A comprehensive analysis of selected medicines collected from private drug outlets of Dhaka city, Bangladesh in a simple random survey.

Comprehensive data are needed to prevent substandard and falsified (SF) medicines as they pose a major risk to human health. To assess the quality of selected medicines, samples were collected from random private drug outlets of Dhaka North and South City Corporation, Bangladesh. Sample analysis included visual observation of the packaging, authenticity of the samples, legitimacy and registration verification of the manufacturer, physicochemical analysis, and price. Chemical analysis of the samples was performed using a portable Raman spectroscopy and high-performance liquid chromatography according to the pharmacopoeia. Several discrepancies were noted in the visual observation of samples. Among the 189 collected samples of esomeprazole (ESM), cefixime (CFIX), and amoxicillin-clavulanic acid (CVA-AMPC), 21.2% were confirmed to be authentic, 91.3% manufacturers were confirmed legitimate, and 2.1% of all samples were unregistered. Chemical analysis of the samples revealed that 9.5% (95% CI 5.7-14.6) of samples were SFs. Falsified samples and quality variation in the same generic branded samples were both detected by Raman spectroscopic analysis. Overall, sample prices were satisfactory relative to the international reference price. This study documents the availability of poor-quality medicines, demonstrating the need for immediate attention by the national medicine regulatory authority.

Financial analysis of large-volume delayed sampling to reduce bacterial contamination of platelets.

BACKGROUND: Effective and financially viable mitigation approaches are needed to reduce bacterial contamination of platelets in the US. Expected costs of large-volume delayed sampling (LVDS), which would be performed by a blood center prior to shipment to a hospital, were compared to those of pathogen reduction (PR), point-of-release testing (PORt), and secondary bacterial culture (SBC). METHODS: Using a Markov-based decision-tree model, the financial and clinical impact of implementing all variants of LVDS, PR, PORt, and SBC described in FDA guidance were evaluated from a hospital perspective. Hospitals were assumed to acquire leukoreduced apheresis platelets, with LVDS adding $30 per unit. Monte Carlo simulations were run to estimate the direct medical costs for platelet acquisition, testing, transfusion, and possible complications associated with each approach. Input parameters, including test sensitivity and specificity, were drawn from existing literature and costs (2018US$) were based on a hospital perspective. A one-way sensitivity analysis varied the assumed additional cost of LVDS. RESULTS: Under an approach of LVDS (7-day), the total cost per transfused unit is $735.78, which falls between estimates for SBC (7-day) and PORt. Assuming 20,000 transfusions each year, LVDS would cost $14.72 million annually. Per-unit LVDS costs would need to be less than $22.32 to be cheaper per transfusion than all other strategies, less than $32.02 to be cheaper than SBC (7-day), and less than $196.19 to be cheaper than PR (5-day). CONCLUSIONS: LVDS is an effective and cost-competitive approach, assuming additional costs to blood centers and associated charges to hospitals are modest.

Detection of adulterated drugs in traditional Chinese medicine and dietary supplements using hydrogen as a carrier gas.

Helium, a minor component of natural gas and radioactive minerals, is most commonly used as a carrier in gas chromatography-mass spectrometry (GC-MS). Its scarcity leads to limited availability and higher costs. In this experiment, hydrogen from a safe source of a hydrogen generator was tested as a substitutive carrier gas for the detection of adulterant in traditional Chinese medicine (TCM) and food supplements by GC-MS analysis. We found that the limits of detection (LODs) of using hydrogen were from 10 to 1000 µg/g. The levels of LODs tested among 170 drugs remain the same whether hydrogen or helium was used as a carrier gas with the exception of 7 drugs-benzbromarone, estradiol benzoate, bezafibrate, mefenamic acid, oxymetholone, piperidenafil and cetilistat. The real sample analysis results using hydrogen were as satisfactory as those using helium. In addition, the retention time was shortened after the chromatographic performance was optimized. In summary, it is worth considering hydrogen as a carrier gas due to its affordable costs, energy efficiency, carbon reduction and chromatographic advantages to detect adulterated drugs in TCM and dietary supplement using GC-MS.

Official control of plant protection products in Poland: detection of illegal products.

