Substandard medicines: a greater problem than counterfeit medicines?

Substandard medicines are medicines which have failed to pass the quality measurements and standards set for them.1 They should be distinguished from counterfeit (falsified) medicines which are deliberately and fraudulently mislabelled. Combining the two together however is not helpful. They are different problems that require different solutions. Substandard and counterfeit medicines are a widespread problem in low-income and lower–middle-income countries. A systematic review showed that the median prevalence of substandard and counterfeit medicines was 28.5%.1 This ranged from 11% to 48% in individual studies. The 15 studies were all limited to antimicrobial drugs, with the majority (13) including antimalarials. Only 2 of the 15 studies within the systematic review differentiated between substandard and counterfeit medicines. Both studies involved antimalarial drugs in South East Asia. They both found that counterfeit medicines were a greater problem than substandard medicines. The biggest problem in relation to the quality of the medicines tested was an inadequate amount of the active ingredient

The Interplay of Hypoxia and Autophagy in Epithelial-Derived Ameloblastoma Cell Survival: A Pilot Study

Ameloblastoma is the most clinically-significant benign odontogenic jaw tumor with a locally-aggressive growth pattern and high malignant transformation rate. Epithelial-derived ameloblastoma cells (EPAMCs) demonstrate enhanced basal autophagy but the etiopathogenesis of ameloblastoma and the roles of hypoxia and autophagy in EPAMCs survival and recurrence are still unknown. The goals of this study were to assess expression of ameloblastoma-specific markers and the roles of hypoxia and autophagy on EPAMC survival. Primary and recurrent ameloblastoma tissues from two patients were immunostained with pan-cytokeratin, vimentin and SQSTM1/p62. Additionally, EPAMCs were subjected to severe hypoxia (0.1% O2) to define responsiveness to hypoxia based on expression of hypoxic and autophagic markers. Human odontoma-derived cells (HODCs) served as control. Both primary and recurrent tissue samples stained positive for pan-cytokeratin. Vimentin and SQSTM1/p62 were undetectable but the connective tissue stained positive for vimentin. Phosphorylated-40S ribosomal protein S6 (pS6) levels were decreased in EPAMC in both hypoxia and post-hypoxia. There were no significant changes among the remainder markers or between the EPAMC and HODCs. While the small sample size of this pilot study limited the statistical power several interesting trends were observed. In EPAMCs, canonical autophagy tended to be active at baseline, hypoxia, and re-oxygenation but did not increase when cells were subjected to hypoxia. Cells displayed reduced levels of pS6 and elevated levels of LC3ABII/LC3ABI and p62 24 hours following hypoxia. The vimentin expression and pan-cytokeratin pattern are consistent with an epithelial origin of ameloblastoma. Our data also suggests EPAMCs are using autophagy to survive severe hypoxia

Magnitude and Time Trend of Acute Respiratory Infections (Aris) Among Male School Students and Employees in Aleith

A setting-based descriptive study was conducted to study magnitude and time trend of acute respiratory infections (ARIs) among male school students and employees in Aleith. Data about Acute Respiratory Infections (ARIs) among school students and employees in Aleith during the last three years were collected by reviewing monthly and annual reports in school health units. The proportion of acute reparatory infections in the last three years among male student and employees in Aleith was high in year 1435 which was 50.2%, followed by the year 1437 which was 47% and 1436 was 43.3%. The time distribution of acute respiratory infections illustrates that the percentage of infection occurred during Jumada-Al-Thani (21.9%) in the year 1435, Moharam and Rabi-Al-Thani (17.3%) in the year 1436 and Jumada-Al-Awwal (18%) in the year 1437. In the year 1435, acute respiratory infection among student was 811(63.7%) and among employees was 462 (36.3%); in the year 1436, the disease was 1177 (71.4%) in students while in employees was 471 (28.6%) and in the year1437, the percentage was 747(64.7%) in students and 408(35.3%) in employees. The high percentages of Acute Respiratory Infections (ARIs) occurred among primary school students was high 35.6%, 45.5% and 48.1% in the years 1435, 1436 and 1437 respectively. The peak of ARIs occurred during the year 1435 and the minimum proportion rate of cases was found in 1436. The study concluded that ARIs were still high and more frequent in winter months

