Predictors of adverse drug reaction-related hospitalisation in Southwest Ethiopia: A prospective cross-sectional study.

PLoS One. 2017;12(10):e0186631

Authors: Angamo MT, Curtain CM, Chalmers L, Yilma D, Bereznicki L

Abstract
BACKGROUND: Adverse drug reactions (ADRs) are important causes of morbidity and mortality in the healthcare system; however, there are no studies reporting on the magnitude and risk factors associated with ADR-related hospitalisation in Ethiopia.
OBJECTIVES: To characterise the reaction types and the drugs implicated in admission to Jimma University Specialized Hospital, Southwest Ethiopia, and to identify risk factors associated with ADR-related hospitalisation.
METHODS: A prospective cross-sectional study was conducted from May 2015 to August 2016 among consenting patients aged ≥18 years consecutively admitted to medical wards taking at least one medication prior to admission. ADR-related hospitalisations were determined through expert review of medical records, laboratory tests, patient interviews and physical observation. ADR causality was assessed by the Naranjo algorithm followed by consensus review with internal medicine specialist. ADR preventability was assessed using Schumock and Thornton's criteria. Only definite and probable ADRs that provoked hospitalisation were considered. Binary logistic regression was used to identify independent predictors of ADR-related hospitalisation.
RESULTS: Of 1,001 patients, 103 (10.3%) had ADR-related admissions. Common ADRs responsible for hospitalisation were hepatotoxicity (35, 29.4%) and acute kidney injury (27, 22.7%). The drug classes most frequently implicated were antitubercular agents (45, 25.0%) followed by antivirals (22, 12.2%) and diuretics (19, 10.6%). Independent predictors of ADR-related hospitalisation were body mass index (BMI) <18.5 kg/m2 (adjusted odd ratio [AOR] = 1.69; 95% confidence interval [CI] = 1.10-2.62; p = 0.047), pre-existing renal disease (AOR = 2.84; 95%CI = 1.38-5.85, p = 0.004), pre-existing liver disease (AOR = 2.61; 95%CI = 1.38-4.96; p = 0.003), number of comorbidities ≥4 (AOR = 2.09; 95%CI = 1.27-3.44; p = 0.004), number of drugs ≥6 (AOR = 2.02; 95%CI = 1.26-3.25; p = 0.004) and history of previous ADRs (AOR = 24.27; 95%CI = 11.29-52.17; p<0.001). Most ADRs (106, 89.1%) were preventable.
CONCLUSIONS: ADRs were a common cause of hospitalisation. The majority of ADRs were preventable, highlighting the need for monitoring and review of patients with lower BMI, ADR history, renal and liver diseases, multiple comorbidities and medications. ADR predictors should be integrated into clinical pathways and pharmacovigilance systems.

PMID: 29036230 [PubMed - indexed for MEDLINE]

Off-label use of medicines.

Br Dent J. 2017 04 07;222(7):495-6

Authors: Yeung CA

PMID: 28387299 [PubMed - indexed for MEDLINE]

[Pharmacological and nutritional problems in pregnant patient on chronic dialysis].

G Ital Nefrol. 2017 Jan-Feb;34(1):

Authors: Giannattasio M, Giannattasio F, Gernone G

Abstract
Many of information on the safety of drugs during pregnancy were obtained many years ago, before the pregnant women were excluded from the study protocols for possible fetal risks. Because randomized trials in pregnancy are complex and considered unethical. For the same reasons, there are no randomized controlled trials in pregnant women on dialysis. Moreover Compared to the normal subject, the pharmacokinetics and pharmacodynamics in these patients are influenced or by pregnancy or from dialysis techniques or from chronic uremia. Protein energy wasting PEW- is largely present in dialysis subjects. Nausea and vomiting are present in over 85% of pregnancy and may aggravate PEW. Therefore, it is necessary to adopt specific measures to prevent the PEW as well as periodic inspections of weight gain during pregnancy.

