Anaphylaxis.

Prim Care. 2016 Sep;43(3):477-85

Authors: Hernandez L, Papalia S, Pujalte GG

Abstract
Anaphylaxis is an acute, systemic reaction mediated by immunoglobulin E hypersensitivity. Release of bioactive factors causes vasodilation and bronchiole constriction that can lead to hypotensive shock and asphyxiation. Differential diagnosis includes acute asthma, localized angioedema, syncope, and anxiety/panic attacks. Diagnostic tests lack specificity. Clinical diagnosis is based on demonstration of specific airway or cardiovascular compromise within proximity of allergen exposure. Treatment includes epinephrine, antihistamines, fluid resuscitation, and airway management. Prevention focuses on awareness/avoidance of triggers, implementation of personalized action plans, as well as immune modulation by desensitization in a closely controlled setting where available.

PMID: 27545736 [PubMed - indexed for MEDLINE]

"Adaptive pathways" to drug authorisation: adapting to industry?

BMJ. 2016 Aug 16;354:i4437

Authors: Davis C, Lexchin J, Jefferson T, Gøtzsche P, McKee M

PMID: 27531201 [PubMed - indexed for MEDLINE]

Safety and tolerability of regadenoson for myocardial perfusion imaging - first Danish experience.

Scand Cardiovasc J. 2016 Jun;50(3):180-6

Authors: Pape M, Zacho HD, Aarøe J, Eggert Jensen S, Petersen LJ

Abstract
OBJECTIVES: Evaluating safety and tolerability of the selective A2A receptor agonist, regadenoson, in patients referred for single photon emission computed tomography myocardial perfusion imaging (MPI).
DESIGN: Observational study of patients referred for MPI stress testing using a 400 μg regadenoson (Rapiscan(®)) bolus. Hemodynamic variables and severity of adverse events (AE) were recorded before, during, and after administration.
RESULTS: A total of 232 patients were included. One or more AE were reported in 90% of patients; the AEs were graded mostly mild to moderate in severity, resolved spontaneously, and were mainly dyspnea, headache, and chest pain. No advanced heart block or bronchospasm were seen. Transient ST-segment changes developed in 10 patients. The maximum increase in heart rate was 19 ± 11 beats/minute. The mean systolic blood pressure decreased from 144 to 139 mmHg (p < 0.0001). Medical intervention was required in three patients: one case with severe hypotension and two cases with chest pain that was relieved with sublingual nitroglycerin. One patient died the day after stress MPI for reasons considered unrelated to regadenoson.
CONCLUSION: Regadenoson for MPI is easy to use with a high frequency of AEs, which are generally mild in severity, transient, and resolve spontaneously.

PMID: 26956081 [PubMed - indexed for MEDLINE]

Medication Errors: A Case-Based Review.

AACN Adv Crit Care. 2016 Feb;27(1):5-11

Authors: Pop M, Finocchi M

PMID: 26909446 [PubMed - indexed for MEDLINE]

Duvoglustat HCl Increases Systemic and Tissue Exposure of Active Acid α-Glucosidase in Pompe Patients Co-administered with Alglucosidase α.

Mol Ther. 2017 Mar 21;:

Authors: Kishnani P, Tarnopolsky M, Roberts M, Sivakumar K, Dasouki M, Dimachkie MM, Finanger E, Goker-Alpan O, Guter KA, Mozaffar T, Pervaiz MA, Laforet P, Levine T, Adera M, Lazauskas R, Sitaraman S, Khanna R, Benjamin E, Feng J, Flanagan JJ, Barth J, Barlow C, Lockhart DJ, Valenzano KJ, Boudes P, Johnson FK, Byrne B

