An evaluation of written materials for supporting hypertensive patient education and counselling when performing a new medicine service in Poland.

BACKGROUND: The New Medicine Service (NMS) was developed in England more than ten years ago, as a three-stage consultation led by community pharmacists to support patients taking new medication for a chronic disease. In Poland, the scheme was officially introduced in January 2023. However, its implementation into common practice has been presented with various obstacles, including the need to develop relationships with general practitioners, resolve the payment structure, and provide training with adequate supporting materials. Hence, written materials have been designed for use as an optional tool for counselling patients receiving an NMS in community pharmacies. METHODS: The present study evaluates the ability of these materials to inform patients about the need to adhere to anti-hypertensive medication. A group of 401 randomly-selected adult visitors to pharmacies and/or healthcare centres were surveyed; one third had hypertension in their history. RESULTS: The structure, grammar and readability of the text achieved the required threshold of 40% according to the Plain Language Index. The designed materials effectively informed the patients about anti-hypertensive medication, reflected in an increased score in a knowledge test, and were rated positively regarding information level, comprehensibility and presentation. CONCLUSION: The proposed material may serve as an additional, "patient-friendly" educational tool for use as part of an NMS.

The molecular mechanisms of fluoroquinolone resistance found in rectal swab isolates of Enterobacterales from men undergoing a transrectal prostate biopsy: the rationale for targeted prophylaxis.

BACKGROUND: Transrectal ultrasound-guided prostate biopsy (TRUS-Bx) is considered an essential urological procedure for the histological diagnosis of prostate cancer. It is, however, considered a "contaminated" procedure which may lead to infectious complications. Recent studies suggest a significant share of fluoroquinolone-resistant rectal flora in post-biopsy infections. METHODS: The molecular mechanisms of fluoroquinolone resistance, including PMQR (plasmid-mediated quinolone resistance) as well as mutation in the QRDRs (quinolone-resistance determining regions) of gyrA, gyrB, parC and parE, among Enterobacterales isolated from 32 of 48 men undergoing a prostate biopsy between November 2015 and April 2016 were investigated. Before the TRUS-Bx procedure, all the patients received an oral antibiotic containing fluoroquinolones. RESULTS: In total, 41 Enterobacterales isolates were obtained from rectal swabs. The MIC of ciprofloxacin and the presence of common PMQR determinants were investigated in all the isolates. Nine (21.9%) isolates carried PMQR with qnrS as the only PMQR agent detected. DNA sequencing of the QRDRs in 18 Enterobacterales (E. coli n = 17 and E. cloacae n = 1) isolates with ciprofloxacin MIC ≥ 0.25 mg/l were performed. Substitutions in the following codons were found: GyrA-83 [Ser → Leu, Phe] and 87 [Asp → Asn]; GyrB codon-605 [Met → Leu], ParC codons-80 [Ser → Ile, Arg] and 84 [Glu → Gly, Met, Val, Lys], ParE codons-458 [Ser → Ala], 461 [Glu → Ala] and 512 [Ala → Thr]. Six isolates with ciprofloxacin MIC ≥ 2 mg/l had at least one mutation in GyrA together with qnrS. CONCLUSIONS: This study provides information on the common presence of PMQRs among Enterobacterales isolates with ciprofloxacin MIC ≥ 0.25 mg/l, obtained from men undergoing TRUS-Bx. This fact may partially explain why some men develop post-TRUS-Bx infections despite ciprofloxacin prophylaxis.

Antimicrobial Resistance and Whole-Genome Characterisation of High-Level Ciprofloxacin-Resistant Salmonella Enterica Serovar Kentucky ST 198 Strains Isolated from Human in Poland.