PMID: 28177093 [PubMed - indexed for MEDLINE]

How do researchers determine the difference to be detected in superiority trials? Results of a survey from a panel of researchers.

BMC Med Res Methodol. 2016 Jul 29;16:89

Authors: Gayet-Ageron A, Jannot AS, Agoritsas T, Rudaz S, Combescure C, Perneger T

Abstract
BACKGROUND: There is currently no guidance for selecting a specific difference to be detected in a superiority trial. We explored 3 factors that in our opinion should influence the difference to be detected (type of outcome, patient age group, and presence of treatment side-effects), and 3 that should not (baseline level of risk, logistical difficulties, and cost of treatment).
METHODS: We conducted an experimental survey using a factorial design among 380 corresponding authors of randomized controlled trials indexed in Medline. Two hypothetical vignettes were submitted to participants: one described a trial of a new analgesic in mild trauma injuries, the other described a trial of a new chemotherapy among cancer patients. The first vignette tested the baseline level of risk, patient age-group, patient recruitment difficulties, and treatment side-effects. The second tested the baseline level of risk, patient age-group, type of outcome, and cost of treatment. The respondents were asked to select the smallest gain of effectiveness that should be detected by the trial.
RESULTS: In vignette 1, respondents selected a median difference to be detected corresponding to an improvement of 7.0 % in pain control with the new treatment. In vignette 2, they selected a median difference to be detected corresponding to a reduction of 5.0 % in mortality or cancer recurrence with the new chemotherapy. In both vignettes, the difference to be detected decreased significantly with the baseline risk. The other factor influencing difference to be detected was the age group, but the impact of this factor was smaller. Cost, side-effects, outcome severity, or mention of logistical difficulties did not significantly impact the difference to be detected selected by participants.
CONCLUSIONS: Three of the anticipated effects conformed to our expectations (the effect of patient age, and absence of effect of the cost of treatment and of patient recruitment difficulties) and the other three did not. These findings can guide future research in determining differences to be detected in trials that can translate to meaningful clinical decision-making.

PMID: 27473336 [PubMed - indexed for MEDLINE]

Mortality due to acute adverse drug reactions in Galicia: 1997-2011.

Adicciones. 2016 Mar 02;28(2):80-9

Authors: Miguel-Arias D, Pereiro Gómez C, Bermejo Barrera AM, López de Abajo Rodríguez B, Sobrido Prieto M

Abstract
The aim of this research is to study all people who died in the Autonomous Community of Galicia from acute death after drugconsumption (ADR) in which there was judicial intervention during the period from 1997 to 2011, according to inclusion and exclusión criteria established by the National Drug Plan for the entire national territory. Sociodemographic and clinical characteristics of deceased subjects were studied, in order to identify key risk factors and/or vulnerable populations.A total of 805 deaths were recorded. The distribution by provinces and municipalities corresponds to the areas of greatest population, incidence of consumption and proximity to the coast. The average age of these patients was 34.34 years, with a gradual increase over years. Most of them were male (91.2%) and single (47.7). 43.5% of the deceased habitually used the parenteral route of administration and 36.4% had positive HIV serology. The most frequently-detected substances corresponded to opiates (heroin: 61.3%, methadone: 35.6%), followed by cocaine (53.7%), although the most common pattern was that of poly-consumption. ADR mortality figures remain relatively stable throughout the study period. The predominant pattern is that of males, opiates and a long history of consumption.

PMID: 26990265 [PubMed - indexed for MEDLINE]

A simple Bayesian approach to quantifying confidence level of adverse event incidence proportion in small samples.

