Identification of Substandard and Falsified Medicines: Influence of Different Tolerance Limits and Use of Authenticity Inquiries.

Substandard and falsified medicines have severe public health and socioeconomic effects, especially in low- and middle-income countries. The WHO has emphasized the need for reliable estimates of the prevalence of such medicines to efficiently respond to this problem. In the present study, we used 601 medicine samples collected in Cameroon, the DR Congo, and Malawi to assess the rates of substandard and falsified medicines based on different criteria. Based on the specifications of the U.S. Pharmacopoeia for the amount of the active pharmaceutical ingredients, the rate of out-of-specification medicines was 9.3%. By contrast, this rate ranged from 3.3% up to 35.0% if the tolerance limits of other pharmacopoeias or recently published medicine quality studies were used. This shows an urgent need for harmonization. Principal methods to assess the rate of falsified medicines are packaging analysis, chemical analysis, and authenticity inquiries. In the present study, we carried out an authenticity inquiry for the aforementioned medicine samples, contacting 126 manufacturers and 42 distributors. Response rates were higher for samples stated to be manufactured in Asia (52.4%) or Europe (53.8%) than for samples manufactured in Africa (27.4%; P < 0.001). One sample had been identified as falsified by packaging analysis by the local researchers and two additional ones by chemical analysis. Notably, seven additional falsified samples were identified by the authenticity inquiries. The total rate of falsified medicines resulted as 1.7%. Considerations are discussed for assessing the rates of "substandard" and "falsified" medicines in future medicine quality studies.

Medication adherence in older people with rheumatoid arthritis is lower according to electronic monitoring than according to pill count.

OBJECTIVES: Suboptimal medication adherence is a serious problem in the treatment of chronic inflammatory diseases. To measure medication adherence, electronic monitoring is regarded as superior to pill count. GLORIA is an ongoing two-year trial on the addition of low-dose (5 mg/d) prednisolone or placebo to standard care in older people (65+ years) with RA. During the entire trial, adherence is measured with electronic caps, and with pill counts. The objective is to describe medication adherence patterns, and to compare the adherence results of the two methods. METHODS: The recorded adherence patterns of patients (blinded for treatment group) were classified according to descriptive categories. The cutoff for good adherence was set at 80% of prescribed pills taken. RESULTS: Trial inclusion closed in 2018 at 451 patients, but trial follow-up is ongoing; the current dataset contains adherence data of 371 patients. Mean number of recorded 90-day periods per patient was 4 (range 1-8). Based on pill count over all periods, 90% of the patients had good adherence; based on cap data, only 20%. Cap data classified 30% of patients as non-user (<20% of days an opening) and 40% as irregular user (different adherence patterns, in or between periods). CONCLUSION: In our trial of older people with RA, the majority appeared to be adherent to medication according to pill count. Results from caps conflicted with those of pill counts, with patterns suggesting patients did not use the bottle for daily dispensing, despite specific advice to do so. TRIAL REGISTRATION: NCT02585258. ClinicalTrials.gov (https://www.clinicaltrials.gov/).

Review of economic data on closed system transfer drug for preparation and administration of hazardous drugs.

OBJECTIVES: The objectives of this study were to review economic data on the use of closed system drug transfer devices (CSTDs) for preparing and administering hazardous drugs, and to evaluate the quality of data reporting as defined by the Consolidated Health Economic Evaluation Reporting Standards (CHEERS). METHODS: All references from a recent Cochrane review about CSTDs were evaluated for inclusion. A literature review was also conducted. Articles containing economic data about the use of CSTDs were retained for analysis. Two researchers independently graded the articles according to the 24-item CHEERS checklist. RESULTS: Of the 138 articles identified initially, 12 were retained for analysis. Nine of these studies did not report acquisition costs or did not detail acquisition costs. Six studies reported economic benefits associated with the used of CSTDs, all related to extending the beyond-use date. The mean number of CHEERS criteria fulfilled by the included articles was 9.2 (SD 2.4). CONCLUSIONS: CSTDs are costly to acquire. However, few studies have examined the economic impact of these devices, and the existing studies are incomplete. As a result, hospitals planning to implement these devices will be unable to make a sound economic evaluation. Robust economic evaluation of CSTDs is needed.

