Showing papers in "American Journal of Therapeutics in 2017"

Antimicrobial Resistant Streptococcus pneumoniae: Prevalence, Mechanisms, and Clinical Implications

Abstract: Background:Streptococcus pneumoniae is a major cause of pneumonia, meningitis, sepsis, bacteremia, and otitis media. S. pneumoniae has developed increased resistance to multiple classes of antibiotics.Study Design:Systematic literature review of prevalence, mechanisms, and clinical implications in S

Prospective Clinical Trial of Rifaximin Therapy for Patients With Primary Sclerosing Cholangitis.

Abstract: Primary sclerosing cholangitis (PSC) is a rare, chronic, cholestatic liver disease in which emerging data suggest that oral antibiotics may offer therapeutic effects. We enrolled patients with PSC in a 12-week, open-label pilot study to investigate the efficacy and safety of 550 mg of oral rifaximin twice daily. The primary end point was serum alkaline phosphatase (ALK) at 12 weeks. Secondary end points included (1) serum bilirubin, gamma-glutamyl transpeptidase, and Mayo PSC risk score; (2) fatigue impact scale, chronic liver disease questionnaire, and short form health survey (SF-36) scores; and (3) adverse effects (AEs). Analyses were performed with nonparametric tests. Sixteen patients were enrolled, among whom the median age was 40 years; 13 (81%) were male, 13 had inflammatory bowel disease, and baseline ALK was 342 IU/mL (interquartile range, 275-520 IU/mL). After 12 weeks of treatment, there were no significant changes in ALK (median increase of 0.9% to 345 IU/mL; P = 0.47) or any of the secondary biochemical end points (all P > 0.05). Similarly, there were no significant changes in fatigue impact scale, chronic liver disease questionnaire, or SF-36 scores (all P > 0.05). Three patients withdrew from the study due to AEs; 4 others reported mild AEs but completed the study. In conclusion, although some antibiotics may have promise in treating PSC, oral rifaximin, based on the results herein, seems inefficacious for this indication. Future studies are needed to understand how the antimicrobial spectra and other properties of antibiotics might determine their utility in treating PSC.

Role of Bismuth in the Eradication of Helicobacter pylori.

Abstract: Bismuth salts exert their activity within the upper gastrointestinal tract through action of luminal bismuth. Bismuth exerts direct bactericidal effect on Helicobacter pylori by different ways: forms complexes in the bacterial wall and periplasmic space, inhibits different enzymes, ATP synthesis, and adherence of the bacteria to the gastric mucosa. Bismuth also helps ulcer healing by acting as a barrier to the aggressive factors and increasing mucosal protective factors such as prostaglandin, epidermal growth factor, and bicarbonate secretion. To date, no resistance to bismuth has been reported. Also synergism between bismuth salts and antibiotics was present. It was shown that metronidazole and clarithromycin resistant H. pylori strains become susceptible if they are administered together with bismuth. Bismuth-containing quadruple therapy was recommended both by the Second Asia-Pacific Consensus Guidelines and by the Maastricht IV/Florence Consensus Report as an alternative first choice regimen to standard triple therapy, in areas with low clarithromycin resistance, and it is recommended as the first-line therapeutic option in areas with a high prevalence of clarithromycin resistance. Greater than 90% eradication success can be obtained by bismuth-containing quadruple therapy. Choosing bismuth as an indispensable part of first-line therapy is logical as both metronidazole and clarithromycin resistances can be overcome by adding bismuth to the regimen.

Magnesium Supplementation in Vitamin D Deficiency.

Abstract: BACKGROUND Vitamin D and magnesium (Mg) are some of the most studied topics in medicine with enormous implications for human health and disease. Majority of the adults are deficient in both vitamin D and magnesium but continue to go unrecognized by many health care professionals. AREAS OF UNCERTAINTY Mg and vitamin D are used by all the organs in the body, and their deficiency states may lead to several chronic medical conditions. Studies described in the literature regarding these disease associations are contradictory, and reversal of any of these conditions may not occur for several years after adequate replacement. One should consider the supplementation therapy to be preventative rather than curative at this time. DATA SOURCES PubMed search of several reported associations between vitamin D and Mg with diseases. RESULTS Vitamin D and Mg replacement therapy in elderly patients is known to reduce the nonvertebral fractures, overall mortality, and the incidence of Alzheimer dementia. CONCLUSIONS Vitamin D screening assay is readily available, but the reported lower limit of the normal range is totally inadequate for disease prevention. Based on the epidemiologic studies, ∼75% of all adults worldwide have serum 25(OH)D levels of <30 ng/mL. Because of the recent increase in global awareness, vitamin D supplementation has become a common practice, but Mg deficiency still remains unaddressed. Screening for chronic magnesium deficiency is difficult because a normal serum level may still be associated with moderate to severe deficiency. To date, there is no simple and accurate laboratory test to determine the total body magnesium status in humans. Mg is essential in the metabolism of vitamin D, and taking large doses of vitamin D can induce severe depletion of Mg. Adequate magnesium supplementation should be considered as an important aspect of vitamin D therapy.

Haloperidol, a Novel Treatment for Cannabinoid Hyperemesis Syndrome.

Abstract: Cannabinoid hyperemesis syndrome (CHS) is typically unresponsive to conventional pharmacologic antiemetics, and patients often require excessive laboratory and radiographic testing and hospital admission. We report 4 cases of CHS that failed standard emergency department therapy but improved significantly after treatment with haloperidol. Although the exact mechanism for CHS remains unclear, dysregulation at cannabinoid type 1 seems to play a role. Recent animal data demonstrate complex interactions between dopamine and cannabinoid type 1 signaling, a potential mechanism for haloperidol success in patients with CHS. Our success with haloperidol in these 4 patients warrants further investigation of haloperidol as an emergency department treatment for CHS.