J Biopharm Stat. 2016;26(3):499-506

Authors: Liu F

Abstract
In both clinical development and post-marketing of a new therapy or a new treatment, incidence of an adverse event (AE) is always a concern. When sample sizes are small, large sample-based inferential approaches on an AE incidence proportion in a certain time period no longer apply. In this brief discussion, we introduce a simple Bayesian framework to quantify, in small sample studies and the rare AE case, (1) the confidence level that the incidence proportion of a particular AE p is over or below a threshold, (2) the lower or upper bounds on p with a certain level of confidence, and (3) the minimum required number of patients with an AE before we can be certain that p surpasses a specific threshold, or the maximum allowable number of patients with an AE after which we can no longer be certain that p is below a certain threshold, given a certain confidence level. The method is easy to understand and implement; the interpretation of the results is intuitive. This article also demonstrates the usefulness of simple Bayesian concepts when it comes to answering practical questions.

PMID: 26098967 [PubMed - indexed for MEDLINE]

Effect of Novel Allosteric Modulators of Metabotropic Glutamate Receptors on Drug Self-administration and Relapse: A Review of Preclinical Studies and Their Clinical Implications.

Biol Psychiatry. 2017 Sep 05;:

Authors: Caprioli D, Justinova Z, Venniro M, Shaham Y

Abstract
Results from preclinical rodent studies during the last 20 years implicated glutamate neurotransmission in different brain regions in drug self-administration and rodent models of relapse. These results, along with evidence for drug-induced neuroadaptations in glutamatergic neurons and receptors, suggested that addiction might be treatable by medications that inhibit glutamatergic responses to drugs of abuse, drug-associated cues, and stressors. This idea is supported by findings in rodent and primate models that drug self-administration and relapse are reduced by systemic injections of antagonists of ionotropic glutamate receptors or metabotropic glutamate receptors (mGluRs) or orthosteric agonists of mGluR2/3. However, these compounds have not advanced to clinical use because of potential side effects and other factors. This state of affairs has led to the development of positive allosteric modulators (PAMs) and negative allosteric modulators (NAMs) of mGluRs. PAMs and NAMs of mGluRs, either of which can inhibit evoked glutamate release, may be suitable for testing in humans. We reviewed results from recent studies of systemically injected PAMs and NAMs of mGluRs in rodents and monkeys, focusing on whether they reduce drug self-administration, reinstatement of drug seeking, and incubation of drug craving. We also review results from rat studies in which PAMs or NAMs of mGluRs were injected intracranially to reduce drug self-administration and reinstatement. We conclude that PAMs and NAMs of mGluRs should be considered for clinical trials.

PMID: 29102027 [PubMed - as supplied by publisher]

Gender-based personalized pharmacotherapy: a systematic review.

Arch Gynecol Obstet. 2017 Jun;295(6):1305-1317

Authors: Islam MM, Iqbal U, Walther BA, Nguyen PA, Li YJ, Dubey NK, Poly TN, Masud JHB, Atique S, Syed-Abdul S

Abstract
PURPOSE: In general, male and female are prescribed the same amount of dosage even if most of the cases female required less dosage than male. Physicians are often facing problem on appropriate drug dosing, efficient treatment, and drug safety for a female in general. To identify and synthesize evidence about the effectiveness of gender-based therapy; provide the information to patients, providers, and health system intervention to ensure safety treatment; and minimize adverse effects.
METHODS: We performed a systematic review to evaluate the effect of gender difference on pharmacotherapy. Published articles from January 1990 to December 2015 were identified using specific term in MEDLINE (PubMed), EMBASE, and the Cochrane library according to search strategies that strengthen the reporting of observational and clinical studies.
RESULTS: Twenty-six studies fulfilled the inclusion criteria for this systematic review, yielding a total of 6309 subjects. We observed that female generally has a lower the gastric emptying time, gastric PH, lean body mass, and higher plasma volume, BMI, body fat, as well as reduce hepatic clearance, difference in activity of Cytochrome P450 enzyme, and metabolize drugs at different rate compared with male. Other significant factors such as conjugation, protein binding, absorption, and the renal elimination could not be ignored. However, these differences can lead to adverse effects in female especially for the pregnant, post-menopausal, and elderly women.
CONCLUSION: This systematic review provides an evidence for the effectiveness of dosage difference to ensure safety and efficient treatment. Future studies on the current topic are, therefore, recommended to reduce the adverse effect of therapy.