Abstract
Duvoglustat HCl (AT2220, 1-deoxynojirimycin) is an investigational pharmacological chaperone for the treatment of acid α-glucosidase (GAA) deficiency, which leads to the lysosomal storage disorder Pompe disease, which is characterized by progressive accumulation of lysosomal glycogen primarily in heart and skeletal muscles. The current standard of care is enzyme replacement therapy with recombinant human GAA (alglucosidase alfa [AA], Genzyme). Based on preclinical data, oral co-administration of duvoglustat HCl with AA increases exposure of active levels in plasma and skeletal muscles, leading to greater substrate reduction in muscle. This phase 2a study consisted of an open-label, fixed-treatment sequence that evaluated the effect of single oral doses of 50 mg, 100 mg, 250 mg, or 600 mg duvoglustat HCl on the pharmacokinetics and tissue levels of intravenously infused AA (20 mg/kg) in Pompe patients. AA alone resulted in increases in total GAA activity and protein in plasma compared to baseline. Following co-administration with duvoglustat HCl, total GAA activity and protein in plasma were further increased 1.2- to 2.8-fold compared to AA alone in all 25 Pompe patients; importantly, muscle GAA activity was increased for all co-administration treatments from day 3 biopsy specimens. No duvoglustat-related adverse events or drug-related tolerability issues were identified.

PMID: 28341561 [PubMed - as supplied by publisher]

Does sevoflurane add to outpatient procedural sedation in children? A randomised clinical trial.

BMC Pediatr. 2017 Mar 24;17(1):86

Authors: Gomes HS, Gomes HS, Sado-Filho J, Costa LR, Costa PS

Abstract
BACKGROUND: There is little evidence concerning the effect of sevoflurane in outpatient procedural sedation, especially in children. We hypothesised that the addition of sevoflurane to a sedation regimen improves children's behaviour with minimal adverse events.
METHODS: This is a randomised, triple-blind clinical trial conducted on an outpatient basis. Participants were 27 healthy children aged 4 to 6 years, who previously refused dental treatment with non-pharmacologic methods. All participants received oral midazolam (0.5 mg/kg, maximum 20 mg) and oral ketamine (3 mg/kg, maximum 50 mg) and, in addition: Group MK - 100% oxygen; Group MKS - inhalational sevoflurane at a sedative dose (final expired concentration between 0.3 and 0.4%). Dental appointments were video recorded for assessment of the children's sleep patterns, crying, movements, and overall behaviour during the procedure with the Houpt scale. Intra- and post-operative adverse events were systematically reported. Data were analysed by bivariate analyses in the IBM SPSS v. 19, at a significance level of 5%.
RESULTS: MK (n = 13) and MKS (n = 14) did not differ regarding the Houpt scores (P > 0.05), but 53.8% of children in the MK group showed hysterical and continuous crying at the time of the local anaesthesia injection, compared to 7.1% of children in the MKS group (P = 0.01; phi = 0.5). There was a trend toward less crying and movement over time during the dental appointment in the MKS group (P = 0.48). Minor adverse events were observed in 10 MK children and 4 MKS children (P = 0.01).
CONCLUSIONS: The addition of sevoflurane to oral midazolam-ketamine improved the children's crying behaviour during local anaesthetic administration, and did not increase the occurrence of adverse events.
TRIAL REGISTRATION: Clinical Trials NCT02284204 . Registered 5 October 2014.

PMID: 28340572 [PubMed - in process]

In vitro testing of basal cytotoxicity: Establishment of an adverse outcome pathway from chemical insult to cell death.

Toxicol In Vitro. 2017 Mar;39:104-110

Authors: Vinken M, Blaauboer BJ

Abstract
In this paper, an in vitro basal cytotoxicity testing strategy is described for new chemical entities that lack any pre-existing information on potential toxicity. Special attention is paid to the selection of the cellular system, cytotoxicity assay and exposure conditions. This approach is based on a newly proposed generic adverse outcome pathway from chemical insult to cell death that consists of 3 steps, including initial cell injury, mitochondrial dysfunction and cell demise. The suggested strategy to consider in vitro basal cytotoxicity as a first step in evaluating the toxicity of new chemical entities can be placed in a tiered strategy that could be continued by evaluating more specific types of toxicity.

PMID: 27939612 [PubMed - indexed for MEDLINE]

Development of the Virtual Physical Assessment Learning Material That Allows the Learners to Check Drug Efficacy and Early Detection of Adverse Effects through Virtual Experience.

