescences on the trunk 3 days after eating Lentinula edodes. Flagellate dermatitis is also known as a cutaneous side effect of bleomycin therapy. PMID:25097492
[Clinical and monitoring experience of isotretinoin in Italy].
Cavicchini, S; Bottoni, A; Caputo, R
1989-01-01
We report the results of a multicentric evaluation on effectiveness and safety of isotretinoin in severe acne, recalcitrant to traditional treatments. 208 patients, suffering especially from cystic acne, have been enrolled in a post-marketing clinical trial in 11 Dermatological Italian Departments. The clinical effectiveness of isotretinoin has been very good in 77% of patients, good in 16% and sufficient in 4%. The tolerability of the drug was considered good in 90% of patients. Finally, isotretinoin might be considered as one of the most effective drugs in the therapy of severe forms of acne, resistant to usual treatment, and often affecting patients on the physical and psychological side.
Driver air bag effectiveness by severity of the crash.
Segui-Gomez, M
2000-01-01
OBJECTIVES: This analysis provided effectiveness estimates of the driver-side air bag while controlling for severity of the crash and other potential confounders. METHODS: Data were from the National Automotive Sampling System (1993-1996). Injury severity was described on the basis of the Abbreviated Injury Scale, Injury Severity Score, Functional Capacity Index, and survival. Ordinal, linear, and logistic multivariate regression methods were used. RESULTS: Air bag deployment in frontal or near-frontal crashes decreases the probability of having severe and fatal injuries (e.g., Abbreviated Injury Scale score of 4-6), including those causing a long-lasting high degree of functional limitation. However, air bag deployment in low-severity crashes increases the probability that a driver (particularly a woman) will sustain injuries of Abbreviated Injury Scale level 1 to 3. Air bag deployment exerts a net injurious effect in low-severity crashes and a net protective effect in high-severity crashes. The level of crash severity at which air bags are protective is higher for female than for male drivers. CONCLUSIONS: Air bag improvement should minimize the injuries induced by their deployment. One possibility is to raise their deployment level so that they deploy only in more severe crashes. PMID:11029991
Zhuang, Yaling; Zhu, Xiufang; Huang, Li-Li
2010-02-01
First-trimester surgical abortion is a common procedure. Pain control during this procedure is still an unsolved problem. In this randomized, double-blind placebo-controlled study, women presenting for first-trimester surgical abortion received intramuscular phloroglucinol (4 mL) or placebo (normal saline, 4 mL). Visual analog scales (VAS) for pain immediately and 30 min after the procedure and side effects of the drug were recorded. There was no significant difference between groups in the pain level immediately and 30 min after the procedure; 70.7% of the phloroglucinol group (n=58 cases) and 56.9% of the placebo group (n=58 cases ) reported mild pain; 27.6% and 34.5%, respectively, reported moderate pain; and 1.7% and 8.6%, respectively, reported severe pain. Thirty minutes after the procedure, the median pain score was reduced to 1.3 in both groups. Postoperative side effects were reported, but there was no significant difference between groups for nausea or vomiting and blood pressure. The use of this dose of phloroglucinol, during first-trimester abortion by suction evacuation under local anesthesia with lidocaine, did not relieve pain, but caused no side effects.
Drug safety evaluation of dronedarone in atrial fibrillation.
De Ferrari, Gaetano M; Dusi, Veronica
2012-11-01
Dronedarone was developed with the intent of replicating the antiarrhythmic effects of amiodarone, while minimizing its side effects. Side effects reported in eight randomized clinical trials are discussed, comparing dronedarone and placebo (DAFNE, EURIDIS, ADONIS, ERATO, ANDROMEDA, ATHENA, PALLAS, total number of patients treated with dronedarone 5347), or dronedarone and amiodarone (DIONYSOS, total number of patients treated with dronedarone 249). The results of the first trials, including ATHENA, set high expectations by suggesting that dronedarone may decrease the risk of hospitalization (and even cardiovascular mortality) among patients with paroxysmal and persistent atrial fibrillation (AF), and that it could be regarded as an easy-to-use drug that could be prescribed by general practitioners; unfortunately, dronedarone has not met these expectations. Dronedarone may increase mortality and heart failure hospitalization in patients with advanced NYHA class and in patients with permanent AF, preventing its use in these settings. In addition to gastrointestinal side effects that may lead to discontinuation in 5 - 10% of patients, dronedarone may induce very rare but severe liver and lung toxicity. Despite these limitations and its relatively limited antiarrhythmic potency, dronedarone may still be a useful drug for well-selected patients.
Gur-Ozmen, S; Mula, M; Agrawal, N; Cock, H R; Lozsadi, D; von Oertzen, T J
2017-09-01
People with epilepsy are at increased risk of accidents and injuries but, despite several studies on this subject, data regarding preventable causes are still contradictory. The aim of this study was to investigate the relationship between injuries, side effects of antiepileptic drugs (AEDs) and depression. Data from a consecutive sample of adult patients with epilepsy attending the outpatient clinics at St George's University Hospital in London were included. All patients were asked if they had had any injury since the last clinic appointment and completed the Liverpool Adverse Event Profile (LAEP) and Neurological Disorders Depression Inventory for Epilepsy. Among 407 patients (243 females, mean age 43.1 years), 71 (17.4%) reported injuries since the last appointment. A two-step cluster analysis revealed two clusters with the major cluster (53.5% of the injured group) showing a total score for LAEP ≥45, a positive Neurological Disorders Depression Inventory for Epilepsy screening and presence of AED polytherapy. A total score for LAEP ≥45 was the most important predictor. Antiepileptic drug treatment should be reviewed in patients reporting injuries in order to evaluate the potential contribution and burden of AED side effects. © 2017 EAN.
Polansky, Hanan; Itzkovitz, Edan; Javaherian, Adrian
2016-12-01
We conducted a clinical study that tested the effect of suppressive treatment with the botanical product Gene-Eden-VIR/Novirin on genital herpes. Our previous paper showed that the treatment decreased the number of genital herpes outbreaks without any side effects. It also showed that the clinical effects of Gene-Eden-VIR/Novirin are mostly better than those reported in the studies that tested acyclovir, valacyclovir, and famciclovir. The current paper reports the effect of suppressive treatment with Gene-Eden-VIR/Novirin on the duration of outbreaks, in severe and mild genital herpes cases. The framework was a retrospective chart review. The population included 137 participants. The treatment was 1-4 capsules per day. The duration of treatment was 2-48 months. The study included three controls: baseline, no-treatment, and dose-response. The treatment decreased the duration of outbreaks in 87 % of participants and decreased the mean duration of outbreaks from 8.77 days and 6.7 days in the control groups to 2.87 days in the treatment group (P < 0.001, both groups). All participants reported no adverse experiences. This paper shows that suppressive treatment with Gene-Eden-VIR/Novirin decreased the duration of genital herpes outbreaks, in both severe and mild cases, without any side effects. Based on the results reported in this and our previous paper, we recommend suppressive treatment with Gene-Eden-VIR/Novirin as a natural alternative to both suppressive and episodic treatments with current drugs, in both severe and mild genital herpes cases. Trial registration ClinicalTrials.gov NCT02715752 Registered 17 March 2016 Retrospectively Registered.
2016-09-01
to treat traumatic injuries by enhanced delivery of oxygen . A concerned side effect of PFC may cause thrombocytopenia (TCYP). FDA requests...Morris, A., Zhu, J., Spiess, B.D., Parsons, J.T. The Effect of Perfluorocarbon Oxygen Therapeutics in a Sheep Survival Model of Severe Hemorrhagic...of effectively oxygenating sensitive tissue in the absence of adequate hemoglobin and/or blood flow. PFC emulsion volumes required for efficacy can
Severity of vehicle bumper location in vehicle-to-pedestrian impact accidents.
Matsui, Yasuhiro; Hitosugi, Masahito; Mizuno, Koji
2011-10-10
Pedestrian protection is one of the key topics for safety measures in traffic accidents all over the world. To analyze the relation between the collision site of the vehicle bumper and the severity of the lower extremity injuries, we performed biomechanical experiments. We compared the applied external force and the risks of subsequent injuries between the impact of the center and side positions of the front bumper. These comparisons were performed by practical impact tests with eight typical different types of cars which were typical of the current vehicle fleets. The tests were made using the TRL legform impactor which was a mechanical substitute of a pedestrian lower extremity. The TRL impactor is used all over the world for assessing the safety of car bumpers. It was found that the risks of lower extremity injuries in the impacts at the side positions, in front of the vehicle's side member, were significantly higher than those at the center. In the tests, we found that foam materials around the rigid front cross member had a significant effect on reducing the lower extremity injury risks and especially tibia fracture risk against vehicle bumper center collisions, but had little effect at the sides of the bumper over the vehicle's side members where the foam was thinner. We also found that the front shape of the vehicle affected the risk of ligaments injuries. According to these results, the information of impact locations of cars in vehicle-to-pedestrian traffic accidents is valuable for clinicians to diagnose patients with lower extremity injuries in traffic accidents and for forensic pathologists to analyze the accident reconstruction. Furthermore, the results suggest that testing of the bumper area in front of the main longitudinal beams should be included in the car safety legislation to require pedestrian safety. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Achterberg, Wilco P; de Ruiter, Corinne M; de Weerd-Spaetgens, Chantal M E E; Geels, Paul; Horikx, Annemieke; Verduijn, Monique M
2012-01-01
Chronic pain in vulnerable elderly people is still poorly recognized and treated, both at home and in hospitals and care and nursing homes. Vulnerable elderly people experience and express pain differently to relatively healthy adults, especially when they suffer from cognitive impairment or specific conditions. Determining the nature and severity of the pain requires the use of pain assessment instruments that have been validated for use in vulnerable elderly people. Effective treatment of pain demands careful diagnosis and pharmacological and non-pharmacological interventions that have proven effectiveness in vulnerable elderly people. The combination of multiple morbidity and poly-pharmacy increases the chance of side-effects and complications. In addition, the pharmacokinetic and pharmacodynamic characteristics of many drugs are different in vulnerable elderly people. The advice is to start with a lower dose of pain medication and gradually build up a level on the basis of pain relief and side-effects ('start low, go slow!').
Open-label trial of atomoxetine hydrochloride in adults with ADHD.
Johnson, Mats; Cederlund, Mats; Råstam, Maria; Areskoug, Björn; Gillberg, Christopher
2010-03-01
While atomoxetine is an established treatment for attention-deficit/hyperactivity disorder in children, few studies have examined its efficacy for adults. Open-label trial of atomoxetine in 20 individuals with ADHD, aged 19-47 years, for 10 weeks, and a total of one year for responders. Ten patients met primary efficacy criteria at 10 weeks. Only one patient completed the whole study. Six patients discontinued before 10 weeks and thirteen at 10 weeks or later, mainly because of side-effects (aggression, depressed mood, raised liver enzymes, thyroid hormones, diastolic blood pressure), decreasing efficacy or non-compliance. Fifty percent responded to treatment, but only one patient (5%) felt sufficient improvement to continue for one year. Dosage may have been too low, and baseline impairment too high, for atomoxetine to have sufficient effect on ADHD symptoms in our group of adults. The majority had few side-effects, but several terminated treatment because of adverse effects.
Cannabinoids: between neuroprotection and neurotoxicity.
Sarne, Yosef; Mechoulam, Raphael
2005-12-01
Cannabinoids, such as the delta9-tetrahydrocannabinol (THC), present in the cannabis plant, as well as anandamide and 2-arachidonoyl glycerol, produced by the mammalian body, have been shown to protect the brain from various insults and to improve several neurodegenerative diseases. The current review summarizes the evidence for cannabinoid neuroprotection in vivo, and refers to recent in vitro studies, which help elucidate possible molecular mechanisms underlying this protective effect. Some of these mechanisms involve the activation of CB1 and CB2 cannabinoid receptors, while others are not dependent on them. In some cases, protection is due to a direct effect of the cannabinoids on neuronal cells, while in others, it results from their effects on non-neuronal elements within the brain. In many experimental set-ups, cannabinoid neurotoxicity, particularly by THC, resides side by side with neuroprotection. The current review attempts to shed light on this dual activity, and to dissociate between the two contradictory effects.
Gold nanoparticles enhance the anti-leukemia action of a 6-mercaptopurine chemotherapeutic agent.
Podsiadlo, Paul; Sinani, Vladimir A; Bahng, Joong Hwan; Kam, Nadine Wong Shi; Lee, Jungwoo; Kotov, Nicholas A
2008-01-15
6-mercaptopurine and its riboside derivatives are some of the most widely utilized anti-leukemic and anti-inflammatory drugs. Their short biological half-life and severe side effects limit their use. A new delivery method for these drugs based on 4-5 nm gold nanoparticles can potentially resolve these issues. We have found substantial enhancement of the antiproliferative effect against K-562 leukemia cells of Au nanoparticles bearing 6-mercaptopurine-9-beta-d-ribofuranoside compared to the same drug in typically administered free form. The improvement was attributed to enhanced intracellular transport followed by the subsequent release in lysosomes. Enhanced activity and nanoparticle carriers will make possible the reduction of the overall concentration of the drug, renal clearance, and, thus, side effects. The nanoparticles with mercaptopurine also showed excellent stability over 1 year without loss of inhibitory activity.
Synoptic Control of Cross-Barrier Precipitation Ratios
NASA Astrophysics Data System (ADS)
Mass, C.; Vargas, R.
2013-12-01
The substantial precipitation contrasts across mountain barriers, with windward enhancement on one side and leeward reduction on the other, have been the subject of several studies and reviews, both observational and theoretical. A lesser number of papers have examined the temporal variability of the orographic precipitation contrasts, including the origins of such variability. For example, Siler et al. (2013) examined the variability of the rain-shadow effect across the Cascade Mountains of Washington State. They found that the intensity of the winter-mean rain shadow was weaker in El Nino than La Nina years, and suggested that the strongest (weakest) rain shadows occurred for warm-sector (warm-frontal) situations. Dettinger et al. (2004) examined the synoptic controls of varying orographic precipitation ratios across the Sierra Nevada of California, with ratios defined by the difference in precipitation between the Central Valley and the western slopes of the barrier. They found increased ratios when the flow was more normal to the terrain and when vertical stability was less, with higher ratios after cold frontal passage compared to the warm sectors of midlatitude cyclones. The latter result appears to contradict the findings of Siler et al (2013). This presentation explores the temporal variations in the intensity of the precipitation gradient across the Cascade Mountains of Washington State and describes the synoptic conditions associated with periods in which precipitation is heavier on the western side, heavier on the eastern side, or nearly equal across the barrier. The talk will begin by summarizing the temporal variations of precipitation on the windward and leeward sides of the Cascades for a several year period. Segregating the hours when precipitation is substantially greater on the windward side, greater on the leeward side, or roughly equal, provides a series of dates used for synoptic composites for these three situations. It is shown that there are coherent and significant synoptic differences between the three precipitation ratio regimes, and these differences are illustrated for several case studies. For example, windward enhancement is greater after the passage of cold or occluded fronts, when stability is reduced and the flow is more westerly. Finally, the physical connection between synoptic flow and the changing cross-barrier precipitation contrasts are discussed.
A unified frame of predicting side effects of drugs by using linear neighborhood similarity.
Zhang, Wen; Yue, Xiang; Liu, Feng; Chen, Yanlin; Tu, Shikui; Zhang, Xining
2017-12-14
Drug side effects are one of main concerns in the drug discovery, which gains wide attentions. Investigating drug side effects is of great importance, and the computational prediction can help to guide wet experiments. As far as we known, a great number of computational methods have been proposed for the side effect predictions. The assumption that similar drugs may induce same side effects is usually employed for modeling, and how to calculate the drug-drug similarity is critical in the side effect predictions. In this paper, we present a novel measure of drug-drug similarity named "linear neighborhood similarity", which is calculated in a drug feature space by exploring linear neighborhood relationship. Then, we transfer the similarity from the feature space into the side effect space, and predict drug side effects by propagating known side effect information through a similarity-based graph. Under a unified frame based on the linear neighborhood similarity, we propose method "LNSM" and its extension "LNSM-SMI" to predict side effects of new drugs, and propose the method "LNSM-MSE" to predict unobserved side effect of approved drugs. We evaluate the performances of LNSM and LNSM-SMI in predicting side effects of new drugs, and evaluate the performances of LNSM-MSE in predicting missing side effects of approved drugs. The results demonstrate that the linear neighborhood similarity can improve the performances of side effect prediction, and the linear neighborhood similarity-based methods can outperform existing side effect prediction methods. More importantly, the proposed methods can predict side effects of new drugs as well as unobserved side effects of approved drugs under a unified frame.
Drug side effect extraction from clinical narratives of psychiatry and psychology patients
Kocher, Jean-Pierre A; Chute, Christopher G; Savova, Guergana K
2011-01-01
Objective To extract physician-asserted drug side effects from electronic medical record clinical narratives. Materials and methods Pattern matching rules were manually developed through examining keywords and expression patterns of side effects to discover an individual side effect and causative drug relationship. A combination of machine learning (C4.5) using side effect keyword features and pattern matching rules was used to extract sentences that contain side effect and causative drug pairs, enabling the system to discover most side effect occurrences. Our system was implemented as a module within the clinical Text Analysis and Knowledge Extraction System. Results The system was tested in the domain of psychiatry and psychology. The rule-based system extracting side effects and causative drugs produced an F score of 0.80 (0.55 excluding allergy section). The hybrid system identifying side effect sentences had an F score of 0.75 (0.56 excluding allergy section) but covered more side effect and causative drug pairs than individual side effect extraction. Discussion The rule-based system was able to identify most side effects expressed by clear indication words. More sophisticated semantic processing is required to handle complex side effect descriptions in the narrative. We demonstrated that our system can be trained to identify sentences with complex side effect descriptions that can be submitted to a human expert for further abstraction. Conclusion Our system was able to extract most physician-asserted drug side effects. It can be used in either an automated mode for side effect extraction or semi-automated mode to identify side effect sentences that can significantly simplify abstraction by a human expert. PMID:21946242
Papadopoulos, C; Hayes, B K
2018-06-01
Previous work has demonstrated a "side-effect effect," such that intentionality is more likely to be attributed to agents who bring about negatively valenced as opposed to positively valenced side effects. The rational-scientist model explains this by suggesting that norm-violating side effects are more informative for inferring intentionality than norm-conforming side effects. In the present study we reexamined this account, addressing limitations of previous empirical tests (e.g., Uttich & Lombrozo, Cognition 116: 87-100, 2010). Side-effect valence and norm status were manipulated factorially, enabling an examination of the impact of norm status on intentionality judgments in both positively and negatively valenced side effects. Additionally, the impact of side-effect norm status on the perceived valences of side effects and agents was examined. Effects of norm status were found for both positive and negative side effects. Violation of an ostensibly neutral norm led to negative perceptions of the side effect. However, a norm status effect on intentionality judgments persisted when these effects were controlled. These results support the view that the side-effect effect is the result of the rational use of social-cognitive evidence.