Environmental sustainability in neurointerventional procedures: a waste audit.

BACKGROUND: Operating rooms contribute between 20% to 70% of hospital waste. This study aimed to evaluate the waste burden of neurointerventional procedures performed in a radiology department, identify areas for waste reduction, and motivate new greening initiatives. METHODS: We performed a waste audit of 17 neurointerventional procedures at a tertiary-referral center over a 3-month period. Waste was categorized into five streams: general waste, clinical waste, recyclable plastic, recyclable paper, and sharps. Our radiology department started recycling soft plastics from 13 December 2019. Hence, an additional recyclable soft plastic waste stream was added from this time point. The weight of each waste stream was measured using a digital weighing scale. RESULTS: We measured the waste from seven cerebral digital subtraction angiograms (DSA), six mechanical thrombectomies (MT), two aneurysm-coiling procedures, one coiling with tumour embolization, and one dural arteriovenous fistula embolization procedure. In total, the 17 procedures generated 135.3 kg of waste: 85.5 kg (63.2%) clinical waste, 28.0 kg (20.7%) general waste, 14.7 kg (10.9%) recyclable paper, 3.5 kg (2.6%) recyclable plastic, 2.2 kg (1.6%) recyclable soft plastic, and 1.4 kg (1.0%) of sharps. An average of 8 kg of waste was generated per case. Coiling cases produced the greatest waste burden (13.1 kg), followed by embolization (10.3 kg), MT (8.8 kg), and DSA procedures (5.1 kg). CONCLUSION: Neurointerventional procedures generate a substantial amount of waste, an average of 8 kg per case. Targeted initiatives such as engaging with suppliers to revise procedure packs and reduce packaging, digitizing paper instructions, opening devices only when necessary, implementing additional recycling programs, and appropriate waste segregation have the potential to reduce the environmental impact of our specialty.

Emergency drug kits at the Danish hospital pharmacies: varying management and challenges.

OBJECTIVES: Access to emergency drug kits (EDK) during medical emergencies can be life-saving; however, recent doubts about the quality of the kits have been expressed. Procurements of pharmaceuticals to the five regional authorities in Denmark are serviced by Amgros, a public sector organisation owned by the regions and established to create economies of scale and achieve administrative savings by centralisation. This means that Amgros calls for tenders for the supply of pharmaceuticals to the hospital pharmacies. The Hospital Pharmacy in the North Denmark Region does not currently have an effective method to manage Amgros procurements in relation to EDKs. Thus, the objectives were to explore how quality in the management and packing of EDKs is assured and maintained at different hospital pharmacies in Denmark and how this is affected by Amgros procurements. METHODS: The hospital pharmacies in Denmark were enrolled in a cross-sectional study. Information about the management and challenges of the EDKs was inquired by means of a questionnaire. Responses were analysed by simple statistics. RESULTS: All eight hospital pharmacies in Denmark completed the questionnaire, and the distribution between single-use and reusable packaging was nearly equal. The hospital pharmacies comply with a variation of regulations of which good distribution practice is the most common. Six hospital pharmacies experience challenges with drug replacements in the EDKs and only one hospital pharmacy complies completely with the Amgros procurement. The majority of the hospital pharmacies use parameters such as price of the new drug and potential expense for new packaging in their decision of whether to comply with the Amgros procurement. CONCLUSION: The management of the EDKs varies greatly among the hospital pharmacies in Denmark, and national requirements are therefore encouraged to ensure the quality. The challenges experienced with drug replacements reflect that complying with the Amgros procurement can be troublesome.

Vaccine dose usage and wastage in the Metropolitan Region of Porto Alegre, Rio Grande do Sul, Brazil: a descriptive study, 2015-2017. / Utilização e perda de doses de vacinas na Região Metropolitana de Porto Alegre, Rio Grande do Sul: um estudo descritivo de 2015-2017.