Market presence of illegal and counterfeit pesticides is now a global problem. According to data published in 2012 by the European Crop Protection Association (ECPA), illegal products represent over 10% of the global market of plant protection products. Financial benefits are the main reason for the prevalence of this practice. Counterfeit and illegal pesticides may contain substances that may pose a threat to the environment, crops, animals, and humans, inconsistent with the label and registration dossier. In Poland, action against illegal and counterfeit plant protection products is undertaken by the Main Inspectorate of Plant Health and Seed Inspection (PIORiN), the police, the prosecution, and the pesticide producers. Results of chemical analyses carried out by the Institute of Plant Protection - National Research Institute Sosnicowice Branch, Pesticide Quality Testing Laboratory (PQTL IPP-NRI Sosnicowice Branch) indicate that a majority of illegal pesticides in Poland are detected in the group of herbicides. Products from parallel trade tend to have the most irregularities. This article describes the official quality control system of plant protection products in Poland and presents the analytical methods for testing pesticides suspected of adulteration and recent test results.

Epidemiological Effectiveness and Cost of a Fungal Meningitis Outbreak Response in New River Valley, Virginia: Local Health Department and Clinical Perspectives.

OBJECTIVE: We evaluated the effectiveness and cost of a fungal meningitis outbreak response in the New River Valley of Virginia during 2012-2013 from the perspective of the local public health department and clinical facilities. The fungal meningitis outbreak affected 23 states in the United States with 751 cases and 64 deaths in 20 states; there were 56 cases and 5 deaths in Virginia. METHODS: We conducted a partial economic evaluation of the fungal meningitis outbreak response in New River Valley. We collected costs associated with the local health department and clinical facilities in the outbreak response and estimated the epidemiological effectiveness by using disability-adjusted life years (DALYs) averted. RESULTS: We estimated the epidemiological effectiveness of this outbreak response to be 153 DALYs averted among the patients, and the costs incurred by the local health department and clinical facilities to be $30,413 and $39,580, respectively. CONCLUSIONS: We estimated the incremental cost-effectiveness ratio of $198 per DALY averted and $258 per DALY averted from the local health department and clinical perspectives, respectively, thereby assisting in impact evaluation of the outbreak response by the local health department and clinical facilities. (Disaster Med Public Health Preparedness. 2018;12:38-46).

A Structural Model of the Retail Market for Illicit Drugs.

We estimate a model of illicit drugs markets using data on purchases of crack cocaine. Buyers are searching for high-quality drugs, but they determine drugs' quality (i.e., their purity) only after consuming them. Hence, sellers can rip off first-time buyers or can offer higher-quality drugs to induce buyers to purchase from them again. In equilibrium, a distribution of qualities persists. The estimated model implies that if drugs were legalized, in which case purity could be regulated and hence observable, the average purity of drugs would increase by approximately 20 percent and the dispersion would decrease by approximately 80 percent. Moreover, increasing penalties may raise the purity and affordability of the drugs traded by increasing sellers' relative profitability of targeting loyal buyers versus first-time buyers.

Is insulin diluted when stored in water?

BACKGROUND: Insulin storage is a challenge in resource-poor countries. In Uganda, patients were noted to store insulin vials by submerging them in water. OBJECTIVE: To examine whether withdrawing insulin from a vial without adding air back causes a vacuum which allows water to enter the vial, resulting in insulin dilution. METHODS: Seven hundred units of insulin were withdrawn from forty 10 mL vials of 100 units/mL insulin [20 neutral protamine hagedorn (NPH), 20 regular]. In half, air was added back. The vials were weighed (baseline). Half of the vials (10 with added air, 10 without) were submerged in water for 24 h and then air-dried for 24 h. Vials that were not submerged sat at room temperature for 48 h. All vials were weighed 48 h from baseline. RESULTS: Addition of air did not impact the change in weight after submersion (air added: -0.002 ± 0.001 g or -0.2 ± 0.1 unit; no air added: -0.003 ± 0.000 g or -0.3 ± 0 unit, p = 0.57). In a subset of vials in which an additional 240 units were withdrawn before submersion for another 24 h, there was still no difference in weight change in those vials with air added (p = 0.2). CONCLUSION: Withdrawing insulin from a vial without adding air did not result in uptake of water or dilution of insulin in the submerged vial, although it made drawing up the insulin easier. This study did not address the larger concern of bacterial contamination of the rubber stopper during water storage.

Russian roulette with unlicensed fat-burner drug 2,4-dinitrophenol (DNP): evidence from a multidisciplinary study of the internet, bodybuilding supplements and DNP users.