BACKGROUND: Salmonella Kentucky belongs to zoonotic serotypes that demonstrate that the high antimicrobial resistance and multidrug resistance (including fluoroquinolones) is an emerging problem. To the best of our knowledge, clinical S. Kentucky strains isolated in Poland remain undescribed. METHODS: Eighteen clinical S. Kentucky strains collected in the years 2018-2019 in Poland were investigated. All the strains were tested for susceptibility to 11 antimicrobials using the disc diffusion and E-test methods. Whole genome sequences were analysed for antimicrobial resistance genes, mutations, the presence and structure of SGI1-K (Salmonella Genomic Island and the genetic relationship of the isolates. RESULTS: Sixteen of 18 isolates (88.9%) were assigned as ST198 and were found to be high-level resistant to ampicillin (>256 mg/L) and quinolones (nalidixic acid MIC ≥ 1024 mg/L, ciprofloxacin MIC range 6-16 mg/L). All the 16 strains revealed three mutations in QRDR of GyrA and ParC. The substitutions of Ser83 → Phe and Asp87 → Tyr of the GyrA subunit and Ser80→Ile of the ParC subunit were the most common. One S. Kentucky isolate had qnrS1 in addition to the QRDR mutations. Five of the ST198 strains, grouped in cluster A, had multiple resistant determinants like blaTEM1-B, aac(6')-Iaa, sul1 or tetA, mostly in SGI1 K. Seven strains, grouped in cluster B, had shorter SGI1-K with deletions of many regions and with few resistance genes detected. CONCLUSION: The results of this study demonstrated that a significant part of S. Kentucky isolates from humans in Poland belonged to ST198 and were high-level resistant to ampicillin and quinolones.

Correction to: The comorbidity burden of type 2 diabetes mellitus: patterns, clusters and predictions from a large English primary care cohort.

The original article [1] contains an omitted grant acknowledgement and affiliation as relates to the contribution of co-author, Rafael Perera-Salazar. As such, the following two amendments should apply to the original article.

Molecular diagnosis of COVID-19 ­ present experiences / Molekularna diagnostyka COVID-19 ­ dotychczasowe doswiadczenia.

Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), a new highly emerging and pathogenic for human RNA virus, is responsible for the present COVID-19 pandemic. Molecular diagnostic methods, including real-time reverse transcription-PCR (RT-PCR) assay are the recommended methods for the identification and laboratory confirmation of COVID-19 cases. RT-PCR allows for detection the RNA of the virus in clinical specimens from patients suspected of COVID-19 with high specificity and sensitivity. Testing is still crucial for rapid detection of infected persons, implementation of appropriate measures to suppress further virus transmission and mitigate its impact. In response to demand of a molecular diagnostic test for SARS-CoV-2, within a first few months ongoing pandemic many commercial kits has become available on the market. However, these tests have varied in number and type of molecular targets, time of reaction as well as quality. In this study we compared different commercial tests for the detection of SARS-CoV-2 in clinical samples sending to Laboratory of Department of Virology, NIPH-NIH.

The comorbidity burden of type 2 diabetes mellitus: patterns, clusters and predictions from a large English primary care cohort.

BACKGROUND: The presence of additional chronic conditions has a significant impact on the treatment and management of type 2 diabetes (T2DM). Little is known about the patterns of comorbidities in this population. The aims of this study are to quantify comorbidity patterns in people with T2DM, to estimate the prevalence of six chronic conditions in 2027 and to identify clusters of similar conditions. METHODS: We used the Clinical Practice Research Datalink (CPRD) linked with the Index of Multiple Deprivation (IMD) data to identify patients diagnosed with T2DM between 2007 and 2017. 102,394 people met the study inclusion criteria. We calculated the crude and age-standardised prevalence of 18 chronic conditions present at and after the T2DM diagnosis. We analysed longitudinally the 6 most common conditions and forecasted their prevalence in 2027 using linear regression. We used agglomerative hierarchical clustering to identify comorbidity clusters. These analyses were repeated on subgroups stratified by gender and deprivation. RESULTS: More people living in the most deprived areas had ≥ 1 comorbidities present at the time of diagnosis (72% of females; 64% of males) compared to the most affluent areas (67% of females; 59% of males). Depression prevalence increased in all strata and was more common in the most deprived areas. Depression was predicted to affect 33% of females and 15% of males diagnosed with T2DM in 2027. Moderate clustering tendencies were observed, with concordant conditions grouped together and some variations between groups of different demographics. CONCLUSIONS: Comorbidities are common in this population, and high between-patient variability in comorbidity patterns emphasises the need for patient-centred healthcare. Mental health is a growing concern, and there is a need for interventions that target both physical and mental health in this population.

Antibiotic choice in UK general practice: rates and drivers of potentially inappropriate antibiotic prescribing.