Tavakolpour, Soheil
2016-01-01
Background: Mucous membrane pemphigoid (MMP) is considered an autoimmune blistering disease that predominantly affects mucous membranes. Various treatments are available for controlling the diseases, but not all of them may respond. Materials and Methods: PubMed and Google Scholar were searched for all the associated studies until 2015, using the keywords such as “cicatricial pemphigoid” or “ocular pemphigoid” or “mucous membrane pemphigoid” or “MMP” and “intravenous immunoglobulin” or “IVIg” to find all the relevant studies. The last search update was for September 2, 2015. Among the searched items, only English studies were included in the review. Results: After excluding nonrelevant studies, 13 studies with a total number of seventy patients with MMP who were under treatment with IVIg were analyzed. The 65 patients responded completely, one did not respond, two had partially responded, and the remaining two patients stopped IVIg therapy, which resulted in ocular cicatricial pemphigoid progression. Majority of the studies reported mild adverse effects while two of them did not report any unwanted side effect. The most common side effect was headache, followed by nausea. Most of the patients who had a cessation of IVIg therapy before achieving clinical remission experienced the disease progression. Conclusion: Overall, it can be concluded that IVIg therapy was very helpful in treatment of MMP patients who did not respond to conventional therapy or stopped using them for various side effects. Adverse effects associated with IVIg therapy were considerably lower than conventional therapy that can lead toward treatment with this agent in patients who suffer from severe side effects. PMID:27904583
[Ketamine as anesthetic agent in electroconvulsion therapy].
Janke, C; Bumb, J M; Aksay, S S; Thiel, M; Kranaster, L; Sartorius, A
2015-05-01
Electroconvulsive therapy (ECT) is a well-established, safe and effective treatment for severe psychiatric disorders. Ketamine is known as a core medication in anesthesiology and has recently gained interest in ECT practice as there are three potential advantages: (1) ketamine has no anticonvulsive actions, (2) according to recent studies ketamine could possess a unique intrinsic antidepressive potential and (3) ketamine may exhibit neuroprotective properties, which again might reduce the risk of cognitive side effects associated with ECT. The use of ketamine in psychiatric patients has been controversially discussed due to its dose-dependent psychotropic and psychotomimetic effects. This study was carried out to test if the occurrence of side effects is comparable and if seizure quality is better with ketamine when compared to thiopental. This retrospective study analyzed a total of 199 patients who received ketamine anesthesia for a total of 2178 ECT sessions. This cohort was compared to patients who were treated with thiopental for 1004 ECT sessions. A repeated measurement multiple logistic regression analysis revealed significant advantages in the ketamine group for seizure concordance and postictal suppression (both are surrogates for central inhibition). S-ketamin also necessitated the use of a higher dose of urapidil and a higher maximum postictal heart frequency. Clinically relevant psychiatric side effects were rare in both groups. No psychiatric side effects occurred in the subgroup of patients with schizophrenia (ketamine: n = 30). The mean dose of S-ketamine used increased in the first years but stabilized at 63 mg per patient in 2014. From these experiences it can be concluded that S-ketamine can be recommended at least as a safe alternative to barbiturates.
Atefi, Najmolsadat; Dalvand, Behzad; Ghassemi, Mahammadreza; Mehran, Golnaz; Heydarian, Amir
2017-09-01
Few studies have focused on therapeutic as well as side effects of tranexamic acid (TXA) as a topical drug compared to other topical drugs in treating melasma. The present study aimed to assess and compare the beneficial therapeutic effects and also side effects of local TXA in comparison with hydroquinone in treating women with melasma. This randomized double-blinded clinical trial was performed on 60 women who suffered from melasma and were referred to the skin disorders clinic at the Rasoul-e-Akram hospital in Tehran in 2015. The patients were then randomly assigned via computerized randomization to two groups: group A received TXA%5 (topically twice a day for 12 weeks in the location of the melasma) and group B (received hydroquinone 2% with the same treatment order). Prior to intervention and at 12 weeks after intervention, the intensity and extension of melasma were assessed based on the Melasma Area and Severity Index (MASI) scoring method. The mean MASI score in both treatment groups decreased considerably after completion of treatment and was not significant between the two groups. No side effects were detected in group A, but 10% of those in group B complained of drug-related side effects including erythema and skin irritation (p = 0.131). Regarding the level of patient satisfaction, the patients in group A had a significantly higher level of satisfaction level of 33.3% compared with 6.7% in group B (p = 0.015) (Fig. 9). Multivariate linear regression modeling with the presence of age, history of systemic disorder, drug history, and family history of melasma demonstrated no difference in the mean MASI between the two groups. Topical use of TXA significantly reduced both melanin level and MASI score. Given its high efficiency and low drug side effects, this regimen results in high patient satisfaction compared with topical hydroquinone. IRCT code: IRCT2016040627220N2.
Brenner, J; Majoie, H J M; van Beek, S; Carpay, J A
2017-11-01
We describe the effectiveness of lacosamide as adjunctive therapy in patients with epilepsy and an intellectual disability. This information is relevant, as few data exist pertaining to this population with a high prevalence of (intractable) epilepsy. We performed a retrospective study in three specialised institutions. Inclusion criteria were (1) focal onset or symptomatic generalized (2) therapy-resistant epilepsy, (3) intellectual disability and (4) residence in a care-facility for people with intellectual disabilities (PWID). The primary outcome variables were the retention rates of lacosamide, estimated through Kaplan-Meier survival analysis. Secondary outcomes were reported seizure control, side effects and clinical factors influencing discontinuation. One hundred and thirty-two patients were included. The median retention time of lacosamide in our cohort was four years. The estimated one-, two- and three-year retention rates of lacosamide were 64%, 57% and 56% respectively. Severity of intellectual disability and seizure type did not influence whether lacosamide was continued. In 48.5% of patients, a reduction of seizure activity was reported. Side effects were at least part of the reason for discontinuing treatment in 26.5% of all patients. Common side effects were tiredness/somnolence (in 30.3%), aggression/agitation (24.2%), and instable gait (15.2%). Five deaths during follow-up were considered unlikely to be related to the use of lacosamide. One patient died unexpectedly within two months of treatment onset, probably this was a case of SUDEP. These retention rates of lacosamide in PWID are similar to rates of previously registered anti-epileptic drugs in PWID. Behavioural side effects were noted in a high proportion compared to the general literature on lacosamide. Other side effects were in line with this literature. Lacosamide seems effective and safe for PWID and refractory epilepsy. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Safety and efficacy of Regadenoson in myocardial perfusion imaging (MPI) stress tests: A review
NASA Astrophysics Data System (ADS)
Ahmed, Ambereen
2018-02-01
Myocardial perfusion imaging (MPI) tests are often used to help diagnose coronary heart disease (CAD). The tests usually involve applying stress, such as hard physical exercise together with administration of vasodilators, to the patients. To date, many of these tests use non-selective A2A adenosine receptor agonists which, however, can be associated with highly undesirable and life-threatening side effects such as chest pain, dyspnea, severe bronchoconstriction and atrioventricular conduction anomalies. Regadenoson is a relatively new, highly selective A2A adenosine receptor agonist, suitable for use in MPI tests which exhibits far fewer adverse side effects and, unlike others testing agents, can be used without the necessity of excessive concomitant exercise. Also, the dose of regadenoson required is not dependent upon patient weight or renal impairment, and it can be rapidly administered by i.v. Injection. Regadenoson use in MPI testing thus has the potential as a simplified, relatively safe, time-saving and cost-effective method for helping diagnose CAD. The present study was designed to review several articles on the safety, efficacy, and suitability of regadenoson in MPI testing for CAD. Overall, the combined studies demonstrated that use of regadenoson in conjunction with low-level exercise in MPI is a highly efficient and relatively safe test for CAD, especially for more severe health-compromised patients.
Side-to-side cavo-cavostomy: a useful aid in "complicated" piggy-back liver transplantation.
Lerut, J; Gertsch, P
1993-01-01
Piggy-back liver transplantation is a useful technical variant of orthotopic liver transplantation. Its success can, however, be compromised by severe stenosis or obstruction of the recipient's inferior vena cava at the level of the anastomosis. A technique is described--side-to-side cavocavostomy--to resolve this difficult intraoperative situation.
Descriptive sensory analysis of marinated and non-marinated wooden breast fillet portions.
Maxwell, A D; Bowker, B C; Zhuang, H; Chatterjee, D; Adhikari, K
2018-05-14
The wooden breast (WB) myopathy influences muscle composition and texture characteristics in broiler breast meat. It is unknown if marination reduces the negative influence of WB on meat sensory quality or if WB effects are uniform throughout the Pectoralis major. The objective of this study was to determine the effects of marination on the sensory attributes and instrumental shear force measurements of the ventral (skin-side) and dorsal (bone-side) portions of normal and severe WB meat. Sixty butterfly fillets (30 normal and 30 severe WB) were selected from the deboning line of a commercial processing plant. Individual fillets were portioned into ventral and dorsal halves. Portions from one side of each butterfly were used as non-marinated controls, and portions from the other side were vacuum-tumble marinated (16 rpm, -0.6 atm, 4°C, 20 min) with 20% (wt/wt) marinade to meat ratio. Marinade was formulated to target a concentration of 0.75% (w/v) salt and 0.45% (w/v) sodium tripolyphosphate in the final product. Descriptive sensory analysis (9 trained panelists) was conducted to evaluate visual, texture, and flavor attributes (0-15 point scale) of breast portions along with Warner-Bratzler shear force. Significant interaction effects between WB and marination were not observed for the sensory attributes. Greater springiness, cohesiveness, hardness, fibrousness, and chewiness scores were observed in WB samples (P < 0.001). Marination decreased cohesiveness, hardness, and chewiness (P < 0.05) and increased juiciness (P = 0.002). The effects of WB on sensory texture attributes were more apparent in the ventral portions of the breast fillets. Flavor attributes (salty and brothy) increased (P < 0.001) with marination. In non-marinated samples, shear force was similar between normal and WB samples. In marinated samples, however, shear force was greater (P < 0.001) in WB samples. Data suggest that the WB effect on meat sensory quality is not uniform throughout the Pectoralis major and that WB-related differences in cooked meat sensory texture attributes are lessened but not eliminated by vacuum-tumbling marination.
[Pharmacotherapy of hyperthyreosis--adverse drug reactions].
Perger, Ludwig; Bürgi, Ulrich; Fattinger, Karin
2011-06-01
The antithyroid drugs mainly include thioimidazole (carbimazole, methimazole=thiamazole) and propylthiouracil. After absorption, carbimazole is rapidly metabolized to methimazole and thus switching between these two drugs should not be considered in case of side effects. Furthermore, in case of side effects, sometimes even cross reactions between thioimidazoles and propylthiouracil occur. Common and typical adverse reactions of antithyroid drugs include dose dependent hypothyroidism and thus thyroid function should be repeatedly checked while the patient is on antithyroid drugs. Furthermore, pruritus and rash may develop. In this case, one might try to switch from thioimidazoles to propylthiouracil or vice versa. Antithyroid drugs may cause mild dose dependent neutropenia or severe allergy-mediated agranulocytosis, which typically occurs during the first three months of treatment, has an incidence of 3 per 10,000 patients and cross reactivity between thioimidazoles to propylthiouracil may occur. Rarely, antithyroid drugs can cause aplastic anemia. Mainly propylthiouracil, but sometimes also methimazole may lead to an asymptomatic transient increase in liver enzymes or to severe, even lethal liver injury of cholestatic or hepatocellular pattern. Since propylthiouracil associated liver injury was observed increasingly among children and adolescent, it has been suggested to prefer thioimidazoles for these patients. Because of these potential serious adverse effects, physicians should advise patients to immediately seek medical help if they get a fever or sore throat or malaise, abdominal complaints or jaundice, respectively. Furthermore, arthralgias may develop in 1-5% of patients under both antithyroid drugs. Since arthralgias may be the first symptom of more serious immunologic side effects, it is recommended to stop the antithyroid drug in this case. Drug induced polyarthritis mainly develops during the first month of therapy, whereas ANCA-positive vasculitis is generally observed only after long term exposure to propylthiouracil or very rarely with the thioimidazoles. The teratogenic risk of the thioimidazoles is somewhat higher (Aplasia cutis congenita), that is why one generally recommends preferring propylthiouracil during pregnancy. During breast feeding both, thioimidazoles or propylthiouracil, may be administered. Nowadays, perchlorate is only used short term in case of latent hyperthyroidism before administering iodine-containing contrast agents. Therefore, the known side effects, which usually are only observed after long term treatment, are not an issue any more.
Prism adaptation improves ego-centered but not allocentric neglect in early rehabilitation patients.
Gossmann, Anja; Kastrup, Andreas; Kerkhoff, Georg; López-Herrero, Carmen; Hildebrandt, Helmut
2013-01-01
Unilateral neglect due to parieto-temporo-frontal lesions has a negative impact on the success of rehabilitation, and prism adaptation (PA) enhances recovery from neglect. However, it is unclear if this effect holds also in severely impaired patients and/or in the postacute phase of rehabilitation. Moreover, it is not known whether PA affects all aspects of neglect recovery or ego-centered spatial orientation only. Sixteen patients in a postacute stage (on average 36 days after a large right cerebrovascular stroke) were entered into a series of single case design studies with 4 measurements: 2 before and 2 after 1 week of PA treatment. All patients had severe neglect (showing trunk, head, and eye deviation; canceling less than 20% of targets in a visual cancellation test). Lesions were transferred to a standard brain to analyze size and location. Patients improved in cued body orientation and in the cancellation task, that is, in ego-centered neglect. However, none of the measures used to evaluate neglect of left side of objects irrespective of their position on the right or left side of the patient (allocentric neglect) showed an improvement. Treatment effects were not influenced by total lesion size, but lesions including the postcentral cortex were related to smaller recovery gains. PA is helpful in treating severely impaired patients in the postacute phase, but the effect is restricted to ego-centered neglect. Lesions in the postcentral cortex (middle occipito-temporal, middle temporal, and posterior parietal areas) seem to limit the effect of PA.
Ašćerić, Mensura; Avdić, Sevleta; Nukić, Sabrija; Vrabac-Mujčinagić, Muamera
2007-01-01
In this work we are going to show results of intensive observation of adverse reactions of cyclosporine therapy during 18 months. The research was applied on 30 patients with kidney transplant. The medium time of kidney transplant survival was 9,7±2,3 years, with time span of 6 to 15 years. All the patients were subjects to several years’ cyclosporine treatment, which was applied on a daily basis with a dosage of 2 to 5 mg/kg of body weight. The concentration of cyclosporine in blood was measured once a month. The concentration of cyclosporine in blood in 19 patients was in referent values of 122,50 nag/ml up to 280,50 nag/ml of blood. In 4 of the patients the concentration was heightened up to 370 to 538 nag/ml (χ=766,37 nag/ml), and in 7 patients cyclosporine was below normal dosage down to 30,78 to 96,30 nag/ml in blood (x=77,12 nag/ml). We noticed these toxic side effects: increased values of systolic and diastolic arterial blood pressure in 5 patients, neurotoxic tremor effects in 4 patients, hyper-plasia gingival and hirsute in 1 patient each.
Paracetamol in Patent Ductus Arteriosus Treatment: Efficacious and Safe?
Bardanzellu, Flaminia; Neroni, Paola; Fanos, Vassilios
2017-01-01
In preterm infants, failure or delay in spontaneous closure of Ductus Arteriosus (DA), resulting in the condition of Patent Ductus Arteriosus (PDA), represents a significant issue. A prolonged situation of PDA can be associated with several short- and long-term complications. Despite years of researches and clinical experience on PDA management, unresolved questions about the treatment and heterogeneity of clinical practices in different centers still remain, in particular regarding timing and modality of intervention. Nowadays, the most reasonable strategy seems to be reserving the treatment only to hemodynamically significant PDA. The first-line therapy is medical, and ibuprofen, related to several side effects especially in terms of nephrotoxicity, is the drug of choice. Administration of oral or intravenous paracetamol (acetaminophen) recently gained attention, appearing effective as traditional nonsteroidal anti-inflammatory drugs (NSAIDs) in PDA closure, with lower toxicity. The results of the studies analyzed in this review mostly support paracetamol efficacy in ductal closure, with inconstant low and transient elevation of liver enzymes as reported side effect. However, more studies are needed to confirm if this therapy shows a real safety profile and to evaluate its long-term outcomes, before considering paracetamol as first-choice drug in PDA treatment. PMID:28828381
Zhou, H L; Hu, B; Zhang, C
2016-07-01
Melasma is a common acquired and distressing pigmentary disorder presenting to dermatology clinics. It is notably difficult to cure and has a tendency to relapse. The efficacy of classical Q-switched laser in treatment of melasma remains controversial. This study aims to investigate the efficacy and safety of 694-nm fractional QSRL combined with sonophoresis on levorotatory vitamin C for the treatment of melasma patients. Twenty-six patients with melasma were enrolled. Each patient received four to six fractional QSRL treatments at pulse energies of 2.5 to 4 J/cm(2) combined with sonophoresis on levorotatory vitamin C at 2-week intervals. The severity and the area of melasma were assessed by two investigators using the melasma area and severity index (MASI). Side effects were documented. Mean MASI score decreased from 15.51 ± 3.00 before treatment to 10.02 ± 4.39 3 months after the final treatment (P < 0.01). Side effects were few and transient. High-density coverage fractional QSRL combined with sonophoresis on levorotatory vitamin C is safe and effective for the treatment of melasma in Chinese patients.
Duma, Stefan M; Hansen, Gail A; Kennedy, Eric A; Rath, Amber L; McNally, Craig; Kemper, Andrew R; Smith, Eric P; Brolinson, P Gunnar; Stitzel, Joel D; Davis, Martin B; Bass, Cameron R; Brozoski, Frederick T; McEntire, B Joseph; Alem, Nabih M; Crowley, John S
2004-11-01
This paper describes a three part analysis to characterize the interaction between the female upper extremity and a helicopter cockpit side airbag system and to develop dynamic hyperextension injury criteria for the female elbow joint. Part I involved a series of 10 experiments with an original Army Black Hawk helicopter side airbag. A 5(th) percentile female Hybrid III instrumented upper extremity was used to demonstrate side airbag upper extremity loading. Two out of the 10 tests resulted in high elbow bending moments of 128 Nm and 144 Nm. Part II included dynamic hyperextension tests on 24 female cadaver elbow joints. The energy source was a drop tower utilizing a three-point bending configuration to apply elbow bending moments matching the previously conducted side airbag tests. Post-test necropsy showed that 16 of the 24 elbow joint tests resulted in injuries. Injury severity ranged from minor cartilage damage to more moderate joint dislocations and severe transverse fractures of the distal humerus. Peak elbow bending moments ranged from 42.4 Nm to 146.3 Nm. Peak bending moment proved to be a significant indicator of any elbow injury (p = 0.02) as well as elbow joint dislocation (p = 0.01). Logistic regression analyses were used to develop single and multiple variate injury risk functions. Using peak moment data for the entire test population, a 50% risk of obtaining any elbow injury was found at 56 Nm while a 50% risk of sustaining an elbow joint dislocation was found at 93 Nm for the female population. These results indicate that the peak elbow bending moments achieved in Part I are associated with a greater than 90% risk for elbow injury. Subsequently, the airbag was re-designed in an effort to mitigate this as well as the other upper extremity injury risks. Part III assessed the redesigned side airbag module to ensure injury risks had been reduced prior to implementing the new system. To facilitate this, 12 redesigned side airbag deployments were conducted using the same procedures as Part I. Results indicate that the re-designed side airbag has effectively mitigated elbow injury risks induced by the original side airbag design. It is anticipated that this study will provide researchers with additional injury criteria for assessing upper extremity injury risk caused by both military and automotive side airbag deployments.