Substandard and counterfeit medicines: a systematic review of the literature

Objective: To explore the evidence available of poor quality (counterfeit and substandard) medicines in the literature. Design: Systematic review. Data sources: Databases used were EMBASE, MEDLINE, PubMed and the International Pharmaceutical Abstracts, including articles published till January 2013. Eligibility criteria: Prevalence studies containing original data. WHO definitions (1992) used for counterfeit and substandard medicines. Study appraisal and synthesis: Two reviewers independently scored study methodology against recommendations from the MEDQUARG Checklist. Studies were classified according to the World Bank classification of countries by income. Data extraction: Data extracted: place of study; type of drugs sampled; sample size; percentage of substandard/counterfeit medicines; formulations included; origin of the drugs; chemical analysis and stated issues of counterfeit/substandard medicines. Results: 44 prevalence studies were identified, 15 had good methodological quality. They were conducted in 25 different countries; the majority were in low-income countries (11) and/or lower middle-income countries (10). The median prevalence of substandard/counterfeit medicines was 28.5% (range 11–48%). Only two studies differentiated between substandard and counterfeit medicines. Prevalence data were limited to antimicrobial drugs (all 15 studies). 13 studies involved antimalarials, 6 antibiotics and 2 other medications. The majority of studies (93%) contained samples with inadequate amounts of active ingredients. The prevalence of substandard/counterfeit antimicrobials was significantly higher when purchased from unlicensed outlets (p<0.000; 95% CI 0.21 to 0.32). No individual data about the prevalence in upper middle-income countries and high-income countries were available. Limitations: Studies with strong methodology were few. The majority did not differentiate between substandard and counterfeit medicines. Most studies assessed only a single therapeutic class of antimicrobials. Conclusions: The prevalence of poor-quality antimicrobial medicines is widespread throughout Africa and Asia in lower income countries and lower middle-income countries . The main problem identified was inadequate amounts of the active ingredients

Substandard and falsified medicines in the UK: a retrospective review of drug alerts (2001-2011)

Objective: To determine the extent of substandard and falsified medicines in the UK. Design: A retrospective review of drug alerts and company-led recalls. Setting: The Medicines and Healthcare Products Regulatory Agency (MHRA) website search for drug alerts issued between 2001 and 2011. Eligibility criteria: Drug alerts related to quality defect in medicinal products. Main outcome measure: Relevant data about defective medicines reported in drug alerts and company-led recalls, including description of the defect, type of formulation, year of the alert and category of the alert. Results: There were 280 substandard medicines of which 222 were recalled. The two most frequent problems were contamination (74 incidents) and issues related to packaging (98 incidents). Formulations for parenteral administration (117 incidents) were the formulation most frequently affected. There were 11 falsified medicines, as defined by the MHRA, reported over the 11-year period. The number of defective medicines reported by the MHRA increased 10-fold from 5 in 2001 to 50 in 2011. Conclusions: Substandard medicines are a significant problem in the UK. It is uncertain whether the increasing number of reports relates to improved detection or an increase in the number of substandard medicine

Lexical, Inflectional and Agreement Production of Arabic Noun Phrase in Agrammatism