OBJECTIVES: To identify the rates of potentially inappropriate antibiotic choice when prescribing for common infections in UK general practices. To examine the predictors of such prescribing and the clustering effects at the practice level. METHODS: The rates of potentially inappropriate antibiotic choice were estimated using 1 151 105 consultations for sinusitis, otitis media and externa, upper respiratory tract infection (URTI) and lower respiratory tract infection (LRTI) and urinary tract infection (UTI), using the Clinical Practice Research Datalink (CPRD). Multilevel logistic regression was used to identify the predictors of inappropriate prescribing and to quantify the clustering effect at practice level. RESULTS: The rates of potentially inappropriate prescriptions were highest for otitis externa (67.3%) and URTI (38.7%) and relatively low for otitis media (3.4%), sinusitis (2.2%), LRTI (1.5%) and UTI in adults (2.3%) and children (0.7%). Amoxicillin was the most commonly prescribed antibiotic for all respiratory tract infections, except URTI. Amoxicillin accounted for 62.3% of prescriptions for otitis externa and 34.5% of prescriptions for URTI, despite not being recommended for these conditions. A small proportion of the variation in the probability of an inappropriate choice was attributed to the clustering effect at practice level (8% for otitis externa and 23% for sinusitis). Patients with comorbidities were more likely to receive a potentially inappropriate antibiotic for URTI, LRTI and UTI in adults. Patients who received any antibiotic in the 12 months before consultation were more likely to receive a potentially inappropriate antibiotic for all conditions except otitis externa. CONCLUSIONS: Antibiotic prescribing did not always align with prescribing guidelines, especially for URTIs and otitis externa. Future interventions might target optimizing amoxicillin use in primary care.

Silencing of angiotensin receptor 1 interferes with angiotensin II oncogenic activity in endometrial cancer.

In mammalian cells, angiotensin II (AngII) binds to 2 distinct high-affinity plasma membrane receptors: angiotensin receptor 1 (AT1R) and angiotensin receptor 2 (AT2R). Healthy human endometrium from women of reproductive age expresses all of the components of the renin-angiotensin system. Many studies suggest that AngII, acting via AT1R, may have a role in the development and progression of cancer, which changes the expression of angiogenic factors, AngII and AT1R are correlated with the presence of endometrial cancer (EC). The aim of the current study was to identify the effects of AngII on the proliferation, cell cycle progression, apoptosis and mobility of ISHIKAWA, MFE296 and MFE280 EC cells with silenced AT1R. It also examines epithelial-mesenchymal transition markers by gene expression analysis. The obtained results suggest that the silencing of AT1R expression alters the migration and invasion ability of EC cells. However, this silencing is not sufficient to inhibit the effects of AngII on EC cells, suggesting that AngII plays a more complex role in the development of EC.

Finding NEMO in preeclampsia.

BACKGROUND: The mechanism of preeclampsia and its way of inheritance are still a mystery. Biochemical and immunochemical studies reveal a substantial increase in tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 concentrations in the blood of women with preeclampsia. The level of these factors is regulated by nuclear facxtor-kappa B, whose activation in a classical pathway requires inhibitory kappa B kinase gamma (known as NEMO or IKBKG). Moreover, NEMO can schedule between cytoplasma and the nucleus. In the nucleus, IKBKG interacts with other proteins, and thus, it is implicated in the regulation of different gene expressions, which are related to cell cycle progression, proliferation, differentiation, and apoptosis. OBJECTIVE: This is the first study investigating the association between the level of NEMO gene expression and the presence of preeclampsia. We tested the hypothesis that the simultaneous increase in NEMO gene expression both in the mother and her fetus may be responsible for the preeclampsia development. Moreover, the relationships between clinical risk factors of preeclampsia and the levels of NEMO gene expression in blood, umbilical cord blood, and placentas were investigated. STUDY DESIGN: A total of 91 women (43 preeclamptic women and 48 controls) and their children were examined. Real-time reverse transcription-polymerase chain reaction was used to assess the amount total NEMO messenger ribonucleic acid (mRNA) content and the mRNA level of each NEMO transcript from exons 1A, 1B, and 1C in maternal blood, umbilical cord blood, and placentas. Univariate analyses and correlation tests were performed to examine the association between NEMO gene expression and preeclampsia. RESULTS: Newborn weight and height, maternal platelet number, and gestational age (week of delivery) were lower in the group of women with preeclampsia than controls. NEMO gene expression level was found to be almost 7 times higher in the group of women with preeclampsia than healthy controls. The correlation analysis found that a simultaneous increase in the expression level of total NEMO mRNA in maternal blood and the mRNA for total NEMO (Rs = 0.311, P < .05), transcripts 1A (Rs = 0.463, P < .01), 1B (Rs = 0.454, P < .01), and 1C (Rs = 0.563, P < .001) in fetal blood was observed in preeclamptic pregnancies. In addition, the mRNA levels for total NEMO and transcripts 1A, 1B, and 1C were lower in placentas derived from pregnancies complicated by preeclampsia. CONCLUSION: Simultaneous increase of NEMO gene expression in maternal and fetal blood seems to be relevant for preeclampsia development. The results of our study also suggest that a decreased NEMO gene expression level in preeclamptic placentas may be the main reason for their intensified apoptosis.

