[Cost-effectiveness analysis of octreotide long acting release and lanreotide slow release for the treatment of postoperative patients with active acromegaly in China].

Zhonghua Yi Xue Za Zhi. 2017 Mar 14;97(10):765-769

Authors: Xuan JW, Zhang ZY, Wang YF, Mao ZG, Lu YJ, Wang RZ

Abstract
Objective: To evaluate the cost-effectiveness of octreotide long acting release (LAR) vs lanreotide slow release (SR) for the treatment of postoperative acromegalic patients with elevated levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) in China. Methods: A decision tree model was constructed and the treatment impact was projected for one year in Chinese setting. The clinical efficacy measure used was the percentage of patients achieving normalization (control) of either IGF-1 or GH levels. Efficacy of octreotide LAR and lanreotide SR, incidence of comorbidities, impact of acromegaly on health-related quality of life, and drug-related side effects data were obtained from literature. The cost of medication was collected through a chart review from five hospitals in five cities of China. Clinical experts from these hospitals were requested to complete a questionnaire to document the utilization of medical resources, costs of comorbidities, side effects as well as cost of administration. One-way sensitivity analysis was performed to evaluate the robustness of the results. Results: Compared to lanreotied SR group, the percentage of patients achieving normalization of IGF-1 and GH levels of octreotide LAR group were 10% and 9% higher, respectively. When either IGF-1 or GH control were used as the efficacy measure, patients in the octreotide LAR group exhibit less comorbidities and need less continued treatment with a second operation and radiotherapy than those in lanreotide SR group. When IGF-1 was used as efficacy measure, octreotide LAR not only achieved better efficacy but resulted in overall cost-saving, with a total cost savings of ￥ 3 792 per patient for one year, which demonstrated that octreotide LAR was a dominant cost-saving strategy. When GH control was used as the efficacy measure, octreotide LAR achieved a better overall clinical efficacy with a slightly higher total costs (￥ 4 121 higher per patient per year). Sensitivity analysis didn't change the conclusion that octreotide LAR remains dominant over lanreotide SR, indicating the robustness of this model. Conclusion: Octreotide LAR achieved better overall biochemical control compared with lanreotide SR which result in less comorbidity rate, second operation and radiotherapy as well as related costs.

PMID: 28316158 [PubMed - in process]

Association of itraconazole and potassium iodide in the treatment of feline sporotrichosis: a prospective study.

Med Mycol. 2016 Oct 01;54(7):684-90

Authors: Reis ÉG, Schubach TM, Pereira SA, Silva JN, Carvalho BW, Quintana MS, Gremião ID

Abstract
Feline sporotrichosis is an endemic disease in Rio de Janeiro, Brazil, where zoonotic transmission of Sporothrix spp. has been reported since 1998. Itraconazole (ITZ) remains the first choice for treating this disease in cats. However, there have been reports of therapeutic failure and a long-term endeavor. Potassium iodide (KI), considered in the past as a drug with variable effectiveness in cats with sporotrichosis, arises as an important option in the treatment of cats from the endemic area of Rio de Janeiro. In order to evaluate the effectiveness of the association of ITZ and KI in naive cats with sporotrichosis, a prospective cohort study was conducted on 30 cats receiving ITZ 100 mg/day and KI 2.5 mg-20 mg/kg/day. Clinical and laboratory adverse effects were assessed once a month according to the standard care protocol. The cure rate was 96.15% within a median of 14 weeks of treatment. Adverse effects were observed in 50% of cats and were managed with a temporary drug suspension and/or a hepatoprotective therapy. The association of ITZ and KI emerges as an effective option for the treatment of feline sporotrichosis.

PMID: 27207412 [PubMed - indexed for MEDLINE]

[Adverse drug reactions in children: 10 years of pharmacovigilance].