PMID: 28378180 [PubMed - indexed for MEDLINE]

Preventing and Managing Toxicities of High-Dose Methotrexate.

Oncologist. 2016 Dec;21(12):1471-1482

Authors: Howard SC, McCormick J, Pui CH, Buddington RK, Harvey RD

Abstract
: High-dose methotrexate (HDMTX), defined as a dose higher than 500 mg/m(2), is used to treat a range of adult and childhood cancers. Although HDMTX is safely administered to most patients, it can cause significant toxicity, including acute kidney injury (AKI) in 2%-12% of patients. Nephrotoxicity results from crystallization of methotrexate in the renal tubular lumen, leading to tubular toxicity. AKI and other toxicities of high-dose methotrexate can lead to significant morbidity, treatment delays, and diminished renal function. Risk factors for methotrexate-associated toxicity include a history of renal dysfunction, volume depletion, acidic urine, and drug interactions. Renal toxicity leads to impaired methotrexate clearance and prolonged exposure to toxic concentrations, which further worsen renal function and exacerbate nonrenal adverse events, including myelosuppression, mucositis, dermatologic toxicity, and hepatotoxicity. Serum creatinine, urine output, and serum methotrexate concentration are monitored to assess renal clearance, with concurrent hydration, urinary alkalinization, and leucovorin rescue to prevent and mitigate AKI and subsequent toxicity. When delayed methotrexate excretion or AKI occurs despite preventive strategies, increased hydration, high-dose leucovorin, and glucarpidase are usually sufficient to allow renal recovery without the need for dialysis. Prompt recognition and effective treatment of AKI and associated toxicities mitigate further toxicity, facilitate renal recovery, and permit patients to receive other chemotherapy or resume HDMTX therapy when additional courses are indicated.
IMPLICATIONS FOR PRACTICE: High-dose methotrexate (HDMTX), defined as a dose higher than 500 mg/m(2), is used for a range of cancers. Although HDMTX is safely administered to most patients, it can cause significant toxicity, including acute kidney injury (AKI), attributable to crystallization of methotrexate in the renal tubular lumen, leading to tubular toxicity. When AKI occurs despite preventive strategies, increased hydration, high-dose leucovorin, and glucarpidase allow renal recovery without the need for dialysis. This article, based on a review of the current associated literature, provides comprehensive recommendations for prevention of toxicity and, when necessary, detailed treatment guidance to mitigate AKI and subsequent toxicity.

PMID: 27496039 [PubMed - indexed for MEDLINE]

Efficacy and safety of grazoprevir + ribavirin for 12 or 24 weeks in treatment-naïve patients with hepatitis C virus genotype 1 infection.

J Viral Hepat. 2016 Oct;23(10):789-97

Authors: Gane E, Ben Ari Z, Mollison L, Zuckerman E, Bruck R, Baruch Y, Howe AY, Wahl J, Bhanja S, Hwang P, Zhao Y, Robertson MN

Abstract
Grazoprevir (GZR) is a second-generation hepatitis C virus NS3/4A protease inhibitor. The aim of this study was to evaluate GZR plus ribavirin (RBV) in patients with HCV GT1 infection. Noncirrhotic, IL28B CC patients with HCV genotype 1 infection were randomized to GZR 100 mg once daily and RBV for 12 or 24 weeks. Patients in the 12-week arm with detectable HCV RNA at treatment week 4 (TW4) had treatment extended to 24 weeks (response-guided therapy, RGT). The primary endpoint was sustained virologic response (SVR12) at follow-up week 12 (HCV RNA <25 IU/mL) in the per-protocol (PP) population (excluding patients with important protocol deviations). Twenty-six patients were randomized and 22 were included in the PP population. SVR12 was 58.3% (7 of 12) and 90% (9 of 10) in the RGT and 24-week arms, respectively. Seven PP patients had virologic failure, including one patient in the 24-week arm who relapsed after follow-up week 12. All three breakthrough patients had wild-type (WT) virus at baseline and developed breakthrough at TW6 or TW12 with Y56H, A156T and D168A/N mutations. Of the five relapse patients, four had WT at baseline (at relapse three had WT and one had V55A and D168A), and one had S122A/T at baseline and S122T at relapse. There were no serious adverse events (AEs), discontinuations due to AEs or grade 3/4 elevations in total and/or direct bilirubin. Grazoprevir plus RBV was associated with a rapid and sustained suppression of HCV RNA. These results support further evaluation of grazoprevir-based regimens (NCT01716156; protocol P039).