The whole-genome expression analysis of peripheral blood mononuclear cells from aspirin sensitive asthmatics versus aspirin tolerant patients and healthy donors after in vitro aspirin challenge.

BACKGROUND: Up to 30% of adults with severe asthma are hypersensitive to aspirin and no unambiguous theory exists which provides a satisfactory explanation for the occurrence of aspirin-induced asthma (AIA) in some asthmatic patients. Therefore, the aim of this study was to compare the AIA expression profile against aspirin tolerant asthma (ATA) and healthy volunteers (HV) profile in peripheral blood mononuclear cells (PBMCs) after in vitro aspirin challenge in Caucasian population. METHODS: PBMCs were separated from blood of three groups of subjects--11 AIA, 7 ATA and 15 HV and then stimulated by either 2 µM lysine aspirin or 20 µM lysine as a control. Subsequently, RNA was isolated, transcribed into cDNA and subjected to microarray and qPCR studies. Simultaneously, protein was extracted from PBMCs and used in further immunoblotting analysis. RESULTS: The validation of results at mRNA level has shown only three genes, whose expression was significantly altered between comprising groups. mRNA expression of CNPY3 in PBMCs in AIA was significantly lower (-0.41 ± 2.67) than in HV (1.04 ± 2.69), (p = 0.02); mRNA expression of FOSL1 in PBMCs in AIA was also significantly decreased (-0.66 ± 2.97) as opposed to HV (0.31 ± 4.83), (p = 0.02). While mRNA expression of ERAS in PBMCs was increased (1.15 ± 0.23) in AIA in comparison to HV (-1.32 ± 0.41), (p = 0.03). At protein level the changed expression of one protein was confirmed. Protein expression of FOSL1 in PBMCs in AIA was both significantly lower (-0.86 ± 0.08) than in ATA (0.39 ± 0.42), (p = 0.046) and in HV (0.9 ± 0.27), (p = 0.007). CONCLUSIONS: This pilot study implies a positive association between CNPY3, ERAS, FOSL1 and aspirin-intolerant asthma, suggesting that these findings would be useful for further investigations of NSAIDs mechanism.

Diverse effect of WWOX overexpression in HT29 and SW480 colon cancer cell lines.

WW-domain-containing oxidoreductase (WWOX) is the tumour suppressor gene from the common fragile site FRA16D, whose altered expression has been observed in tumours of various origins. Its suppressive role and influence on basic cellular processes such as proliferation and apoptosis have been confirmed in many in vitro and in vivo studies. Moreover, its protein is thought to take part in the regulation of tissue morphogenesis and cell differentiation. However, its role in colon cancer formation remains unclear. The aim of this study was to characterize the influence of WWOX on the process of colon cancerogenesis, the basic features of the cancer cell and its expression profiles. Multiple biological tests, microarray experiments and quantitative reverse transcriptase (RT)-PCR were performed on two colon cancer cell lines, HT29 and SW480, which differ in morphology, expression of differentiation markers, migratory characteristics and metastasis potential and which represent negative (HT29) and low (SW480) WWOX expression levels. The cell lines were subjected to retroviral transfection, inducting WWOX overexpression. WWOX was found to have diverse effects on proliferation, apoptosis and the adhesion potential of modified cell lines. Our observations suggest that in the HT29 colon cancer cell line, increased expression of WWOX may result in the transition of cancer cells into a more normal colon epithelium phenotype, while in SW480, WWOX demonstrated well-known tumour suppressor properties. Our results also suggest that WWOX does not behave as classical tumour suppressor gene, and its influence on cell functioning is more global and complicated.

