Assessing the quality of antenatal corticosteroids in low- and middle-income countries: A systematic review.

BACKGROUND: The World Health Organization (WHO) recommends the administration of intramuscular antenatal corticosteroids to women at risk of preterm birth to prevent preterm-associated neonatal mortality and morbidity. Poor quality medicines are a major problem for health services in low- and middle-income countries (LMICs), however the quality of antenatal corticosteroids is not well understood. We aimed to conduct a systematic review of available studies describing the quality of recommended injectable antenatal corticosteroids (dexamethasone or betamethasone) in LMICs. METHODS: Structured search strategy was applied to six databases (MEDLINE, EMBASE, CINAHL, International Pharmaceutical Abstracts, Global Index Medicus, WHO Medicines Quality Database), without year or language restrictions. Any primary study reporting any medicine quality parameter (Active Pharmacological Ingredient, pH and sterility) for injectable dexamethasone or betamethasone was eligible. Two authors independently screened studies for eligibility, extracted data on included studies and applied Medicine Quality Assessment Reporting Guidelines tool to assess study quality. Results were reported narratively, stratified by country of manufacture, organisation type and level of care. RESULTS: In total, 15,547 citations were screened with two eligible studies identified that focussed on dexamethasone quality (no studies of betamethasone were identified). One study included 19 samples from 9 LMICs, and the other included "less than 100 samples" from India. The prevalence of failed dexamethasone samples ranged from 3.14% to 32.2% due to inadequate Active Pharmacological Ingredient. A higher prevalence of failed dexamethasone samples were seen at the point of care and the public sector. CONCLUSIONS: Poor quality maternal and newborn health medicines can endanger women and newborns. Though available evidence on antenatal corticosteroids quality in LMICs is limited, results suggested poor quality dexamethasone may be prevalent in some countries. More primary studies are required to confirm these findings and guide policymakers on procurement of good-quality maternal and newborn health medicines.

Inadvertent tissue adhesive tarsorrhaphy of the eyelid: a review and exploratory trial of removal methods of Histoacryl.

OBJECTIVE: The use of tissue adhesives has become a popular option for closure of wounds in the ED. There have been a growing number of reports of inadvertent tissue adhesive injuries including closure of the eyelids. We aim to identify and compare various removal methods of tissue adhesives described in the literature in an exploratory trial. METHODS: A review was first conducted to establish all published methods for the removal of medical-grade tissue adhesives as well as commercial cyanoacrylates. This search was conducted on PubMed, Google Scholar and Google. All articles that reported attempts at removal of cyanoacrylate glues were included. These methods were then tested on a porcine model in an exploratory trial. Incisions were made on pigskin and closed with Histoacryl, a tissue adhesive. Three removal methods were tested-gentle rubbing with test compound after 45 or 90 s, as well as soaking in test compound. Removal methods that were successful underwent repeat testing. RESULTS: A total of 37 sources were reviewed with 13 different removal methods suggested. Based on the information, we tested 24 different compounds. Soaking of Histoacryl-closed wounds in Polydexa ear/eye drops displayed consistent success in achieving complete separation of incision edges after 2 hours. Several other soapy substances and antibiotic ointments showed potential but were not as consistent. CONCLUSION: In conclusion, in our trial of removal methods of Histoacryl, soaking in Polydexa antibiotic drops consistently facilitated removal after 2 hours. This approach can be attempted after inadvertent Histoacryl injury.

ED treatment of migraine patients has changed.

STUDY OBJECTIVES: Numerous studies have shown benefits of nonnarcotic treatments for emergency department (ED) migraine patients. Our goal was to determine if ED treatment of migraine patients and the rate of return within 72 h have changed. METHODS: Design: Multi-hospital retrospective cohort. POPULATION: Consecutive ED patients from 1-1-1999 to 9-31-2014. PROTOCOL: For determining treatments, we examined charts at the beginning (1999-2000) and end (2014) of the time period. We combined similar medications into the following groups: parenteral narcotics, oral narcotics, antihistamines and dopamine receptor antagonists prochlorperazine/metoclopramide (DRA). We calculated the percent of migraine patients given each treatment in each time period. We identified those who returned to the same ED within 72 h, and calculated the difference in annual return rates between 1999-2000 and 2014. RESULTS: Of the 2,824,710 total visits, 8046 (0.28%) were for migraine. We reviewed 290 charts (147 in 1999-2000 and 143 in 2014) to determine migraine treatments. The use of IV fluids, DRA, ketorolac and dexamethasone increased from 1999-2000 to 2014, whereas narcotic use and discharge prescriptions for narcotics decreased. Of the 8046 migraine patients, 624 (8%) returned within 72 h. The return rate decreased from 1999-2000 to 2014 from 12% to 4% (difference = 8%, 95% CI 5%-11%). CONCLUSION: For ED migraine patients, the use of IV fluids, DRA, ketorolac and dexamethasone increased whereas the use of narcotics and discharge prescriptions for narcotics decreased. The return rates for migraines decreased. We speculate that the increased use of non-narcotic medications contributed to this decrease.