Yakugaku Zasshi. 2016;136(10):1439-1444

Authors: Tokunaga J, Takamura N, Kourogi Y, Imada M, Kozasa A, Komori K, Ono C, Nishimura A, Ogata K, Setoguchi N, Matsuoka T, Kai M, Sato K, Arimori K

Abstract
 We utilized the information and communication technology to develop the physical assessment (PA) learning materials in the virtual experience type. This learning material consists of two parts which include case learning and basic learning. We created example scenarios about various conditions that a pharmacist may experience in medical scenes such as in a hospital ward, community pharmacy, home, and drugstore. Illustrations of a virtual patient's avatar before and after taking the medicines were incorporated in the learning materials. The virtual training includes a stethoscope that was used in examining sounds (heart, pulmonary and bowel sounds) that served as evidences in the confirmation of drug efficacy and its possible adverse effects. In addition, we included the images of each body part, the 24 format question items, the palpation (rate and rhythm) of the radial artery, brachial artery and pedal artery, the clinical data obtained from several medical equipment, the pupillary reflex, and the urine dipstick test. This way, learners are able to experience PA with reference to the subjective and objective data from patient reception and questions. The virtual patient's avatar displayed on the monitor features auscultatory sounds on the stethoscope. It also features clinical data obtained from other medical equipment that can give the learners an interactive way of learning about various medical conditions. For evaluation, we gave out questionnaires on the virtual PA to pharmacy students. As a result, a high evaluation was reflected in terms of the degree of usefulness for both case learning and basic learning.

PMID: 27725393 [PubMed - indexed for MEDLINE]

Recommendations to improve adverse event reporting in clinical trial publications: a joint pharmaceutical industry/journal editor perspective.

BMJ. 2016 Oct 03;355:i5078

Authors: Lineberry N, Berlin JA, Mansi B, Glasser S, Berkwits M, Klem C, Bhattacharya A, Citrome L, Enck R, Fletcher J, Haller D, Chen TT, Laine C

PMID: 27697753 [PubMed - indexed for MEDLINE]

History repeats itself: the family medication history and pharmacogenomics.

Pharmacogenomics. 2016 05;17(7):669-78

Authors: Smith TR, Kearney E, Hulick PJ, Kisor DF

Abstract
Related to many drug gene-product interactions, application of pharmacogenomics can lead to improved medication efficacy while decreasing or avoiding adverse drug reactions. However, utilizing pharmacogenomics without other information does not allow for optimal medication therapy. Currently, there is a lack of documentation of family medication history, in other words, inefficacy and adverse reactions across family members throughout generations. The family medication history can serve as an impetus for pharmacogenomic testing to explain lack of medication efficacy or an adverse drug reaction and pre-emptive testing can drive recognition and documentation of medication response in family members. We propose combining the family medication history via pedigree construction with pharmacogenomics to further optimize medication therapy. We encourage clinicians to combine family medication history with pharmacogenomics.

PMID: 27143300 [PubMed - indexed for MEDLINE]

Activation of the NRF2-ARE signalling pathway by the Lentinula edodes polysaccharose LNT alleviates ROS-mediated cisplatin nephrotoxicity.

Int Immunopharmacol. 2016 Jul;36:1-8

Authors: Chen Q, Peng H, Dong L, Chen L, Ma X, Peng Y, Dai S, Liu Q

Abstract
The nephrotoxicity of cisplatin (cis-DDP) limits its general clinical applications. Lentinan (LNT), a dextran extracted from the mushroom Lentinula edodes, has been shown to have multiple pharmacological activities. The primary objective of the current study was to determine whether and how LNT alleviates cis-DDP- induced cytotoxicity in HK-2 cells and nephrotoxicity in mice. LNT did not interfere with cisplatin's anti-tumour efficacy in vitro and functioned cooperatively with cis-DDP to inhibit activity in HeLa and A549 tumour cells. LNT alleviated the cis-DDP-induced decrease in HK-2 cell viability, caspase-3 activation and cleavage of the DNA repair enzyme PARP, decreased HK-2 cell apoptosis and inhibited reactive oxygen species (ROS) accumulation in HK-2 cells. The inhibitor of ROS (N-acetyl-L-cysteine, NAC) could decreased the apoptosis of HK-2 cell. In addition, LNT significantly prevented cis-DDP-induced kidney injury in vivo. LNT itself could not eliminate ROS levels in vitro. Further studies demonstrated that LNT induced NF-E2 p45-related factor 2 (Nrf2) protein and mRNA expression in a time- and dose-dependent manner. LNT promoted Nrf2 translocation to the nucleus and binding to the antioxidant-response element (ARE) sequence and induced the transcription and translation of heme oxygenase 1 (HO-1), aldo-keto reductases 1C1 and 1C2 (AKR1C), and NADP(H):quinone oxidoreductase 1 (NQO1). Finally, we used hNrf2 siRNA and an Nrf2 agonist (tBHQ) to inhibit or enhance Nrf2 expression. The results demonstrated that the LNT-mediated alleviation of cis-DDP-induced nephrotoxicity was achieved by preventing the accumulation of ROS in a manner that depended on the activation of the Nrf2-ARE signalling pathway.