Effects of rocuronium pretreatment on muscle enzyme levels following succinylcholine.
Farhat, Kulsoom; Waheed, Akbar; Pasha, Anwar Kamal; Tariq, Muhammad
2013-09-01
Succinylcholine revolutionized anaesthetic practice by providing intense neuromuscular blockade of very rapid onset and ultrashort duration, thereby greatly easing the maneuver of tracheal intubation. However the worth of succinylcholine is limited by the frequent occurrence of muscular side effects which manifest biochemically in the form of rise in serum creatine kinase (CK). The administration of small doses of nondepolarizing muscle relaxants before the administration of succinylcholine has been shown to decrease the incidence and severity of muscular side effects experienced by the patients. This study was aimed at evaluating the efficacy of technique in reducing the muscular side effects of succinylcholine, biochemically manifested as rise in CK. Sixty healthy adults were enrolled in the study who were scheduled for minor muscle cutting surgeries under general anaesthesia. They were assigned at random to two groups of thirty patients each. They randomly received succinylcholine for intubation and a precurarization dose of rocuronium followed by succinylcholine for intubation. Blood samples were drawn for estimation of serum creatinine kinase. There was a significantly raised CK in the succinylcholine group. In the precurarization group the rise in CK was prevented and the levels were significantly less as compared to the group which received succinylcholine alone. Present study concluded that precurarization with rocuronium was effective in reducing the succinylcholine-induced rise in creatinine kinase.
Eschweiler, Gerhard W; Vonthein, Reinhard; Bode, Ruediger; Huell, Michael; Conca, Andreas; Peters, Oliver; Mende-Lechler, Stefan; Peters, Julia; Klecha, Dorothee; Prapotnik, Michael; DiPauli, Jan; Wild, Barbara; Plewnia, Christian; Bartels, Mathias; Schlotter, Wilfried
2007-08-01
In most studies right unilateral electroconvulsive therapy (ECT) has been shown to cause fewer cognitive side effects but less antidepressant efficacy compared with bi(fronto)temporal ECT at certain intensities. To compare the short-term efficacy and side effects of right unilateral ECT and bifrontal ECT. In a double-blind randomised controlled clinical trial, 92 patients diagnosed with pharmaco-resistant major depression received either six right unilateral ECT treatments (250% stimulus intensity of titrated threshold) or six bifrontal ECT (150% of threshold) treatments over a 3-week period. Concomitant psychotropic medications were continued during ECT treatments. The severity of depression and cognitive status was assessed prior to the first ECT and one day after the sixth ECT using the 21-item Hamilton Depression Rating Scale and the modified Mini Mental State Examination. Eight patients did not complete the course of the study due to minor side effects or withdrawal of consent. The mean Hamilton Depression score decreased from 27 to 17 points in both groups of 46 patients, resulting in 12 responders (primary endpoint defined as a decrease >50%) in each patient group (95% confidence interval for the odds ratio from 0.35 to 2.8). There was no reduction in the modified Mini Mental State score (mean score 86 of 100 points). Both bifrontal and right unilateral electrode placements in ECT were reasonably safe and moderately efficacious in reducing symptoms of pharmaco-resistant major depression.
Selecting Random Distributed Elements for HIFU using Genetic Algorithm
NASA Astrophysics Data System (ADS)
Zhou, Yufeng
2011-09-01
As an effective and noninvasive therapeutic modality for tumor treatment, high-intensity focused ultrasound (HIFU) has attracted attention from both physicians and patients. New generations of HIFU systems with the ability to electrically steer the HIFU focus using phased array transducers have been under development. The presence of side and grating lobes may cause undesired thermal accumulation at the interface of the coupling medium (i.e. water) and skin, or in the intervening tissue. Although sparse randomly distributed piston elements could reduce the amplitude of grating lobes, there are theoretically no grating lobes with the use of concave elements in the new phased array HIFU. A new HIFU transmission strategy is proposed in this study, firing a number of but not all elements for a certain period and then changing to another group for the next firing sequence. The advantages are: 1) the asymmetric position of active elements may reduce the side lobes, and 2) each element has some resting time during the entire HIFU ablation (up to several hours for some clinical applications) so that the decreasing efficiency of the transducer due to thermal accumulation is minimized. Genetic algorithm was used for selecting randomly distributed elements in a HIFU array. Amplitudes of the first side lobes at the focal plane were used as the fitness value in the optimization. Overall, it is suggested that the proposed new strategy could reduce the side lobe and the consequent side-effects, and the genetic algorithm is effective in selecting those randomly distributed elements in a HIFU array.
Trichostatin A accentuates doxorubicin-induced hypertrophy in cardiac myocytes
Karagiannis, Tom C; Lin, Ann JE; Ververis, Katherine; Chang, Lisa; Tang, Michelle M; Okabe, Jun; El-Osta, Assam
2010-01-01
Histone deacetylase inhibitors represent a new class of anticancer therapeutics and the expectation is that they will be most effective when used in combination with conventional cancer therapies, such as the anthracycline, doxorubicin. The dose-limiting side effect of doxorubicin is severe cardiotoxicity and evaluation of the effects of combinations of the anthracycline with histone deacetylase inhibitors in relevant models is important. We used a well-established in vitro model of doxorubicin-induced hypertrophy to examine the effects of the prototypical histone deacetylase inhibitor, Trichostatin A. Our findings indicate that doxorubicin modulates the expression of the hypertrophy-associated genes, ventricular myosin light chain-2, the alpha isoform of myosin heavy chain and atrial natriuretic peptide, an effect which is augmented by Trichostatin A. Furthermore, we show that Trichostatin A amplifies doxorubicin-induced DNA double strand breaks, as assessed by γH2AX formation. More generally, our findings highlight the importance of investigating potential side effects that may be associated with emerging combination therapies for cancer. PMID:20930262
Trichostatin A accentuates doxorubicin-induced hypertrophy in cardiac myocytes.
Karagiannis, Tom C; Lin, Ann J E; Ververis, Katherine; Chang, Lisa; Tang, Michelle M; Okabe, Jun; El-Osta, Assam
2010-10-01
Histone deacetylase inhibitors represent a new class of anticancer therapeutics and the expectation is that they will be most effective when used in combination with conventional cancer therapies, such as the anthracycline, doxorubicin. The dose-limiting side effect of doxorubicin is severe cardiotoxicity and evaluation of the effects of combinations of the anthracycline with histone deacetylase inhibitors in relevant models is important. We used a well-established in vitro model of doxorubicin-induced hypertrophy to examine the effects of the prototypical histone deacetylase inhibitor, Trichostatin A. Our findings indicate that doxorubicin modulates the expression of the hypertrophy-associated genes, ventricular myosin light chain-2, the alpha isoform of myosin heavy chain and atrial natriuretic peptide, an effect which is augmented by Trichostatin A. Furthermore, we show that Trichostatin A amplifies doxorubicin-induced DNA double strand breaks, as assessed by γH2AX formation. More generally, our findings highlight the importance of investigating potential side effects that may be associated with emerging combination therapies for cancer.
Kinesiology taping as an adjunct for pain management in cancer?
Banerjee, Gourav; Rebanks, Jonathan; Briggs, Michelle; Johnson, Mark I
2016-07-14
We present the case of a 46-year-old woman who developed severe pain described as 'tearing' and 'searing' in the left side of the mid-trapezius region near the thoracic 8 vertebra (T8). The patient had undergone surgery for T8 fracture which had resulted from metastasis (secondary breast cancer). A community nurse referred the patient for physiotherapy assessment and treatment for her musculoskeletal pain and related symptoms that had affected her mobility and functional activities. The patient was treated with soft tissue therapy with the addition of kinesiology taping on follow-up visits. Kinesiology tape was applied over her left side trapezius region and left shoulder. The patient reported significant reductions in pain severity and felt greater control and stability over her left shoulder region, which resulted in better function and overall quality of life measures. She did not report any adverse effects. 2016 BMJ Publishing Group Ltd.
Changes in the Severity and Injury Sources of Thoracic Aorta Injuries due to Vehicular Crashes
Ryb, Gabriel; Dischinger, Patricia; Kerns, Timothy; Burch, Cynthia; Rabin, Joseph; Ho, Shiu
2013-01-01
Research using the National Automotive Sampling System-Crashworthiness Data System (NASS-CDS) suggested a decreased adjusted risk of thoracic aorta injuries (TAI) for newer vehicles during near-side crashes and an increased adjusted TAI risk during frontal crashes. This study attempted to explore possible explanations of these findings. Adult front seat occupants in the Crash Injury Research and Engineering Network (CIREN) database through June 2012 were studied. TAI cases were compared with remaining cases in relation to crash and vehicular characteristics. TAI cases of later crash year (CY) (2004–2012) were compared to those in earlier CY (1996–2003) in relation to TAI severity (minor, moderate, severe and non-survivable). TAI cases in newer model year (MY) vehicles (1999–2012) were compared to those in older vehicles (1988–98) in relation to injury source (steering wheel, front, left, seat belt, air bag and other or unknown). Analysis was stratified by direction of impact (frontal and near-side) and the use of restraints. The similar TAI severity of earlier and later CY among frontal crashes suggests that the observed changes in the adjusted odds of injury seen in NASS-CDS are not due to an increase in injury detection. The decrease in TAI severity among newer vehicles in near-side crashes of later CY is consistent with a beneficial effect of crashworthiness improvements for this crash configuration. A shift of injury source in frontal crashes from the steering wheel in older vehicles to “front of vehicle structures”, “seat belts” and “unknown and other” in newer vehicles should suggest potential sites for crashworthiness improvements. PMID:24406956
Segan, Catherine J; Baker, Amanda L; Turner, Alyna; Williams, Jill M
2017-01-01
Smokers with mental illness and their health care providers are often concerned that smoking cessation will worsen mental health. Smokers with mental illness tend to be more nicotine-dependent and experience more severe symptoms of nicotine withdrawal, some of which are difficult to distinguish from psychiatric symptoms. In addition, smoking cessation can increase the blood levels and hence side effects of some psychotropic medications. Improved monitoring of nicotine withdrawal and medication side effects may help distinguish temporary withdrawal symptoms from psychiatric symptoms and facilitate targeted treatment to help smokers with mental illness manage the acute phase of nicotine withdrawal. The aim of this research was to examine the acceptability and feasibility to quitline counselors of implementing structured assessments of nicotine withdrawal and common medication side effects in people with mental illness who are quitting smoking using a telephone smoking cessation service. Monitoring involves administering (once pre-cessation and at each contact post-cessation) (1) the Minnesota Nicotine Withdrawal Scale, assessing eight symptoms: anger, anxiety, depression, cravings, difficulty concentrating, increased appetite, insomnia, and restlessness and (2) an adverse side effects checklist of 5 to 10 symptoms, for example, dry mouth and increased thirst. Following a 1-day update training in mental health, quitline counselors were asked to offer these assessments to callers disclosing mental illness in addition to usual counseling. Group interviews with counselors were conducted 2 months later to examine implementation barriers and benefits. Barriers included awkwardness in integrating a new structured practice into counseling, difficulty in limiting some callers to only the content of new items, and initial anxieties about how to respond to changes in some symptoms. Benefits included the ability to provide objective feedback on changes in symptoms, as this identified early benefits of quitting, provided reassurance for clients, and provided an opportunity for early intervention where symptoms worsened. Structured monitoring of withdrawal symptoms and medication side effects was able to be integrated into the quitline's counseling and was valued by counselors and clients. Given evidence of its benefits in this limited pilot study, we recommend it be considered for larger-scale adoption by quitlines.
Eide, K; Stubhaug, A; Oye, I; Breivik, H
1995-05-01
The effect of continuous subcutaneous (s.c.) infusion of ketamine on nerve injury pain was examined in patients with post-herpetic neuralgia. Five patients that reported pain relief after acute intravenous injection of ketamine were included in this open prospective study. Ketamine was administered continuously in increasing doses using a portable infusion pump (CADD-PLUS, Pharmacia), and the treatment period for each infusion rate (0.05, 0.075, 0.10, or 0.15 mg/kg/h) was 7 days and nights. Relief of continuous pain, as evaluated daily by visual analogue scales, was observed at the infusion rate of 0.05 mg/kg/h, but was most marked during infusion of 0.15 mg/kg/h. All the patients reported that ketamine reduced the severity of continuous pain as well as reduced the severity and number of attacks of spontaneous pain. Changes in evoked pain (allodynia and wind-up-like pain) were recorded before change of infusion rate. Allodynia was maximally reduced 59-100% after 1 week infusion of 0.05 mg/kg/h, and wind-up-like pain was maximally reduced 60-100% after 1 week infusion of 0.15 mg/kg/h. Itching and painful indurations at the injection site was the most bothersome side-effect and for this reason 1 patient discontinued treatment after 2 weeks. Other common side-effects were nausea, fatigue and dizziness. The present results show that continuous, spontaneous and evoked pain in patients with post-herpetic neuralgia is reduced by continuous s.c. infusion of ketamine, but is associated with intolerable side effects.
Ibrahim, Zeinab A; Gheida, Shereen F; El Maghraby, Gamal M; Farag, Zeinab E
2015-06-01
Various treatments are currently available for melasma. However, results are often disappointing. 1 To assess the efficacy and safety of combinations of hydroquinone, glycolic acid, and hyaluronic acid in the treatment of melasma after topical application. 2 To evaluate the dermoscopy as a tool in diagnosis and follow-up of melasma treatment. One hundred patients with mild, moderate-to-severe melasma were divided into five groups. Group I (twenty patients were treated with cream formula containing 4% hydroquinone), group II (twenty patients were treated with cream formula containing 4% hydroquinone + 10% glycolic acid), group III (twenty patients were treated with cream formula containing 4% hydroquinone + 0.01% hyaluronic acid), group IV (twenty patients were treated with cream formula containing 4% hydroquinone + 10% glycolic acid + 0.01% hyaluronic acid), and group V (twenty patients were treated with placebo cream). All patients were subjected to dermoscopic examination and digital photographs before and after treatment. The response and side effects were evaluated. Groups I, III, and IV showed highly significant changes in modified Melasma Area and Severity Index (mMASI) score after using the treatment. Group II showed significant change in mMASI score after using the treatment. The side effects were more reported in group II, followed by group IV, followed by group I, followed by group III. There was highly significant difference between the dermoscopic color findings before and after treatment. Vascularization was another dermoscopic finding. A cream formula containing 4% hydroquinone + 10% glycolic acid + 0.01% hyaluronic acid was very effective in treatment of melasma with tolerable side effects. Dermoscope is a valuable noninvasive tool in the diagnosis and follow-up of melasma treatment. © 2015 Wiley Periodicals, Inc.
Sposato, Luciano A; Cohen, Geoffrey; Wardlaw, Joanna M; Sandercock, Peter; Lindley, Richard I; Hachinski, Vladimir
2016-12-01
In patients with acute ischemic stroke, whether involvement of the insular cortex influences outcome is controversial. Much of the apparent adverse outcome may relate to such strokes usually being severe. We examined the influence of right and left insular involvement on stroke outcomes among patients from the IST-3 study (Third International Stroke Trial) who had visible ischemic stroke on neuroimaging. We used multiple logistic regression to compare outcomes of left versus right insular and noninsular strokes across strata of stroke severity, on death, proportion dead or dependent, and level of disability (ordinalized Oxford Handicap Score) at 6 months, with adjustment for the effects of age, lesion size, and presence of atrial fibrillation. Of 3035 patients recruited, 2099 had visible ischemic strokes limited to a single hemisphere on computed tomography/magnetic resonance scans. Of these, 566 and 714 had infarction of right and left insula. Six months after randomization, right insular involvement was associated with increased odds of death when compared with noninsular strokes on the left side (adjusted odds ratio, 1.83; 95% confidence interval, 1.33-2.52), whereas the adjusted odds ratio comparing mortality after insular versus noninsular strokes on the left side was not significant. Among mild/moderate strokes, outcomes for right insular involvement were worse than for left insular, but among more severe strokes, the difference in outcomes was less substantial. We found an association between right insular involvement and higher odds of death and worse functional outcome. The difference between right- and left-sided insular lesions on outcomes seemed to be most evident for mild/moderate strokes. URL: http://www.isrctn.com. Unique identifier: ISRCTN25765518. © 2016 American Heart Association, Inc.
ERIC Educational Resources Information Center
Ryan, Joseph B.; Reid, Robert; Ellis, Cynthia
2008-01-01
The use of psychotropic interventions to manage the inappropriate behaviors displayed by students with emotional and behavior disorders has become more common over the past several decades. The efficacious use of these medications requires monitoring students for desired behavioral outcomes as well as potential side effects. Educators are in an…
Increasing Access by Waiving Tuition: Evidence from Haiti
ERIC Educational Resources Information Center
Adelman, Melissa; Holland, Peter; Heidelk, Tillmann
2017-01-01
Despite recent gains in increasing access, an estimated 58 million children worldwide are still out of school. Abolishing school fees has increased enrollment rates in several countries where enrollments were low and fees were high. However, such policies may be less effective, or even have negative consequences, when supply-side responses are…
ERIC Educational Resources Information Center
Mumthas, N. S.; Munavvir, Jouhar; Abdul Gafoor, K.
2014-01-01
Inculcating self-discipline is important for systematic pursuit of learning, development of interest and potential in the child. Punishments involve employing a noxious or painful stimulus that generates a variety of problems and negative side effects to the child. Corporal punishments severely affect the human dignity of children. This study…
Blast Effects of Recoilless Guns
1947-02-01
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Advanced Analgesic Drug Delivery and Nanobiotechnology.
