Current Issue : January - March Volume : 2017 Issue Number : 1 Articles : 5 Articles
Background: High dose interleukin-2 (HD IL-2) can induce durable responses in a subset of patients leading\nto long-term survival. Immune checkpoint blockade (ICB) has demonstrated similarly durable responses in a\nlarger proportion of patients. However, not all patients respond to immune checkpoint blockade and subsequent\ntherapeutic options need to be explored.\nMethods: The PROCLAIM database was queried for patients with metastatic melanoma who had received HD IL-2\nafter treatment with ipilimumab or without prior ICB. Patient characteristics, toxicity and efficacy were analyzed.\nResults: A total of 52 metastatic melanoma patients were treated with high dose IL-2 after ipilimumab and 276\npatients were treated with high dose IL-2 without prior ICB. The overall response rate in the prior ipilimumab\ngroup was 21 % as compared to 12 % in the group that had not received prior ipilimumab. The median overall\nsurvival, measured from the initiation of HD IL-2 therapy, was 19.3 months in the prior ipilimumab group and 19.\n4 months in the no prior ICB group. Toxicities observed on HD IL-2 were relatively equivalent between the\ngroups although there were cases of CTLA4 antibody-induced colitis reported after HD IL-2 treatment and a\nCTLA4 antibody-induced colitis related death.\nConclusion: In this retrospective analysis HD IL-2 therapy displayed antitumor activity in melanoma patients\nwho progressed following treatment with ipilimumab. Most HD IL-2 toxicity was not worsened by prior ipilimumab\ntherapy except for one treatment related death from colitis. Care should be taken to avoid reactivation of CTLA4\nantibody-induced colitis....
Background: In 2012, the World Health Organization recommended the addition of single low-dose primaquine\n(SLDPQ, 0.25 mg base/kg body weight) to artemisinin combination therapies to block the transmission of\nPlasmodium falciparum without testing for glucose-6-phosphate dehydrogenase deficiency. The targeted group\nwas non-pregnant patients aged ââ?°Â¥ 1 year (later changed to ââ?°Â¥ 6 months) with acute uncomplicated falciparum\nmalaria, primarily in countries with artemisinin-resistant P. falciparum (ARPf). No dosing regimen was suggested,\nleaving malaria control programmes and clinicians in limbo. Therefore, we designed a user-friendly, age-based\nSLDPQ regimen for Cambodia, the country most affected by ARPf.\nMethods: By reviewing primaquineââ?¬â?¢s pharmacology, we defined a therapeutic dose range of 0.15ââ?¬â??0.38 mg base/\nkg (9ââ?¬â??22.5 mg in a 60-kg adult) for a therapeutic index of 2.5. Primaquine doses (1ââ?¬â??20 mg) were tested using a\nmodelled, anthropometric database of 28,138 Cambodian individuals (22,772 healthy, 4119 with malaria and 1247\nwith other infections); age distributions were: 0.5ââ?¬â??4 years (20.0 %, n = 5640), 5ââ?¬â??12 years (9.1 %, n = 2559), 13ââ?¬â??17\nyears (9.1 %, n = 2550), and ââ?°Â¥ 18 years (61.8 %, n = 17,389). Optimal age-dosing groups were selected according to\ncalculated mg base/kg doses and proportions of individuals receiving a therapeutic dose.\nResults: Four age-dosing bands were defined: (1) 0.5ââ?¬â??4 years, (2) 5ââ?¬â??9 years, (3) 10ââ?¬â??14 years, and (4) ââ?°Â¥15 years to\nreceive 2.5, 5, 7.5, and 15 mg of primaquine base, resulting in therapeutic doses in 97.4 % (5494/5640), 90.5 %\n(1511/1669), 97.7 % (1473/1508), and 95.7 % (18,489/19,321) of individuals, respectively. Corresponding median\n(1stââ?¬â??99th centiles) mg base/kg doses of primaquine were (1) 0.23 (0.15ââ?¬â??0.38), (2) 0.29 (0.18ââ?¬â??0.45), (3) 0.27 (0.15ââ?¬â??0.\n39), and (4) 0.29 (0.20ââ?¬â??0.42).\nConclusions: This age-based SLDPQ regimen could contribute substantially to malaria elimination and requires\nurgent evaluation in Cambodia and other countries with similar anthropometric characteristics. It guides\nprimaquine manufacturers on suitable tablet strengths and doses for paediatric-friendly formulations.\nDevelopment of similar age-based dosing recommendations for Africa is needed....