PMID: 27093515 [PubMed - indexed for MEDLINE]

Health care cost associated with the use of enzyme-inducing and non-enzyme-active antiepileptic drugs in the UK: a long-term retrospective matched cohort study.

BMC Neurol. 2017 Mar 23;17(1):59

Authors: Borghs S, Thieffry S, Noack-Rink M, Dedeken P, Hong LS, Byram L, Logan J, Chan J, Kiri V

Abstract
BACKGROUND: Some antiepileptic drugs (AEDs) induce expression of hepatic enzymes. This can contribute to comorbidities via interference with metabolic pathways and concomitant drug metabolization, thereby increasing the likelihood of health care interventions. Using medical records, we compared the direct health care cost in patients initiating epilepsy therapy with enzyme-inducing AEDs (EIAEDs) vs non-enzyme-active AEDs (nEAAEDs) over up to 12 years.
METHODS: Patients with untreated epilepsy were indexed in the UK Clinical Practice Research Datalink and Hospital Episode Statistics database when prescribed a new EIAED or nEAAED between January 2001 and December 2010. Propensity score matching reduced confounding factors between cohorts. Patients were followed until cohort treatment failure or data cut-off. The primary outcome was the median standardized monthly direct health care cost during follow-up in 2014 £GBP, calculated using published reference costs and compared using a Mann-Whitney U test.
RESULTS: The unmatched EIAED cohort (n = 2752) was older (54 vs 46 years), more likely to be male, had more comorbidities, and higher health care resource use/cost during the 1-year pre-index period (median £3014 vs £2516) than the nEAAED cohort (n = 2,137). The most common index EIAED and nEAAED were carbamazepine (63.3%) and lamotrigine (58.0%), respectively. After matching, cohorts had similar features (n = 951 each). Over up to 12 years of follow-up, the median standardized monthly direct health care cost was £229 for the EIAED and £188 for the nEAAED cohorts (p = 0.0091). The median cost was higher for the EIAED cohort in every year of follow-up. In the two cohorts, 25.1% and 20.1% of total mean cost during follow-up was epilepsy-related, with approximately 4.6% and 3.0% for AED acquisition, respectively. The median time to cohort treatment failure was shorter in the matched EIAED cohort (468 vs 1194 days).
CONCLUSIONS: Patients in the UK who initiated epilepsy therapy with an EIAED appeared to be at higher risk of complications associated with enzyme induction. In long-term matched cohort analyses, the median total direct health care cost associated with EIAED therapy was higher than with nEAAEDs. Changing current treatment practices could potentially improve patient outcomes and reduce costs.

PMID: 28335764 [PubMed - in process]

Genetic Determinants of Methotrexate Toxicity in Tunisian Patients with Rheumatoid Arthritis: A Study of Polymorphisms Involved in the MTX Metabolic Pathway.