[Depression in patients after coronary artery bypass grafting]. / Depresja u chorych po pomostowaniu aortalno-wienowym.

Surgical revascularization is a recognized method of treatment ofischaemic heart disease. The number of patients undergoing coronary artery bypass grafting (CABG) is constantly increasing, both in a population of young patients with coronary heart disease and in elderly patients. It is estimated that even one out of three patients undergoing CABG in the perioperative period can develop symptoms of depression. Numerous individual factors as well as factors related to the surgery have an impact on the occurrence of depression. The most common factors are: age, sex, socio-economic status, co-existing diseases, and the occurrence ofpreoperative depression. Researchers are currently looking for biochemical markers concentration of which before surgery could serve as a predicator for the occurrence of post-CABG depression. It is suggested that inflammatory response, particularly intense in the perioperative period, is linked to the occurrence of depression after surgical revascularization. Recognizing these factors is of utmost importance since it will help develop a stratification aiming at the identification of patients who are particularly prone to the occurrence of postoperative depression. Due to the fact that depression not only lowers the quality of life but also affects the short-term and long-term prognosis, identifying patients at risk is significantly important.

Correlation between VEGFR-2 receptor kinase domain-containing receptor (KDR) mRNA and angiotensin II receptor type 1 (AT1-R) mRNA in endometrial cancer.

PURPOSE: Angiogenesis, a multistep process that results in new blood vessel formation from preexisting vasculature is essential for both the growth of solid tumour and for metastasis. Stimulation of vascular endothelial growth factor receptor (VEGFR), a transmembrane glycoprotein, results in mitogenesis. Within this family of receptors, VEGFR 2/kinase-insert-domain containing receptor appears to be principally upregulated during tumorigenesis. The aim of this study was to determine the expression of VEGFR-2/kinase-insert-domain containing receptor (KDR) and its correlation with angiotensin receptor type 1 (AT1-R) and clinical factors in endometrial carcinoma. METHODS: The expression of KDR and AT1-R was studied in endometrial carcinoma and normal endometrium by Real-time RT-PCR and Western blot analysis in 136 samples. The expression profile was correlated with the clinicopathological characteristics of endometrial adenocarcinoma. RESULTS: We noted a significant correlation between the expression of KDR and AT1-R in tumour grade G1, G2 and G3 (R(s)=0.50; p=0.002, R(s)=0.69; p=0.0001, R(s)=0.52; p=0.005, respectively). In stage I and stage II carcinoma, a significant correlation was also found between the expression of KDR and AT1-R (R(s)=0.70, p=0.0001, R(s)=0.67; p=0.001, respectively). Moreover significant correlation was observed between both KDR and AT1-R in tissue with different myometrial invasion (R(s)=0.54, p=0.0001, R(s)=0.68; p=0.0001; respectively for tumours with invasion into the inner half and invasion into the outer half). CONCLUSIONS: Basing on received correlation between AT1-R and KDR expression and previous results we speculate that angiotensin through AT1-R modulates KDR expression and thus have influence on local VEGF level. However, further studies are required to clarify the biological interaction between KDR, AT1-R and other hormonal regulators in endometrial carcinoma.

A Single-Centre Retrospective Analysis of Radial Versus Femoral Prostate Artery Embolization.

Purpose: To determine whether route of access, transradial or transfemoral, leads to any discernible differences in patient radiation or contrast medium exposure as well as procedure time in elective prostate artery embolization (PAE).Methods: This retrospective study included sixty patients in total: n = 30 in the radial PAE group, and n = 30 in the femoral PAE group. All procedures were performed in a single angiography suite between May 2018 and January 2021, using a standard kit for each type of vascular access, the same microcatheter/wire combination and embolic agent to super-selectively target and embolize one or both prostate arteries. Outcome measures included dose area product (DAP, µGym2), air kerma (mGy), fluoroscopy time (mins), procedure time (mins) and volume of contrast medium used (mL). Adverse events were also recorded.Results: The radial and femoral groups were matched for age (73.2 ± 7.5 vs 71.3 ± 10.14, P = .41) and body mass index (27.53 ± 5.08 vs 26.41 ± 3.93, P = .38).No significant difference in dose area product, air kerma, fluoroscopy time, procedure time or volume of contrast medium used was found between radial and femoral PAE. No adverse events occurred in either group.Conclusion: Radial PAE is safe and comparable to femoral PAE with respect to patient radiation exposure, contrast medium usage, and procedure duration. Radial access is a useful skill to add to the armament of the interventional radiologist in elective PAE.