PMID: 27291249 [PubMed - indexed for MEDLINE]

Phase I trial of bortezomib daily dose: safety, pharmacokinetic profile, biological effects and early clinical evaluation in patients with advanced solid tumors.

Invest New Drugs. 2017 Nov 02;:

Authors: Bahleda R, Le Deley MC, Bernard A, Chaturvedi S, Hanley M, Poterie A, Gazzah A, Varga A, Touat M, Deutsch E, Massard C, Van De Velde H, Hollebecque A, Sallansonnet-Froment M, Ricard D, Taillia H, Angevin E, Ribrag V, Soria JC

Abstract
Purpose This phase I study investigated bortezomib in solid tumors used as a daily subcutaneous regimen. Previous regimens showed only modest activity in solid tumors which was potentially related to sub-optimal tumor penetration. We aimed at exploring if daily low dose administration of bortezomib may allow a greater and tolerable pharmacokinetic exposure which might be required for antitumor activity in solid tumors. Patients and methods This 3 + 3 design, dose escalation, monocentric study aimed at defining the maximum tolerated dose of daily low dose schedule of bortezomib. Tolerability, pharmacokinetics, pharmacodynamics, antitumor activity, biomarkers for proteasome inhibition, pre- and post-treatment tumor biopsies were also evaluated. Results A total of eighteen patients were dosed in 3 bortezomib cohorts (0.5, 0.6 and 0.7 mg/m2), with 3, 11 and 4 patients respectively. Three patients experienced dose-limiting toxicities: Grade (G) 3 Sweet's syndrome (at 0.6 mg/m2), G3 asthenia and anorexia or ataxia (2 patients at 0.7 mg/m2). The most common study drug-related adverse events (all grades) were thrombocytopenia (72%), fatigue (56%), neuropathy (50%), anorexia (44%) and rash (39%). Dose 0.6 mg/m2 of bortezomib was considered as the recommended phase II dose. A significant tumor shrinkage (-36% according to WHO criteria) was observed in one patient with heavily pre-treated GIST, and 2 minor responses (-20%) were recorded in two patients with melanoma and mesothelioma. Conclusion This daily subcutaneous regimen of bortezomib showed a dose dependent plasma exposure, evidence of target inhibition and preliminary signs of clinical activity. However, cumulative neurological toxicity of this dose-dense daily regimen might preclude its further clinical development.

PMID: 29094232 [PubMed - as supplied by publisher]

[Side effects of psychotropic medication: Suggestions for clinical practice].

Dtsch Med Wochenschr. 2017 Nov;142(22):1690-1700

Authors: Grunze A, Mago R, Grunze H

Abstract
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.

PMID: 29078215 [PubMed - indexed for MEDLINE]

Pigmentary changes in patients treated with targeted anticancer agents: A systematic review and meta-analysis.