Potential Clinical and Economic Impact of Switching Branded Medications to Generics

Abstract: Switching branded to generic medications has become a common cost-containment measure. Although this is an important objective for health care systems worldwide, the impact of this practice on patient outcomes needs to be carefully considered. We reviewed the literature summarizing the potential clinical and economic consequences of switching from branded to generic medications on patient outcomes. A literature search of peer-reviewed articles published 2003-2013 using key words of "generic switching" or "substitution" was conducted using PubMed, OvidSP, and ScienceDirect. Of 30 articles identified and reviewed, most were related to the diseases of the central nervous system, especially epilepsy. Based on our review, potential impacts of switching fell into 3 broad categories: patient attitudes and adherence, clinical and safety outcomes, and cost and resource utilization. Although in many cases generics may represent an appropriate alternative to branded products, this may not always be the case. Specifically, several studies suggested that switching may negatively impact medication adherence, whereas other studies found that generic switching was associated with poorer clinical outcomes and more adverse events. In some instances, switching accomplished cost savings but did so at increased total cost of care because of increased physician visits or hospitalizations. Although in many cases generics may represent an appropriate alternative, mandatory generic switching may lead to unintended consequences, especially in certain therapeutic areas. Although further study is warranted, based on our review, it may be medically justifiable for physicians and patients to retain the right to request the branded product in certain cases.

A Randomized, Placebo-Controlled Clinical Trial of Efficacy and Safety: Modafinil in the Treatment of Fatigue in Patients With Primary Biliary Cirrhosis.

Abstract: Background and aims Fatigue is a common symptom of primary biliary cirrhosis (PBC), and is associated with an impaired quality of life. Study question No studies have assessed the use of modafinil in fatigue related to PBC in a controlled manner. Study design, measures, and outcomes A randomized, double-blind, placebo-controlled study was conducted to determine the safety and efficacy of modafinil for the treatment of fatigue in PBC. Forty patients were randomized to modafinil (n = 20) or placebo (n = 20) for 12 weeks. A verbal report of fatigue for at least 6 months was required for enrollment. Modafinil was administered at 100 mg by mouth once daily; a change by 50 mg every 2 weeks (maximum: 200 mg once daily) was allowed, depending on the subject's response to treatment. The primary outcome was defined as a ≥50% improvement in fatigue severity [quantified by the Fisk Fatigue Impact Scale (FFIS)] after 12 weeks of treatment, compared with baseline values. Results Thirty-three PBC patients completed the study. After 12 weeks of therapy, only 5 patients had a ≥50% reduction in FFIS scores: 3 patients (17.6%) in the modafinil arm and 2 (12.5%) in the placebo arm (P = 1.00). Change in median FFIS score was not statistically different between patients in the 2 treatment groups (P = 0.36). Modafinil was associated with minimal adverse events (headaches, diarrhea, and rash). Conclusions In patients with PBC who have fatigue, treatment with modafinil for 12 weeks was safe and fairly well tolerated; however, it did not result in beneficial effects on fatigue compared with patients treated with placebo (CONSORT Table 1). ClinicalTrials.gov identifier NCT00943176.

Radiofrequency Thermocoagulation in Relieving Refractory Pain of Knee Osteoarthritis.

Abstract: To investigate the efficacy of radiofrequency thermocoagulation (RFTC) in relieving refractory pain of knee osteoarthritis (OA), we selected 54 patients with chronic knee OA pain, 27 treated with RFTC (case group) and 27 receiving regular treatments (control group). Response evaluations were conducted before treatment, and at the termination of treatment, and 3-month follow-up, applying the visual analog scale, the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), and American Knee Society Score (AKSS). Data analyses were performed with SPSS 21.0. At the termination of treatments and 3-month follow-ups, cases gained significantly increased scores in vitality, bodily pain, general health perceptions, physical functioning, and social role functioning by SF-36 scaling and in pain, range of motion, stability, walking, and stair climbing by AKSS (all P < 0.05). Controls received higher scores by AKSS in pain at the termination of treatments and in pain, range of motion, and walking at the termination of 3-month follow-ups (all P < 0.05). Both cases and controls presented significant difference between visual analog scale scores before treatments and those at the termination of 3-month follow-ups (both P < 0.05). All patients felt less pain after treatments, cases presenting better improvement (P < 0.05). Pain was stronger in females compared with males and in a positive correlation with age while had no obvious relation to disease course. In conclusion, RFTC may have better efficacy in relieving refractory pain and promoting function recovery in patients with knee OA than regular treatment.

A Non-Inferiority Study: Modified Dual Therapy Consisting Higher Doses of Rabeprazole Is as Successful as Standard Quadruple Therapy in Eradication of Helicobacter pylori.

Abstract: The aim is to compare high-dose rabeprazole and amoxicillin containing modified dual therapy (MDT) with bismuth subcitrate containing standard quadruple therapy (SQT) as the first-line Helicobacter pylori eradication treatment in terms of efficacy, safety, and adherence to treatment. A total of 200 consecutive patients diagnosed endoscopically with nonulcer dyspepsia with H. pylori infection were randomly assigned into 2 groups, 1 treated with amoxicillin 750 mg thrice daily plus rabeprazole 20 mg thrice daily (MDT group) or rabeprazole 20 mg b.i.d., bismuth subcitrate 120 mg q.i.d., tetracycline 500 mg q.i.d., metronidazole 500 mg t.i.d. (SQT group). Overall, 196 patients (98 in the MDT group and 98 in the SQT group) completed the study. H. pylori eradication was achieved in 84.7% of patients in the MDT group by intention to treat analysis and 84.9% by per-protocol analysis, which were comparable with SQT group (87.8% and 88.8%, respectively). Adverse events including nausea (P = 0.03), dysgeusia (P < 0.001), diarrhea (P = 0.001), black colored stool (P < 0.001), headache (P = 0.01), and abdominal pain (P = 0.05) were significantly higher in SQT group. The MDT is an efficient and safe treatment choice that could be recommended in the first-line eradication treatment of H. pylori.