Agrammatism is a language disorder due to an acquired brain damage. Studying agrammatism in highly inflectional languages like Arabic can be very revealing for linguistic theories and highly significant for speech language pathology. The Arabic noun phrase exhibits one of the richest morpho-syntactic structures in Arabic. Despite being morpho-syntactically rich, the Arabic noun phrase did not receive enough attention in aphasia literature. The current study aims to explore the production of the noun phrase by Arabic speakers with agrammatism to increase knowledge of morpho-syntax in aphasia. The study examines the lexical, inflectional and agreement production in three types of Arabic noun phrase: the adjectival noun phrase, the construct state noun phrase, and the non-construct state noun phrase. This study is the first study that addresses the production of these different Arabic noun phrase types in agrammatism. Nine Saudi Arabic speakers with aphasia and agrammatism demonstrating varying degrees of severity participated in the study. A testing tool was developed to elicit the production of the three Arabic noun phrase types. The test development resulted in four linguistic subtests: the Number and Gender Agreement Subtest, the Definiteness Agreement Subset, the Construct State Subtest and the Non-Construct State Subtest. A pilot study was carried on the test instrument prior to conducting the main experiment to test the reliability and the validity of the instrument. The results of the four linguistic subtests revealed that there was higher accuracy for masculine than for feminine and for singular than for plural forms. The indefinite forms tended to be produced for definite forms. Most gender and number errors were due to production of masculine singular inflection, and the feminine plural was more impaired than masculine ii plural. Lastly, most ungrammatical phrases were due to inflectional errors in either the adjective or the particle, and most lexical errors in the Number and Gender Agreement Subtest and Non-construct State Subtest were modifiers’ lexical errors. The results contributed to the morph-syntactic characterisation of noun phrase production in aphasia and agrammatism within Arabic and cross-linguistically. The data were mainly analysed from a neurolinguistic perspective taking into consideration a range of different morpho-syntactic theories of NP and agrammatism. The data were also considered within psycholinguistic accounts of gender and number processing, and recent accounts of language production in aphasia instantiated in usage-based accounts of grammar. Patterns of error have been accounted for by all three theoretical accounts, but no one single account could interpret all error patterns. The study has provided a number of theoretical implications, and has implied directions for future research of Arabic NP in agrammatism

Qualitative modelling of place location on the linked data web and GIS

When asked to define where a geographic place is, people normally resort to using qualitative expressions of location, such as north of and near to. This is evident in the domain of social geography, where qualitative research methods are used to gauge people’s understanding of their neighbourhood. Using a GIS to represent and map the location of neighbourhood boundaries is needed to understand and compare people’s perceptions of the spatial extent of their neighbourhoods. Extending the GIS to allow for the qualitative modelling of place will allow for the representation and mapping of neighbourhoods. On the other hand, a collaborative definition of place on the web will result in the accumulation of large sets of data resources that can be considered “location-poor”, where place location is defined mostly using single point coordinates and some random combinations of relative spatial relationships. A qualitative model of place location on the Linked Data Web (LDW) will allow for the homogenous representation and reasoning of place resources. This research has analysed the qualitative modelling of place location on the LDW and in GIS. On the LDW, a qualitative model of place is proposed, which provides an effective representation of individual place location profiles that allow place information to be enriched and spatially linked. This has been evaluated using the application of qualitative spatial reasoning (QSR) to automatic reasoning over place profiles, to check the completeness of the representation, as well as to derive implicit links not defined by the model. In GIS, a qualitative model of place is proposed that provides a basis for mapping qualitative definitions of place location in GIS, and this has been evaluated using an implementation-driven approach. The model has been implemented in a GIS and demonstrated through a realistic case study. A user-centric approach to development has been adopted, as users were involved throughout the design, development and evaluation stages

Reasoning with place information on the Linked Data Web

The Linked Data Web (LDW) is an evolution of the traditional Web from a global information space of linked documents to one where both documents and data are linked. A significant amount of geographic information about places are currently being published on this LDW. These are used to qualify the location of other types of datasets. This paper examines the limitations in the nature of location representation in some typical examples of these Resource Description Framework (RDF) resources, primarily resulting from the simplified geometric representation of location and the incomplete and random use of spatial relationships to link place information. The paper proposes a qualitative model of place location that enforces an ordered representation of relative spatial relationships between places. The model facilitates the application of qualitative spatial reasoning on places to extract a potentially large percentage of implicit links between place resources, thus allowing place information to be linked and to be explored more fully and more consistently than what is currently possible. The paper describes the model and presents experimental results demonstrating the effectiveness of the model on realistic examples of geospatial RDF resources