J Am Acad Dermatol. 2017 Nov;77(5):902-910.e2

Authors: Dai J, Belum VR, Wu S, Sibaud V, Lacouture ME

Abstract
BACKGROUND: The discovery of signaling networks that drive oncogenic processes has led to the development of targeted anticancer agents. The burden of pigmentary adverse events from these drugs is unknown.
OBJECTIVE: To conduct a systematic review and meta-analysis of published clinical trials and determine the incidence and risk of development of targeted therapy-induced pigmentary changes.
METHODS: A comprehensive search was conducted to identify studies reporting targeted therapy-induced pigmentary changes. The incidence and relative risk were calculated. Case reports and series were reviewed to understand clinical characteristics.
RESULTS: A total of 8052 patients from 36 clinical trials were included. The calculated overall incidences of targeted cancer therapy-induced all-grade pigmentary changes in the skin and hair were 17.7% (95% confidence interval [CI], 11.9-25.4) and 21.5% (95% CI, 14.9-30.1), respectively. The relative risk of all-grade pigmentary changes of skin and hair were 93.7 (95% CI, 5.86-1497.164) and 20.1 (95% CI, 8.35-48.248). Across 53 case reports/series (N = 75 patients), epidermal growth factor receptor and breakpoint cluster region-abelson inhibitors were the most common offending agents.
LIMITATIONS: Potential under-reporting and variability in oncologists reporting these events.
CONCLUSION: There is a significant risk of development of pigmentary changes during treatment with targeted anticancer therapies. Appropriate counseling and management are critical to minimize psychosocial impairment and deterioration in quality of life.

PMID: 28918974 [PubMed - indexed for MEDLINE]

Serious infections among a large cohort of subjects with systemically treated psoriasis.

J Am Acad Dermatol. 2017 Nov;77(5):838-844

Authors: Dobry AS, Quesenberry CP, Ray GT, Geier JL, Asgari MM

Abstract
BACKGROUND: Biologic therapy is effective for treatment of moderate-to-severe psoriasis but may be associated with an increased risk for serious infection.
OBJECTIVE: To estimate the serious infection rate among patients with psoriasis treated with biologic as compared with nonbiologic systemic agents within a community-based health care delivery setting.
METHODS: We identified 5889 adult Kaiser Permanente Northern California health plan members with psoriasis who had ever been treated with systemic therapies and calculated the incidence rates and 95% confidence intervals (CIs) for serious infections over 29,717 person-years of follow-up. Adjusted hazard ratios (aHRs) were calculated using Cox regression.
RESULTS: Adjusting for age, sex, race or ethnicity, and comorbidities revealed a significantly increased risk for overall serious infection among patients treated with biologics as compared with those treated with nonbiologics (aHR, 1.31; 95% CI, 1.02-1.68). More specifically, there was a significantly elevated risk for skin and soft tissue infection (aHR, 1.75; 95% CI, 1.19-2.56) and meningitis (aHR, 9.22; 95% CI, 1.77-48.10) during periods of active biologic use.
LIMITATIONS: Risk associated with individual drugs was not examined.
CONCLUSION: We found an increased rate of skin and soft tissue infections among patients with psoriasis treated with biologic agents. There also was a signal suggesting increased risk for meningitis. Clinicians should be aware of these potential adverse events when prescribing biologic agents.

PMID: 28917384 [PubMed - indexed for MEDLINE]

Beyond anxiety and agitation: A clinical approach to akathisia.

Aust Fam Physician. 2017;46(5):296-298

Authors: Tachere RO, Modirrousta M

Abstract
BACKGROUND: When patients suddenly become restless and are unable to sit or stand still, especially in general medical settings, anxiety is often the topmost differential on every clinician's mind. However, the possibility of the very subjectively distressing condition called 'akathisia' should always be considered.
OBJECTIVE: The aim of this article is to discuss a clinical approach to the management of akathisia, drawing on the presentation of a patient who was admitted to a general medical ward.
DISCUSSION: Akathisia, a subjective and very distressing feeling of restlessness, has been found to be caused by a wide range of medications used in general medical settings, such as azithromycin, antiemetics and antipsychotics. Despite its high incidence and association with an increase in suicidal thoughts, it often goes unrecognised. This paper highlights the need for its early recognition, provides a diagnostic guide and an approach to its management.

PMID: 28472575 [PubMed - indexed for MEDLINE]

Current Evidence on Safety and Practical Considerations for Administration of Sublingual Allergen Immunotherapy (SLIT) in the United States.