Emergency Department Treatment of Cannabinoid Hyperemesis Syndrome: A Review.

Abstract: Background Cannabinoid hyperemesis syndrome (CHS) is a syndrome of cyclic vomiting associated with chronic cannabis use. As cannabis consumption steadily increases each year, CHS is becoming a commonplace and costly occurrence in hospitals nationwide. Currently, there are no best treatment strategies agreed upon universally. Areas of uncertainty Thus far, most data about CHS have come from case reports and case series. Consequently, the pathophysiology of the syndrome is unclear, and its occurrence in some cannabis users, but not others, is not understood. Data sources A literature search was conducted through PubMed, Embase, and Google Scholar from inception until 2017. Publications only in English describing the epidemiology, pathophysiology, diagnostic criteria, and treatments of CHS were incorporated after thorough evaluation. National government surveys were also referred to for current information about the CHS patient population. Results CHS should be considered in the differential diagnosis of any patient presenting with persistent nausea and vomiting. In particular, the diagnosis is suggested if the patient demonstrates regular and chronic cannabis use, intractable nausea and vomiting, cyclical vomiting, relief of symptoms with hot baths, and resolution of symptoms after cannabis cessation. There are currently many possible explanations regarding the mechanisms behind CHS. A variety of treatment options have also been examined, including hot water baths, haloperidol, capsaicin, and benzodiazepines. Conclusions CHS is becoming an increasingly prevalent and complicated problem for health care providers and patients. Further research must be done to address the diagnostic and therapeutic challenges of this syndrome.

Pilot Study of the Tart Cherry Juice for the Treatment of Insomnia and Investigation of Mechanisms.

Abstract: BACKGROUND Insomnia is common in the elderly and is associated with chronic disease, but use of hypnotics increases the incidence of falls. Montmorency tart cherry juice has improved insomnia by self-report questionnaire. STUDY QUESTION Is insomnia confirmed by polysomnography and is tryptophan availability a potential mechanism for treating insomnia? STUDY DESIGN A placebo-controlled balanced crossover study with subjects older than 50 years and insomnia were randomized to placebo (2 weeks) or cherry juice (2 weeks) (240 mL 2 times/d) separated by a 2-week washout. MEASURES AND OUTCOMES Sleep was evaluated by polysomnography and 5 validated questionnaires. Serum indoleamine 2,3-dioxygenase (IDO), the kynurenine-to-tryptophan ratio, and prostaglandin E2 were measured. In vitro, Caco-2 cells were stimulated with interferon-gamma, and the ability of cherry juice procyanidin to inhibit IDO which degrades tryptophan and stimulates inflammation was measured. The content of procyanidin B-2 and other major anthocyanins in cherry juice were determined. RESULTS Eleven subjects were randomized; 3 with sleep apnea were excluded and referred. The 8 completers with insomnia increased sleep time by 84 minutes on polysomnography (P = 0.0182) and sleep efficiency increased on the Pittsburgh Sleep Quality Index (P = 0.03). Other questionnaires showed no significant differences. The serum kynurenine-to-tryptophan ratio decreased, as did the level of prostaglandin E2 (both P < 0.05). In vitro, cherry juice procyanidin B-2 dose-dependently inhibited IDO. CONCLUSIONS Cherry juice increased sleep time and sleep efficiency. Cherry juice procyanidin B-2 inhibited IDO, increased tryptophan availability, reduced inflammation, and may be partially responsible for improvement in insomnia.

The Impact of Proton Pump Inhibition on Dabigatran Levels in Patients With Atrial Fibrillation.

Abstract: BACKGROUND Proton pump inhibition (PPI) administrated together with dabigatran reduces the risk of gastrointestinal hemorrhage. However, there is a discussion regarding possible PPI-dabigatran interaction that may reduce the efficacy of this therapy. STUDY QUESTION To determine the impact of concomitant PPI on dabigatran plasma levels in patients with nonvalvular atrial fibrillation (NV-AF). STUDY DESIGN A pilot prospective study in patients with NV-AF on dabigatran therapy was performed; 31 patients were enrolled. PPI with either omeprazole or pantoprazole was administrated in 19 patients. MEASURES AND OUTCOMES Blood samples were taken for the assessment of the dabigatran trough and peak levels. Dabigatran concentration was measured with the Hemoclot Thrombin Inhibitor Assay. RESULTS There were significant differences in dabigatran trough level comparing patients treated with PPI and patients without PPI (58.86 ± 36.76 ng/mL vs. 110.72 ± 88.47 ng/mL, P < 0.05). Similarly, there were significant differences in dabigatran peak level between compared groups (88.0 ± 20.5 ng/mL vs. 174.4 ± 139.64 ng/mL, P < 0.05). CONCLUSIONS This pilot study demonstrated the interaction between PPI and dabigatran levels in patients with NV-AF.

Droxidopa in the Treatment of Postural Orthostatic Tachycardia Syndrome.

