Exploring pharmacists' perspectives about substandard and falsified medical products through interviews.

Background: The problem with substandard and falsified (SF) medical products may grow in high-income countries when e-commerce of medicines increases. Unauthorized websites offer medicines of insufficient quality. This underscores the importance of evaluating how the problem with SF medical products can be prevented from escalating. However, little is known about what knowledge and experience professionals working primarily with medicines have about the phenomenon. Objective: This study was conducted to explore purposively selected pharmacists' experience and knowledge about SF medical products. Methods: Twelve individual interviews were conducted with purposively selected pharmacists between May 2021 and September 2021. An interview guide was used with specific questions about e-commerce, which focused on exploring pharmacists' experience and knowledge about SF medical products. The interviews lasted, on average, 49 min and were analyzed using inductive qualitative content analysis. Results: A main theme 'Pharmacists as guardians of safe medicines' emerged. This theme consisted of three categories pinpointing 'risk factors', 'protective factors', and 'opportunities for improvement' regarding SF medical products. Findings suggest that pharmacists can play a role in preventing the problem with SF medical products from escalating. Participants emphasized they were in this line of work to help patients and increase patient safety. Conclusions: Pharmacists have the opportunity to empower the public with knowledge about SF medical products since they discuss medicines with many people every day. Awareness of risk factors for SF medical products enables pharmacists to guide patients to avoid risky purchases from unauthorized websites. To do this, better communication, and cooperation with patients and other healthcare professionals are needed.

Swedish community pharmacy employees' knowledge and experience of substandard and falsified medical products: a cross-sectional descriptive survey.

OBJECTIVES: Substandard and falsified medical products are, according to the World Health Organization, a global threat to public health. To evaluate if community pharmacy employees can guide the public to safer medication purchases, their knowledge and experience about SF medical products was examined. METHODS: A digital questionnaire was distributed to the five dominating pharmacy companies in Sweden, representing 97% of the community pharmacies (1391/1433), giving the theoretical possibility of reaching 6200 employees. Three companies published a link to the questionnaire on their intranets, one distributed the link via e-mail to the responsible pharmacist for quality and knowledge, respectively. The fifth company did not pass on, due to technical problems. Employees aged 18 years or older with customer contact were invited to participate. KEY FINDINGS: The questionnaire was available for 74% of all community pharmacies (1067/1433), having approximately 4900 employees with customer contact. The response rate was 5% (228/4900). Of the respondents, 89% were pharmacists (203/228), 84% were women (191/228) and 43% were 35-49 years (98/228). The respondents worked in pharmacies of different size, located both in rural and urban areas. The definition of substandard and falsified medical products was known by 182 of the 228 respondents (80%) and the main source of knowledge was media (61%, 111/228). The common European logo for authorized online pharmacies was not recognized by 74% (169/228). CONCLUSIONS: For pharmacy employees to guide the public to safer medication purchases, knowledge about substandard and falsified medical products needs to be enhanced specially about legal international e-commerce.

Tumour budding correlates with local recurrence of rectal cancer.

AIM: Predictive tools for local recurrence (LR) of rectal cancer are needed. This study assessed the predictive value of tumour budding detected by MNF-116 and laminin-5 γ2 chain (Ln-5 γ2). METHOD: In a case-control study, the surgical specimens of 48 patients with LR after from primary resection of rectal carcinoma and 82 control patients matched for gender and preoperative radiation from a population of 1180 patients operated with total mesorectal excision were studied. The presence of budding was examined using immunohistochemistry with Ln-5 γ2 and pan-cytokeratin staining with MNF-116. RESULTS: Tumour budding counts ranged from 0 to 106 buds (mean 43, median 38) for all patients. Significantly more tumours with more than 35 buds were seen in the LR than in the control group (67 vs 44%; P = 0.02). The spread of budding was also more extensive in the LR than in the control group (63 vs 49%, P = 0.03). In a multivariate analysis with tumour, node, metastasis stage, MNF-116-stained budding was an independent predictor of local failure (P = 0.02). The budding frequency was higher in irradiated tumours in comparison with tumours that had not received irradiation (mean 53 vs 38, P = 0.03). For Ln-5 γ2, more tumours with ≥ 10 buds were seen in the group with LR than among the control patients, but this difference was not statistically significant (73 vs 57%; P = 0.09). No additive value was found in the multivariate logistic regression model when Ln-5 γ2-stained budding frequency was added to MNF-116 and tumour, node, metastasis stage. The agreement between budding frequency determined by MNF-116 and Ln-5 γ2 was moderate, with a κ-coefficient of 0.34 (0.16-0.51). CONCLUSION: Tumour budding determined by MNF-116 staining may serve as a predictive marker for LR in rectal cancer.

Association studies on 11 published colorectal cancer risk loci.