Arch Pediatr. 2016 May;23(5):468-76

Authors: Damien S, Patural H, Trombert-Paviot B, Beyens MN

Abstract
BACKGROUND: Knowledge of drug tolerance and safety in children is limited. The study of spontaneous notifications of adverse events (AEs) can be an important source of information.
OBJECTIVE: Describe the characteristics of drug adverse effects (DAEs) in children 0-17 years of age reported to the pharmacovigilance center of Saint-Étienne in 2004-2013.
METHODS: This retrospective descriptive study was conducted based on DAE notifications, classified according to age, sex, severity of organ affected (using classification by the System organ class [SOC]) and by suspected drug (Anatomical therapeutic chemical [ATC] drugs).
RESULTS: A total of 371 notifications were analyzed. The male:female ratio was 1. Serious cases accounted for 36%, of which 73% resulted in hospitalization or prolongation of hospitalization. The most frequent DAEs were cutaneous (21.1%), infection (13.5%) and general (11.5%). The most frequently involved therapeutic classes were anti-infectives for systemic use (38.7%), mainly vaccines and antibiotics, as well as antineoplastic and immunomodulatory therapy (19.2%) and drugs acting on the nervous system (12.5%).
CONCLUSIONS: The analysis of notifications of adverse drug reactions is an important source of information and is underutilized in pediatrics. The data from this study confirm those of European databases with spontaneous reporting. The majority of anti-infectives including antibiotics raises the question of the proper use of this class in this population. Larger studies focused on the drugs at risk would improve the knowledge and safe use of medicines in children.

PMID: 27062190 [PubMed - indexed for MEDLINE]

Impressions of pharmacogenomic testing among Certified Registered Nurse Anesthetists: a mixed-method study.

Pharmacogenomics. 2016 04;17(6):593-602

Authors: Riddle D, Gregoski M, Baker K, Dumas B, Jenkins CH

Abstract
AIM: Pharmacogenomic testing is useful in helping to predict and explain patient responsiveness to medication. In clinical practice, the use of pharmacogenomic testing has been shown to help reduce adverse drugs events and increase patient satisfaction with their healthcare. Prior to a test being useful, it must have clinical utility. There is a gap in the literature about the perceived clinical utility of pharmacogenomic testing among anesthesia providers.
METHODS: This qualitative-quantitative sequential mixed-method study used focused interviews to formulate probes for a quantitative survey aimed at quantifying the perceptions of anesthesia providers about pharmacogenomic testing.
RESULTS: The results indicate anesthesia providers do not have enough knowledge about pharmacogenomic testing for it to be considered clinically useful in anesthesia practice.
CONCLUSION: Although outcomes data indicate pharmacogenomic testing can help predict outcomes, anesthesia providers do not have enough knowledge and have concerns about the ethical implications of pharmacogenomic testing.

PMID: 27023204 [PubMed - indexed for MEDLINE]

Thiopurine S-methyltransferase testing for averting drug toxicity in patients receiving thiopurines: a systematic review.

Pharmacogenomics. 2016 04;17(6):633-56

Authors: Roy LM, Zur RM, Uleryk E, Carew C, Ito S, Ungar WJ

Abstract
AIM: Thiopurine S-methyltransferase (TPMT) testing is used in patients receiving thiopurines to identify enzyme deficiencies and risk for adverse drug reactions. It is uncertain whether genotyping is superior to phenotyping. The objectives were to conduct a systematic review of TPMT-test performance studies.
MATERIALS & METHODS: Electronic and grey literature sources were searched for studies reporting test performance compared with a reference standard. Sixty-six eligible studies were appraised for quality.
RESULTS: Thirty phenotype-genotype and six phenotype-phenotype comparisons were of high quality. The calculated sensitivity and specificity for genotyping to identify a homozygous mutation ranged from 0.0-100.0% and from 97.8-100.0%, respectively.
CONCLUSION: Clinical decision-makers require high-quality evidence of clinical validity and clinical utility of TPMT genotyping to ensure appropriate use in patients.

PMID: 27020704 [PubMed - indexed for MEDLINE]

30-Day Potentially Avoidable Readmissions Due to Adverse Drug Events.