Abstract: Background Postural orthostatic tachycardia syndrome (POTS) is a constellation of signs and symptoms that occur when a patient is upright and relieved by recumbence. Currently, no drugs are labeled for the treatment for POTS. Droxidopa is an orally administered amino acid that is converted to norepinephrine and thought to improve both blood pressure and symptoms in patients with orthostatic intolerance. Study question To appraise the effect of Droxidopa in a clinical setting in patients with POTS refractory to other forms of treatment. Study design A retrospective study of patients with POTS at our Syncope and Autonomic Disorders Center. Three hundred fifty-two patients were screened, 54 of them were prescribed Droxidopa and found to be eligible to include in our study. Measures and outcome Symptoms of orthostatic intolerance, side effects of therapy and response to treatment. Statistical analyses were done using SPSS software. Thirty-seven patients were included in data analysis. Patients who failed to follow up, didn't obtain Droxidopa due to insurance and cost concerns, had hypertensive response to therapy or had allergic reaction were excluded from data analysis. Results The most frequently reported symptom was dizziness in 91.9% of patients, followed by syncope and fatigue in 70.3% and 67.6% of patients, respectively. Symptoms of dizziness, syncope and fatigue were reported less after treatment; 75.7%, 51.4% and 40.5%, respectively. There was no statistically significant difference in standing or sitting blood pressure before and after treatment. Despite the improvement in some symptoms. Only 27% of patients reported improved quality of life after treatment. Of total, 40.5% of patients stopped the treatment either due to side effects or ineffectiveness. Conclusion Droxidopa appears to improve some symptoms of orthostatic intolerance in patients with POTS but has diminutive impact on quality of life and blood pressure. Further assessment in large clinical trials is needed to evaluate its efficacy.

Comparison of the Clinical Effectiveness of PFNA, PFLCP, and DHS in Treatment of Unstable Intertrochanteric Femoral Fracture.

Abstract: In this study, a randomized trial was conducted to compare the clinical effectiveness of proximal femoral locking compression plate (PFLCP), dynamic hip screw (DHS), and proximal femoral nail antirotation (PFNA) for unstable intertrochanteric femoral fracture treatment. Ninety patients diagnosed with unstable intertrochanteric femoral fracture were enrolled in this study at the department of orthopedics at Linyi Second People's Hospital between May 2010 and May 2012. Fractures were classified according to Tronzo-Evans classification, and the patients were randomly divided into 3 groups, PFLCP, DHS, and PFNA, with 30 patients in each group. The length of incision, operative time, intraoperative blood loss, postoperative drainage, postoperative weight-bearing ambulation time, and duration of fracture union were significantly lower in patients who underwent PFNA and PFLCP compared to patients treated with DHS. Furthermore, when the same clinical parameters were used for comparison, the PFNA group showed markedly lower values compared with the PFLCP group. The total incidence of postoperative complications was significantly different among the PFNA, PFLCP, and DHS groups, with the PFNA group exhibiting markedly lower complication rates compared with PFLCP and DHS groups. However, PFLCP and DHS groups did not show significant differences in the incidence of postoperative complications. Notably, the Harris hip score of PFNA group was markedly higher than the DHS group. In conclusion, our results provide convincing evidence that PFNA may be the most effective internal fixation treatment of unstable intertrochanteric femoral fracture.

Immunoresponsive Autonomic Neuropathy in Sjögren Syndrome-Case Series and Literature Review.

Abstract: Background Sjogren syndrome (SS) is one of the most common autoimmune disorders that classically affects exocrine glands, resulting in keratoconjunctivitis sicca and xerostomia, and frequently is associated with other systemic symptoms. SS appears to have a particular predilection for involving the autonomic nervous system. Study question Does immunotherapy improve signs and symptoms of autonomic nervous system impairment in SS? Study design This is a retrospective review of patients seen in the autonomic clinic at our institution who underwent an evaluation for a suspected autonomic disorder that ultimately was attributed to SS. SS patients who were treated with immunotherapy and completed autonomic testing before and after treatment were included in this review. Results A total of 4 patients were identified who were treated for SS-related autonomic dysfunction with immunotherapy and underwent repeat autonomic testing after treatment. Marked clinical and functional improvement was seen after treatment with intravenous immunoglobulin in all patients and adjunctive rituximab therapy in 1 patient. The clinical improvement with immunotherapy in these patients correlated with markedly improved findings on autonomic testing in all. Measures and outcomes Clinical symptoms and results of autonomic testing prior to and following immunotherapy were assessed. Conclusions Autonomic signs and symptoms in SS are potentially immunoresponsive, but immunotherapy in these patients may require repeated, ongoing, or adjunctive therapy for optimal and sustained improvement.

Efficacy and Safety of Proton Pump Inhibitors in the Long-Term Aspirin Users: A Meta-Analysis of Randomized Controlled Trials.