Examining non-linearity in the association between age and reported opioid use in different socioeconomic strata: cohort study using Health Survey for England waves from 1997 to 2014.

BACKGROUND: Age and socioeconomic status (SES) predict several health-related outcomes, including prescription opioid use. Contrasting findings from previous literature found higher prevalence of opioid use in both people over 65 years old and the working-age population of 35-55 years old. This study aimed to analyse if the association between age and opioid use is non-linear and differs in adults with different SES levels. METHODS: This cohort study used the Health Survey for England waves 1997-2014 data to investigate the shape of the correlation between reported opioid use and income decile, employment status and educational level. A semiparametric Generalised Additive Model was employed, so that linearity of correlation was not assumed. The shape of the relationship was assessed using the effective degrees of freedom (EDF). RESULTS: Positive correlation between age and reported opioid use, more linear in people in the highest income decile (EDF: 1.01, p<0.001) and higher education (EDF: 2.03, p<0.001) was observed. In people on lower income and with lower levels of education, the highes probability of reported opioid use was at around 40-60 years old and slowly decreased after that. Higher income decile and higher levels of education were predictors of a lower probability of reported opioid use (OR: 0.27, 95% CI: 0.21 to 0.36 and OR: 0.48, 95% CI: 0.41 to 0.57, respectively). There was no statistically significant difference in opioid use between employed and unemployed people. CONCLUSION: The relationship between age and the probability of prescribed opioid use varies greatly across different income and educations strata, highlighting different drivers in opioid prescribing across population groups. More research is needed into exploring patterns in opioid use in older people, particularly from disadvantaged socioeconomic backgrounds.

TGFα-EGFR pathway in breast carcinogenesis, association with WWOX expression and estrogen activation.

WWOX is a tumor-suppressive steroid dehydrogenase, which relationship with hormone receptors was shown both in animal models and breast cancer patients. Herein, through nAnT-iCAGE high-throughput gene expression profiling, we studied the interplay of estrogen receptors and the WWOX in breast cancer cell lines (MCF7, T47D, MDA-MB-231, BT20) under estrogen stimulation and either introduction of the WWOX gene by retroviral transfection (MDA-MB-231, T47D) or silenced with shRNA (MCF7, BT20). Additionally, we evaluated the consequent biological characteristics by proliferation, apoptosis, invasion, and adhesion assays. TGFα-EGFR signaling was found to be significantly affected in all examined breast cancer cell lines in response to estrogen and strongly associated with the level of WWOX expression, especially in ER-positive MCF7 cells. Under the influence of 17ß-estradiol presence, biological characteristics of the cell lines were also delineated. The study revealed modulation of adhesion, invasion, and apoptosis. The obtained results point at a complex role of the WWOX gene in the carcinogenesis of the breast tissue, which seems to be closely related to the presence of estrogen α and/or ß receptors.

WWOX oxidoreductase--substrate and enzymatic characterization.

WWOX is a tumour suppressor gene that spans the common fragile site FRA16D. Analysis of the WWOX expression pattern in normal human tissues showed the highest expression in testis, prostate, and ovary. Its altered expression has been demonstrated in different tissues and tumour types. The WWOX gene encodes a 414-amino acids protein, which is the first discovered protein with a short-chain dehydrogenase/reductase (SDR) central domain and two WW domains at the NH2 terminus. Due to its potential role in sex-steroid metabolism, using two bacterial expression systems, we have cloned WWOX fusion proteins showing oxidoreductase activity in a crude extract, defined a course of enzymatic reactions for selected steroid substrates, and determined related Km values. Our results show that the SDR domain of the WWOX protein has dehydrogenase activity and is reactive both in the presence of NAD+ and NADP+ for all examined steroid substrates. On the other hand, with the same substrates and reduced cofactors (NADH and NADPH) reduction activity was not observed.

Association of socioeconomic deprivation with opioid prescribing in primary care in England: a spatial analysis.