BACKGROUND: 2,4-Dinitrophenol (DNP) poses serious health-risks to humans. The aims of this three-stage multidisciplinary project were, for the first time, to assess the risks to the general public from fraudulent sale of or adulteration/contamination with DNP; and to investigate motives, reasons and risk-management among DNP-user bodybuilders and avid exercisers. METHODS: Using multiple search-engines and guidance for Internet research, online retailers and bodybuilding forums/blogs were systematically explored for availability of DNP, advice offered on DNP use and user profiles. Ninety-eight pre-workout and weight-loss supplements were purchased and analysed for DNP using liquid-chromatography-mass-spectrometry. Psychosocial variables were captured in an international sample of 35 DNP users (26.06 ± 6.10 years, 94.3 % male) with an anonymous, semi-qualitative self-reported survey. RESULTS: Although an industrial chemical, evidence from the Internet showed that DNP is sold 'as is', in capsules or tablets to suit human consumption, and is used 'uncut'. Analytical results confirmed that DNP is not on the supplement market disguised under fictitious supplement names, but infrequently was present as contaminant in some supplements (14/98) at low concentration (<100mcg/kg). Users make conscious and 'informed' decisions about DNP; are well-prepared for the side-effects and show nonchalant attitude toward self-experimentation with DNP. Steps are often taken to ensure that DNP is genuine. Personal experience with performance- and appearance enhancing substances appears to be a gateway to DNP. Advice on DNP and experiences are shared online. The significant discrepancy between the normative perception and the actual visibility suggests that DNP use is-contrary to the Internet accounts-a highly concealed and lonesome activity in real life. Positive experiences with the expected weight-loss prevail over the negative experiences from side effects (all but two users considered using DNP again) and help with using DNP safely is considered preferable over scare-tactics. CONCLUSION: Legislation banning DNP sale for human consumption protects the general public but DNP is sold 'as is' and used 'uncut' by determined users who are not dissuaded from experimenting with DNP based on health threats. Further research with stakeholders' active participation is imperative for targeted, proactive public health policies and harm-reduction measures for DNP, and other illicit supplements.

High-frequency drug purity and price series as tools for explaining drug trends and harms in Victoria, Australia.

AIMS: Methamphetamine-related harms in Victoria have increased recently in the context of stable or declining use prevalence. We determine how changes in price and purity of methamphetamine compared to other drugs such as heroin may, in part, explain these divergent patterns. METHODS: Detailed methamphetamine and heroin purchase price data from 2152 participant interviews from the Melbourne Injecting Drug User cohort study were used to generate drug price series for the period January 2009-June 2013. Data on drug purity from 8818 seizures made within Victoria were used to generate drug purity series during the same period. Purity-adjusted price data for methamphetamine and heroin were obtained for the period 2009-13 by combining the two data sets. RESULTS: While the average purity of heroin seizures remained consistent and low, the average purity of powder and of crystal methamphetamine seizures increased from 12% [95% confidence interval (CI) = 10-14%] to 37% (95% CI = 20-54%) and 21% (95% CI = 18-23%) to 64% (95% CI = 60-68%), respectively. Crystal methamphetamine purity was bimodal, with observations generally less than 20% or greater than 70%. The average unadjusted price per gram for heroin decreased from $374 (95% CI = $367-381) to $294 (95% CI = $280-308), powder methamphetamine did not change significantly from $252 (95% CI = $233-271), and crystal methamphetamine increased substantially from $464 (95% CI = $416-511) in 2009 to $795 (95% CI = $737-853) in 2011. This increase was offset by an even greater increase in purity, meaning the average purity-adjusted price per gram declined. Furthermore, pure prices of both methamphetamine forms were similar, whereas their unadjusted prices were not. The pure price of heroin fluctuated with no ongoing trends. CONCLUSIONS: Decreases in methamphetamine purity-adjusted price along with the bimodality of crystal methamphetamine purity may account for some of the recent increase in methamphetamine-related harm. For a given amount spent, methamphetamine purchase power has increased and the presence of extreme purity variations may challenge individuals' control of consumption.

Economic assessment of aseptic compounding rooms in hospital pharmacies in five European countries.