Abstract: BACKGROUND Long-term aspirin use in cardiovascular disease prevention may result in gastrointestinal bleeding. Although proton pump inhibitors (PPI) have been shown to reduce the risks of peptic ulcers and dyspeptic symptoms in long-term aspirin users in the randomized controlled trials, there are safety concerns about the long-term use of PPI. STUDY QUESTION What is the safety and efficacy of PPI in patients using aspirin in long term for prevention of cardiovascular diseases and stroke? METHODS We searched MEDLINE, EMBASE, CENTRAL, CINAHL, ProQuest, and relevant references from inception through February 2015, and used random-effects model for meta-analysis. RESULTS A total of 10 publications from 9 studies (n = 6382) were included in the meta-analysis. Compared with control, PPI reduced the risks of peptic ulcers [risk ratio (RR): 0.19; 95% confidence interval: 0.13-0.26; P < 0.00001], gastric ulcers [0.24 (0.16-0.35); P < 0.00001], duodenal ulcers [0.12 (0.05-0.29); P < 0.00001], bleeding ulcers [0.22 (0.10-0.51); P = 0.0004], and erosive esophagitis [0.14 (0.07-0.28); P < 0.00001]. PPI increased the resolution of epigastric pain [1.13 (1.03-1.25); P = 0.01], heartburn [1.24 (1.18-1.31); P < 0.00001], and regurgitation [1.26 (1.13-1.40); P < 0.0001], but did not increase the risks of all-cause mortality [1.72 (0.61-4.87); P = 0.31], cardiovascular mortality [1.80 (0.59-5.44); P = 0.30], nonfatal myocardial infarction/ischemia [0.56 (0.22-1.41); P = 0.22], ischemic stroke/transient ischemic attack [1.09 (0.34-3.53); P = 0.89] and other adverse events. CONCLUSIONS The PPI seems to be effective in preventing peptic ulcers and erosive esophagitis and in resolution of dyspeptic symptoms without increasing adverse events, cardiac risks or mortality in long-term aspirin users.

MiR-221 Exacerbate Cell Proliferation and Invasion by Targeting TIMP3 in Papillary Thyroid Carcinoma.

Abstract: MiR-221 is frequently upregulated in papillary thyroid cancer (PTC) tissues and cell lines, and this study was designed to validate the association of miR-221 with PTC proliferation, apoptosis, and migration. We observed that miR-221 suppressed TIMP3 expression by binding to 3' untranslated region of TIMP3 mRNA, and TIMP3 expression was increased with the presence of miR-221 inhibitors; TIMP3 siRNA could reverse the effects of miR-221 inhibitors on PTC cells. The results indicated that miR-221 exacerbated PTC by downregulating the expression of TIMP3. The effects of miR-221 and TIMP3 in vivo were also confirmed by human PTC-bearing mice models which suggest consistent results with those in vitro studies. In summary, miR-221 could aggravate cell proliferation and invasion of PTC by targeting TIMP3.

Comparison of 3-Factor Versus 4-Factor Prothrombin Complex Concentrate With Regard to Warfarin Reversal, Blood Product Use, and Costs

Abstract: BACKGROUND Prothrombin complex concentrates (PCCs) are drug products containing varying amounts of vitamin K-dependent coagulation factors II, VII, IX, and X. The evidence comparing 3-factor PCC (3-PCC) versus 4-factor PCC (4-PCC) for warfarin reversal is conflicting. It has been hypothesized that 3-PCC may be less effective than 4-PCC because of relatively lower factor VII content. STUDY QUESTION The primary objective of this study was to compare international normalized ratio (INR) reversal between 3-PCC and 4-factor PCC (4-PCC) in warfarin-treated patients. The secondary objectives include comparing blood product use, total reversal costs, and cost-effectiveness between the groups. STUDY DESIGN This was a retrospective cohort study conducted in 2 affiliated, academic institutions in the United States. Consecutive adult patients who received 3-PCC or 4-PCC for warfarin reversal were included. MEASURES AND OUTCOMES The primary outcome was adequate INR reversal defined as a final INR ≤1.5. Secondary outcomes were the utilization of plasma, red blood cells and platelets, reversal costs, and the cost-effectiveness ratio. RESULTS There were 89 patients who were included in the overall cohort (3-PCC = 57, 4-PCC = 32). Adequate INR reversal occurred less commonly with 3-PCC (45.6%) compared with 4-PCC (87.5%) (P < 0.001). There was no significant difference in the proportion of patients who received plasma (32% vs. 28%, P = 0.813), red blood cells (37% vs. 47%, P = 0.377), or platelets (16% vs. 28%, P = 0.180) between the 3-PCC and 4-PCC groups, respectively. The median reversal cost of 3-PCC ($3663) was lower than 4-PCC ($5105) (P = 0.001). The cost-effective ratio favored 4-PCC ($5105/87.5% = $5834) compared with 3-PCC ($3663/45.6% = $8033). CONCLUSIONS Four-PCC was more effective than 3-PCC with regard to INR reversal in patients taking warfarin, but blood product use was similar. Although 4-PCC is associated with increased reversal costs, it may be cost-effective in terms of INR reversal.

Selected Food/Herb-Drug Interactions: Mechanisms and Clinical Relevance.

Abstract: Background Food/Herb-drug interactions have become a major problem in health care. These interactions can lead to loss of therapeutic efficacy or toxic effects of drugs. Areas of uncertainty To probe the clinical relevance of such interactions, the impact of food/herb intake on the clinical effects of drug administration has to be evaluated. Failure to identify and efficiently manage food-drug interactions can lead to serious consequences. A comprehensive knowledge of the mechanisms that underpin variability in disposition will help optimize therapy. Data sources Electronic search of literatures from relevant databases were conducted. A total of 58 original scientific reports/review articles were obtained with the search strategy; of which 25 were found eligible to be included in the present review. Required data were extracted from these studies, and their methodologies were assessed. Results and conclusions This review updates our knowledge on clinical food-drug interactions with emphasis on mechanism and clinical implications. Results obtained from literature search identified interactions with selected foods/herbs generated from in vivo and in vitro studies. For example, interaction studies in humans revealed a reduction in the bioavailability of mercaptopurine when taken concurrently with substances containing xanthine oxidase (eg, cow milk); a reduction in the bioavailability of quinine with Garcinia kola; increased bioavailability/toxicity of felodipine, nifedipine, saquinavir, sildenafil with grape juice; increased bioavailability of felodipine, cisapride with red wine and diminished bioavailability of fexofenadine with apple. Pharmacokinetic and/or pharmacodynamic mechanisms are implicated in many of these interactions. By evaluating the dietary patterns of patients and use of prescribed medications, health professionals will be well informed of potential interactions and associated adverse effects.