OBJECTIVE: to estimate usage and wastage of multi-dose and single-dose vaccine vials in the Metropolitan Region of Porto Alegre, Rio Grande do Sul, Brazil, from 2015 to 2017. METHODS: a descriptive study was carried out based on secondary data from the National Immunization Program Information System (SIPNI) and the Strategic Health Supplies Information System (SIES). RESULTS: a total of 12,342 records were examined; mean wastage rate was 45.8% (95%CI 39.5;51.7), while usage rate was 54.2% (95%CI 48.3;60.5); vaccines with the highest mean annual wastage rate were MMR (68.8% - 95%CI 66.5;71.1), BCG (68.1% - 95%CI 65.4;70.7), Hepatitis B (56.4% - 95%CI 53.0-59.7) and Yellow Fever (55.9% - 95%CI 51.4;60.4). CONCLUSION: the highest rates of vaccine wastage were for multi-dose vials; although single-dose vaccines also exceeded the acceptable limit defined by the World Health Organization.

Effectiveness of Electronic Medication Packaging Devices on Medication Adherence: A Scoping Review.

Poor adherence to complex medication regimens is a global problem that affects the treatment of chronic diseases, which involves polypharmacy and requires long-term administration of medications. The most significant barrier to medication adherence in older adults is patient-related factors. The purpose of this study was to find evidence from the current literature to evaluate the effectiveness of electronic medication packaging (EMP) devices on improving medication adherence in older patients. MEDLINE and EMBASE databases were searched based on inclusion/exclusion criteria, focusing on medication adherence and EMP devices with specific technological features. Search results included studies with experiences of patients with four different devices and various medical conditions. Study results indicated that EMP devices may improve medication adherence in older patients. However, due to insufficient evidence that supports their effectiveness specifically in the aging population, further clinical validation in older adults is recommended to draw strong conclusions. [Journal of Gerontological Nursing, 46(3), 27-36.].

Comparison of traditional methods versus SAFEcount for filling prescriptions: A pilot study of an innovative pill counting solution in eSwatini.

BACKGROUND: Packaging medications is a crucial component of health system efficiency and quality. In developing countries, medications often arrive in bulk containers that need to be counted by hand. Traditional counting is time-consuming, inaccurate and tedious. SAFEcount is a novel and inexpensive handheld device that may improve the accuracy and speed of pill-counting in resource limited settings. We designed a head-to-head trial to compare traditional and SAFEcount prescription filling in eSwatini. METHODS: We recruited 31 participants from 13 health facilities throughout eSwatini. Speed and accuracy for each prescription was recorded while each participant filled prescriptions of various quantities using both the traditional and SAFEcount methods. RESULTS: Traditional pill counting resulted in an error rate of 12.6% inaccurate prescriptions compared to 4.8% for SAFEcount (p<0.0001). SAFEcount was 42.3% faster than traditional counting (99.9 pills per minute versus 70.2; p<0.0001). Using SAFEcount was preferred over traditional pill counting by 97% (29/30) of participants. CONCLUSIONS: The SAFEcount device is a preferred alternative by counting personnel and is significantly faster and more accurate compared to traditional counting methods. SAFEcount could help improve the efficiency and quality of health care delivery in place of traditional hand counting.

Assessment of "look-alike" packaging designs related to medication errors using information technology.