BACKGROUND: The increasing trends in opioid prescribing and opioid-related deaths in England are concerning. A greater understanding of the association of deprivation with opioid prescribing is needed to guide policy responses and interventions. METHODS: The 2018/2019 English national primary care prescribing data were analysed spatially. Prescribing of opioids in general practice was quantified by defined daily doses (DDD) and attributed to 32 844 lower layer super output areas (LSOAs), the geographical units representing ~1500 people. Linear regression was used to model the effect of socioeconomic deprivation (quintiles) on opioid prescribing while accounting for population demographics and the prevalence of specific health conditions. Adjusted DDD estimates were compared at each deprivation level within higher organisational areas (Clinical Commissioning Groups, CCGs). RESULTS: In total, 624 411 164 DDDs of opioids were prescribed. LSOA-level prescribing varied between 1.7 and 121.04 DDD/1000 population/day. Prescribing in the most deprived areas in the North of England was 1.2 times higher than the national average for areas with similar deprivation levels and 3.3 times higher than the most deprived areas in London. Prescribing in the most deprived areas was on average 9.70 DDD/1000 people/day (95% CI 9.41 to 10.00) higher than the least deprived areas. Deprivation-driven disparities varied between individual CCGs. In the most unequal CCG, prescribing in the most deprived areas was twice that in the least deprived areas. CONCLUSION: Opioid prescribing varied substantially across England and deprivation was strongly associated with prescribing. This paper provides evidence for guiding policy interventions and allocation of resources to areas with the highest levels of opioid prescribing.

Breast cancer relapse prediction based on multi-gene RT-PCR algorithm.

BACKGROUND: Breast cancer is very heterogeneous disease at both the clinical and molecular levels. Most research is based on analysis of a single gene, but only complex investigation of genes involved in different cell processes such as apoptosis or signal transduction can help to better understand the biology of this type of tumour. Novel techniques such as microarrays and real-time RT-PCR allow performance of such complex research. Only this kind of approach can improve cancer treatment through individualisation of disease cases with different molecular backgrounds. MATERIAL/METHODS: We performed quantitative RT-PCR to analyze levels of expression of 10 genes in 119 patient samples: 4 with known good prognosis signature (WWOX, ESR1, CDH, BAX) and 6 previously reported as bad prognosis markers of breast cancer (KRT5, KRT14, KRT17, CCNE1, BCL2, BIRC5). RESULTS: The algorithm composed of 10 genes distinguishes 2 statistically significant groups of patients with different rates of disease-free survival. However, when patients were divided into 2 groups according to estrogen receptor status, this algorithm could be applied only for a group with estrogen receptor negative breast cancer. High algorithm value is a good prognostic factor of disease-free survival for patients with estrogen negative breast cancers (HR=0.26; p=0.0039), but not for patients with ER positive tumors (p>0.05). CONCLUSIONS: The presented multigene algorithm may be used for outcome evaluation for estrogen receptor-negative breast cancer patients.

Comprehensive Evaluation of the Safety and Efficacy of BAFASAL® Bacteriophage Preparation for the Reduction of Salmonella in the Food Chain.

Bacteriophages are bacterial predators, which are garnering much interest nowadays vis-à-vis the global phenomenon of antimicrobial resistance. Bacteriophage preparations seem to be an alternative to antibiotics, which can be used at all levels of the food production chain. Their safety and efficacy, however, are of public concern. In this study, a detailed evaluation of BAFASAL® preparation was performed. BAFASAL® is a bacteriophage cocktail that reduces Salmonella in poultry farming. In vivo acute and sub-chronic toxicity studies on rats and tolerance study on targeted animals (chicken broiler) conducted according to GLP and OECD guidelines did not reveal any signs of toxicity, which could be associated with BAFASAL® administration. In addition, no evidences of genotoxicity were observed. The tolerance study with 100-times concentrated dose also did not show any statistically significant differences in the assessed parameters. The in vitro crop assay, mimicking normal feed storage and feed application conditions showed that BAFASAL® reduced the number of Salmonella bacteria in experimentally contaminated feed. Moreover, reductions were observed for all examined forms (liquid, powder, spray). Furthermore, the in vivo efficacy study showed that treatment with BAFASAL® significantly decreased Salmonella content in caeca of birds infected with Salmonella Enteritidis. Detailed examination of BAFASAL® in terms of safety and efficacy, adds to the body of evidence that bacteriophages are harmless to animals and effective in the struggle against bacteria.