J Patient Saf. 2017 Mar 17;:

Authors: Dalleur O, Beeler PE, Schnipper JL, Donzé J

Abstract
OBJECTIVE: To analyze the patterns of potentially avoidable readmissions due to adverse drug events (ADEs) to identify the most appropriate risk reduction interventions.
METHODS: In this observational study, we analyzed a random sample of 534 potentially avoidable 30-day readmissions from 10,275 consecutive discharges from the medical department of an academic hospital. Readmissions due to ADEs were reviewed to identify the causative drugs and the severity and interventions to prevent them.
RESULTS: Seventy cases (13.1%) of readmission were partially or predominantly due to ADEs, of which, 58 (82.9%) were serious ADEs. Overall, 65 (92.9%) of the ADEs have been confirmed to be preventable. Inappropriate prescribing was identified as the cause of ADE in 34 cases (48.6%) mainly involving diuretics, analgesics, or antithrombotics: misprescribing n = 19 (27.1%), underprescribing n = 8 (11.4%), and overprescribing n = 7 (10.0%). The remaining half of preventable ADEs (n = 36; 51.4%) were related to suboptimal patient monitoring/education, such as adherence issues (n = 6; 8.6%) or lack of monitoring (n = 31; 44.3%). In 64 cases (91.4%), the readmission could have been potentially prevented by better monitoring for drug efficacy/disease control, or for predictable side effect. Thirty-three (97.1%) of the 34 ADEs due to inappropriate prescribing could have also been prevented by better monitoring.
CONCLUSIONS: Adverse drug events accounted for approximately 13% of 30-day preventable readmissions. A half were due to prescription errors involving mainly diuretics, analgesics, or antithrombotics, and the other half were due to suboptimal patient monitoring/education, most frequently with antineoplastics. Both these avoidable causes may represent opportunities to reduce the total drug-related adverse events.

PMID: 28306610 [PubMed - as supplied by publisher]

Adverse Effects of Statins-Reply.

JAMA. 2017 03 14;317(10):1080

Authors: Thompson PD

PMID: 28291889 [PubMed - indexed for MEDLINE]

Adverse Effects of Statins.

JAMA. 2017 03 14;317(10):1079-1080

Authors: Malachowski SJ, Quattlebaum AM, Miladinovic B

PMID: 28291886 [PubMed - indexed for MEDLINE]

Adverse Effects of Statins.

JAMA. 2017 03 14;317(10):1079

Authors: Goldstein LB

PMID: 28291885 [PubMed - indexed for MEDLINE]

Pharmaceuticals and Medical Devices: FDA Oversight.

Issue Brief Health Policy Track Serv. 2016 Dec 27;2016:1-74

Authors: White RS, Thomson Reuters Accelus

PMID: 28252887 [PubMed - indexed for MEDLINE]

Media coverage of statins may have led to 2000 cardiovascular events.

BMJ. 2016 Jun 30;353:i3630

Authors: Galliver M

PMID: 27364525 [PubMed - indexed for MEDLINE]

Authors' reply to Cunningham and Messerli and colleagues.

BMJ. 2016 Jun 07;353:i3141

Authors: Kotecha D, Altman DG, Collins PD, Flather MD

PMID: 27268202 [PubMed - indexed for MEDLINE]

Research into "real world" older patients is needed.

BMJ. 2016 Jun 07;353:i3136

Authors: Cunningham CJ

PMID: 27268071 [PubMed - indexed for MEDLINE]

Adverse effects and tolerability of β blockers.

BMJ. 2016 Jun 07;353:i3142

Authors: Messerli FH, Bangalore S, Grossman E

PMID: 27268029 [PubMed - indexed for MEDLINE]

Managing Infusion-Related Reactions for Patients With Chronic Lymphocytic Leukemia Receiving Obinutuzumab.

Clin J Oncol Nurs. 2016 Apr;20(2):E41-8

Authors: Dawson K, Moran M, Guindon K, Wan H

Abstract
BACKGROUND: In patients with previously untreated chronic lymphocytic leukemia (CLL) and comorbidities, treatment with the glycoengineered, type II anti-CD20 monoclonal antibody obinutuzumab (Gazyva®) (GA101) plus chlorambucil (Leukeran®) was associated with superior outcomes to rituximab (Rituxan®) plus chlorambucil, with a similar safety profile. However, a higher occurrence of infusion-related reactions (IRRs) was reported with obinutuzumab. These reactions typically require additional management.
OBJECTIVES: The focus of this article is to provide oncology nurses and physicians with advice for obinutuzumab IRR management based on clinical trial data and nursing experience.
METHODS: The authors reviewed the published management strategies for IRRs with obinutuzumab that were identified during the phase III CLL11 trial and an expanded access phase IIb study (ML28979). Practical advice for obinutuzumab IRR management was developed based on available clinical trial information and nursing experience.
FINDINGS: IRRs with obinutuzumab are generally manageable. Most IRRs (all grades), and all grade 3-4 IRRs, occurred during the first infusion. Therefore, IRR management could be improved substantially with extra vigilance at this early stage.