This study aimed to assess the similarity among press-through pack (PTP) sheets of pharmaceutical products in Japan. The appearance of PTPs was assessed using a pharmaceutical design database (PDD) of 2,750 pharmaceutical tablets comprising approximately 40 % of the 6,840 products marketed in Japan. Package sheet color (Sc), tablet color (Tc), character color (Cc), sheet line color (SLc), and upper color (Uc) were used to evaluate the uniformity of PTP sheet design. To assess the risk of misidentification, 1,000 prescriptions for 82,273 cancer patients were retrieved from 21,026,742 records in the claims database of the Japan Medical Data Center Co. Ltd., Tokyo, Japan. The most frequent PTP sheet colors for 143 drugs were Sc (silver), Tc (white), Cc (blue), SLc (none), and Uc (silver). The prescribing pattern of 1000 randomly chosen prescriptions was analyzed. Database records of prescriptions without tablets (n = 69), including only one PTP tablet (n = 292), and those with lack of PDD prescription data (n = 388) were excluded. Eventually, 236 prescriptions were evaluated. Fourteen prescriptions (5.9%) had PTP sheets with five matching elements and 29 had with four matching elements (12.3%). This novel PDD database for information technology concept easily identified similar PTP sheets involved in prescriptions dispensed in 18 % of evaluated cancer patients. The concept seems to be applicable for preventing look-alike dispensing errors.

Drug identification by the patient: Perception of patients, physicians and pharmacists.

INTRODUCTION: Faced with the increasing number of pharmaceutical products on the market, several pharmacovigilance notifications regarding confusion between look-alike and sound-alike drugs have been reported. This study of perception among patients, family physicians and pharmacists aims to evaluate drug identification factors and the risk of errors of confusion for patients. MATERIAL AND METHODS: Patients were systematically approached in randomly selected pharmacies within the Midi-Pyrénées region in France and invited to complete a questionnaire. Two other questionnaires were respectively sent to family physicians and pharmacists in the same region asking for their opinion on patients' perception of the identification of prescribed medicines. RESULTS: Of the 768 patients interviewed, most report identifying their medications by name (brand name: 50%; generic: 21%), while a smaller number cite physical appearance (box: 16%, tablet: 7% and blister packaging: 3%). In practice the factors considered most likely to cause confusion by patients relate to drug appearance (look-alike tablets: 28%, look-alike boxes: 20% and look-alike blister packaging: 13%). In contrast, look-alike and sound-alike names (generic and brand names combined) were cited in 31% of cases. Physicians (n=345) and pharmacists (n=198) understimate that patients identify their treatment by name (physicians: 46%; pharmacists: 26% vs. patients: 71%), reporting instead that problems arise mainly from the appearance of medicines (physicians: identification: 52% and risk factors for confusion: 74%; pharmacists: identification: 74% and risk factors for confusion: 83%; versus patients: identification: 26%; risk factors for confusion: 61%). DISCUSSION: Our study highlights the critical role of medication name in identifying drugs among patients. However, confusion of look-alike tablets or pills figures prominently among fears surrounding medication errors. Despite several notifications of pharmacovigilance, this issue appears to be underestimated within the body of medical literature. Proper identification of medicines by patients is essential to improving medication safety and therapeutic compliance. Concrete measures can be undertaken to reach this goal.

Little filtered cigars: US sales, flavours, package sizes and prices.

OBJECTIVE: At least four varieties of little filtered cigars (LFCs) violate the US prohibition on flavoured cigarettes other than menthol. This study characterises the sales of prohibited products and other LFCs by flavour category and pack size, as well as the price of LFCs relative to cigarettes. METHODS: Using retail sales data for 2016, we computed the sales volume in dollars and equivalent units and the percentage of total sales by flavour and pack size for the USA by region and state. Paired t-tests compared the prices for LFCs and cigarettes sold in same-sized packs and cartons. RESULTS: LFC sales totalled 24 033 equivalent units per 100 000 persons in 2016. Flavoured LFC varieties accounted for almost half (47.5%) of the total sales. LFCs were sold in 12 different pack sizes, but 79.7% of sales were packs of 20. The price of 20-packs averaged $2.41 (SD=$1.49), which was significantly less than cigarettes (M=$5.90, SD=$0.85). Regional differences suggest a greater proportion of menthol/mint LFCs and lower prices in the South than in other regions. CONCLUSION: Classifying all LFCs as cigarettes would require that they be offered in a minimum package of 20, eliminate flavoured varieties other than menthol and increase prices through applicable state and local cigarette taxes.