PURPOSE: The aims of the study are to make an inventory of fixtures of aseptic compounding structures, to compare, using real examples, the design and operating costs of controlled atmosphere area (CAA) with isolators and CAA with laminar flow biological safety cabinets (BSCs) in order to determine the most economical scheme in hospitals and to give a final facilities cost calculated for one workstation. METHODS: Forty-three hospitals were interviewed (21 French and 22 from four European countries) over seven months. Hospital pharmacists completed a form with 390 items. Hospitals are compared according to their workstation type: BSCII or BSCIII (group B) and isolator (group I), using Mann and Whitney's statistical test and Monte-Carlo modeling. RESULTS: Twenty-one hospitals responded (11 French and 10 from other European countries). All European compounding unit organizations are not significantly different. The study compared items such as infrastructure cost, equipment cost, staff cost, consumable cost, cleaning cost and control cost. A synthesis of all costs has been drafted to calculate an estimated preparation cost which seemed to be higher for group B than for group I when staff costs were included ($46 and $31, respectively, in study conditions). CONCLUSIONS: The different costs studied have revealed little significant difference between group B and I. The preparation cost in group B appears higher than in group I. This pilot study has resulted in the calculation of an estimated manufactured preparation cost but this work should be completed to help optimize resources and save money.

End-preparation assessments and tests for compounded sterile preparations.

Outsourcing has become a necessity to obtain sterile products that are currently on backorder. Because of the expense of outsourcing sterile compounding, pharmacy leadership in health systems are now considering the option of insourcing and batch preparing compounded sterile preparations, which can be a viable option for a health system. It can significantly decrease drug-spending costs, and the pharmacy has a complete record of the compounding process. The key to preparing high-quality, safe, sterile preparations and meeting United States Pharmacopeia standards is end-preparation assessments and tests.

Co-phenylcaine Forte spray: innovative ways of minimising cost.

OBJECTIVE: To investigate whether multiple-use Co-phenylcaine Forte® spray was more cost-effective than single-use vials. METHODS: A literature review was conducted to determine the risk of cross-contamination associated with multiple-use topical nasal anaesthetic spray. The costs of multiple-use Co-phenylcaine Forte and single-use co-phenylcaine were compared, and potential savings were calculated. The cost of procuring these drugs from other sources was also examined. RESULTS: Switching to multiple-use Co-phenylcaine Forte spray would lead to at least 40 per cent savings if bought from our local retailer. Potential savings of more than 70 per cent could be made if the drugs were procured from sources other than our local distributor. CONCLUSION: Multiple-use Co-phenylcaine Forte spray is safe to use and more cost-effective than single-use vials. This paper illustrates how money can be saved within the National Health Service through changes in drug procurement. Similar cost savings to those calculated for our department could be made in other ENT departments nationally, depending on their annual consumption of co-phenylcaine.

Economic and microbiologic evaluation of single-dose vial extension for hazardous drugs.

PURPOSE: The update of US Pharmacopeia Chapter <797> in 2008 included guidelines stating that single-dose vials (SDVs) opened and maintained in an International Organization for Standardization Class 5 environment can be used for up to 6 hours after initial puncture. A study was conducted to evaluate the cost of discarding vials after 6 hours and to further test sterility of vials beyond this time point, subsequently defined as the beyond-use date (BUD). METHODS: Financial determination of SDV waste included 2 months of retrospective review of all doses prescribed. Additionally, actual waste log data were collected. Active and control vials (prepared using sterilized trypticase soy broth) were recovered, instead of discarded, at the defined 6-hour BUD. RESULTS: The institution-specific waste of 19 selected SDV medications discarded at 6 hours was calculated at $766,000 annually, and tracking waste logs for these same medications was recorded at $770,000 annually. Microbiologic testing of vial extension beyond 6 hours showed that 11 (1.86%) of 592 samples had one colony-forming unit on one of two plates. Positive plates were negative at subsequent time points, and all positives were single isolates most likely introduced during the plating process. CONCLUSION: The cost of discarding vials at 6 hours was significant for hazardous medications in a large academic medical center. On the basis of microbiologic data, vial BUD extension demonstrated a contamination frequency of 1.86%, which likely represented exogenous contamination; vial BUD extension for the tested drugs showed no growth at subsequent time points and could provide an annual cost savings of more than $600,000.

Diethylene glycol in health products sold over-the-counter and imported from Asian countries.