J Allergy Clin Immunol Pract. 2017 Jan - Feb;5(1):34-40.e2

Authors: Epstein TG, Calabria C, Cox LS, Dreborg S

Abstract
Liquid sublingual allergen immunotherapy (SLIT) has been used off-label for decades, and Food and Drug Administration (FDA)-approved grass and ragweed SLIT tablets have been available in the United States since 2014. Potentially life-threatening events from SLIT do occur, although they appear to be very rare, especially for FDA-approved products. Practice guidelines that incorporate safety precautions regarding the use of SLIT in the United States are needed. This clinical commentary attempts to address unresolved issues including controversy regarding the FDA mandate for the prescription of epinephrine autoinjectors for patients on SLIT; how to approach polysensitized patients; optimal timing and duration of SLIT administration; how to address gaps in therapy; whether antihistamines can prevent local reactions, if certain patient populations (such as persistent asthmatics) should not receive SLIT; and when to instruct patients to self-administer epinephrine. Key points are that physicians should focus on educating patients regarding: (1) when not to administer SLIT; (2) how to recognize a potentially serious allergic reaction to SLIT; and (3) when to administer epinephrine and seek emergency care.

PMID: 27815065 [PubMed - indexed for MEDLINE]

Local Side Effects of Sublingual and Oral Immunotherapy.

J Allergy Clin Immunol Pract. 2017 Jan - Feb;5(1):13-21

Authors: Passalacqua G, Nowak-Węgrzyn A, Canonica GW

Abstract
Sublingual immunotherapy (SLIT) is increasingly used worldwide, and several products have been recently registered as drugs for respiratory allergy by the European Medicine Agency and the Food and Drug Administration. Concerning inhalant allergens, the safety of SLIT is overall superior to that of subcutaneous immunotherapy in terms of systemic adverse events. No fatality has been ever reported, and episodes of anaphylaxis were described only exceptionally. Looking at the historical and recent trials, most (>90%) adverse events are "local" and confined to the site of administration. For this reason, a specific grading system has been developed by the World Allergy Organization to classify and describe local adverse events. There is an increasing amount of literature concerning oral desensitization for food allergens, referred to as oral immunotherapy. Also, in this case, local side effects are predominant, although systemic adverse events are more frequent than with inhalant allergens. We review herein the description of local side effects due to SLIT, with a special focus on large trials having a declared sample size calculation. The use of the Medical Dictionary for Regulatory Activities nomenclature for adverse events is mentioned in this context, as recommended by regulatory agencies. It is expected that a uniform classification/grading of local adverse events will improve and harmonize the surveillance and reporting on the safety of SLIT.

PMID: 27527548 [PubMed - indexed for MEDLINE]

Serious Adverse Events Reports: Analysis and Outcome of Review by an Institutional Ethics Committee of a Tertiary Care Hospital in Mumbai, India.

J Empir Res Hum Res Ethics. 2016 Jul;11(3):267-73

Authors: Tripathi RK, Marathe PA, Kapse SV, Shetty YC, Kamat SK, Thatte UM

Abstract
The Indian regulations for clinical trials were amended in January 2013 regarding reporting time lines, relatedness, and compensation for Serious Adverse Events (SAEs). Our study assessed the extent of regulatory compliance in reporting SAEs to the Institutional Ethics Committee (IEC) over 4 years (January 2009-January 2013) before and 18 months after (February 2013-July 2014) the amended regulations. SAE reports were studied retrospectively for reporting time lines, relatedness, compensation, and IEC response before and after the law revision. Before 2013 had 89/160 (55.6%) SAEs reports submitted late while in the after period, only 2/11 reports were delayed (18%). In the before period, 26 SAE reports mentioned "relatedness" of which only 15 (57.6%) stated about compensation. After 2013, all the 9 non-death reports were complete. The IEC took median 17 days to respond before 2013, while after 2013 responded within 5 days. Thus, there was poor compliance in terms of SAE reporting time lines before the revision of the law.