Influence of an inconsistent appearance of antipsychotics on drug adherence in patients with schizophrenia.

In this study, we aimed to determine whether an inconsistent appearance of antipsychotic drugs dispensed was associated with poorer adherence in patients with schizophrenia.To conduct this study, we linked information from different administrative healthcare databases from the Basque Country. Patients with a medication possession ratio (<80%) were considered to be nonadherent.More than a quarter of the study population (26.9%, 1294/4810) was nonadherent to antipsychotics. Different brands of the same antipsychotic were dispensed to 8.5% of the patients. Inconsistent appearance was not associated with nonadherence to antipsychotics. Lower adherence to antipsychotics was associated with several other factors: age ≥65 or <30 years, prescription of typical antipsychotics or of long-acting injectable compounds, and nonadherence to antihypertensive and lipid-lowering drugs.Contrary to our expectations, we did not find a significant association between inconsistent appearance of prescribed antipsychotics and poorer adherence. The percentage of patients who were dispensed different brands of the same antipsychotics was also lower than expected.

Characteristics of Adults Managing Vitamins/Supplements and Prescribed Medications-Who Is Using, Not Using, and Abandoning Use of Pillboxes?: A Descriptive Study.

PURPOSE: Evidence suggests pillboxes are effective for improving medication adherence. However, prior descriptive studies about pillbox use are limited to studies of older adults or condition-specific studies. This study describes characteristics of adults with chronic conditions and their use of pillboxes. METHODS: A survey questionnaire link was posted on a social media recruitment page from August 2016 to April 2017. RESULTS: The sample of 179 people was middle-age (47.7 ± 15.4 years), predominantly white (90.4%), educated (>93% educated beyond high school), female (n = 148; men n = 26), married/partner (58.2%), and working full time (55.9%). Pillboxes were used by 66% (n = 118) of the sample at some point; 22.9% reported pillbox abandonment. Compared with people who never used a pillbox, current pillbox users were older (53.2 ± 14.3 vs 42.0 ± 14.4 years; P < .001) and took more vitamins/supplements (3.9 ± 3.8 vs 2 ± 1.8, P = .002) and prescribed medications (4.2 ± 2.2 vs 2.6 ± 1.9, P < .001). Adherence did not differ between groups; pillbox users were more likely to refill medications before running out compared with those abandoning use, P < .001. CONCLUSION: Age and number of medications may affect pillbox use. Future research should explore barriers to continued use of pillboxes and uptake in younger populations.

Comparison of treatment records and inventory of empty drug containers to quantify antimicrobial usage in dairy herds.

Assessment of antimicrobial use (AMU) is vital for interpreting the origin of changes in antimicrobial resistance (AMR). The objectives of the present study were to estimate the association between AMU determined using on-farm treatment records (TR) and inventory of empty drug containers (INV). Herds were selected to represent Canadian dairy farms. Producers were asked to record animal health events and treatments on a standard General Health Event form. For inventory data, 40-L receptacles were placed at various locations considered convenient to deposit all empty drug containers. Antimicrobial defined-daily dosages (ADD) were calculated for 51 Canadian herds using the 2 methods. Estimation of AMU was 31,840 ADD using the INV and 14,487 ADD using the TR, indicating that for every TR entry, 2.20 times more treatments were observed using the INV. Mastitis, reproductive conditions, and dry cow therapy were the most frequent reasons for antimicrobial therapy when assessing TR. For all antimicrobials evaluated, mean ADD was higher using the INV versus TR. Regardless, a strong positive correlation (0.80) was observed between the 2 methods, indicating that herds with increased number of ADD recorded using the INV also had increased number of ADD recorded using TR. Furthermore, a positive association was observed for the 6 most commonly used antimicrobials. In comparison to methods used in surveillance programs on AMU in livestock that assume a constant use in all herds (i.e., sales data), INV provided a herd-level specific quantity of AMU positively correlated with AMU recorded at the animal level in general. The INV was easy to implement and provided a measure of total AMU in the herd. Availability of such information would be valuable for interpreting changes in AMR at the herd level and enabling evaluation of interventions for decreasing AMR.