PMID: 26991722 [PubMed - indexed for MEDLINE]

Medication-associated gastrointestinal tract injury.

Virchows Arch. 2017 Mar;470(3):245-266

Authors: Vieth M, Montgomery E

Abstract
Medication-associated gastrointestinal (GI) tract injury has been known for centuries for some medications. The more recently introduced biologicals are a class of drugs that constantly increases, and as such, the spectrum of GI tract side effects is steadily growing. This review covers not only long-known GI tract side effects of drugs but also those more recently described. A comprehensive but concise list of medications used in daily practice and associated with GI tract injury is presented.

PMID: 28133700 [PubMed - indexed for MEDLINE]

Recent Advances in Assessing Immunogenicity of Therapeutic Proteins: Impact on Biotherapeutic Development.

J Immunol Res. 2016;2016:8141269

Authors: Lu Y, Khawli LA, Purushothama S, Theil FP, Partridge MA

PMID: 27642612 [PubMed - indexed for MEDLINE]

SEC Based Method for Size Determination of Immune Complexes of Therapeutic Antibodies in Animal Matrix.

J Immunol Res. 2016;2016:9096059

Authors: Boysen M, Schlicksupp L, Dreher I, Loebbert R, Richter M

Abstract
Therapeutic monoclonal antibodies (mAbs) represent a milestone in pharmacological development. Their superiority is based on the combination of high specificity, low toxicity, and long half-life that characterizes biologics. If biologics have Achilles' heel, it is their potential immunogenicity. To better understand the impact of the size of immune complexes of mAbs on anti-drug antibody (ADA) dependent adverse reactions in Macaca fascicularis, we developed an efficient high-throughput size exclusion chromatography- (SEC-) based methodology that enables analysis of the size, size distribution, and ratio of free and ADA-complexed mAb in serum allowing for assessment of formation and clearance of circulating ADA-mAb immune complexes (CIC).

PMID: 27556050 [PubMed - indexed for MEDLINE]

Predictive models of cytotoxicity as mediated by exposure to chemicals or drugs.

SAR QSAR Environ Res. 2016 Jun;27(6):455-68

Authors: Moon H, Cong M

Abstract
Predicting cytotoxicity is a challenging task because of the complex biological mechanisms behind it. Cytotoxicity due to toxin - biologically produced poison - is known to play a substantial role in a disease process. Two objectives in this research are to derive robust general predictive cytotoxicity models to minimize unnecessary toxicity. The first objective is to build accurate predictive statistical models for cytotoxicity data based on lymphoblastoid cell lines obtained from in vitro studies. This could be an important step for accomplishing a goal in biomedecial/biophamarceutical research, by obtaining the best medical outcomes by minimizing toxicity in regard to a person's genetic profile. The second objective is to build predictive models to predict population-level cytotoxicity for unknown compounds based on chemical structural features. These two objectives were accomplished by a proposed variable selection process, the random forests, and the least absolute shrinkage and selection operator method. We achieved an excellent prediction result with the random forests algorithm using SNP markers from the proposed approach, having the smallest root mean squared error among the teams which participated in the DREAM Toxicogenetics Challenge. Since chemical compounds for drugs have great influence on human health, the predictive statistical models for these objectives could be helpful to government agencies in relevant decision-making.

PMID: 27442234 [PubMed - indexed for MEDLINE]

A review of adverse events caused by immune checkpoint inhibitors.

Nihon Rinsho Meneki Gakkai Kaishi. 2016;39(1):30-6

Authors: Fukushima S

Abstract
  There has been no effective therapy in the unresectable melanoma for more than 40 years. Anti-PD-1 antibody and anti-CTLA-4 antibody have totally changed the situation. They have clearly shown the survival benefits of the patients with metastatic melanoma. However, immune checkpoint inhibitors sometimes induce various kinds of immune-related adverse events (irAEs). It is very important for the clinicians to know the reported cases of irAEs and to keep in mind the symptoms of irAEs for the early detection. This review describes the previously reported irAEs and adequate managements for irAEs induced by immune checkpoint inhibitors.

PMID: 27181232 [PubMed - indexed for MEDLINE]