PMID: 27353243 [PubMed - indexed for MEDLINE]

DOUBLE-BLIND, PLACEBO-CONTROLLED, RANDOMIZED TRIAL OF SELENIUM IN GRAVES' HYPERTHYROIDISM.

J Clin Endocrinol Metab. 2017 Sep 19;:

Authors: Kahaly GJ, Riedl M, König J, Diana T, Schomburg L

Abstract
Context: Supplemental Selenium (Se) may impact the clinical course of Graves' disease (GD).
Objective: Evaluate efficacy of add-on Se on medical treatment in GD.
Design: Double-blind, placebo-controlled, randomized, supplementation trial.
Setting: Academic endocrine outpatient clinic.
Patients: Seventy untreated hyperthyroid patients with GD.
Intervention: Additionally to methimazole (MMI), patients received during 24 weeks either sodium selenite 300 µg/day p.o. or placebo. MMI was discontinued at 24 weeks in euthyroid patients.
Main Outcome Measures: Response rate (week 24), recurrence rate (week 36), and safety.
Results: A response was registered in 25 of 31 patients (80%) and in 27 of 33 (82%) at week 24, odds ratio 0.93 (95% CI 0.26-3.25, p=0.904) in the Se (+MMI) and placebo (+MMI) groups, respectively. During a 12-week follow-up, 11 of 23 (48%) and 12 of 27 (44%) relapsed (OR 1.13, 0.29-2.66, p=0.81) in the Se and placebo groups, respectively. Serum concentrations of Se and selenoprotein P were unrelated to response and/or recurrence rates. At week 36, 12 of 29 (41%) and 15 of 33 (45%) were responders and still in remission in the Se and placebo groups, respectively (OR 0.85, 0.31-2.32, p=0.80). Serum levels of fT3/fT4, TSH-R-Ab, prevalence of moderate-to-severe Graves' orbitopathy, thyroid volume and MMI starting dose were significantly lower in responders versus non-responders. 56 and 63 adverse events occurred in the Se and placebo groups, respectively (p=0.164), while only one drug related side-effect (2.9%) was noted in 35 patients on placebo +MMI.
Conclusions: Supplemental Se did not impact response or recurrence rate in GD.

PMID: 29092078 [PubMed - as supplied by publisher]

Movement Disorders in Children and Adolescents Receiving Antipsychotic Pharmacotherapy: A Population-Based Study.

J Child Adolesc Psychopharmacol. 2017 Nov 01;:

Authors: Biscontri RG, Jha S, Collins DM, Bugden S, Katz LY, Alessi-Severini S

Abstract
OBJECTIVES: To describe a cohort of young users of risperidone and quetiapine in the province of Manitoba (Canada) and assess the risk for movement disorders in the two treatments.
METHODS: This was a population-based study conducted on all residents of the province of 19 years of age and younger who received prescriptions for risperidone or quetiapine between April 1, 1996, and March 31, 2011. Incident rates of antipsychotic use were reported. The risk for movement disorders in patients treated with quetiapine compared with those treated with risperidone was assessed by time-to-event analysis using Cox proportional hazards models.
RESULTS: Between April 1, 1996, and March 31, 2011, 23,888 youth (age ≤19 years) were prescribed an antipsychotic agent. Among them, 8756 were identified as new incident users. After applying exclusion criteria, 2594 individuals comprised the cohort of users of risperidone and quetiapine. The use of quetiapine was associated with a lower risk of extrapyramidal symptoms (EPSs) adverse events. The unadjusted and adjusted hazard ratios (95% confidence interval [CI]) for quetiapine versus risperidone were 0.83 (0.56-1.25) and 0.53 (0.34-0.83), respectively.
CONCLUSION: EPS diagnoses have been detected in children treated with quetiapine; however, the risk of movement disorders appears to be higher with treatment with risperidone. Clinicians should always take into consideration the risk-benefit before treating children with antipsychotic medications and should be vigilant of the onset of drug-induced adverse events.

PMID: 29091743 [PubMed - as supplied by publisher]