Contact Allergy to Topical Mometasone Furoate Confirmed by Rechallenge and Patch Test.

Abstract: To the Editor: A 65-year-old woman consulted for an itchy rash of the upper limbs. The patient’s history in the last 3 years revealed hands’ dryness, redness, and fissures aggravated by dishwashers and cold season. Her General Practitioner prescribed topical corticosteroids with temporary relief. Three weeks before consultation while applying mometasone furoate (MF) ointment twice daily, skin lesions worsened and the rash spread. The itchy rash was first erythematosquamous then began to ooze and to spread from hands and wrists to the popliteal fossae. No other topical agent and no systemic treatment were in use at this time. Clinical examination showed erythematosquamous, pruriginous lesions with discrete fissuring on the carpal–metacarpophalangeal joints and a pruriginous area with erythema and crusting on cubital fosse. Suspicion of palmar psoriasis or contact dermatitis to MF wase made. Cessation of the MF ointment was associated with the prescription of tacrolimus ointment at 0.1% in alternance with petrolatum. The rash reappeared once more after 4 days after reapplication (by mistake of the patient). Patch test was positive for MF and for budesonide. It was negative for tixocortol-21pivalate (the other topical steroid available for patch testing), lanoline, propilenglycol, and stearilic alcohol (vehicle ingredients). The patch test was also negative for bisphenol-A-diglycidyl ether leachables from aluminum tubes. The testing concentration for MF was 0.01%, and the first reading of the test was performed at day 72 hours because the antiinflammatory action may suppress an allergic reaction at an earlier reading. The patient denied the previous use of budesonide. She previously used as topical treatment hydrocortisone 17butyrate, triamcinolone acetonide, flumethasone pivalate, fluocinolone acetonide, betamethasone dipropionate, fluticasone propionate, and methylprednisolone aceponate (MA) without cutaneous side effects such as contact dermatitis and no efficiency on the skin condition. She used clobetasol propionate without induced contact dermatitis and with a slight improvement of the skin condition. MF, a synthetic 16 alpha-methyl analog of beclomethasone, is classified as a potent glucocorticoid for dermatological use. It is available as 0.1% cream, ointment, and lotion formulations for the treatment of patients with inflammatory dermatoses. The effect of MF 0.1% applied once daily over 2–3 weeks were similar to betamethasone dipropionate 0.05% twice daily and MA 0.1% once daily.1 Transient, mild local adverse effects such as burning, stinging, folliculitis, dryness, acneiform eruptions, and signs of skin atrophy have been reported with MF. It has shown a low risk of primary sensitization and cross reactions with other steroids when they have a common chemical structure.1 Oh-i T2 classify steroids reported to cause allergy into the following types: (1) The type recognizing betamethasone and/or dexamethasone. Regardless of whether the methyl group at the C-16 position of the D ring is on the alpha/beta side, the size of the blocking group of the hydroxy residue seems to be associated with the reaction; (2) The type in which a cis-diaxial-diol side chain in the alpha side of C-16 and C-17 positions of the ring D or its ketal blocking group seems to be associated with the reaction. Up to 5% of dermatitis patients are allergic to corticosteroids. Because such allergy may be difficult to suspect because of the anti-inflammatory action of the corticosteroid, markers for corticosteroid allergy such as budesonide and tixocortol-21-pivalate should be present in any standard series.3 The patch test concentration for a given corticosteroid is important. A falsenegative reaction may follow despite the patient being allergic, if too high a test concentration is used, because of the anti-inflammatory action of the corticosteroid. Patch test readings must be performed not only on day 3 or 4 but also on day 7 after test application because the anti-inflammatory action may suppress an allergic reaction at an early reading.4,5 Once a patient has reacted to a corticosteroid, an extensive corticosteroid series should be tested, so that information may be given on which corticosteroids to use and which to avoid.5 American Journal of Therapeutics 0, 1–2 (2017)

Comparison of Haploidentical Hematopoietic Stem Cell Transplantation and Immunosuppressive Therapy for the Treatment of Acquired Severe Aplastic Anemia in Pediatric Patients

Abstract: This study aimed to compare the efficacy and safety between haploidentical hematopoietic stem cell transplantation (HHCT) and immunosuppressive therapy (IST) for the treatment of pediatric acquired severe aplastic anemia (SAA). The clinical data of 28 children with SAA treated from June 2010 to October 2014 at our hospital were retrospectively reviewed. Of these patients, 18 were treated with HHCT and 10 with IST. The median follow-up time was 23.5 months (range, 3-52 months). There was no significant difference in overall survival rate between the HHCT group and the IST group (66.7% vs. 70%, P > 0.05). Graft-versus-host disease occurred in 83.3% (15/18) of the HHCT group, including 5 cases with grade III or higher. In comparison with IST, HHCT has similar efficacy and safety profiles in the treatment of pediatric SAA.

Ipilimumab-Induced Sarcoidosis and Thyroiditis.

Abstract: antigens are presented by major histocompatibility complex class II, activating helper T cells that subsequently recruit cytotoxic T cells, B cells, and natural killer cells, and hepatocytes finally undergo apoptosis. Neoantigens also prompt development of autoantibodies to cytochrome P450. Oxidative stress and mitochondrial dysfunction also play an important role.6 This case demonstrates the importance of recognizing autoimmune-like hepatotoxicity associated with nitrofurantoin because it can lead to cirrhosis. Clinicians should always outweigh the benefits versus risks when prescribing nitrofurantoin and monitor liver function tests periodically when prescribed long -term.