Eur J Drug Metab Pharmacokinet. 2016 Aug;41(4):385-93

Authors: Chaabane S, Marzouk S, Akrout R, Ben Hamad M, Achour Y, Rebai A, Keskes L, Fourati H, Bahloul Z, Maalej A

Abstract
BACKGROUND AND OBJECTIVE: Methotrexate (MTX) is a disease-modifying anti-rheumatic drug used in the treatment of rheumatoid arthritis (RA). It is the first line drug in the treatment of this disease. However, MTX-related adverse drug reactions (ADRs) are seen in 40 % of the patients. The aim of this study was to determine the impact of six genetic polymorphisms located in five genes encoding proteins involved in the MTX metabolic pathway in Tunisian RA patients and evaluate its association with MTX toxicity.
METHODS: Genotyping of 5,10 methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), dihydrofolate reductase (DHFR 19-base pair deletion allele), thymidylate synthase (TYMS 2R/3R), methionine synthase (MTR A2756G) and methionine synthase reductase (MTRR A66G) was performed using PCR and PCR-RFLP method in 141 RA patients treated with MTX. Demographic and clinical characteristics were obtained and ADRs were recorded. Association analyses with regard to MTX toxicity were performed using the χ (2) test, the toxicogenetic risk index (TRI) and the Mann-Whitney U-test.
RESULTS: The analysis highlighted a significant association of the T/T genotype of MTHFR C677T polymorphism with increased MTX toxicity. However, the MTHFR A1298C, DHFR 19-base pair deletion allele, MTR A2756G and MTRR A66G polymorphisms were not associated with increased MTX toxicity. The TYMS 2R/3R polymorphism had a protective effect against MTX toxicity.
CONCLUSION: The results demonstrated that the C677T polymorphism in the MTHFR gene is associated with MTX toxicity in Tunisian RA patients. In contrast, the TYMS 2R/3R polymorphism is associated with a protective effect against overall MTX toxicity.

PMID: 26077125 [PubMed - indexed for MEDLINE]

First-in-human Clinical Trial of Oral ONC201 in Patients with Refractory Solid Tumors.

Clin Cancer Res. 2017 Mar 22;:

Authors: Stein MN, Bertino JR, Kaufman HL, Mayer T, Moss R, Silk A, Chan N, Malhotra J, Rodriguez-Rodriguez L, Aisner J, Aiken RD, Haffty BG, DiPaola RS, Saunders T, Zloza A, Damare S, Beckett Y, Yu B, Najmi S, Gabel C, Dickerson S, Zheng L, El-Deiry WS, Allen J, Stogniew M, Oster W, Mehnert JM

Abstract
Purpose ONC201 is a small molecule selective antagonist of the G protein-coupled receptor DRD2 that is the founding member of the imipridone class of compounds. A first-in-human phase I study of ONC201 was conducted to determine its recommended phase II dose (RP2D). Experimental Design This open-label study treated 10 patients during dose escalation with histologically-confirmed advanced solid tumors. Patients received ONC201 orally once every 3 weeks, defined as one cycle, at doses from 125 to 625 mg using an accelerated titration design. An additional 18 patients were treated at the RP2D in an expansion phase to collect additional safety, pharmacokinetic (PK), and pharmacodynamic (PD) information. Results No Grade >1 drug-related adverse events occurred and the RP2D was defined as 625 mg. PK analysis revealed a Cmax of 1.5 - 7.5µg/mL (~3.9-19.4µM), mean half-life of 11.3 hours, and mean AUC of 37.7 h.ug/L. Pharmacodynamic assays demonstrated induction of caspase-cleaved keratin 18 and prolactin as serum biomarkers of apoptosis and DRD2 antagonism, respectively. No objective responses by RECIST were achieved, however, radiographic regression of several individual metastatic lesions was observed along with prolonged stable disease (> 9 cycles) in prostate and endometrial cancer patients. Conclusion ONC201 is a selective DRD2 antagonist that is well tolerated, achieves micromolar plasma concentrations, and is biologically active in advanced cancer patients when orally administered at 625 mg every 3 weeks.

PMID: 28331050 [PubMed - as supplied by publisher]

Dementia with Lewy bodies presenting marked tongue protrusion and bite due to lingual dystonia: A case report.