Stoicea, Nicoleta; Fiorda-Diaz, Juan; Joseph, Nicholas; Shabsigh, Muhammad; Arias-Morales, Carlos; Gonzalez-Zacarias, Alicia A; Mavarez-Martinez, Ana; Marjoribanks, Stephen; Bergese, Sergio D
2017-07-01
Transdermal administration of analgesic medications offers several benefits over alternative routes of administration, including a decreased systemic drug load with fewer side effects, and avoidance of drug degradation by the gastrointestinal tract. Transdermal administration also offers a convenient mode of drug administration over an extended period of time, particularly desirable in pain medicine. A transdermal administration route may also offer increased safety for drugs with a narrow therapeutic window. The primary barrier to transdermal drug absorption is the skin itself. Transdermal nanotechnology offers a novel method of achieving enhanced dermal penetration with an extended delivery profile for analgesic drugs, due to their small size and relatively large surface area. Several materials have been used to enhance drug duration and transdermal penetration. The application of nanotechnology in transdermal delivery of analgesics has raised new questions regarding safety and ethical issues. The small molecular size of nanoparticles enables drug delivery to previously inaccessible body sites. To ensure safety, the interaction of nanoparticles with the human body requires further investigation on an individual drug basis, since different formulations have unique properties and side effects.
The evidence of neuraxial administration of analgesics for cancer-related pain: a systematic review.
Kurita, G P; Benthien, K S; Nordly, M; Mercadante, S; Klepstad, P; Sjøgren, P
2015-10-01
The present systematic review analysed the existing evidence of analgesic efficacy and side effects of opioids without and with adjuvant analgesics delivered by neuraxial route (epidural and subarachnoid) in adult patients with cancer. Search strategy was elaborated with words related to cancer, pain, neuraxial route, analgesic and side effects. The search was performed in PubMed, EMBASE, and Cochrane for the period until February 2014. Studies were analysed according to methods, results, quality of evidence, and strength of recommendation. The number of abstracts retrieved was 2147, and 84 articles were selected for full reading. The final selection comprised nine articles regarding randomised controlled trials (RCTs) divided in four groups: neuraxial combinations of opioid and adjuvant analgesic compared with neuraxial administration of opioid alone (n = 4); single neuraxial drug in bolus compared with continuous administration (n = 2); single neuraxial drug compared with neuraxial placebo (n = 1); and neuraxial opioid combined with or without adjuvant analgesic compared with other comprehensive medical management than neuraxial analgesics (n = 2). The RCTs presented clinical and methodological diversity that precluded a meta-analysis. They also presented several limitations, which reduced study internal validity. However, they demonstrated better pain control for all interventions analysed. Side effects were described, but there were few significant differences in favour of the tested interventions. Heterogeneous characteristics and several methodological limitations of the studies resulted in evidence of low quality and a weak recommendation for neuraxial administration of opioids with or without adjuvant analgesics in adult patients with cancer. © 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
Rothery, Claire; Bojke, Laura; Richardson, Gerry; Bojke, Chris; Moverley, Anna; Coates, Laura; Thorp, Liz; Waxman, Robin; Helliwell, Philip
2016-12-01
The objective of this study is to assess patient preferences for treatment-related benefits and risk of disease relapse in the management of low disease states of psoriatic arthritis (PsA). Focus groups with patients and a literature review were undertaken to determine the characteristics of treatment and symptoms of PsA important to patients. Patient preferences were assessed using a discrete choice experiment which compared hypothetical treatment profiles of the risk and benefits of treatment withdrawal. The risk outcome included increased risk of disease relapse, while benefit outcomes included reduced sickness/nausea from medication and changes in health-related quality of life. Each patient completed 12 choice sets comparing treatment profiles. Preference weights were estimated using a logic regression model, and the maximum acceptable risk in disease relapse for a given improvement in benefit outcomes was elicited. Final sample included 136 patients. Respondents attached the greatest importance to eliminating severe side effects of sickness/nausea and the least importance to a change in risk of relapse. Respondents were willing to accept an increase in the risk of relapse of 32.6 % in order to eliminate the side effects of sickness/nausea. For improvements in health status, the maximum acceptable risk in relapse was comparable to a movement from some to no sickness/nausea. The study suggests that patients in low disease states of PsA are willing to accept greater risks of relapse for improvements in side effects of sickness/nausea and overall health status, with the most important benefit attribute being the elimination of severe sickness or nausea.
Geier, David A.; Kern, Janet K.; Davis, Georgia; King, Paul G.; Adams, James B.; Young, John L.; Geier, Mark R.
2011-01-01
Summary Background L-carnitine was proposed as a potential treatment for patients diagnosed with an autism spectrum disorder to improve mitochondrial dysfunction, but no prior randomized controlled trials have been conducted. Material/Methods Thirty subjects diagnosed with an ASD were randomly assigned to receive a standardized regimen (50 mg L-carnitine/kg bodyweight/day) of liquid L-carnitine (n=19) or placebo (n=11) for 3-months. Measures included changes in professionally completed Childhood Autism Rating Scale (CARS), hand muscle testing, and modified clinical global impression (CGI) forms; parent completed Autism Treatment Evaluation Checklist (ATEC), treatment adherence measurement (TAM), frequency and intensity of side effect rating (FISER)/global rating of side effect burden (GRSEB)/patient report of incidence of side effects (PRISE) forms; and lab testing. Results Significant improvements were observed in CARS (−2.03, 95% CI=−3.7 to −0.31), CGI (−0.69, 95% CI=−1.1 to −0.06), and ATEC scores. Significant correlations between changes in serum free-carnitine levels and positive clinical changes were observed for hand muscle strength (R2=0.23, P=0.046), cognitive scores (R2=0.27, P=0.019), and CARS scores (R2=0.20, P=0.047). Study subjects were protocol-compliant (average adherence was >85%) and generally well-tolerated the L-carnitine therapy given. Conclusions L-carnitine therapy (50 mg/kilogram-bodyweight/day) administered for 3-months significantly improved several clinical measurements of ASD severity, but subsequent studies are recommended. PMID:21629200
Brouillet, Denis; Milhau, Audrey; Brouillet, Thibaut
2015-01-01
Since the work of Casasanto (2009), it is now well established that valence and laterality are associated. Participants tend to prefer objects presented on their dominant side over items presented on their non-dominant side, and to place good items on their dominant side and bad items on the other side. Several studies highlight that those associations of valence and laterality are accounted for by the greater motor fluency of the dominant hand and various studies noted that these associations could be reversed depending on the way people interact with their environment. Consistently with the Theory of Event Coding, the aim of this work is to show that the consequences of motor actions could also reverse the associations between valence and laterality. Thus, if participants had to place two animals (one good, one bad) on two supports, one stable (no risk of falling), one unstable (risk of falling), we hypothesized that the good item would be placed on the stable support, regardless of the side where it would be put (i.e., on the dominant or non-dominant side). We expected the opposite for the bad item. The results of two experiments are consistent with this prediction and support the claim that the consequences of motor action bias the hedonic connotation of our dominant side.
Brouillet, Denis; Milhau, Audrey; Brouillet, Thibaut
2015-01-01
Since the work of Casasanto (2009), it is now well established that valence and laterality are associated. Participants tend to prefer objects presented on their dominant side over items presented on their non-dominant side, and to place good items on their dominant side and bad items on the other side. Several studies highlight that those associations of valence and laterality are accounted for by the greater motor fluency of the dominant hand and various studies noted that these associations could be reversed depending on the way people interact with their environment. Consistently with the Theory of Event Coding, the aim of this work is to show that the consequences of motor actions could also reverse the associations between valence and laterality. Thus, if participants had to place two animals (one good, one bad) on two supports, one stable (no risk of falling), one unstable (risk of falling), we hypothesized that the good item would be placed on the stable support, regardless of the side where it would be put (i.e., on the dominant or non-dominant side). We expected the opposite for the bad item. The results of two experiments are consistent with this prediction and support the claim that the consequences of motor action bias the hedonic connotation of our dominant side. PMID:25798122
Investigation of the flow in the impeller side clearances of a centrifugal pump with volute casing
NASA Astrophysics Data System (ADS)
Will, Björn-Christian; Benra, Friedrich-Karl; Dohmen, Hans-Josef
2012-06-01
The paper is concerned with the fluid flow in the impeller side clearances of a centrifugal pump with volute casing. The flow conditions in these small axial gaps are of significant importance for a number of effects such as disk friction, leakage losses or hydraulic axial thrust to name but a few. In the investigated single stage pump, the flow pattern in the volute turns out to be asymmetric even at design flow rate. To gain a detailed insight into the flow structure, numerical simulations of the complete pump including the impeller side clearances are accomplished. Additionally, the hydraulic head and the radial pressure distributions in the impeller side clearances are measured and compared with the numerical results. Two configurations of the impeller, either with or without balancing holes, are examined. Moreover, three different operating points, i.e.: design point, part load or overload conditions are considered. In addition, analytical calculations are accomplished to determine the pressure distributions in the impeller side clearances. If accurate boundary conditions are available, the 1D flow models used in this paper can provide reasonable results for the radial static pressure distribution in the impeller side clearances. Furthermore, a counter rotating wake region develops in the rear impeller side clearances in absence of balancing holes which severely affects the inflow and outflow conditions of the cavity in circumferential direction.
Sigrist, Hannes; Seifritz, Erich; Fikse, Lianne; Bosker, Fokko J.; Schoevers, Robert A.; Klein, Hans C.
2017-01-01
Electroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental animals is electroconvulsive seizure (ECS). Rodent studies have provided valuable insights into potential mechanisms underlying the antidepressant and side effects of ECT. However, relatively few studies have investigated the effects of ECS in animal models with a depression-relevant manipulation such as chronic stress. In the present study, mice were first exposed to chronic social stress (CSS) or a control procedure for 15 days followed by ECS or a sham procedure for 10 days. Behavioral effects were investigated using an auditory fear conditioning (learning) and expression (memory) test and a treadmill-running fatigue test. Thereafter, immunohistochemistry was conducted on brain material using the microglial marker Iba-1 and the cholinergic fibre marker ChAT. CSS did not increase fear learning and memory in the present experimental design; in both the control and CSS mice ECS reduced fear learning and fear memory expression. CSS induced the expected fatigue-like effect in the treadmill-running test; ECS induced increased fatigue in CSS and control mice. In CSS and control mice ECS induced inflammation in hippocampus in terms of increased expression of Iba-1 in radiatum of CA1 and CA3. CSS and ECS both reduced acetylcholine function in hippocampus as indicated by decreased expression of ChAT in several hippocampal sub-regions. Therefore, CSS increased fatigue and reduced hippocampal ChAT activity and, rather than reversing these effects, a repeated ECS regimen resulted in impaired fear learning-memory, increased fatigue, increased hippocampal Iba-1 expression, and decreased hippocampal ChAT expression. As such, the current model does not provide insights into the mechanism of ECT antidepressant function but does provide evidence for pathophysiological mechanisms that might contribute to important ECT side-effects. PMID:28910337
van Buel, Erin M; Sigrist, Hannes; Seifritz, Erich; Fikse, Lianne; Bosker, Fokko J; Schoevers, Robert A; Klein, Hans C; Pryce, Christopher R; Eisel, Ulrich Lm
2017-01-01
Electroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental animals is electroconvulsive seizure (ECS). Rodent studies have provided valuable insights into potential mechanisms underlying the antidepressant and side effects of ECT. However, relatively few studies have investigated the effects of ECS in animal models with a depression-relevant manipulation such as chronic stress. In the present study, mice were first exposed to chronic social stress (CSS) or a control procedure for 15 days followed by ECS or a sham procedure for 10 days. Behavioral effects were investigated using an auditory fear conditioning (learning) and expression (memory) test and a treadmill-running fatigue test. Thereafter, immunohistochemistry was conducted on brain material using the microglial marker Iba-1 and the cholinergic fibre marker ChAT. CSS did not increase fear learning and memory in the present experimental design; in both the control and CSS mice ECS reduced fear learning and fear memory expression. CSS induced the expected fatigue-like effect in the treadmill-running test; ECS induced increased fatigue in CSS and control mice. In CSS and control mice ECS induced inflammation in hippocampus in terms of increased expression of Iba-1 in radiatum of CA1 and CA3. CSS and ECS both reduced acetylcholine function in hippocampus as indicated by decreased expression of ChAT in several hippocampal sub-regions. Therefore, CSS increased fatigue and reduced hippocampal ChAT activity and, rather than reversing these effects, a repeated ECS regimen resulted in impaired fear learning-memory, increased fatigue, increased hippocampal Iba-1 expression, and decreased hippocampal ChAT expression. As such, the current model does not provide insights into the mechanism of ECT antidepressant function but does provide evidence for pathophysiological mechanisms that might contribute to important ECT side-effects.
Efficacy of rivastigmine tartrate, transdermal system, in Alzheimer's disease.
Nieto, Rachel A; Deardorff, William James; Grossberg, George T
2016-01-01
As the most common major neurocognitive disorder, Alzheimer's disease (AD) will play an increasingly important role both socially and financially as the population ages. Approved treatments for AD are symptomatic in nature and show modest improvements in cognition and global functioning among patients with AD. This article focuses on the pharmacokinetics, pharmacodynamics, efficacy, and safety of the transdermal patch form of the cholinesterase inhibitor rivastigmine. The rivastigmine transdermal system is approved for the treatment of patients with mild, moderate, and severe AD. Three randomized trials have shown the rivastigmine patch to be efficacious and tolerable across all stages of AD. The rivastigmine patch offers several advantages over the capsule form, including decreased peak to trough plasma fluctuations, reduced rates of nausea and vomiting, better treatment adherence, higher probability of reaching the target dose, ease of administration, and greater satisfaction among caregivers. These factors may be especially important in patients with severe AD, in which patients are more vulnerable to adverse side effects from higher doses. While the patch is more expensive than generic therapies, patient populations that may benefit from the patch include those that are particularly sensitive to GI side effects, have chronic gastrointestinal problems, have difficulty swallowing medications, or have failed to respond with high doses of other generic options.
Love, Brad; Moskowitz, Michal C; Crook, Brittani; Thompson, Charee M; Donovan-Kicken, Erin; Stegenga, Kristin; Macpherson, Catherine Fiona; Johnson, Rebecca H
2013-07-01
To describe topics, needs, and concerns related to nutrition and exercise that adolescents and young adults affected by a serious illness (cancer) discuss online. Investigators conducted a qualitative content analysis of messages related to nutrition and exercise posted on an online young adult cancer forum. AYAs described several functions achieved through nutrition and exercise, such as fighting cancer, losing weight, obtaining nutrients despite side effects of treatment, promoting general health, enjoyment, and promoting mental/emotional health. AYAs also discussed several problems that interfere with nutrition and exercise goals, such as side effects of steroids, physiological problems with eating, safety concerns or physical limitations due to treatment, poor follow through with behavioral change, stress, and low energy. AYAs discuss specific ways nutrition and exercise help achieve a variety of functions that may be physical or psychological, cancer-specific or general. AYAs describe several concerns and barriers that impede their nutrition and exercise goals. Clinicians should also consider relevant medical and personal variables that partly determine nutrition and exercise concerns. Clinicians can anticipate barriers to desired nutrition/exercise change and develop interventions that address these barriers in appropriately tailored ways, including using digital media. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Powers, Jarrod; Brewer, Shannon K.; Long, James M.; Campbell, Thomas
2015-01-01
Side-scan sonar is a valuable tool for mapping habitat features in many aquatic systems suggesting it may also be useful for locating sedentary biota. The objective of this study was to determine if side-scan sonar could be used to identify freshwater mussel (unionid) beds and the required environmental conditions. We used side-scan sonar to develop a series of mussel-bed reference images by placing mussel shells within homogenous areas of fine and coarse substrates. We then used side-scan sonar to map a 32-km river reach during spring and summer. Using our mussel-bed reference images, several river locations were identified where mussel beds appeared to exist in the scanned images and we chose a subset of sites (n = 17) for field validation. The validation confirmed that ~60% of the sites had mussel beds and ~80% had some mussels or shells present. Water depth was significantly related to our ability to predict mussel-bed locations: predictive ability was greatest at depths of 1–2 m, but decreased in water >2-m deep. We determined side-scan sonar is an effective tool for preliminary assessments of mussel presence during times when they are located at or above the substrate surface and in relatively fine substrates excluding fine silt.
Topical tranexamic acid as an adjuvant treatment in melasma: Side-by-side comparison clinical study.
Chung, Jong Yoon; Lee, Jong Hee; Lee, Joo Heung
2016-08-01
Tranexamic acid (TNA) is a novel therapeutic agent for hyperpigmented skin disorders. The efficacy and safety of topical TNA in patients with melasma has not been heretofore studied. The main objective of this study is to evaluate the efficacy and safety of topical TNA combined with intense pulsed light (IPL) treatment in Asians with melasma. A randomized, split-face (internally controlled) study was conducted in 15 women who received four monthly sessions of IPL to both sides of the face. Topical TNA or vehicle was applied to a randomly assigned side during and after IPL treatment. Patients were followed up for 12 weeks after completing the IPL treatments. Baseline and follow-up melanin index (MI; measured by Mexameter®, Courage and Khazaka, Cologne, Germany) and modified melasma area and severity index (mMASI) scores were determined. Thirteen subjects completed the study without serious adverse events. MI and mMASI decreased significantly from baseline to 12 weeks after the last IPL treatment on the topical TNA side but not on the vehicle side. The efficacy of topical TNA in preventing rebound pigmentation after IPL treatment was also statistically significant. Topical TNA can be considered an effective and safe adjuvant to conventional treatment for melasma.
Waldmann, Elisa; Vogt, Anja; Crispin, Alexander; Altenhofer, Julia; Riks, Ina; Parhofer, Klaus G
2017-04-01
In this study, we evaluated the effect of mipomersen in patients with severe LDL-hypercholesterolaemia and atherosclerosis, treated by lipid lowering drugs and regular lipoprotein apheresis. This prospective, randomized, controlled phase II single center trial enrolled 15 patients (9 males, 6 females; 59 ± 9 y, BMI 27 ± 4 kg/m 2 ) with established atherosclerosis, LDL-cholesterol ≥130 mg/dL (3.4 mmol/L) despite maximal possible drug therapy, and fulfilling German criteria for regular lipoprotein apheresis. All patients were on stable lipid lowering drug therapy and regular apheresis for >3 months. Patients randomized to treatment (n = 11) self-injected mipomersen 200 mg sc weekly, at day 4 after apheresis, for 26 weeks. Patients randomized to control (n = 4) continued apheresis without injection. The primary endpoint was the change in pre-apheresis LDL-cholesterol. Of the patients randomized to mipomersen, 3 discontinued the drug early (<12 weeks therapy) for side effects. For these, another 3 were recruited and randomized. Further, 4 patients discontinued mipomersen between 12 and 26 weeks for side effects (moderate to severe injection site reactions n = 3 and elevated liver enzymes n = 1). In those treated for >12 weeks, mipomersen reduced pre-apheresis LDL-cholesterol significantly by 22.6 ± 17.0%, from a baseline of 4.8 ± 1.2 mmol/L to 3.7 ± 0.9 mmol/L, while there was no significant change in the control group (+1.6 ± 9.3%), with the difference between the groups being significant (p=0.02). Mipomersen also decreased pre-apheresis lipoprotein(a) (Lp(a)) concentration from a median baseline of 40.2 mg/dL (32.5,71) by 16% (-19.4,13.6), though without significance (p=0.21). Mipomersen reduces LDL-cholesterol (significantly) and Lp(a) (non-significantly) in patients on maximal lipid-lowering drug therapy and regular apheresis, but is often associated with side effects. Copyright © 2017 Elsevier B.V. All rights reserved.