Noninvasive detection of counterfeited ampoules of dexamethasone using NIR with confirmation by HPLC-DAD-MS and CE-UV methods.

Application of near-infrared (NIR) measurements together with chemometric data processing is widely used for counterfeit drug detection. The most difficult counterfeits to detect are the "high quality fakes", which have the proper composition but are produced in violation of technological regulations by underground manufacturers. This study uses such forgeries and addresses important issues. The first is the possibility of applying the NIR/chemometric approach to the detection of injectable formulations of drugs (in this case dexamethasone), which are aqueous solutions with low concentration of active ingredients, directly in the closed ampoules. The second issue is the comparison of NIR/chemometric conclusions with detailed chemical analysis.

Delayed emesis: moderately emetogenic chemotherapy.

Data on the incidence and efficacy of antiemetic prophylaxis against delayed emesis induced by moderately emetogenic chemotherapy are scanty. An overview of the literature has been done that showed the efficacy of dexamethasone in two of three randomized trials. Its optimal dose and duration of administration has not been defined. Only one of four randomized studies showed a statistically significant efficacy of 5-HT(3) antagonists. Finally, only weak evidence has been published on the efficacy of dopamine receptor antagonists.

The combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) is feasible and can be an option for relapsed/refractory multiple myeloma.

INTRODUCTION: Thalidomide has recently proven to be a useful drug for treatment of refractory and relapsed multiple myeloma patients, up to 35% of whom achieve remission. However, little is known about the potential additive or synergistic effect upon its association with other drugs with proven efficacy in MM. MATERIAL AND METHODS: The present pilot study was designed to evaluate the toxicity and response rate of the association of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) in 22 refractory or relapsed MM patients. The protocol scheduled the administration of thalidomide at escalating doses (200 to 800 mg/day), daily oral cyclophosphamide (CTX) (50 mg/day) and pulsed dexamethasone (40 mg/day, four days every three weeks). RESULTS: Adverse effects were moderate (grade or=2 were noted. Other side effects included grade 50% M-component reduction (two of them with a complete remission). Only two responders have already progressed, with a projected event free survival of 51% at 12 months. Seven patients have died due to disease progression (n=5), sudden death (n=1) and infection (n=1). CONCLUSION: This study shows that ThaCyDex is a feasible and promising therapeutic approach for patients with relapsed/refractory MM.

Time course of recovery and complications of HELLP syndrome with two different treatments: heparin or dexamethasone.

HELLP syndrome is a severe complication of pregnancy characterized by microangiopathic hemolytic anemia, hepatic dysfunction and thrombocytopenia. Though delivery is the ultimate therapeutic option, medical treatments, including the use of heparin or corticosteroids, have been employed in the attempt to improve maternal prognosis. The aim of this retrospective study was to compare the time course of recovery and the incidence of complications in women with HELLP syndrome receiving either heparin or dexamethasone. Between January 1990 and December 1998, 32 patients with HELLP syndrome were cared for at the Institute of Obstetrics and Gynecology of the University of Florence: 20 patients were treated with heparin, administered subcutaneously at a dose of 5000 IU every 12 h, whereas 12 women received dexamethasone, administered intravenously at a dose of 10 mg every 12 h. Categorical data were evaluated with chi-square and Fisher's exact test; continuous data were analyzed with Mann-Whitney U test; P < .05 was considered significant. In the subgroup treated with heparin the incidence of disseminated intravascular coagulation (DIC) (P < .02), the number of patients requiring blood transfusion (P < .05) and the length of stay at the Intensive Care Unit (ICU) (P < .04) were significantly increased as compared with the subgroup receiving dexamethasone; in this latter subgroup, significantly higher platelet count and hematocrit values, and significantly lower levels of lactate dehydrogenase (LDH) could be documented starting from day 2 after delivery. The results of our investigation suggest that the use of dexamethasone in patients with HELLP syndrome is associated with faster regression and lower incidence of complications in comparison to heparin.

Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91-01.

The Dana-Farber Cancer Institute (DFCI) acute lymphoblastic leukemia (ALL) Consortium Protocol 91-01 was designed to improve the outcome of children with newly diagnosed ALL while minimizing toxicity. Compared with prior protocols, post-remission therapy was intensified by substituting dexamethasone for prednisone and prolonging the asparaginase intensification from 20 to 30 weeks. Between 1991 and 1995, 377 patients (age, 0-18 years) were enrolled; 137 patients were considered standard risk (SR), and 240 patients were high risk (HR). Following a 5.0-year median follow-up, the estimated 5-year event-free survival (EFS) +/- SE for all patients was 83% +/- 2%, which is superior to prior DFCI ALL Consortium protocols conducted between 1981 and 1991 (P =.03). There was no significant difference in 5-year EFS based upon risk group (87% +/- 3% for SR and 81% +/- 3% for HR, P =.24). Age at diagnosis was a statistically significant prognostic factor (P =.03), with inferior outcomes observed in infants and children 9 years or older. Patients who tolerated 25 or fewer weeks of asparaginase had a significantly worse outcome than those who received at least 26 weeks of asparaginase (P <.01, both univariate and multivariate). Older children (at least 9 years of age) were significantly more likely to have tolerated 25 or fewer weeks of asparaginase (P <.01). Treatment on Protocol 91-01 significantly improved the outcome of children with ALL, perhaps due to the prolonged asparaginase intensification and/or the use of dexamethasone. The inferior outcome of older children may be due, in part, to increased intolerance of intensive therapy.

[Dexamethasone Sodium Phosphate Reference Standard (Control 001) of National Institute of Health Sciences].

The raw material for dexamethasone sodium phosphate was examined for the preparation of the "Dexamethasone Sodium Phosphate Reference Standard (Control 001)". The analytical data obtained were: pH, 8.0; optical rotation, [alpha]D20 = +79.6 degrees; UV spectrum, lambda max of 242 nm and specific absorbance in water at 242 nm = 313.6; IR spectrum, same as that of the Dexamethasone Sodium Phosphate Reference Standard (Control 893); free phosphoric acid, 0.06%; free dexamethasone, 0.07%; thin-layer chromatography, no impurities were detected until 100 micrograms; high-performance liquid chromatography, total amount of impurities estimated to be less than 0.2%; residual solvent, 4.3% (ethanol); water, 7.3%. Based on the above results, the raw material was authorized as the Dexamethasone Sodium Phosphate Reference Standard (Control 001) of the National Institute of Health Sciences.

Pulsed intravenous high-dose dexamethasone in adults with chronic idiopathic thrombocytopenic purpura.

The role of pulsed high-dose dexamethasone (DXM) in the treatment of patients with chronic idiopathic thrombocytopenic purpura (ITP) is still uncertain. Following an early report in which it was described as an effective and well-tolerated treatment with a sustained platelet response in 100% of cases, a number of subsequent studies have failed to confirm such favorable results. As all these studies were conducted on small numbers of patients, we investigated further the effectiveness and side effects of this therapeutic modality in a larger cohort. Thirty-two patients with chronic ITP were scheduled to receive six monthly courses of intravenous DXM at the dose of 40 mg/day for 4 consecutive days. All patients had ITP that had been resistant to between two and five different therapeutic regimens, including 9 patients who had already failed splenectomy. All patients had to be seen 2 weeks after each cycle to asses their response as well as secondary effects. Three patients failed to respond and clinically required other therapy. Thirteen patients (41%) had a partial (platelet count between 50 and 100 x 10(9)/liter) or complete (platelet count >100 x 10(9)/liter) response to treatment, responses being mostly transient. Responses were observed early during the course of treatment, usually right after the first cycle of DXM. There were no late responses. Side effects were mild and did not require discontinuation of treatment. No clinical or laboratory parameter was found to predict treatment outcome. We conclude that high-dose DXM has a limited effect in patients with chronic ITP. Novel approaches and controlled multicenter trials may help identify new therapeutic strategies for this disease.

Comparison of results of adrenocorticotropic hormone stimulation and low-dose dexamethasone suppression tests with necropsy findings in dogs: 81 cases (1985-1995).