Rinsho Shinkeigaku. 2016 Jun 22;56(6):418-23

Authors: Shiga Y, Kanaya Y, Kono R, Takeshima S, Shimoe Y, Kuriyama M

Abstract
We report the patient of a 53-year-old woman who developed subacute-onset marked tonge protrusion and bite. She was diagnosed as dementia with Lewy bodies (DLB) from the clinical features including progressive cognitive decline, visual hallucinations, parkinsonism, and severe insomnia and depression, and the radiological finding of low dopamine transported uptake in basal ganglia by Dat SCAN and low blood circulation in occipital lobe of cerebrum. The patient received 600 mg doses of levodopa for over a year, followed by rotigotine and ropinirole with a rapid increase of dosage. It is believed that these treatments stimulated and sensitized dopamine D1 receptors, thereby inducing lingual dystonia. Furthermore, the patient demonstrated dyspnea and attacks of apnea caused by the closure of bilateral vocal cords due to laryngeal dyskinesia. After initiation of the neuroleptic, olanzapine, for a short duration, the high dose of levodopa overlapped with neuroleptic sensitivity, suggesting DOPA-induced dystonia and dyskinesia. This interaction can sometimes lead to lethal adverse events, and must be considered very important when treating patients with DLB.

PMID: 27212676 [PubMed - indexed for MEDLINE]

A combined in vitro approach to improve the prediction of mitochondrial toxicants.

Toxicol In Vitro. 2016 Aug;34:161-70

Authors: Eakins J, Bauch C, Woodhouse H, Park B, Bevan S, Dilworth C, Walker P

Abstract
Drug induced mitochondrial dysfunction has been implicated in organ toxicity and the withdrawal of drugs or black box warnings limiting their use. The development of highly specific and sensitive in vitro assays in early drug development would assist in detecting compounds which affect mitochondrial function. Here we report the combination of two in vitro assays for the detection of drug induced mitochondrial toxicity. The first assay measures cytotoxicity after 24h incubation of test compound in either glucose or galactose conditioned media (Glu/Gal assay). Compounds with a greater than 3-fold toxicity in galactose media compared to glucose media imply mitochondrial toxicity. The second assay measures mitochondrial respiration, glycolysis and a reserve capacity with mechanistic responses observed within one hour following exposure to test compound. In order to assess these assays a total of 72 known drugs and chemicals were used. Dose-response data was normalised to 100× Cmax giving a specificity, sensitivity and accuracy of 100%, 81% and 92% respectively for this combined approach.

PMID: 27083147 [PubMed - indexed for MEDLINE]

Adverse Effects of Plant Food Supplements and Plants Consumed as Food: Results from the Poisons Centres-Based PlantLIBRA Study.

Phytother Res. 2016 Jun;30(6):988-96

Authors: Lüde S, Vecchio S, Sinno-Tellier S, Dopter A, Mustonen H, Vucinic S, Jonsson B, Müller D, Veras Gimenez Fruchtengarten L, Hruby K, De Souza Nascimento E, Di Lorenzo C, Restani P, Kupferschmidt H, Ceschi A

Abstract
Plant food supplements (PFS) are products of increasing popularity and wide-spread distribution. Nevertheless, information about their risks is limited. To fill this gap, a poisons centres-based study was performed as part of the EU project PlantLIBRA. Multicentre retrospective review of data from selected European and Brazilian poisons centres, involving human cases of adverse effects due to plants consumed as food or as ingredients of food supplements recorded between 2006 and 2010. Ten poisons centres provided a total of 75 cases. In 57 cases (76%) a PFS was involved; in 18 (24%) a plant was ingested as food. The 10 most frequently reported plants were Valeriana officinalis, Camellia sinensis, Paullinia cupana, Melissa officinalis, Passiflora incarnata, Mentha piperita, Glycyrrhiza glabra, Ilex paraguariensis, Panax ginseng, and Citrus aurantium. The most frequently observed clinical effects were neurotoxicity and gastro-intestinal symptoms. Most cases showed a benign clinical course; however, five cases were severe. PFS-related adverse effects seem to be relatively infrequent issues for poisons centres. Most cases showed mild symptoms. Nevertheless, the occurrence of some severe adverse effects and the increasing popularity of PFS require continuous active surveillance, and further research is warranted. Copyright © 2016 John Wiley & Sons, Ltd.

PMID: 26948409 [PubMed - indexed for MEDLINE]

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[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]