J.M. Castillo; G. Enriques; M. Nakahara; D. Weise; L. Ford; R. Moraga; R. Vihnanek
2007-01-01
Crimson fountaingrass (Pennisetum setaceum) is a nonnative invasive grass that has occupied a significant portion of the western side of the island of Hawai`i. As a result, several fires in excess of 4,049 ha have occurred in the area over the past 20 y. We are studying the effectiveness of cattle grazing, aerial application of glyphosate herbicide, and prescribed...
Electromigration Failure Mechanism in Sn-Cu Solder Alloys with OSP Cu Surface Finish
NASA Astrophysics Data System (ADS)
Chu, Ming-Hui; Liang, S. W.; Chen, Chih; Huang, Annie T.
2012-09-01
Organic solderable preservative (OSP) has been adopted as the Cu substrate surface finish in flip-chip solder joints for many years. In this study, the electromigration behavior of lead-free Sn-Cu solder alloys with thin-film under bump metallization and OSP surface finish was investigated. The results showed that severe damage occurred on the substrate side (cathode side), whereas the damage on the chip side (cathode side) was not severe. The damage on the substrate side included void formation, copper dissolution, and formation of intermetallic compounds (IMCs). The OSP Cu interface on the substrate side became the weakest point in the solder joint even when thin-film metallization was used on the chip side. Three-dimensional simulations were employed to investigate the current density distribution in the area between the OSP Cu surface finish and the solder. The results indicated that the current density was higher along the periphery of the bonding area between the solder and the Cu pad, consistent with the area of IMC and void formation in our experimental results.
Vilchez, Gustavo; Dai, Jing; Lagos, Moraima; Sokol, Robert J
2018-01-01
Evidence supports the need of dose-adjustment of several drugs according to body mass index (BMI) to prevent toxicity in the underweight, and ensure efficacy in obese women. However, for MgSO 4 neuroprotection, the effect of BMI on maternal toxicity and fetal neuroprotection is understudied. We analyze the effect of BMI on maternal/infant outcomes after MgSO 4 . Secondary analysis of a clinical trial that studied MgSO 4 neuroprotection. Maternal side effects, magnesium cord levels, and offspring cerebral palsy/death were analyzed along BMI strata using ANOVA and chi-square test. Logistic regression was used to calculate adjusted odds ratios according to the treatment and BMI, using nonobese that received placebo as reference. Interaction analyses were performed to validate differential efficacy of BMI. From 2241 women, more side effects and higher magnesium cord levels were seen in underweight women (p = 0.05). MgSO 4 neuroprotection was effective in the non-obese (p = 0.02), but not in obese women (p = 1.00). In multivariate analyses, MgSO 4 significantly reduced cerebral palsy only in nonobese women. Interaction analyses showed the moderator effect of BMI (p = 0.169). Increasing MgSO 4 dose in obese mothers may ensure neuroprotective efficacy without representing increased maternal risks. Considering costs of studying this association, current analysis may form the basis for reasonable practice.
Hong, Ming; Li, Sha; Tan, Hor Yue; Wang, Ning; Tsao, Sai-Wah; Feng, Yibin
2015-01-01
Chronic liver dysfunction or injury is a serious health problem worldwide. Chronic liver disease involves a wide range of liver pathologies that include fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The efficiency of current synthetic agents in treating chronic liver disease is not satisfactory and they have undesirable side effects. Thereby, numerous medicinal herbs and phytochemicals have been investigated as complementary and alternative treatments for chronic liver diseases. Since some herbal products have already been used for the management of liver diseases in some countries or regions, a systematic review on these herbal medicines for chronic liver disease is urgently needed. Herein, we conducted a review describing the potential role, pharmacological studies and molecular mechanisms of several commonly used medicinal herbs and phytochemicals for chronic liver diseases treatment. Their potential toxicity and side effects were also discussed. Several herbal formulae and their biological effects in chronic liver disease treatment as well as the underlying molecular mechanisms are also summarized in this paper. This review article is a comprehensive and systematic analysis of our current knowledge of the conventional medicinal herbs and phytochemicals in treating chronic liver diseases and on the potential pitfalls which need to be addressed in future study. PMID:26633388
Bordag, Natalie; Klie, Sebastian; Jürchott, Kathrin; Vierheller, Janine; Schiewe, Hajo; Albrecht, Valerie; Tonn, Jörg-Christian; Schwartz, Christoph; Schichor, Christian; Selbig, Joachim
2015-11-03
Glucocorticoids are indispensable anti-inflammatory and decongestant drugs with high prevalence of use at (~)0.9% of the adult population. Better holistic insights into glucocorticoid-induced changes are crucial for effective use as concurrent medication and management of adverse effects. The profiles of 214 metabolites from plasma of 20 male healthy volunteers were recorded prior to and after ingestion of a single dose of 4 mg dexamethasone (+20 mg pantoprazole). Samples were drawn at three predefined time points per day: seven untreated (day 1 midday - day 3 midday) and four treated (day 3 evening - day 4 evening) per volunteer. Statistical analysis revealed tremendous impact of dexamethasone on the metabolome with 150 of 214 metabolites being significantly deregulated on at least one time point after treatment (ANOVA, Benjamini-Hochberg corrected, q < 0.05). Inter-person variability was high and remained uninfluenced by treatment. The clearly visible circadian rhythm prior to treatment was almost completely suppressed and deregulated by dexamethasone. The results draw a holistic picture of the severe metabolic deregulation induced by single-dose, short-term glucocorticoid application. The observed metabolic changes suggest a potential for early detection of severe side effects, raising hope for personalized early countermeasures increasing quality of life and reducing health care costs.
The therapeutic potential of cannabis and cannabinoids.
Grotenhermen, Franjo; Müller-Vahl, Kirsten
2012-07-01
Cannabis-based medications have been a topic of intense study since the endogenous cannabinoid system was discovered two decades ago. In 2011, for the first time, a cannabis extract was approved for clinical use in Germany. Selective literature review. Cannabis-based medications exert their effects mainly through the activation of cannabinoid receptors (CB1 and CB2). More than 100 controlled clinical trials of cannabinoids or whole-plant preparations for various indications have been conducted since 1975. The findings of these trials have led to the approval of cannabis-based medicines (dronabinol, nabilone, and a cannabis extract [THC:CBD=1:1]) in several countries. In Germany, a cannabis extract was approved in 2011 for the treatment of moderate to severe refractory spasticity in multiple sclerosis. It is commonly used off label for the treatment of anorexia, nausea, and neuropathic pain. Patients can also apply for government permission to buy medicinal cannabis flowers for self-treatment under medical supervision. The most common side effects of cannabinoids are tiredness and dizziness (in more than 10% of patients), psychological effects, and dry mouth. Tolerance to these side effects nearly always develops within a short time. Withdrawal symptoms are hardly ever a problem in the therapeutic setting. There is now clear evidence that cannabinoids are useful for the treatment of various medical conditions.
Limbus Impact on Off-angle Iris Degradation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Karakaya, Mahmut; Barstow, Del R; Santos-Villalobos, Hector J
The accuracy of iris recognition depends on the quality of data capture and is negatively affected by several factors such as angle, occlusion, and dilation. Off-angle iris recognition is a new research focus in biometrics that tries to address several issues including corneal refraction, complex 3D iris texture, and blur. In this paper, we present an additional significant challenge that degrades the performance of the off-angle iris recognition systems, called the limbus effect . The limbus is the region at the border of the cornea where the cornea joins the sclera. The limbus is a semitransparent tissue that occludes amore » side portion of the iris plane. The amount of occluded iris texture on the side nearest the camera increases as the image acquisition angle increases. Without considering the role of the limbus effect, it is difficult to design an accurate off-angle iris recognition system. To the best of our knowledge, this is the first work that investigates the limbus effect in detail from a biometrics perspective. Based on results from real images and simulated experiments with real iris texture, the limbus effect increases the hamming distance score between frontal and off-angle iris images ranging from 0.05 to 0.2 depending upon the limbus height.« less
Hong, Ming; Li, Sha; Tan, Hor Yue; Wang, Ning; Tsao, Sai-Wah; Feng, Yibin
2015-12-02
Chronic liver dysfunction or injury is a serious health problem worldwide. Chronic liver disease involves a wide range of liver pathologies that include fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The efficiency of current synthetic agents in treating chronic liver disease is not satisfactory and they have undesirable side effects. Thereby, numerous medicinal herbs and phytochemicals have been investigated as complementary and alternative treatments for chronic liver diseases. Since some herbal products have already been used for the management of liver diseases in some countries or regions, a systematic review on these herbal medicines for chronic liver disease is urgently needed. Herein, we conducted a review describing the potential role, pharmacological studies and molecular mechanisms of several commonly used medicinal herbs and phytochemicals for chronic liver diseases treatment. Their potential toxicity and side effects were also discussed. Several herbal formulae and their biological effects in chronic liver disease treatment as well as the underlying molecular mechanisms are also summarized in this paper. This review article is a comprehensive and systematic analysis of our current knowledge of the conventional medicinal herbs and phytochemicals in treating chronic liver diseases and on the potential pitfalls which need to be addressed in future study.
Fredriksen, Mats; Dahl, Alv A; Martinsen, Egil W; Klungsøyr, Ole; Haavik, Jan; Peleikis, Dawn E
2014-12-01
How to generalize from randomized placebo controlled trials of ADHD drug treatment in adults to 'real-world' clinical practice is intriguing. This open-labeled prospective observational study examined the effectiveness of long-term stimulant and non-stimulant medication in adult ADHD including dose, side-effects and comorbidity in a clinical setting. A specialized ADHD outpatient clinic gave previously non-medicated adults (n=250) with ADHD methylphenidate as first-line drug according to current guidelines. Patients who were non-tolerant or experiencing low efficacy were switched to amphetamine or atomoxetine. Primary outcomes were changes of ADHD-symptoms evaluated with the Adult ADHD Self-Report Scale (ASRS) and overall severity by the Global Assessment of Functioning (GAF). Secondary outcomes were measures of mental distress, and response on the Clinical-Global-Impressions-Improvement Scale. Data at baseline and follow-ups were compared in longitudinal mixed model analyses for time on-medication, dosage, comorbidity, and side-effects. As results, 232 patients (93%) completed examination at the 12 month endpoint, and 163 (70%) remained on medication. Compared with the patients who discontinued medication, those still on medication had greater percentage reduction in ASRS-scores (median 39%, versus 13%, P<0.001) and greater improvement of GAF (median 20% versus 4%, P<0.001) and secondary outcomes. Continued medication and higher cumulated doses showed significant associations to sustained improvement. Conversely, psychiatric comorbidity and side-effects were related to lower effectiveness and more frequent termination of medication. Taken together, one-year treatment with stimulants or atomoxetine was associated with a clinically significant reduction in ADHD symptoms and mental distress, and improvement of measured function. No serious adverse events were observed. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.
Bariatric surgery in adolescents with severe obesity: Review and state of the art in France.
Coutant, Régis; Bouhours-Nouet, Natacha; Donzeau, Aurélie; Fauchard, Mathilde; Decrequy, Anne; Malka, Jean; Riquin, Elise; Beaumesnil, Marion; Sallé, Agnès; Briet, Claire; Topart, Philippe; Schmitt, Françoise
2017-10-01
Severe obesity (body mass index>120% of BMI IOTF-30 cut off) and morbid obesity (BMI>140% of BMI IOTF-30 cut off) affect 5 to 10% of obese adolescents in France. Organic complications can be found in about 50% of these patients, and depressive symptoms in one-third of them. Finally, over 70% will suffer from adult morbid obesity associated with a marked increase in morbidity and mortality. However, the reversion of obesity strongly decreases, and may even cancels, these risks. In controlled randomized studies, lifestyle interventions have limited effectiveness on BMI in children (and none in adolescents). Bariatric surgery has been shown to have short-term effectiveness in adolescents with severe and morbid obesity: the average BMI loss after gastric banding was 11.6kg/m 2 (95% confidence interval from 9.8 to 13.4), 16.6kg/m 2 (95% confidence interval from 13.4 to 19.8) after bypass, and 14.1kg/m 2 (95% confidence interval 10.8 to 17.5) after sleeve gastrectomy. The resolution of comorbidities was the main aim, as well as the improvement of quality of life. This is not a simple surgical intervention, and minor side effects have been reported in approximately 10-15% of teenagers who underwent surgery (more common with the gastric band), and severe side effects in nearly 1-5% (mainly with bypass). In France, recommendations regarding indications, the care pathway, multidisciplinary meetings, reference management structures and postoperative care have been published by the French National Health Authority (HAS) in 2016 to provide a framework for bariatric surgery in underage patients. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Matro, Rebecca; Tupchong, Keegan; Daskalakis, Constantine; Gordon, Victoria; Katz, Leo; Kastenberg, David
2012-11-29
Colonic bubbles associated with polyethylene glycol-electrolyte solution (PEG-ELS) are common and obscure mucosal visualization. This study aimed to determine whether adding simethicone decreases the incidence of bubbles. Prospective, single-blind, randomized comparison of split dose PEG-ELS vs. PEG-ELS+simethicone (PEG-S) for outpatient colonoscopy. Bubble severity for colonic segments was assessed on withdrawal as A=no/minimal bubbles, B=moderate bubbles/interfere with detecting 5 mm polyp, C=severe bubbles/interfere with detecting 10 mm polyp. Primary end point was Grade B or C bubbles in any colon segment. Secondary end points were cleansing quality, incidence and severity of side effects, and polyp detection. One hundred and thirty nine patients enrolled; 13 withdrew before colonoscopy. Of 123 patients evaluated, 62 took PEG-S and 61 PEG-ELS. The incidence of grade B or C bubbles was much lower with PEG-S compared with PEG-ELS (2% vs. 38%; P=0.001). Overall cleansing (excellent or good) quality was not significantly different for either the whole colon (89% PEG-ELS, 94% of PEG-S, P=0.529) or right colon (88% PEG-ELS, 94% PEG-S, P=0.365). More PEG-S patients had excellent rather than good preps (whole colon 53% vs. 28%, P=0.004; right colon 53% vs. 35%, P=0.044). Need for any flushing was less with PEG-S (38% vs. 70%, P=0.001). The groups were not significantly different with respect to total procedure and withdrawal times, incidence or severity of side effects, or number of polyps/patient or adenomas/patient. Adding simethicone to PEG-ELS effectively eliminates bubbles, substantially reduces the need for flushing, and results in more excellent preparations.
Matro, Rebecca; Tupchong, Keegan; Daskalakis, Constantine; Gordon, Victoria; Katz, Leo; Kastenberg, David
2012-01-01
OBJECTIVES: Colonic bubbles associated with polyethylene glycol-electrolyte solution (PEG-ELS) are common and obscure mucosal visualization. This study aimed to determine whether adding simethicone decreases the incidence of bubbles. METHODS: Prospective, single-blind, randomized comparison of split dose PEG-ELS vs. PEG-ELS+simethicone (PEG-S) for outpatient colonoscopy. Bubble severity for colonic segments was assessed on withdrawal as A=no/minimal bubbles, B=moderate bubbles/interfere with detecting 5 mm polyp, C=severe bubbles/interfere with detecting 10 mm polyp. Primary end point was Grade B or C bubbles in any colon segment. Secondary end points were cleansing quality, incidence and severity of side effects, and polyp detection. RESULTS: One hundred and thirty nine patients enrolled; 13 withdrew before colonoscopy. Of 123 patients evaluated, 62 took PEG-S and 61 PEG-ELS. The incidence of grade B or C bubbles was much lower with PEG-S compared with PEG-ELS (2% vs. 38% P=0.001). Overall cleansing (excellent or good) quality was not significantly different for either the whole colon (89% PEG-ELS, 94% of PEG-S, P=0.529) or right colon (88% PEG-ELS, 94% PEG-S, P=0.365). More PEG-S patients had excellent rather than good preps (whole colon 53% vs. 28%, P=0.004; right colon 53% vs. 35%, P=0.044). Need for any flushing was less with PEG-S (38% vs. 70%, P=0.001). The groups were not significantly different with respect to total procedure and withdrawal times, incidence or severity of side effects, or number of polyps/patient or adenomas/patient. CONCLUSIONS: Adding simethicone to PEG-ELS effectively eliminates bubbles, substantially reduces the need for flushing, and results in more excellent preparations. PMID:23238113
[Side effects of biologic therapies in psoriasis].
Altenburg, A; Augustin, M; Zouboulis, C C
2018-04-01
The introduction of biologics has revolutionized the treatment of moderate to severe plaque psoriasis. Due to the continuous expansion of biological therapies for psoriasis, it is particularly important to acknowledge efficacy and safety of the compounds not only in clinical trials but also in long-term registry-based observational studies. Typical side effects and significant risks of antipsoriatic biologic therapies considering psoriatic control groups are presented. A selective literature search was conducted in PubMed and long-term safety studies of the psoriasis registries PsoBest, PSOLAR and BADBIR were evaluated. To assess the long-term safety of biologics, the evaluation of the course of large patient cohorts in long-term registries is of particular medical importance. Newer biologic drugs seem to exhibit a better safety profile than older ones.
Autistic spectrum disorder, epilepsy, and vagus nerve stimulation.
Hull, Mariam Mettry; Madhavan, Deepak; Zaroff, Charles M
2015-08-01
In individuals with a comorbid autistic spectrum disorder and medically refractory epilepsy, vagus nerve stimulation may offer the potential of seizure control and a positive behavioral side effect profile. We aimed to examine the behavioral side effect profile using longitudinal and quantitative data and review the potential mechanisms behind behavioral changes. We present a case report of a 10-year-old boy with autistic spectrum disorder and epilepsy, who underwent vagus nerve stimulation subsequent to unsuccessful treatment with antiepileptic medication. Following vagus nerve stimulation implantation, initial, if temporary, improvement was observed in seizure control. Modest improvements were also observed in behavior and development, improvements which were observed independent of seizure control. Vagus nerve stimulation in autistic spectrum disorder is associated with modest behavioral improvement, with unidentified etiology, although several candidates for this improvement are evident.
Yellow fever vaccination in organ transplanted patients: is it safe? A multicenter study.