Bullous Reactions Associated With COX-2 Inhibitors.

Abstract: CASE REPORTA 52-year-old man presented with a rash, which had been present for 2 days before his clinic visit. The rash developed 8 days after inception of oral treatment with etoricoxib, 60 mg o.d. for persistent joint pains (Figure 1A). Examination revealed a rash comprising bullae some on erythem

Limitations of Sacubitril/Valsartan in the Management of Heart Failure.

Abstract: BACKGROUND The PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure) trial was a double-blind trial that randomized 8442 patients with heart failure (HF) with reduced ejection fraction (HFrEF) to receive twice daily dosing of either 200 mg of LCZ696 or 10 mg of enalapril in addition to standard medical therapy for HF. AREAS OF UNCERTAINTY Limitations of this trial include (1) sacubitril has not been tested by itself in the treatment of HFrEF; (2) the maximum recommended dose of valsartan for the treatment of HFrEF was used in this trial, but the maximum recommended dose of enalapril for the treatment of HFrEF was not used; (3) a run-in phase was used in this trial to test the tolerability of LCZ696, and patients who had adverse effects in this period were excluded from randomization; (4) the percent of blacks enrolled in this trial was only 5%; (5) LCZ696 caused a 14% incidence of hypotension; (6) neprilysin inhibition might favor the development of Alzheimer dementia, which was not assessed in the PARADIGM-HF trial; (7) patients with severe symptomatic HF were underrepresented in this trial; (8) major exclusions from this trial included an acute coronary event in the last 3 months, severe pulmonary disease, hepatic impairment, and an estimated glomerular filtration rate <30 mL per minute per 1.73 m. DATA SOURCES Review of the PARADIGM-HF trial. RESULTS At 27-month follow-up, the PARADIGM-HF trial showed that compared with enalapril, LCZ696 reduced the composite of cardiovascular death or hospitalization for HF 20% (absolute risk reduction 4.7%, P < 0.001). CONCLUSIONS The numerous limitations discussed under the areas of uncertainty should be considered when prescribing LCZ696 for the treatment of HFrEF.

Misuse of Prescribed Pain Medication in a Military Population-A Self-Reported Survey to Assess a Correlation With Age, Deployment, Combat Illnesses, or Injury?

Abstract: Opioid misuse is a growing epidemic among the civilian and military communities. Five hundred prospective, anonymous surveys were collected in the emergency department waiting room of a military tertiary care hospital over 3 weeks. Demographics, medical and military characteristics were investigated for association with opioid use. Univariate logistic models were used to characterize the probability of misuse in relation to the demographic, medical, and military-specific variables. Traumatic brain injury (TBI) and posttraumatic stress disorder were investigated within different age cohorts with adjustment for deployment. The opioid misuse rate disclosed by the subject was 31%. Subjects with TBI were less likely to misuse opioids. We found a trend among younger cohorts to have a higher likelihood for misusing opioids when diagnosed with TBI or posttraumatic stress disorder with history of deployment in the past 5 years. The most common form of misuse was using a previously prescribed medication for a new pain. Traumatic brain injury and/or enrollment in post-deployment recovery programs maybe protective against opioid misuse. Chronic opioid use among young soldiers maybe viewed as a weakness that could influence opioid misuse. Younger cohorts of active duty service members could be at higher risk for misuse. Efforts to enhance close monitoring of misuse should address these at-risk populations.

Use of Sugammadex in Patients With Obesity: A Pooled Analysis.

Abstract: A growing proportion of patients undergoing surgical procedures are obese, providing anesthesiologists with numerous challenges for patient management. The current pooled analysis evaluated recovery times following sugammadex reversal of neuromuscular blockade by body mass index (BMI) in general, and in particular, in patients with BMIs ≥30 kg/m (defined as obese) and <30 kg/m (defined as non-obese). Data were pooled from 27 trials evaluating recommended sugammadex doses for reversal of moderate [reappearance of the second twitch of the train-of-four (TOF); sugammadex 2 mg/kg] or deep (1-2 post-tetanic counts or 15 minutes after rocuronium; sugammadex 4 mg/kg) rocuronium- or vecuronium-induced neuromuscular blockade. All doses of sugammadex were administered based on actual body weight. The recovery time from sugammadex administration to a TOF ratio ≥0.9 was the primary efficacy variable in all individual studies and in the pooled analysis. This analysis comprised a total of 1418 adult patients treated with sugammadex; 267 (18.8%) of these patients had a BMI ≥30 kg/m. The average time to recovery of the TOF ratio to 0.9 was 1.9 minutes for rocuronium-induced blockade and 3.0 minutes for vecuronium-induced blockade. No clinically relevant correlation was observed between BMI and recovery time. The recommended sugammadex doses based on actual body weight provide rapid recovery from neuromuscular blockade in both obese and non-obese patients; no dose adjustments are required in the obese patient.

Acute Opiate Overdose: An Update on Management Strategies in Emergency Department and Critical Care Unit.