Type of oral solid medication packaging and medication preparation time in nursing homes: A direct observation study.

WHAT IS KNOWN AND OBJECTIVE: Medication administration is a substantial portion of the workday in nursing homes, with the medication preparation step being the most time-consuming. However, little is known about how medication preparation time is affected by the type of packaging used for oral solid medications (ie, tablets/capsules). We examined the effects of two types of packaging. As fewer steps are associated with strip packaging compared to bingo card packaging, we hypothesized that the increase in medication preparation seconds per resident with each additional oral solid medication would be smaller when strip packaging was used. METHODS: A total of 430 medication preparations conducted by eight nurses during the regularly scheduled morning medication administration period in two nursing homes-using strip packaging and bingo card packaging, respectively-were observed. Each medication preparation observation was matched to its corresponding medication administration record and observations averaged across resident. Using the resident sample (N=149), we estimated three regression models (adjusting the standard errors for the clustering of resident by nurse). The first model regressed medication preparation seconds on the number of oral solid medications. The second model added the type of packaging used and the control variables (type of unit [long-term care, post-acute care], the number of one-half pills and the dosage form diversity in the preparation). To test our hypothesis, the third model added an interaction term between the number of oral solid medications and the type of packaging used. RESULTS AND DISCUSSION: As hypothesized, all else equal, the number of oral solid medications tended to increase medication preparation time per resident in both nursing homes, but the increase was smaller in the strip packaging nursing home (P<.05). Each additional oral solid medication in the bingo card packaging nursing home increased medication preparation by an average of 13 seconds (b=13.077), whereas each oral solid medication administered in the strip packaging nursing home increased medication preparation by an average of only 8 seconds (13.077-5.092=7.985). This is a difference on average of about 5 seconds per oral solid medication. WHAT IS NEW AND CONCLUSION: To our knowledge, we were the first to examine the effect of type of oral solid medication packaging on medication preparation time in nursing homes. Type of packaging matters. The time saved using strip packaging (vs bingo card packaging) has implications for quality of care and the movement towards person-centred care in the nursing home sector. Nurses (or other staff tasked with medication preparation) in nursing homes using strip packaging potentially have more time to devote to nurturing a relationship with the resident. However, time saved in medication preparation by strip packaging is counterproductive if a serious error results. Thus, future studies should investigate the effects of type of packaging on medication preparation errors.

Readability assessment of package inserts of biological medicinal products from the European medicines agency website.

BACKGROUND: Package inserts that accompany medicines are a common source of information aimed at patients and should match patient abilities in terms of readability. OBJECTIVE: Our objective was to determine the degree of readability of the package inserts for biological medicinal products commercially available in 2007 and compare them with the readability of the same package inserts in 2010. METHODS: A total of 33 package inserts were selected and classified into five groups according to the type of medicine: monoclonal antibody-based products, cytokines, therapeutic enzymes, recombinant blood factors and other blood-related products, and recombinant hormones. The package inserts were downloaded from the European Medicines Agency website in 2007 and 2010. Readability was evaluated for the entire text of five of the six sections of the package inserts and for the 'Annex' when there was one. Three readability formulas were used: SMOG (Simple Measure of Gobbledygook) grade, Flesh-Kincaid grade level, and Szigriszt's perspicuity index. RESULTS: No significant differences were found between the readability results for the 2007 package inserts and those from 2010 according to any of the three readability indices studied (p>0.05). However, there were significant differences (p<0.05) between the readability scores of the sections of the package inserts in both 2007 and 2010. The readability of the package inserts was above the recommended sixth grade reading level (ages 11-12) and may lead to difficulties of understanding for people with limited literacy. CONCLUSIONS: All the sections should be easy to read and, therefore, the readability of the medicine package inserts studied should be improved.