Azevedo, L S; Lasmar, E P; Contieri, F L C; Boin, I; Percegona, L; Saber, L T S; Selistre, L S; Netto, M V P; Moreira, M C V; Carvalho, R M; Bruno, R M; Ferreira, T C A; David-Neto, E
2012-06-01
Yellow fever (YF) may be very serious, with mortality reaching 50%. Live attenuated virus YF vaccine (YFV) is effective, but may present, although rare, life-threatening side effects and is contraindicated in immunocompromised patients. However, some transplant patients may inadvertently receive the vaccine. A questionnaire was sent to all associated doctors to the Brazilian Organ Transplantation Association through its website, calling for reports of organ transplanted patients who have been vaccinated against YF. Twelve doctors reported 19 cases. None had important side effects. Only one had slight reaction at the site of YFV injection. Eleven patients were male. Organs received were 14 kidneys, 3 hearts, and 2 livers. Twelve patients received organs from deceased donors. Mean age at YFV was 45.6 ± 13.6 years old (range 11-69); creatinine: 1.46 ± 0.62 mg/dL (range 0.8-3.4); post-transplant time: 65 ± 83.9 months (range 3-340); and time from YFV at the time of survey: 45 ± 51 months (range 3-241). Immunosuppression varied widely with different drug combinations: azathioprine (7 patients), cyclosporine (8), deflazacort (1), mycophenolate (10), prednisone (11), sirolimus (3), and tacrolimus (4). YFV showed no important side effects in this cohort of solid organ transplanted patients. However, owing to the small number of studied patients, it is not possible to extend these findings to the rest of the transplanted population, assuring safety. Therefore, these data are not strong enough to safely recommend YFV in organ transplanted recipients, as severe, even life-threatening side effects may occur. © 2011 John Wiley & Sons A/S.
Determinants of patient-rated and clinician-rated illness severity in schizophrenia.
Fervaha, Gagan; Takeuchi, Hiroyoshi; Agid, Ofer; Lee, Jimmy; Foussias, George; Remington, Gary
2015-07-01
The contribution of specific symptoms on ratings of global illness severity in patients with schizophrenia is not well understood. The present study examined the clinical determinants of clinician and patient ratings of overall illness severity. This study included 1,010 patients with a DSM-IV diagnosis of schizophrenia who participated in the baseline visit of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study conducted between January 2001 and December 2004 and who had available symptom severity, side effect burden, cognition, and community functioning data. Both clinicians and patients completed the 7-point Clinical Global Impressions-Severity of Illness scale (CGI-S), the primary measure of interest in the present study. Symptoms were rated using the Positive and Negative Syndrome Scale and the Calgary Depression Scale for Schizophrenia, and functional status with the Quality of Life Scale. Neurocognition, insight, and medication-related side effects were also evaluated. Clinicians rated illness severity significantly higher than patients (P < .001). There was moderate overlap between CGI-S ratings made by clinicians and patients, with almost one third of patients showing substantial (ie, greater than 1 point) discrepancies with clinician ratings. Clinician-rated CGI-S scores were most strongly associated with positive symptoms, with additional independent contributions made by negative, disorganized, and depressive symptoms, as well as functional outcome (all P values < .01). Patient-rated CGI-S scores, on the other hand, were most closely related to depressive symptoms, with additional independent contributions made by positive and anxiety symptoms, clinical insight, and neurocognition (all P values < .01). Depressive symptoms were the strongest predictor of patient-rated CGI-S scores even in patients with good clinical insight (P < .001). Patient and clinician views of overall illness severity are not necessarily interchangeable and differ in their clinical correlates. Taking these differences into account may enhance patient engagement in care and improve outcomes. ClinicalTrials.gov identifier: NCT00014001. © Copyright 2014 Physicians Postgraduate Press, Inc.
Chen, Li-Kuei; Chen, Shiou-Sheng; Huang, Chi-Hsiang; Yang, Hong-Jyh; Lin, Chen-Jung; Chien, Kuo-Liong; Fan, Shou-Zen
2013-01-01
A cohort, double blind, and randomized study was conducted to investigate the effect of a single nucleotide polymorphism of the μ-opioid receptor at nucleotide position 118 (OPRM1:c.118A>G) on the association with the most common side effects (nausea or vomiting) induced by intravenous patient control analgesia (IVPCA) with morphine, including incidence and severity analysis. A total of 129 Taiwanese women undergoing gynecology surgery received IVPCA with pure morphine for postoperative pain relief. Blood samples were collected and sequenced with high resolution melting analysis to detect three different genotypes of OPRM1 (AA, AG, and GG). All candidates 24 h postoperatively will be interviewed to record the clinical phenotype with subjective complaints and objective observations. The genotyping after laboratory analysis showed that 56 women (43.4%) were AA, 57 (44.2%) were AG, and 16 (12.4%) were GG. The distribution of genotype did not violate Hardy-Weinberg equilibrium test. There was no significant difference neither between the severity and incidence of IVPCA morphine-induced side effects and genotype nor between the association between morphine consumption versus genotype. However, there was significant difference of the relation between morphine consumption and the severity and incidence of IVPCA morphine-induced nausea and vomiting. The genetic analysis for the severity and incidence of IVPCA morphine-induced nausea or vomiting showed no association between phenotype and genotype. It might imply that OPRM1:c.118A>G does not protect against IVPCA morphine-induced nausea or vomiting. PMID:23431434
Mansour, Heidi M; Sohn, Minji; Al-Ghananeem, Abeer; Deluca, Patrick P
2010-09-15
Controlled release delivery is available for many routes of administration and offers many advantages (as microparticles and nanoparticles) over immediate release delivery. These advantages include reduced dosing frequency, better therapeutic control, fewer side effects, and, consequently, these dosage forms are well accepted by patients. Advances in polymer material science, particle engineering design, manufacture, and nanotechnology have led the way to the introduction of several marketed controlled release products and several more are in pre-clinical and clinical development.
Mansour, Heidi M.; Sohn, MinJi; Al-Ghananeem, Abeer; DeLuca, Patrick P.
2010-01-01
Controlled release delivery is available for many routes of administration and offers many advantages (as microparticles and nanoparticles) over immediate release delivery. These advantages include reduced dosing frequency, better therapeutic control, fewer side effects, and, consequently, these dosage forms are well accepted by patients. Advances in polymer material science, particle engineering design, manufacture, and nanotechnology have led the way to the introduction of several marketed controlled release products and several more are in pre-clinical and clinical development. PMID:20957095
Itami, Yasuo; Mihata, Teruhisa; Shibano, Koji; Sugamoto, Kazuomi; Neo, Masashi
2016-07-01
Humeral retroversion in baseball players is greater in the dominant shoulder than in the nondominant shoulder. However, the site and severity of the humeral rotational deformity remain unclear. To evaluate the site of side-to-side differences in humeral retroversion in baseball players and the severity of these changes through 3-dimensional computed tomographic (3D CT) bone models. Cross-sectional study; Level of evidence, 3. From 2008 to 2014, we studied 25 baseball players (12 pitchers, 13 fielders) who underwent surgery for throwing-related injuries (shoulder injury, 15 players; elbow injury, 10 players). The mean age (±SD) at the time of surgery was 20.0 ± 5.9 years. A reconstructed 3D CT model of the entire humerus was divided into 15 segments of equal height (overall mean, 21.4 ± 1.0 mm). The side-to-side difference in humeral retroversion in each segment was calculated by superimposing the model of the dominant side over the mirror-image model of the nondominant side. The overall mean increase in humeral retroversion was 13.0° ± 6.2° on the dominant side. Significant side-to-side differences in retroversion were present throughout the humerus. The largest side-to-side difference in humeral retroversion was seen at the insertions of the internal rotator muscles (2.5° ± 4.3°) and around the proximal physis (2.5° ± 1.4°). At the insertions of shoulder capsule and rotator cuff tendons, the superior half of the humeral head was more retroverted than the inferior half (P < .0001). The side-to-side difference in humeral retroversion was significantly greater in the pitchers (16.2° ± 5.1°) than in the fielders (10.0° ± 5.7°) (P = .009), particularly at the proximal physis. Baseball players exhibited significant side-to-side differences in humeral retroversion at multiple sites throughout the humerus, including the proximal humerus near the epiphyseal plate and at the insertions of the internal rotator muscles, the middle of the humeral shaft, and the distal third of the humerus. Therefore, the increased humeral retroversion at multiple sites throughout the humerus needs to be considered when we perform physical examinations, provide treatment, or undertake biomechanical studies for any throwing-related injuries. © 2016 The Author(s).
Tavil, Betül; Ok-Bozkaya, İkbal; Tezer, Hasan; Tunç, Bahattin
2014-01-01
Human fascioliasis (HF), caused by the common liver fluke Fasciola hepatica, is an endemic infection in many parts of tropical countries. HF can also be seen in some of the non-tropical countries. This report describes two girls with severe iron deficiency anemia and eosinophilia, who were diagnosed as HF. The infection was successfully eliminated with the administration of triclabendazole. No side effects or recurrence was observed after the treatment. It should be kept in mind that marked eosinophilia with severe iron deficiency anemia should alert pediatricians to the possibility of F. hepatica infection.
Kim, Aram; Lee, Kyu-Sung; Jung, Rangrhee; Na, Selee; Kim, Joon-Chul; Kim, Hyeong Gon; Choo, Myung-Soo
2017-09-01
Drug therapy is the mainstay of treatment for overactive bladder (OAB), but antimuscarinic agents possess side-effects. These side-effects decrease the patients' quality of life. We therefore assessed the impact of side-effects on health-related quality of life (HR-QoL) through an analysis of EQ-5D questionnaire. This study was designed to investigate the patients' satisfaction by quality weight of health status as affected by the side-effects of OAB medications. Patients who had OAB symptoms lasting longer than 3 months and have experienced side-effects after any antimuscarinic treatments filled in the EQ-5D questionnaire. The enrolled patients had two EQ-5D questionnaires for two different health statuses, i.e., presence or absence of side-effects. Quality weight was calculated using the ED-5D health status score with Korean tariff. One hundred patients were enrolled and completed the HR-QoL questionnaire. The most prevalent side-effect was dry mouth (61%) and 28% patients had dry mouth and constipation concurrently. Most of the patients with side-effects tried to endure and overcome these side-effects (79%), but 10% desired a change in medication, and 6% stopped medication altogether. The quality weight of EQ-5D without side-effects was 0.863, while the quality weight with side-effects was 0.666 (P < 0.001). The VAS score was 79 in patient without side-effects and 57 in those with side-effects, supporting the results of quality weight assessment. Overactive bladder patients may enjoy a better quality of life if side-effects associated with antimuscarinic therapy are fewer. © 2016 John Wiley & Sons Australia, Ltd.
The effects of bariatric surgery: will understanding its mechanism render the knife unnecessary?
Browning, Kirsteen N; Hajnal, Andras
2014-01-01
The incidence of obesity is increasing worldwide at a dramatic rate, accompanied by an associated increase in comorbid conditions. Bariatric surgery is the most effective treatment for morbid obesity with Roux-en-Y gastric bypass being the most commonly performed procedure, yet the underlying mechanisms by which it induces a wide-array of beneficial effects remains obscure. From basic science as well as clinical standpoints, there are several areas of current interest that warrant continued investigation. Several major focus areas have also emerged in current research that may guide future efforts in this field, particularly with regards to using novel, non-surgical approaches to mimic the success of bariatric surgery while minimizing its adverse side effects.
Opioid adjuvant strategy: improving opioid effectiveness.
Bihel, Frédéric
2016-01-01
Opioid analgesics continue to be the mainstay of pharmacologic treatment of moderate to severe pain. Many patients, particularly those suffering from chronic pain, require chronic high-dose analgesic therapy. Achieving clinical efficacy and tolerability of such treatment regimens is hampered by the appearance of opioid-induced side effects such as tolerance, hyperalgesia and withdrawal syndrome. Among the therapeutic options to improve the opioid effectiveness, this current review focuses on strategies combining opioids to other drugs that can modulate opioid-mediated effects. We will discuss about experimental evidences reported for several potential opioid adjuvants, including N-methyl-D-aspartate receptor antagonists, 5-HT7 agonists, sigma-1 antagonists, I2-R ligands, cholecystokinin antagonists, neuropeptide FF-R antagonists and toll-like receptor 4 antagonists.
Durrant, Jacob D.; Amaro, Rommie E.; Xie, Lei; Urbaniak, Michael D.; Ferguson, Michael A. J.; Haapalainen, Antti; Chen, Zhijun; Di Guilmi, Anne Marie; Wunder, Frank; Bourne, Philip E.; McCammon, J. Andrew
2010-01-01
Conventional drug design embraces the “one gene, one drug, one disease” philosophy. Polypharmacology, which focuses on multi-target drugs, has emerged as a new paradigm in drug discovery. The rational design of drugs that act via polypharmacological mechanisms can produce compounds that exhibit increased therapeutic potency and against which resistance is less likely to develop. Additionally, identifying multiple protein targets is also critical for side-effect prediction. One third of potential therapeutic compounds fail in clinical trials or are later removed from the market due to unacceptable side effects often caused by off-target binding. In the current work, we introduce a multidimensional strategy for the identification of secondary targets of known small-molecule inhibitors in the absence of global structural and sequence homology with the primary target protein. To demonstrate the utility of the strategy, we identify several targets of 4,5-dihydroxy-3-(1-naphthyldiazenyl)-2,7-naphthalenedisulfonic acid, a known micromolar inhibitor of Trypanosoma brucei RNA editing ligase 1. As it is capable of identifying potential secondary targets, the strategy described here may play a useful role in future efforts to reduce drug side effects and/or to increase polypharmacology. PMID:20098496
Excimer laser for the treatment of psoriasis: safety, efficacy, and patient acceptability
Abrouk, Michael; Levin, Ethan; Brodsky, Merrick; Gandy, Jessica R; Nakamura, Mio; Zhu, Tian Hao; Farahnik, Benjamin; Koo, John; Bhutani, Tina
2016-01-01
Introduction The 308 nm excimer laser is a widely used device throughout the field of dermatology for many diseases including psoriasis. Although the laser has demonstrated clinical efficacy, there is a lack of literature outlining the safety, efficacy, and patient acceptability of the excimer laser. Methods A literature search on PubMed was used with combinations of the terms “excimer”, “excimer laser”, “308 nm”, “psoriasis”, “protocol”, “safety”, “efficacy”, acceptability”, “side effects”, and “dose”. The search results were included if they contained information pertaining to excimer laser and psoriasis treatment and description of the safety, efficacy, and patient acceptability of the treatment. Results The 308 nm excimer laser is generally safe and well tolerated with minimal side effects including erythema, blistering, and pigmentary changes. It has a range of efficacies depending on the protocol used with several different treatment protocols, including the induration protocol, the minimal erythema dose protocol, and the newer minimal blistering dose protocol. Conclusion Although the excimer laser is not a first-line treatment, it remains an excellent treatment option for psoriasis patients and has been demonstrated to be an effective treatment with little to no side effects. PMID:29387603
Fatal hypermagnesemia in a child treated with megavitamin/megamineral therapy.
McGuire, J K; Kulkarni, M S; Baden, H P
2000-02-01
We report a case of fatal hypermagnesemia resulting from the unsupervised use of high doses of magnesium oxide administered as part of a regimen of megavitamin and megamineral therapy to a child with mental retardation, spastic quadriplegia, and seizures. The treatment regimen was given at the recommendation of a dietician working as a private nutritional consultant without the involvement or notification of the child's pediatrician. Hypermagnesemia is an uncommon but serious side effect of the use of magnesium containing compounds. These compounds are widely used as laxatives and dietary supplements, and serious side effects are uncommon when used in appropriate dosages and with adequate supervision. The use of alternative medical therapies, including megavitamin/megamineral therapy, is widespread. Many patients use alternative medicine or seek care from alternative medicine practitioners without the recommendation or knowledge of their primary physicians. Despite unproved benefit, many alternative therapies may be safe. However, unsupervised use of generally safe treatments can result in serious side effects. This case report serves to illustrate the characteristic pathophysiologic changes of severe hypermagnesemia, an entity rarely seen in pediatric practice, and more importantly, it alerts primary care and subspecialty pediatricians to be aware of and monitor the use of alternative medical therapies in their patients.
Durrant, Jacob D; Amaro, Rommie E; Xie, Lei; Urbaniak, Michael D; Ferguson, Michael A J; Haapalainen, Antti; Chen, Zhijun; Di Guilmi, Anne Marie; Wunder, Frank; Bourne, Philip E; McCammon, J Andrew
2010-01-22
Conventional drug design embraces the "one gene, one drug, one disease" philosophy. Polypharmacology, which focuses on multi-target drugs, has emerged as a new paradigm in drug discovery. The rational design of drugs that act via polypharmacological mechanisms can produce compounds that exhibit increased therapeutic potency and against which resistance is less likely to develop. Additionally, identifying multiple protein targets is also critical for side-effect prediction. One third of potential therapeutic compounds fail in clinical trials or are later removed from the market due to unacceptable side effects often caused by off-target binding. In the current work, we introduce a multidimensional strategy for the identification of secondary targets of known small-molecule inhibitors in the absence of global structural and sequence homology with the primary target protein. To demonstrate the utility of the strategy, we identify several targets of 4,5-dihydroxy-3-(1-naphthyldiazenyl)-2,7-naphthalenedisulfonic acid, a known micromolar inhibitor of Trypanosoma brucei RNA editing ligase 1. As it is capable of identifying potential secondary targets, the strategy described here may play a useful role in future efforts to reduce drug side effects and/or to increase polypharmacology.
Development of universal antidotes to control aptamer activity
Oney, Sabah; Lam, Ruby T S; Bompiani, Kristin M; Blake, Charlene M; Quick, George; Heidel, Jeremy D; Liu, Joanna Yi-Ching; Mack, Brendan C; Davis, Mark E; Leong, Kam W; Sullenger, Bruce A
2010-01-01
With an ever increasing number of people taking numerous medications, the need to safely administer drugs and limit unintended side effects has never been greater. Antidote control remains the most direct means to counteract acute side effects of drugs, but, unfortunately, it has been challenging and cost prohibitive to generate antidotes for most therapeutic agents. Here we describe the development of a set of antidote molecules that are capable of counteracting the effects of an entire class of therapeutic agents based upon aptamers. These universal antidotes exploit the fact that, when systemically administered, aptamers are the only free extracellular oligonucleotides found in circulation. We show that protein-and polymer-based molecules that capture oligonucleotides can reverse the activity of several aptamers in vitro and counteract aptamer activity in vivo. The availability of universal antidotes to control the activity of any aptamer suggests that aptamers may be a particularly safe class of therapeutics. PMID:19801990
Targeting interleukin-6 for noninfectious uveitis
Lin, Phoebe
2015-01-01
Interleukin-6 (IL-6) is a pleiotropic cytokine implicated in the pathogenesis of many immune-mediated disorders including several types of non-infectious uveitis. These uveitic conditions include Vogt-Koyanagi-Harada syndrome, uveitis associated with Behçet disease, and sarcoidosis. This review summarizes the role of IL-6 in immunity, highlighting its effect on Th17, Th1, and plasmablast differentiation. It reviews the downstream mediators activated in the process of IL-6 binding to its receptor complex. This review also summarizes the biologics targeting either IL-6 or the IL-6 receptor, including tocilizumab, sarilumab, sirukumab, olokizumab, clazakizumab, and siltuximab. The target, dosage, potential side effects, and potential uses of these biologics are summarized in this article based on the existing literature. In summary, anti-IL-6 therapy for non-infectious uveitis shows promise in terms of efficacy and side effect profile. PMID:26392750
Merikangas, K R; Merikangas, J R
1995-11-01
This paper presents the results of a study comparing the effectiveness of a beta-adrenergic blocking agent, atenolol, a monoamine oxidase inhibitor (MAO-I), phenelzine, and the combination in treatment of 61 adults with migraine headache. The goals of the study are (1) to investigate the safety of concomitant treatment of migraine with beta-blockers and phenelzine, (2) to assess whether orthostatic hypertension and other side effects would be relieved, and (3) to compare the results of this open trial of phenelzine to those of a previous study using similar methods. Phenelzine was associated with a large decrease in the frequency and severity of migraine attacks. Anxiety and depression were also reduced by phenelzine both alone, and in combination with a beta-blocker. The results show that the combination of MAO-I's and beta-blockers can be administered safely, and can lead to the reduction in the side effects with either drug alone.