BACKGROUND: Recently, several genome-wide association studies (GWAS) have independently found numerous loci at which common single-nucleotide polymorphisms (SNPs) modestly influence the risk of developing colorectal cancer. The aim of this study was to test 11 loci, reported to be associated with an increased or decreased risk of colorectal cancer: 8q23.3 (rs16892766), 8q24.21 (rs6983267), 9p24 (rs719725), 10p14 (rs10795668), 11q23.1 (rs3802842), 14q22.2 (rs4444235), 15q13.3 (rs4779584), 16q22.1 (rs9929218), 18q21.1 (rs4939827), 19q13.1 (rs10411210) and 20p12.3 (rs961253), in a Swedish-based cohort. METHODS: The cohort was composed of 1786 cases and 1749 controls that were genotyped and analysed statistically. Genotype-phenotype analysis, for all 11 SNPs and sex, age of onset, family history of CRC and tumour location, was performed. RESULTS: Of eleven loci, 5 showed statistically significant odds ratios similar to previously published findings: 8q23.3, 8q24.21, 10p14, 15q13.3 and 18q21.1. The remaining loci 11q23.1, 16q22.1, 19q13.1 and 20p12.3 showed weak trends but somehow similar to what was previously published. The loci 9p24 and 14q22.2 could not be confirmed. We show a higher number of risk alleles in affected individuals compared to controls. Four statistically significant genotype-phenotype associations were found; the G allele of rs6983267 was associated to older age, the G allele of rs1075668 was associated with a younger age and sporadic cases, and the T allele of rs10411210 was associated with younger age. CONCLUSIONS: Our study, using a Swedish population, supports most genetic variants published in GWAS. More studies are needed to validate the genotype-phenotype correlations.

Undifferentiated pelvic adenocarcinomas: diagnostic potential of protein profiling and multivariate analysis.

BACKGROUND AND AIMS: Despite improved techniques, the determination of tumor origin in poorly differentiated adenocarcinomas still remains a challenge for the pathologist. Here we report the use of protein profiling combined with principal component analysis to improve diagnostic decision-making in tumor samples, in which standard pathologic investigations cannot present reliable results. MATERIALS AND METHODS: A poorly differentiated adenocarcinoma of unknown origin located in the pelvis, infiltrating the sigmoid colon as well as the ovary, served as a model to evaluate our proteomic approach. Firstly, we characterized the protein expression profiles from eight advanced colon and seven ovarian adenocarcinomas using two-dimensional gel electrophoresis (2-DE). Qualitative and quantitative patterns were recorded and compared to the tumor of unknown origin. Based on these protein profiles, match sets from the different tumors were created. Finally, a multivariate principal component analysis was applied to the entire 2-DE data to disclose differences in protein patterns between the different tumors. RESULTS: Over 89% of the unknown tumor sample spots could be matched with the colon standard gel, whereas only 63% of the spots could be matched with the ovarian standard. In addition, principal component analysis impressively displayed the clustering of the unknown case within the colon cancer samples, whereas this case did not cluster at all within the group of ovarian adenocarcinomas. CONCLUSION: These results show that 2-DE protein expression profiling combined with principal component analysis is a sensitive method for diagnosing undifferentiated adenocarcinomas of unknown origin. The described approach can contribute greatly to diagnostic decision-making and, with further technical improvements and a higher throughput, become a powerful tool in the armentarium of the pathologist.

Tumour budding detected by laminin-5 {gamma}2-chain immunohistochemistry is of prognostic value in epidermoid anal cancer.

BACKGROUND: Markers for guidance with regard to individual prognosis and treatment planning are sought in epidermoid anal cancer. This study assessed the prognostic and predictive value of tumour budding. PATIENTS AND METHODS: From a population-based consecutive series of patients who were prospectively recorded, it was possible to investigate 209 (76%) of the pretreatment biopsies. Immunohistochemistry with a monoclonal antibody for the gamma2 chain of laminin-5 was used to detect tumour budding (defined as dissociated single cancer cells or clusters of up to five cells). RESULTS: Tumour budding was detected in 104 (50%) of the 209 samples. No significant correlation was found between tumour budding and clinicopathological characteristics. Patients with tumour budding had a statistically significantly better 5-year overall survival rate compared with patients lacking tumour budding (74% versus 64%, P <0.05). Albeit not statistically significant, other outcome variables such as tumour-specific survival, recurrence after initial complete response and rate of distant metastases, were all in favour of patients with tumour budding. Multivariate analysis reveals tumour budding as an independent positive prognostic factor. CONCLUSIONS: Tumour budding detected by laminin-5 immunohistochemistry may be of prognostic value in the treatment of epidermoid anal cancer. However, further studies are needed to clarify the possible clinical implications.

Laminin 5 gamma 2 chain expression: a marker of early invasiveness in colorectal adenomas.