OBJECTIVE: Comparison of diagnostic accuracy of results of low-dose dexamethasone suppression (LDDS) and ACTH stimulation tests with necropsy findings in 81 dogs. DESIGN: Retrospective study. ANIMALS: 81 dogs that had undergone screening tests for hyperadrenocorticism and that had a complete necropsy report. PROCEDURE: Medical records were evaluated for results of CBC, serum biochemical analysis, urinalysis, endocrine testing, signalment, treatment, and necropsy findings. Each dog was definitively classified as having true-positive, true-negative, false-positive, or false-negative results. Statistical analyses included determination of prevalence, apparent prevalence, accuracy, number of dogs misclassified, sensitivity, specificity, and positive- and negative-predictive values. RESULTS: Of the 81 dogs that fit the criteria for selection, 40 (49%) were confirmed as having hyperadrenocorticism (30 had pituitary-dependent disease and 10 had adrenal gland tumors). Forty-one dogs had illnesses attributable to a cause other than disease of the adrenal glands. Sensitivity of ACTH stimulation and LDDS tests were 95 and 96%, respectively. Specificity for the ACTH stimulation test was higher (91%) than that of the LDDS test (70%). When prevalence of the disease in the study population was taken into consideration, the positive-predictive value for the ACTH stimulation test was 91%, compared with 76% for the LDDS test. CLINICAL IMPLICATIONS: The ACTH stimulation test was more specific than the LDDS test, although sensitivity was similar for both tests. The ACTH stimulation test also had a significantly higher positive-predictive value than the LDDS test when a prevalence of 25% was taken into consideration.

Epidemiology and susceptibilities to mercury preservatives of staphylococci isolated from used eye-drops preserved with thiomersal.

Minimum inhibitory concentrations (MICs) of seven independent isolates of Staphylococcus hominis isolated in the same week from used eye-drops, preserved with thiomersal and collected from wards and clinics in the same hospital, ranged between 1 and 0.03 mg L-1 for thiomersal, 1 and 0.01 mg L-1 for phenyl mercuric nitrate and 10 and 3 mg L-1 for mercuric chloride. Although MIC values determined on solid nutrient medium indicated a 100-fold variation in susceptibility to the bacteriostatic effect of phenyl mercuric nitrate, after 5 h in an aqueous solution containing the bactericidal concentration of 10 mg L-1 phenyl mercuric nitrate, the survival levels of the six S. hominis isolates were similar, with a mean of 13.4% (s.d. 11.0), compared with 100 and 0.8%, respectively, for the most resistant and most sensitive control staphylococcal strains tested. Antibiotic susceptibilities and plasmid profiles of the S. hominis isolates indicated they were the same strain. It is concluded that laboratory indicators of preservative efficacy, such as MIC determination or susceptibility to bactericidal concentrations of preservatives, do not necessarily correlate with the epidemiology of contaminating bacterial strains or their survival in preserved pharmaceuticals.

[The Dexamethasone Reference Standard (Control 931) of the National Institute of Health Sciences].

Raw dexamethasone material was tested for preparation of the "Dexamethasone Reference Standard (Control 931)". Analytical data obtained were as follows: melting point, 245.1 degrees C (decomposition); infrared spectrum, the same as that of the JP Dexamethasone Reference Standard; optical rotation, -alpha-20D = + 76.75 degrees; thin-layer chromatography, two impurities were detected; high-performance liquid chromatography (HPLC), one impurity was detected; loss on drying, 0.14%; assay result, 99.4% by HPLC. Based on the above findings, the raw material was authorized as the JP Dexamethasone Reference Standard (Control 931).

[Dexamethasone Sodium Phosphate Reference Standard (Control 891) of National Institute of Hygienic Sciences].

The raw material of dexamethasone sodium phosphate was examined for preparation of the "Dexamethasone Sodium Phosphate Reference Standard". Analytical results were as follows: UV spectrum indicates absorption maxima at 242 nm and absorptivity at 242 nm is E1%1cm 304; optical rotation +79.0%; pH 7.7; ethanol 5.2%; water 6.0%; HPLC analysis indicates small amounts of three impurities and the purity was assumed to be 99.8%; assay by HPLC indicated 100.9% against the USP Reference Standard of "Dexamethasone Phosphate". Based on the results, the present raw material was authorized to be the Reference Standard of the National Institute of Hygienic Sciences.