Uncovering the Origin of Skin Side Effects from EGFR-Targeted Therapies | Center for Cancer Research
The epidermal growth factor receptor (EGFR), a key regulator of cell proliferation, is often mutated or overexpressed in a variety of cancer types. EGFR-targeted therapies, including monoclonal antibodies and small molecule inhibitors, can effectively treat patients whose tumors depend on aberrant EGFR signaling. Within a few weeks of initiating therapy, however, patients develop a characteristic rash with leukocyte infiltration into the skin accompanied by pruritus (itching), scaling of the skin, hair loss, and even changes in skin cell differentiation. The side effects can become so severe that patients take reduced doses, which can limit efficacy, or stop treatment altogether. To understand how EGFR inhibitors cause these skin changes in the hopes of identifying a means of preventing them, Stuart Yuspa, M.D., of CCR’s Laboratory of Cancer Biology and Genetics, and his colleagues examined patient samples and generated a mouse model of EGFR loss in the skin.
Schnell, Thomas; Koethe, Dagmar; Krasnianski, Anna; Gairing, Stefanie; Schnell, Knut; Daumann, Jörg; Gouzoulis-Mayfrank, Euphrosyne
2014-01-01
Clozapine is considered to be particularly effective in the treatment of dually diagnosed (DD) patients with psychosis and substance use disorders. However, its use is restricted by potentially severe side effects. The aim of the present pilot study was to compare the effects of clozapine with the newer second generation antipsychotic (SGA) ziprasidone in DD-patients. Thirty (n = 30) patients with schizophrenia and cannabis abuse/dependence were randomized to ziprasidone or clozapine and were followed up for up to 12 months. Cannabis use was reduced in both groups during follow-up. Clozapine treatment was associated with less positive symptoms of schizophrenia, more side effects and poorer compliance with treatment. Results from this small pilot RCT suggest beneficial effects of both clozapine and ziprasidone in the treatment of cannabis use disorders in psychotic patients. Larger-scale RCTs are needed in order to assess advantages and disadvantages of the different SGAs in dually diagnosed populations. © American Academy of Addiction Psychiatry.
Dietary and botanical anxiolytics
Alramadhan, Elham; Hanna, Mirna S.; Hanna, Mena S.; Goldstein, Todd A.; Avila, Samantha M.; Weeks, Benjamin S.
2012-01-01
Summary Drugs used to treat anxiety have many negative side effects including addiction, depression, suicide, seizures, sexual dysfunction, headaches and more. Anxiolytic medications do not restore normal levels of neurotransmitters but instead manipulate the brain chemistry. For example, selective serotonin reuptake inhibitors (SSRIs) prevent the reuptake of serotonin from the synapse allowing serotonin to remain in the area of activity for a longer period of time but does not correct the lack of serotonin production. Benzodiazepines, such as Valium and Xanax®, stimulate GABA receptors, thus mimicking the calming effects of GABA but again do not fix the lack of GABA production. Often, the brain becomes accustomed to these medications and they often lose their effectiveness, requiring higher doses or different drugs. In contrast to anxiolytic drugs, there are herbs and nutrients which can stimulates neurotransmitter synthesis and more naturally effect and even adjust brain chemistry in the absence of many of the side effects experienced with drugs. Therefore this paper explores several herbal and nutritional approaches to the treatment of anxiety. PMID:22460105
Explanations for side effect aversion in preventive medical treatment decisions
Waters, Erika A.; Weinstein, Neil D.; Colditz, Graham A.; Emmons, Karen
2008-01-01
Objective Many laypeople demonstrate excessive sensitivity to negative side effects of medical treatments, which may lead them to refuse beneficial therapies. This Internet-based experiment investigated three possible explanations for such “side effect aversion.” One was derived from mental accounting, one examined the mere presence of a side effect, and one focused on computational difficulties. Design Participants (N = 5,379) were presented with a hypothetical cancer preventive treatment situation that was or was not accompanied by one or two small side effects. The side effects were either beneficial or harmful. In all conditions the net absolute risk reduction associated with the treatment was 15%. Main Outcome Measures Participants indicated their willingness to accept treatment and their perceptions of the treatment’s effects on their overall cancer risk. Results Data were consistent only with the “mere presence” explanation of side effect aversion, the idea that side effects act as a strong negative cue that directly affects treatment appraisal. The number of negative side effects did not influence treatment willingness. Conclusion Side effect aversion is a challenge to informed decision making. Specific mechanisms that produce side effect aversion should be identified. PMID:19290712
Non-injection routes for allergen immunotherapy: focus on sublingual immunotherapy.
Passalacqua, Giovanni; Guerra, Laura; Pasquali, Mercedes; Canonica, Giorgio Walter
2006-01-01
Allergen specific immunotherapy, together with drugs and allergen avoidance, is a cornerstone in the management of respiratory allergy. The non-injection or local routes were developed with the main goal of improving the safety and minimizing the risk of those side effects, which can accompany the injection route. The pure oral route and the bronchial route showed, in the clinical trials, only a marginal efficacy with not negligible side effects. Therefore, these routes are no longer recommended for clinical use. The nasal route proved effective and safe, but its efficacy is strictly limited to the nose. Moreover, the practical problems with administration have made the use of nasal immunotherapy progressively declining. The efficacy of the sublingual route is confirmed by numerous controlled trials, and a meta analysis (in allergic rhinitis). The safety profile, as derived from clinical trials and post marketing surveillance studies, is satisfactory, with mild gastrointestinal complaints being the more frequent side effect reported. Recent studies have also demonstrated that SLIT has a long-lasting effect and a preventive effect on the onset of new skin sensitizations, and interesting data on adherence and mechanisms of action have become recently available. Based on these experimental data, SLIT is now officially accepted as a viable alternative to the subcutaneous route in adults and children. Several points still need to be elucidated, including: mechanisms of action, optimal dosages, and indications in pediatric patients.
Yoon, Eileen L.; Kim, Seung Young; Kim, Jeong Han; Lee, Ju-Han; Lee, Young Sun; Lee, Hyun Jung; Jung, Sung Woo; Lee, Sang Woo; Choi, Jai Hyun
2010-01-01
Acute hepatitis A is currently outbreaking in Korea. Although prognosis of acute hepatitis A is generally favorable, a minority of patients are accompanied by fatal complications. Severe cholestasis is one of the important causes of prolonged hospitalization in patients with acute hepatitis A. In such cases, higher chances of additional complications and increased medical costs are inevitable. We report three cases of severely cholestatic hepatitis A, who showed favorable responses to oral corticosteroids. Thirty milligram of prednisolone was initiated and tapered according to the responses. Rapid improvement was observed in all cases without side effects. We suggest that corticosteroid administration can be useful in hepatitis A patients with severe cholestasis who do not show improvement by conservative managements. Clinical trial will be needed to evaluate effectiveness of corticosteroids in these patients. PMID:20924218
Smith, Tess E; Martel, Michelle M; DeSantis, Alan D
2017-03-21
Side effects of prescribed and nonprescribed psychostimulant use are understudied. The study examined side effects of prescribed and nonprescribed psychostimulant use in a college sample with attention to possible gender differences. 2716 undergraduates (1448 male) between the ages of 17 and 57 years (M = 19.43 years, SD = 1.7 years) completed an online survey that included questions about the subjective side effects of prescribed and nonprescribed psychostimulant use. Results suggested that prescribed users more frequently reported side effects, compared to nonprescribed users. For prescribed users, females more frequently reported appetite, somatic, and anxiety-related side effects compared to males. For nonprescribed users, while females reported more somatic and anxiety-related side effects, males more frequently reported loss of sex drive and sweating as side effects. Conclusions/Importance: These findings suggest prescribed users of psychostimulants more frequently report side effects with prominent gender differences in line with gender roles.
Sexual side effects associated with conventional and atypical antipsychotics.
Compton, M T; Miller, A H
2001-01-01
The sexual side effects of psychotropic medications are becoming increasingly recognized in clinical psychiatry. The magnitude of the problem of sexual side effects associated with antipsychotic medications has yet to be fully elucidated, but a multitude of references in the literature demonstrate the importance of these side effects in both men and women. All currently used antipsychotic medications are associated with sexual side effects of various types. Although each antipsychotic medication may have a specific side effect profile determined by its various receptor affinities and by the degree to which it elevates serum prolactin, there is currently no evidence that specific side effects can be predicted. Sexual side effects can be categorized according to the phase of the sexual response cycle with which they interfere. Suggestions for clinical evaluation and treatment options are provided, including risk factor modification, dose reduction, switching agents, and addition of other agents. Sexual side effects associated with conventional and atypical antipsychotic medications represent an underestimated and understudied set of side effects that may diminish a patient's quality of life and lead to treatment noncompliance. Clinicians prescribing antipsychotic medications should be familiar with the classification, evaluation, and treatment of these side effects.
Anti-diabetic and hypolipidemic effects of Sargassum yezoense in db/db mice
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kim, Su-Nam, E-mail: snkim@kist.re.kr; Lee, Woojung; Bae, Gyu-Un
2012-08-10
Highlights: Black-Right-Pointing-Pointer Sargassum yezoense (SY) treatment improved glucose and lipid impairment in vivo. Black-Right-Pointing-Pointer This pharmacological action is associated with PPAR{alpha}/{gamma} dual activation. Black-Right-Pointing-Pointer It decreases the expression of G6Pase for gluconeogenesis in liver. Black-Right-Pointing-Pointer It increases the expression of UCP3 for lipid metabolism in adipose tissue. Black-Right-Pointing-Pointer There are no significant side effects such as body weight gain and hepatomegaly. -- Abstract: Peroxisome proliferator-activated receptors (PPARs) have been considered to be desirable targets for metabolic syndrome, even though their specific agonists have several side effects including body weight gain, edema and tissue failure. Previously, we have reported in vitromore » effects of Sargassum yezoense (SY) and its ingredients, sargaquinoic acid (SQA) and sargahydroquinoic acid (SHQA), on PPAR{alpha}/{gamma} dual transcriptional activation. In this study, we describe in vivo pharmacological property of SY on metabolic disorders. SY treatment significantly improved glucose and lipid impairment in db/db mice model. More importantly, there are no significant side effects such as body weight gain and hepatomegaly in SY-treated animals, indicating little side effects of SY in liver and lipid metabolism. In addition, SY led to a decrease in the expression of G6Pase for gluconeogenesis in liver responsible for lowering blood glucose level and an increase in the expression of UCP3 in adipose tissue for the reduction of total and LDL-cholesterol level. Altogether, our data suggest that SY would be a potential therapeutic agent against type 2 diabetes and related metabolic disorders by ameliorating the glucose and lipid metabolism.« less
Rosa, Gian Marco; Bianco, Daniele; Parodi, Antonello; Valbusa, Alberto; Zawaideh, Camilla; Bizzarri, Nicolò; Ferrero, Simone; Brunelli, Claudio
2014-12-01
Atrial fibrillation (AF) is the most common arrhythmia and is associated with increased morbidity and mortality. Dronedarone is a recent antiarrhythmic drug that has been developed for treatment of AF, with electrophysiological properties similar to amiodarone but with a lower incidence of side effects. This review evaluates the efficacy, safety, tolerability and side effects of dronedarone in the treatment of AF. In particular, the review includes studies comparing: dronedarone and placebo (ANDROMEDA, ATHENA, DAFNE, ERATO, EURIDIS/ADONIS, HESTIA, PALLAS trials), dronedarone and amiodarone (DIONYSOS trial), ranolazine and dronedarone given alone and in combination (HARMONY trial). Dronedarone is an interesting antiarrhythmic agent in well-selected groups of patients. It also has several other pleiotropic effects that may potentially be beneficial in clinical practice, such as the reduction of the risk of stroke and acute coronary syndromes. In addition, combination therapies such as those with dronedarone and ranolazine, currently being investigated in the HARMONY trial, may provide another interesting approach to increase the antiarrhythmic efficacy and further reduce the incidence of side effects. A better understanding of the mechanisms underlying dronedarone's pleiotropic actions is expected to facilitate the selection of patients benefiting from dronedarone, as well as the development of novel antiarrhythmic drugs for AF.
FoodWiki: a Mobile App Examines Side Effects of Food Additives Via Semantic Web.
Çelik Ertuğrul, Duygu
2016-02-01
In this article, a research project on mobile safe food consumption system (FoodWiki) is discussed that performs its own inferencing rules in its own knowledge base. Currently, the developed rules examines the side effects that are causing some health risks: heart disease, diabetes, allergy, and asthma as initial. There are thousands compounds added to the processed food by food producers with numerous effects on the food: to add color, stabilize, texturize, preserve, sweeten, thicken, add flavor, soften, emulsify, and so forth. Those commonly used ingredients or compounds in manufactured foods may have many side effects that cause several health risks such as heart disease, hypertension, cholesterol, asthma, diabetes, allergies, alzheimer etc. according to World Health Organization. Safety in food consumption, especially by patients in these risk groups, has become crucial, given that such health problems are ranked in the top ten health risks around the world. It is needed personal e-health knowledge base systems to help patients take control of their safe food consumption. The systems with advanced semantic knowledge base can provide recommendations of appropriate foods before consumption by individuals. The proposed FoodWiki system is using a concept based search mechanism that performs on thousands food compounds to provide more relevant information.
Clomiphene Stair-Step Protocol for Women With Polycystic Ovary Syndrome.
Jones, Tiffanny; Ho, Jacqueline R; Gualtieri, Marc; Bruno-Gaston, Janet; Chung, Karine; Paulson, Richard J; Bendikson, Kristin A
2018-01-01
To compare time to ovulation, ovulation rates, and side effect profile of traditional and the stair-step protocol for ovulation induction using clomiphene citrate in women with polycystic ovary syndrome (PCOS). We performed a retrospective study of women seeking care for infertility with a diagnosis of PCOS at a university-based infertility clinic from July 2012 to July 2014. We included patients who were resistant to the initial starting dose of 50 mg clomiphene. The primary outcome was time to ovulation. Secondary outcomes included ovulation rates, clinical pregnancy rates, and mild and moderate-to-severe side effects based on dose. For the traditional protocol, higher doses of clomiphene were used each subsequent month if no ovulation occurred. For the stair-step protocol, higher doses of clomiphene were given 7 days after the last dose if no dominant follicles were seen on ultrasonography. Our study had 80% power to detect a 20% difference in ovulation. One hundred nine patients were included in the analysis with 66 (60.6%) in the traditional and 43 (39.4%) in the stair-step protocol. Age and body mass index were similar between groups. The time to ovulation was decreased in the stair-step protocol group compared with the traditional protocol group (23.1±0.9 days vs 47.5±6.3 days). Ovulation rates were increased in the stair-step group compared with the traditional group at 150 mg (16 [37%] vs 8 [12%], P=.004) and at 200 mg (9 [21%] vs 3 [5%], P=.01). Pregnancy rates were similar between groups once ovulation was achieved (12 [18.1%] vs 7 [16.3%], P=.08). The stair-step protocol had an increased incidence of mild side effects (vasomotor flushes, headaches, gastrointestinal disturbance, mastalgia, changes in mood; 18 [41%] vs 8 [12%]), but there was no difference in the incidence of severe side effects (headaches, visual disturbances). For women with PCOS, the stair-step clomiphene protocol is associated with decreased time to ovulation and increased ovulation rates at higher doses when compared with the traditional protocol.
Navier-Stokes Computations of a Wing-Flap Model With Blowing Normal to the Flap Surface
NASA Technical Reports Server (NTRS)
Boyd, D. Douglas, Jr.
2005-01-01
A computational study of a generic wing with a half span flap shows the mean flow effects of several blown flap configurations. The effort compares and contrasts the thin-layer, Reynolds averaged, Navier-Stokes solutions of a baseline wing-flap configuration with configurations that have blowing normal to the flap surface through small slits near the flap side edge. Vorticity contours reveal a dual vortex structure at the flap side edge for all cases. The dual vortex merges into a single vortex at approximately the mid-flap chord location. Upper surface blowing reduces the strength of the merged vortex and moves the vortex away from the upper edge. Lower surface blowing thickens the lower shear layer and weakens the merged vortex, but not as much as upper surface blowing. Side surface blowing forces the lower surface vortex farther outboard of the flap edge by effectively increasing the aerodynamic span of the flap. It is seen that there is no global aerodynamic penalty or benefit from the particular blowing configurations examined.
Reirradiation of recurrent canine nasal tumors.
Bommarito, David A; Kent, Michael S; Selting, Kim A; Henry, Carolyn J; Lattimer, Jimmy C
2011-01-01
Canine nasal tumors are typically treated with radiation therapy but most patients develop local recurrence. Our purpose was to evaluate tumor and normal tissue response to reirradiation in nine dogs. The median dose delivered with the first protocol was 50 Gy (range 44-55 Gy) and the median fraction number was 18 (range 15-20). For the second protocol, the median dose was lower intentionally, median of 36 Gy (range 23-44 Gy), without changing the median fraction number of 18 (range 14-20) to avoid late effects. The median time between protocols was 539 days (range 258-1652 days). Median survival was 927 days (95% confidence interval [CI] 423-1767 days). Median time to progression following the first and second courses was 513 days (95% CI 234-1180 days) and 282 days (95% CI 130-453 days), respectively. These were not significantly different (P=0.086). The qualitative response assessment was better for the first course compared with the second (P=0.018). Severity and timing of skin, mucous membrane, and ocular effects were similar for early side effects between the two courses (P>0.05 for all comparisons). All dogs experienced some late side effects, with two out of nine being classified as severe. These severe effects were blindness in each dog, possibly related to tumor recurrence. Reirradiation of canine nasal tumors resulted in a second clinical remission in eight of nine dogs, although the second response was less complete. Acute and late effects for seven of nine patients were not life threatening, indicating that reirradiation of canine nasal tumors may be a viable treatment option after recurrence. © 2010 Veterinary Radiology & Ultrasound.