Diethylene glycol (DEG), a chemical that has been implicated in multiple medication-associated mass poisonings, can result in renal and neurological toxicity if ingested. Three previous such mass poisonings implicated Chinese manufacturers as the origin of contaminated ingredients. No literature exists on potential DEG or triethylene glycol (TEG), a related compound, contamination of health products imported from Asian countries to the USA. Our primary objective was to quantitatively assess the amount of DEG present in a convenience sampling of these health products. The study's secondary objectives were to: (1) evaluate for, and quantify TEG levels in these samples; (2) compare DEG and TEG levels in these products directly to levels in medications implicated in previous similar mass poisonings; and (3) to estimate DEG dose (in mg/kg) based on the manufacturer's instructions and compare these values to toxic doses from past mass poisonings and the literature. A quantitative assessment of DEG and TEG was performed in a convenience sampling of over-the-counter health products imported from Asian countries. Results were converted to volume to volume (v/v) % and compared with DEG levels in medications implicated in previous mass poisonings. Estimated doses (based on the manufacturer's instructions) of each product with detectable levels of DEG for a 70 kg adult were compared to toxic doses of DEG reported in the literature. Seventeen of 85 (20%) samples were not able to be analyzed for DEG or TEG due to technical reasons. Fifteen of 68 (22%) samples successfully tested had detectable levels of DEG (mean, 18.8 µg/ml; range, 0.791-110.1 µg/ml; and volume to volume (v/v) range, 0.00007-0.01%). Two of 68 (3%) samples had TEG levels of 12.8 and 20.2 µg/ml or 0.0012% and 0.0018% TEG v/v. The product with the highest DEG% by v/v was 810 times less than the product involved in the Panama DEG mass poisoning (8.1%). The lowest reported toxic dose from a past DEG mass poisoning (14 mg/kg) was more than 150 times higher than the highest daily dose estimated in our study (0.09 mg/kg). Sixty-eight of 85 (80%) samples were able to be successfully analyzed for DEG and TEG. DEG and TEG were detectable in 15/68 (22%) and 2/68 (3%) samples, respectively. Based on current standards, these levels probably do not represent an acute public health threat. Additional research focusing on why DEG is found in these products and on the minimum amount of DEG needed to result in toxicity is needed.

Cost savings from intravenous immunoglobulin manufactured from chromotography/caprylate (IGIV-C) in persons with primary humoral immunodeficiency disorder.

OBJECTIVE: Human intravenous immunoglobulin manufactured with chromatography and caprylate methods (IGIV-C, 10%) was associated with a reduction in validated infections (pneumonia and sinusitis) compared with treatment with a licensed immunoglobulin product manufactured using standard solvent-detergent methods (IGIV-SD, 10%) in participants with primary humoral immunodeficiency disorder (PIDD). Our objective was to determine the cost-consequences of using IGIV-C instead of IGIV-SD. METHODS: Economic analysis of a double-blind, randomized, clinical trial was used. Participants were randomly assigned to IGIV-C (N = 87) or IGIV-SD (N = 85) and monitored for the development of validated infections over the course of 9 months. Consumed resources were enumerated including cost of physician and emergency room visits, medications (prescription and over-the-counter), work productivity losses, and hospitalizations. Resource data was obtained from case report forms, patient diaries and the trial medication database. Because the amount of IGIV-SD used exceeded that of IGIV-C (nonstatistically significant difference) and the products are equivalently priced, we conservatively excluded investigational product acquisition cost to avoid artificially biasing incremental cost differences. We used a societal perspective with indirect costs, measured in 2003 US dollars. Pricing of both IGIV products is anticipated to be equivalent. RESULTS: In a multivariate analysis, annual mean per participant costs were significantly lower between those receiving IGIV-C compared with IGIV-SD for prescription medications [-US 302 dollars, 95% confidence interval (CI) -US 598 dollars to -US 6 dollars], hospitalization (-US 1454 dollars, 95% CI -US 1828 dollars to -US 1080 dollars) and total costs (-US 1304 dollars, 95% CI -US 1867 dollars to -US 742 dollars). Costs associated with lost work productivity and physician visits were similar in both groups (P > 0.10). In sensitivity analyses, varying costs of concomitant medications, hospitalization and outpatient care, did not significantly change our results. CONCLUSION: IGIV-C is cost-saving compared with IGIV-SD among persons with PIDD.