Abstract: Background Opioids are natural, semisynthetic, or synthetic substances that act on opioid receptors in the central nervous system. Clinically, they are prescribed for pain management. Opioid overdose (OOD) occurs when the central nervous system and respiratory drive are suppressed because of excessive consumption of the drug. Symptoms of OOD include drowsiness, slow breathing, pinpoint pupils, cyanosis, loss of consciousness, and death. Due to their addictive potential and easy accessibility opioid addiction is a growing problem worldwide. Emergency medical services and the emergency department often perform initial management of OOD. Thereafter, some patients require intensive care management because of respiratory failure, metabolic encephalopathy, acute kidney injury, and other organ failure. Areas of uncertainty We sought to review the literature and present the most up-to-date treatment strategies of patients with acute OOD requiring critical care management. Data sources A PubMed search was conducted to review all articles between 1950 and 2017 and the relevant articles were cited. Results & conclusions Worldwide, approximately 69,000 people die of OOD each year, and approximately 15 million people have opioid addiction. In the United States, death from OOD has increased almost 5-fold from 2001 to 2013. OOD leading to intensive care unit admission has increased by 50% from 2009 to 2015. At the same time, the mortality associated with these admissions has doubled. The management strategies include airway management, use of reversal agents, assessing and treating coingestions and associated complications, treatment of opioid withdrawal with alpha-agonists, and psychosocial support to help with opiate addiction and withdrawal. This warrants awareness among clinicians regarding the adverse effects associated with opioid use, management strategies, and calls for a multidisciplinary approach to treating these patients.

Preadmission Use of Calcium Channel Blockers and Outcomes After Hospitalization With Pneumonia: A Retrospective Propensity-Matched Cohort Study.

Abstract: In sepsis, an overwhelming immune response, as mediated by the release of various inflammatory mediators, can lead to shock, multiple organ damage, and even death. Pneumonia is the leading cause of sepsis. In animal septic models, sepsis could induce uncontrolled calcium (Ca) leaking, raising cytosolic Ca to a toxic level, causing irreversible cellular injuries and organ failure. All types of calcium channel blockers (CCBs), by inhibiting Ca influx, have been shown to decrease overall mortality in various septic animal models. However, to our best knowledge, no clinical study had been conducted to investigate the beneficial effect(s) of CCBs in sepsis. We conducted a retrospective propensity-matched cohort study after screening 2214 patients hospitalized for pneumonia from year 2012 to 2014 at our institution. We identified 387 preadmission CCB users and 387 nonusers by propensity score matching. Logistic regression analysis was then used to determine the association between preadmission CCB use and outcomes in pneumonia. Our study showed that the odds for development of severe sepsis was significantly lower in the CCB user group [odds ratio (OR), 0.466; 95% confidence interval (CI), 0.311-0.697; P = 0.002]. Preadmission CCB use was associated with a lower risk of contracting bacteremia (OR, 0.498; 95% CI, 0.262-0.99; P = 0.0327), lower risk of acute respiratory insufficiency (OR, 0.573; 95% CI, 0.412-0.798; P = 0.001), lower risk of intensive care unit admission (OR, 0.602; 95% CI, 0.432-0.840; P = 0.0028). In conclusion, our study suggested preadmission CCB use was associated with a reduction in the risks of development of respiratory insufficiency, bacteremia, and severe sepsis in patients admitted to the hospital with pneumonia.

Hypomagnesemia Among Outpatient Long-Term Proton Pump Inhibitor Users.

Abstract: Proton pump inhibitors (PPIs) are extensively prescribed drugs usually used for a long period. Recent reports linked PPI use with development of hypomagnesemia. However, there is still uncertainty regarding risk of hypomagnesemia in outpatients who were on long-term PPI use. Thus, we aimed to evaluate frequency of hypomagnesemia among a well-defined outpatient patient cohort with no other possible risk factors affecting serum magnesium levels. This was a case-control study carried out at the outpatient gastroenterology clinic of a University hospital. Patients who were on PPI therapy for at least 6 months without diuretic use and chronic kidney disease were included. Patients who were subjected to the same inclusion and exclusion criteria and not using PPI were included as control subjects. One hundred fifty-four patients and 84 control subjects were included. The mean duration of PPI use was 27.5 ± 2.5 months. Mean serum magnesium levels of PPI users and nonusers were 2.17 ± 0.20 mg/dL and 2.19 ± 0.15 mg/dL, respectively. None of the patient had a serum magnesium level below laboratory lower range of 1.7 mg/dL. Our results showed that for typical gastroenterology outpatient clinic patients with no other risk factors affecting serum magnesium levels, long-term PPI use did not affect serum magnesium levels.

Efficacy and Safety of Zoledronic Acid for Treatment of Postmenopausal Osteoporosis: A Meta-Analysis of Randomized Controlled Trials.

Abstract: We conducted a meta-analysis based on eligible studies to assess the efficacy and safety of zoledronic acid treatment for postmenopausal women with osteoporosis. PubMed, Web of Science, and Embase were searched for eligible studies that assessed the efficacy of zoledronic acid in the prevention of fractures among postmenopausal women with osteoporosis. The primary outcomes were new vertebral fracture, nonvertebral fracture, and hip fracture. Secondary outcomes were bone mineral density (BMD) and safety outcomes. A fixed-effect or random-effect model was used to pool the estimates according to the heterogeneity among the included studies. Eight randomized controlled trials, involving 13,335 patients, were included in this meta-analysis. Pooled results showed that treatment with zoledronic acid significantly reduced the incidences of nonvertebral fractures, vertebral fractures, and hip fractures, as compared with placebo. Zoledronic acid was also associated with significant improvement in BMD at lumbar spine, total hip, femoral neck, and trochanter. However, the incidence of any adverse events was higher in the zoledronic acid group than that in the control group, and serious adverse events were comparable between the 2 groups. This meta-analysis indicated that zoledronic acid could significantly reduce the fracture risk and increase BMD in postmenopausal women with osteoporosis. Furthermore, it would not result in serious adverse events. Zoledronic acid could be used as an effective and well-tolerated treatment for postmenopausal women with osteoporosis.