Heidarifar, Reza; Mehran, Nahid; Heidari, Akram; Tehran, Hoda Ahmari; Koohbor, Mohammad; Mansourabad, Mostafa Kazemian
2014-01-01
Background: Dysmenorrhea has negative effects on women's life. Due to side-effects of chemical drugs, there is growing trend toward herbal medicine. The aim of this study was to assess the effect of Dill compared to mefenamic acid on primary dysmenorrhea. Materials and Methods: This double-blind, randomized, clinical trial study was conducted on 75 single female students between 18 and 28 years old educating in Nursing and Midwifery School and Paramedical Faculty of Qom University of Medical Sciences of Iran in 2011. They were allocated randomly into one of the three groups: In Dill group, they took 1000 mg of Dill powder q12h for 5 days from 2 days before the beginning of menstruation for two cycles. Other groups received 250 mg mefenamic acid or 500 mg starch capsule as placebo, respectively. Dysmenorrhea severity was determined by a verbal multidimensional scoring system and a visual analog scale (VAS). Students with mild dysmenorrhea were excluded. Data were analyzed by SPSS using the descriptive statistic, paired-samples t-test, Wilcoxon signed-rank test, Mann-Whitney test, and Kruskal-Wallis test. Results: There were no significant differences between three groups for demographic or descriptive variables. Comprising the VAS showed that the participants of Dill and mefenamic acid groups had lower significant pain in the 1st and the 2nd months after treatment, whereas in the placebo group this was only significant in the 2nd month (P < 0.05). Conclusion: Dill was as effective as mefenamic acid in reducing the pain severity in primary dysmenorrhea. Further studies regarding side-effects of Dill and its interactivity are recommended. PMID:25097605
2D trajectory estimation during free walking using a tiptoe-mounted inertial sensor.
Sagawa, Koichi; Ohkubo, Kensuke
2015-07-16
An estimation method for a two-dimensional walking trajectory during free walking, such as forward walking, side stepping and backward walking, was investigated using a tiptoe-mounted inertial sensor. The horizontal trajectory of the toe-tip is obtained by double integration of toe-tip acceleration during the moving phase in which the sensor is rotated before foot-off or after foot-contact, in addition to the swing phase. Special functions that determine the optimum moving phase as the integral duration in every one step are developed statistically using the gait cycle and the resultant angular velocity of dorsi/planter flexion, pronation/supination and inversion/eversion so that the difference between the estimated trajectory and actual one gives a minimum value during free walking with several cadences. To develop the functions, twenty healthy volunteers participated in free walking experiments in which subjects performed forward walking, side stepping to the right, side stepping to the left, and backward walking at 39 m down a straight corridor with several predetermined cadences. To confirm the effect of the developed functions, five healthy subjects participated in the free walking experiment in which each subject performed free walking with different velocities of normal, fast, and slow based on their own assessment in a square course with 7 m side. The experimentally obtained results of free walking with a combination of forward walking, backward walking, and side stepping indicate that the proposed method produces walking trajectory with high precision compared with the constant threshold method which determines swing phase using the size of the angular velocity. Copyright © 2015 Elsevier Ltd. All rights reserved.
Schmidhammer, Helmut; Spetea, Mariana
2012-01-01
One of the most important functions of the opioid system is the control of pain. Among the three main opioid receptor classes (μ, δ, κ), the μ (MOR) is the main type targeted for pharmacotherapy of pain. Opioid analgesics such as morphine, oxycodone and fentanyl are agonists at the MOR and are the mainstay for the treatment of moderate-to-severe pain. However, adverse effects related to opioid use are severe and often lead to early discontinuation and inadequate analgesia. The development of more effective and safer medications for the management of pain still remains a major direction in pharmaceutical research. Chemical approaches towards the identification of novel MOR analgesics with reduced side effects include structural modifications of 14-alkoxy-N-methylmorphinan-6-ones in key positions that are important for binding, selectivity, potency, and efficacy at opioid receptors. This paper describes a representative strategy to improve the therapeutic usefulness of opioid analgesics from the morphinan class of drugs by targeting position 5. The focus is on chemical and biological studies and structure-activity relationships of this series of ligands. We report on 14-alkoxymorphinan-6-ones having a methyl and benzyl group at position 5 as strong opioid antinociceptive agents with reduced propensity to cause undesired effects compared to morphine although interacting selectively with MORs.
On one-sided filters for spectral Fourier approximations of discontinuous functions
NASA Technical Reports Server (NTRS)
Wei, Cai; Gottlieb, David; Shu, Chi-Wang
1991-01-01
The existence of one-sided filters, for spectral Fourier approximations of discontinuous functions, which can recover spectral accuracy up to discontinuity from one side, was proved. A least square procedure was also used to construct such a filter and test it on several discontinuous functions numerically.
Coimpairments: strength and balance as predictors of severe walking disability.
Rantanen, T; Guralnik, J M; Ferrucci, L; Leveille, S; Fried, L P
1999-04-01
Little information is available on the joint effects of multiple impairments (coimpairments) on the risk of disability. Our aim was to study the joint effects of strength and balance impairments on severe walking disability. The data are from the baseline of the Women's Health and Aging Study (WHAS), a study of moderately to severely disabled women. A total of 1,002 women aged 65 and older participated in the tests, which took place in their homes. Severe walking disability was defined as self-reported inability to walk one-quarter mile and customary walking speed in a 4-meter test of < or =0.4 m/s. Balance was measured as an ability to hold progressively more difficult stands (feet side-by-side, semitandem and tandem stands). Maximal knee extension strength was measured using a hand-held dynamometer. There were 129 women who were severely walking disabled but able to walk at least minimally. In logistic regression analysis, balance and knee extension strength were independent predictors of severe walking disability. To study the combined effects, nine groups were formed on the basis of strength tertiles by balance categories in the entire population. In the best balance category, the crude prevalences of severe walking disability were 1.2%, 4.9%, and 14.3% in the highest to lowest strength tertiles. In the middle balance category, the rates were 2.9%, 10.0%, and 45.4.1%, and in the poorest balance category 4.9%, 22.1%, and 42.6%, correspondingly. The age, body weight, and height-adjusted odds ratios (OR) showed that the risk of severe walking disability in the subgroup with best balance and strength was less than 5% of the risk in the subgroup with poorest balance and strength (OR .034, 95% confidence interval [CI] .007-.166). Correspondingly, in the subgroups with poorest strength and best balance (OR .097, 95% CI .025-.38) or poorest balance and best strength (OR .102, 95% CI .012-.866) the risk was about 10%. The age-specific estimates of prevalence of severe walking disability in women were: 2.0% for ages 65-74 years, 3.4% for ages 75-84 years, and 9.1% for ages 85 years and older. The burden of coimpairments seems to be greater than the sum of single impairments involved. An effective way to reduce severe disabilities could be prevention of coimpairments.
Megestrol acetate in cachexia and anorexia
Yeh, Shing-shing; Schuster, Michael W
2006-01-01
The aim is to review major clinical trials that have used megestrol acetate (MA) in the treatment of cachexia across several disease states. A review of general usage and potential side-effects are discussed. A theory that the newly approved nanocrystal formation of MA can better deliver this potent medication for treatment will also be reviewed. PMID:17722275
Perspective-Taking Judgments Among Young Adults, Middle-Aged, and Elderly People
ERIC Educational Resources Information Center
Ligneau-Herve, Catherine; Mullet, Etienne
2005-01-01
Perspective-taking judgments among young adults, middle-aged, and elderly people were examined. In 1 condition, participants were instructed to judge the likelihood of acceptance of a painkiller as a function of 3 cues: severity of the condition, potential side effects, and level of trust in the health care provider. In the other condition,…
The Elimination of a Self-Injurious Avoidance Response through a Forced Running Consequence.
ERIC Educational Resources Information Center
Borreson, Paul M.
1980-01-01
The self-injurious avoidance responses of a 22-year-old severely mentally retarded male were eliminated through a forced running consequence. Side effects, such as reduced noise, increase in smiling, and faster progress toward instructional objectives, were also noted. The results were maintained over a period of two years. (Author/PHR)
McLean, Estelle; Ddaaki, William; Odongo, Fred; Bukenya, Dominic; Wamoyi, Joyce; Bonnington, Oliver; Seeley, Janet; Zaba, Basia; Wringe, Alison
2017-01-01
Objectives To explore the bodily and relational experience of taking antiretroviral therapy (ART) and the subsequent effect on retention in HIV care in six sub-Saharan African countries. Methods In-depth interviews were conducted with 130 people living with HIV (PLHIV) who had initiated ART, 38 PLHIV who were lost to follow-up and 53 healthcare workers (HCWs) in Kenya, Uganda, Tanzania, Malawi, Zimbabwe and South Africa. PLHIV were purposely selected to include a range of HIV treatment histories. Deductive and inductive analysis was guided by aspects of practice theory; retention in HIV care following ART initiation was the practice of interest. Results PLHIV who were engaged in HIV care took ART every day, attended clinic appointments and ate as well as possible. For PLHIV, biomedical markers acted as reassurance for their positive treatment progression. However, many described ART side effects ranging from dizziness to conditions severe enough to prevent them from leaving home or caring for themselves or others. In all settings, the primary concern of HCW was ensuring patients achieved viral suppression, with management of side effects seen as a lower priority. Where PLHIV tolerated side effects, they were deemed the lesser of two evils compared with their pre-ART illnesses. Participants who reported feeling well prior to starting ART were often less able to tolerate side effects, and in many cases these events triggered their disengagement from HIV care. Conclusions Retention in ART care is rarely an outcome of rational decision-making, but the consequence of bodily and relational experiences. Initiatives to improve retention should consider how bodily experiences of PLHIV relate to the rest of their lives and how this can be respected and supported by service providers to subsequently improve retention in care. PMID:28736390
NASA Astrophysics Data System (ADS)
Mutrikah, N.; Winarno, H.; Amalia, T.; Djakaria, M.
2017-08-01
The objective of this study was to compare conventional and conformal techniques of external beam radiotherapy (EBRT) in terms of the dose distribution, tumor response, and side effects in the treatment of locally advanced cervical cancer patients. A retrospective cohort study was conducted on cervical cancer patients who underwent EBRT before brachytherapy in the Radiotherapy Department of Cipto Mangunkusumo Hospital. The prescribed dose distribution, tumor response, and acute side effects of EBRT using conventional and conformal techniques were investigated. In total, 51 patients who underwent EBRT using conventional techniques (25 cases using Cobalt-60 and 26 cases using a linear accelerator (LINAC)) and 29 patients who underwent EBRT using conformal techniques were included in the study. The distribution of the prescribed dose in the target had an impact on the patient’s final response to EBRT. The complete response rate of patients to conformal techniques was significantly greater (58%) than that of patients to conventional techniques (42%). No severe acute local side effects were seen in any of the patients (Radiation Therapy Oncology Group (RTOG) grades 3-4). The distribution of the dose and volume to the gastrointestinal tract affected the proportion of mild acute side effects (RTOG grades 1-2). The urinary bladder was significantly greater using conventional techniques (Cobalt-60/LINAC) than using conformal techniques at 72% and 78% compared to 28% and 22%, respectively. The use of conformal techniques in pelvic radiation therapy is suggested in radiotherapy centers with CT simulators and 3D Radiotherapy Treatment Planning Systems (RTPSs) to decrease some uncertainties in radiotherapy planning. The use of AP/PA pelvic radiation techniques with Cobalt-60 should be limited in body thicknesses equal to or less than 18 cm. When using conformal techniques, delineation should be applied in the small bowel, as it is considered a critical organ according to RTOG consensus guidelines.
Estimating preferences for treatments in patients with localized prostate cancer.
Ávila, Mónica; Becerra, Virginia; Guedea, Ferran; Suárez, José Francisco; Fernandez, Pablo; Macías, Víctor; Mariño, Alfonso; Hervás, Asunción; Herruzo, Ismael; Ortiz, María José; Ponce de León, Javier; Sancho, Gemma; Cunillera, Oriol; Pardo, Yolanda; Cots, Francesc; Ferrer, Montse
2015-02-01
Studies of patients' preferences for localized prostate cancer treatments have assessed radical prostatectomy and external radiation therapy, but none of them has evaluated brachytherapy. The aim of our study was to assess the preferences and willingness to pay of patients with localized prostate cancer who had been treated with radical prostatectomy, external radiation therapy, or brachytherapy, and their related urinary, sexual, and bowel side effects. This was an observational, prospective cohort study with follow-up until 5 years after treatment. A total of 704 patients with low or intermediate risk localized prostate cancer were consecutively recruited from 2003 to 2005. The estimation of preferences was conducted using time trade-off, standard gamble, and willingness-to-pay methods. Side effects were measured with the Expanded Prostate Index Composite (EPIC), a prostate cancer-specific questionnaire. Tobit models were constructed to assess the impact of treatment and side effects on patients' preferences. Propensity score was applied to adjust for treatment selection bias. Of the 580 patients reporting preferences, 165 were treated with radical prostatectomy, 152 with external radiation therapy, and 263 with brachytherapy. Both time trade-off and standard gamble results indicated that the preferences of patients treated with brachytherapy were 0.06 utilities higher than those treated with radical prostatectomy (P=.01). Similarly, willingness-to-pay responses showed a difference of €57/month (P=.004) between these 2 treatments. Severe urinary incontinence presented an independent impact on the preferences elicited (P<.05), whereas no significant differences were found by bowel and sexual side effects. Our findings indicate that urinary incontinence is the side effect with the highest impact on preferences and that brachytherapy and external radiation therapy are more valued than radical prostatectomy. These time trade-off and standard gamble preference assessments as well as the willingness-to-pay estimation could be useful to perform respectively cost-utility or cost-benefit analyses, which can guide health policy decisions. Copyright © 2015 Elsevier Inc. All rights reserved.
Estimating Preferences for Treatments in Patients With Localized Prostate Cancer
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ávila, Mónica; CIBER en Epidemiología y Salud Pública; Universitat Pompeu Fabra, Barcelona
Purpose: Studies of patients' preferences for localized prostate cancer treatments have assessed radical prostatectomy and external radiation therapy, but none of them has evaluated brachytherapy. The aim of our study was to assess the preferences and willingness to pay of patients with localized prostate cancer who had been treated with radical prostatectomy, external radiation therapy, or brachytherapy, and their related urinary, sexual, and bowel side effects. Methods and Materials: This was an observational, prospective cohort study with follow-up until 5 years after treatment. A total of 704 patients with low or intermediate risk localized prostate cancer were consecutively recruited from 2003more » to 2005. The estimation of preferences was conducted using time trade-off, standard gamble, and willingness-to-pay methods. Side effects were measured with the Expanded Prostate Index Composite (EPIC), a prostate cancer-specific questionnaire. Tobit models were constructed to assess the impact of treatment and side effects on patients' preferences. Propensity score was applied to adjust for treatment selection bias. Results: Of the 580 patients reporting preferences, 165 were treated with radical prostatectomy, 152 with external radiation therapy, and 263 with brachytherapy. Both time trade-off and standard gamble results indicated that the preferences of patients treated with brachytherapy were 0.06 utilities higher than those treated with radical prostatectomy (P=.01). Similarly, willingness-to-pay responses showed a difference of €57/month (P=.004) between these 2 treatments. Severe urinary incontinence presented an independent impact on the preferences elicited (P<.05), whereas no significant differences were found by bowel and sexual side effects. Conclusions: Our findings indicate that urinary incontinence is the side effect with the highest impact on preferences and that brachytherapy and external radiation therapy are more valued than radical prostatectomy. These time trade-off and standard gamble preference assessments as well as the willingness-to-pay estimation could be useful to perform respectively cost-utility or cost-benefit analyses, which can guide health policy decisions.« less
Safety and efficacy of fixed-dose 10 mg daily isotretinoin treatment for acne vulgaris in Malaysia.
Yap, Felix Boon-Bin
2017-09-01
Low-dose isotretinoin is used to reduce side effects albeit higher relapse. This study aimed to determine the efficacy and safety of fixed-dose 10 mg daily isotretinoin for the treatment of acne. This prospective study was performed between 2011 and 2015. All 150 patients were given 10 mg daily isotretinoin until a cumulative dose of 90-110 mg/kg. The mean age was 26.6 years with 64.7% moderate acne, 29.3% severe, and 6% very severe. The mean cumulative dose was 98.8 ± 6.05 mg/kg. All 150 patients had total clearance with a mean time to clearance of 24.0 weeks. Patients with severe/very severe acne had higher cumulative dosage (102.1 vs. 97.0, P < 0.001) and longer duration to clearance (32.9 weeks vs. 19.1 weeks, P < 0.001). Mild relapse was seen in 4%. The mean time to relapse was 32.3 weeks. Lip dryness was the commonest side effects (100%). Mild transient elevation of liver enzymes was detected in 3.3% and a slight increase of serum lipid in 2.7% with no treatment discontinuation. Fixed-dose 10 mg daily treatment with isotretinoin until a cumulative dose of 90-110 mg/kg is safe with low relapse rate. © 2016 Wiley Periodicals, Inc.
Sutters, Kimberly A; Holdridge-Zeuner, Danielle; Waite, Steven; Paul, Steven M; Savedra, Marilyn C; Lanier, Brent; Mahoney, Karla; Miaskowski, Christine
2012-03-01
The purpose of this study, in a sample of preschool children (ages 3-5 years; N = 47), was to evaluate the feasibility of scheduled analgesic dosing following outpatient tonsillectomy in order to optimize pain management. Parents were instructed to give their child acetaminophen with hydrocodone (167 mg/5 mL) every 4 hours around the clock for the first 3 days following surgery. Parents recorded ratings of their child's pain with/without swallowing using the Faces, Legs, Activity, Cry, and Consolability (FLACC) behavioral pain scale, pain relief ratings, and severity of analgesic side effects in a home diary. Audiotaped interviews were conducted with parents to document descriptions of their experiences in managing their child's pain at home. Mean FLACC scores with/without swallowing were less than two at each measurement time and pain relief scores increased over time. Total analgesic dose decreased, and the number of missed doses increased over the first 3 days after surgery. Moderate-to-severe daytime sedation, nausea, vomiting, and constipation were reported by parents. Study results suggest that acetaminophen with hydrocodone is effective in relieving preschool children's pain following tonsillectomy and that parental adherence to a scheduled analgesic regimen decreases over time. Time-contingent dosing was associated with moderate to severe side effects and should be addressed in discharge teaching with parents. Findings provide insight into parents' perspective of pain management at home following tonsillectomy and methods for relieving their child's pain. Wiley Periodicals, Inc.