AIM: Polyps of the colon and rectum are considered to be premalignant lesions in the development of colorectal cancer. However, knowledge of how normal epithelial cells gain invasive properties is limited. Laminin 5 gamma 2 chain expression was investigated to determine the role of laminin 5 as a marker of potential invasiveness in colorectal polyps. MATERIAL/METHODS: Sixty seven polyps of different types (15 hyperplastic polyps, 12 serrated adenomas, 16 tubular adenomas, and 24 adenomas with a villous component) were assessed for gamma 2 chain expression of laminin 5 by immunohistochemistry on archival, paraffin wax embedded sections. RESULTS: Ten polyps stained positive and the number of polyps expressing the laminin 5 gamma 2 chain increased significantly as the phenotype of the adenomas became more atypical: none of the 15 hyperplastic polyps, two of the 16 tubular adenomas (12.5%), and six of the 24 adenomas with a villous component (25%) were positive. Two of 12 (17%) serrated adenomas, regarded as a distinct form of colorectal neoplasia, showed gamma 2 chain expression. Furthermore, laminin 5 gamma 2 chain expression correlated with lesion size. Polyps smaller than 10 mm expressed the gamma 2 chain less frequently than did those equal to or larger than 10 mm. CONCLUSION: Laminin 5 gamma 2 chain expression was found to increase progressively towards a more atypical phenotype of adenoma. The results suggest that, in the future, laminin 5 gamma 2 chain expression may be used as an indicator of incipient malignant transformation of a benign colorectal adenoma.

Laminin-5 gamma 2 chain expression correlates with unfavorable prognosis in colon carcinomas.

Expression of the gamma 2 chain at the invasive front of different tumors has indicated an important role for laminin-5 in cell migration during tumor invasion and tissue remodeling. As there is considerable need for reliable invasion and prognostic markers we evaluated the correlation of laminin-5 gamma 2 chain expression with clinicopathologic parameters and patient survival in 93 primary colon carcinomas. Epithelial cells of normal mucosa were consistently negative for staining. In contrast, positive cytoplasmic staining was observed in 89 tumors (96%). Twenty-four (26%) cases were scored as sparse, 34 (37%) as moderate, and 31 (33%) as frequent gamma 2 chain expression. There was a significant association of laminin-5 gamma 2 chain expression and local invasiveness of colon carcinomas according to Dukes stage (A-C) (p=0.001) and tumor budding (p<0.001). A statistical significance could also be noted in decreasing tumor differentiation (p<0.001) and correlation to tumor size (p=0.032). No correlation was observed to tumor site. Univariate analysis identified laminin-5 (p=0.010), tumor differentiation (p=0.006) and Dukes grade (p<0.001) as significant variables in predicting prognosis. However, by multivariate analyses, this study could not demonstrate that laminin-5 gamma 2 chain expression is an independent predictive factor for survival. The results indicate that laminin-5 gamma 2 chain expression is up-regulated during the progression of human colon cancer and that it plays a role in the aggressiveness of these tumors. Demonstration of laminin-5 gamma 2 chain positivity also facilitates detection of individual cells or minor cell clusters invading the surrounding stroma. Figures on http://www.esacp.org/acp/2001/22-4/lenander.htm.

Ulcerative colitis and colorectal carcinoma: DNA-profile, laminin-5 gamma2 chain and cyclin A expression as early markers for risk assessment.

BACKGROUND: Ulcerative colitis patients are at increased risk for developing colorectal carcinomas. Despite expensive surveillance programmes, clinical practice reflects an uncertainty in individual risk assessment. The aim of the study was to evaluate independent cellular features with possible predictive value. METHODS: Two patient groups were selected: group A comprised 8 patients with ulcerative colitis-associated colorectal carcinomas, group B comprised 16 ulcerative colitis patients with risk factors (duration of disease, extent of inflammation, epithelial dysplasias). A total of 683 paraffin-embedded mucosal biopsies were retrospectively evaluated for inflammatory activity, grade of dysplasia, ploidy status, laminin-5 gamma2 chain and cyclin A expression. RESULTS: Mild or moderate inflammatory activity was present in 78% of all biopsies, low- or high-grade dysplasia in 5.5%. There was no difference in inflammatory activity and dysplasia between patient groups. In group A, 75% of the biopsies exhibited aneuploid DNA distribution patterns. Group B showed mainly proliferative-diploid cell populations (85% / P = 0.006). Laminin-5 gamma2 chain was expressed in 13% of all biopsies, with a higher frequency in group A (P = 0.002). Cyclin A expression was found in 98% of all biopsies, with a higher number of immunopositive cells in group A biopsies (P = 0.014). CONCLUSIONS: Combined nuclear DNA assessment, laminin-5 gamma2 chain and cyclin A expression may help to identify ulcerative colitis patients with an increased risk for cancer development.