Background: Ultrasound guidance has reduced the amount of local anesthetics to achieve a successful block.\nPrevious studies of the relationship between the volume or concentration of local anesthetics and the effects of the\nblock were based on relatively high doses of local anesthetics. We tested the hypothesis that providing low dose of\nropivacaine at three combinations of volumes and concentrations for ultrasound-guided interscalene brachial\nplexus block would produce different effects in the aspect of onset time, pain control and the incidence of side\neffects.\nMethods: Ninety-nine patients undergoing elective arthroscopic shoulder surgery were randomized to receive an\nultrasound guided combined with nerve stimulator mediated interscalene block with ropivacaine 0.75 % (6.7 ml,\nGroup 0.75), 0.5 % (10 ml, Group 0.5) or 0.25 % (20 ml, Group 0.25). The primary end point was the onset time of\nthe sensory blockade, assessed by using a pinprick in the C5-6 dermatome. The secondary end points included the\nonset time of the motor blockade, block success rate, postoperative pain rating score, rescue analgesics\nrequirement, sleep quality, strength of the hand on the block side,and the incidence of hemi-diaphragmatic paresis\nwhich was evaluated by ultrasonography.\nResults: There was a statistically significant difference of the sensory block median onset times among Group 0.75\n(5 min), Group 0.5 (10 min) and Group 0.25 (20 min). One patient in Group 0.5 and 20 patients in Group 0.25 did\nnot achieve a complete motor block within 30 min, which were also significantly different. No significant difference\nwas observed in postoperative analgesia, decrease of handgrip strength and the incidence of hemi-diaphragmatic\nparesis among the 3 groups.\nConclusions: This study demonstrates that ropivacaine 50 mg as 0.25, 0.5 or 0.75 % solution for interscalene\nbrachial plexus block before arthroscopic shoulder surgery produces comparable blockade with few side effects,\nwhile 0.75 % seems to be more preferable as it is associated with faster onset time....
Drug dosing in critically ill patients is challenging due to the altered drug pharmacokineticsââ?¬â??pharmacodynamics\nassociated with systemic therapies. For many drug therapies, there is potential to use the respiratory system as an\nalternative route for drug delivery. Aerosol drug delivery can provide many advantages over conventional therapy.\nGiven that respiratory diseases are the commonest causes of critical illness, use of aerosol therapy to provide high local\ndrug concentrations with minimal systemic side effects makes this route an attractive option. To date, limited evidence\nhas restricted its wider application. The efficacy of aerosol drug therapy depends on drug-related factors (particle size,\nmolecular weight), device factors, patient-related factors (airway anatomy, inhalation patterns) and mechanical\nventilation-related factors (humidification, airway). This review identifies the relevant factors which require attention for\noptimization of aerosol drug delivery that can achieve better drug concentrations at the target sites and potentially\nimprove clinical outcomes.\nAbbreviations: ARDS, Acute respiratory distress syndrome; CF, Cystic fibrosis; COPD, Chronic obstructive pulmonary\ndisease; DPI, Dry powder inhaler; ED, Emitted dose; EUCAST, European Committee on Antimicrobial Suceptibility\nTesting; FDA, Food and Drugs Administration; FiO2, Fraction of inspired oxygen; FPF, Fine particle fraction; HH, Heated\nhumidifier; HME, Heat and moisture exchanger; kDa, Kilodaltons; MIC, Minimum inhibitory concentration;\nMV, Mechanical ventilation; MW, Molecular weight; NIV, Non- invasive ventilator; PaO2, Partial pressure of oxygen;\nPD, Pharmacodynamics; PEEP, Positive end-expiratory pressure; PK, Pharmacokinetics; pMDI, Pressurized metered dose\ninhaler; VHC, Valved holding chamber; VMN, Vibrating mesh nebulizer...
Background: Streptozocin (STZ) based chemotherapy is recommended for patients with metastatic pancreatic\nneuroendocrine tumors (pNET). Temozolomide as mono- or combination therapy has been suggested to be a\npromising alternative. However, the treatment is costly and not approved for the treatment of pNETs. Dacarbazine\n(DTIC) shares the active metabolite with temozolomide and is broadly available at a low cost. The aim of this study was\na retrospective evaluation of the efficacy and tolerability of a lower dose DTIC-regimen in patients with progressive\nadvanced NETs.\nMethods: We retrospectively analyzed 75 patients with NETs predominantly of pancreatic origin treated at our center\nbetween 1998 and 2013. 650 mg/m2 of DTIC were administered intravenously over 60 min every 4 weeks.\nMorphological response was assessed according to RECIST1.1 criteria. The median progression free survival (PFS) was\ncalculated using Kaplan-Meier and Cox regression methods, respectively. Univariate analyses of possible prognostic\nmarkers were performed.\nResults: The objective response rate (ORR) was 27 % for the entire cohort and 32 % in 50 pNET patients, respectively.\nStable disease (SD) was documented in 29 patients (39 %). Median PFS (mPFS) in patients receiving DTIC was 7 months\n(3.9ââ?¬â??10; 95 % confidence interval). Radiological and biochemical response were the only significant prognostic markers\nfor longer PFS in univariate analysis. Treatment was well tolerated. Nausea was the most common side effect (31 %),\nonly one case (1.3 %) of grade 3 toxicity (vomiting) occurred.\nConclusion: Low dose DTIC chemotherapy is an effective and well-tolerated treatment option in patients with\nprogressive well differentiated neuroendocrine neoplasms, especially of pancreatic origin....
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