Category: Nevin Manimala

Arthritis Res Ther. 2021 Aug 31;23(1):226. doi: 10.1186/s13075-021-02610-y.

ABSTRACT

OBJECTIVE: To compare C-reactive protein (CRP) and matrix metalloproteinase-generated neoepitope of CRP (CRPM) as biomarkers of inflammation and radiographic severity in patients with knee osteoarthritis.

METHODS: Participants with symptomatic osteoarthritis (n=25) of at least one knee underwent knee radiographic imaging and radionuclide etarfolatide imaging to quantify inflammation of the knees and other appendicular joints. For purposes of statistical analysis, semi-quantitative etarfolatide and radiographic imaging scores were summed across the knees; etarfolatide scores were also summed across all joints to provide a multi-joint synovitis measure. Multiple inflammation and collagen-related biomarkers were measured by ELISA including CRP, CRPM, MMP-generated neoepitopes of type I collagen and type III collagen in serum (n=25), and CD163 in serum (n=25) and synovial fluid (n=18).

RESULTS: BMI was associated with CRP (p=0.001), but not CRPM (p=0.753). Adjusting for BMI, CRP was associated with radiographic knee osteophyte score (p=0.002), while CRPM was associated with synovitis of the knee (p=0.017), synovitis of multiple joints (p=0.008), and macrophage marker CD163 in serum (p=0.009) and synovial fluid (p=0.03). CRP correlated with MMP-generated neoepitope of type I collagen in serum (p=0.045), and CRPM correlated with MMP-generated neoepitope of type III collagen in serum (p<0.0001). No biomarkers correlated with age, knee pain, or WOMAC pain.

CONCLUSIONS: To our knowledge, this is the first time that CRPM has been shown to be associated with knee and multi-joint inflammation based on objective imaging (etarfolatide) and biomarker (CD163) measures. These results demonstrate the capability of biomarker measurements to reflect complex biological processes and for neoepitope markers to more distinctly reflect acute processes than their precursor proteins. CRPM is a promising biomarker of local and systemic inflammation in knee OA that is associated with cartilage degradation and is independent of BMI. CRPM is a potential molecular biomarker alternative to etarfolatide imaging for quantitative assessment of joint inflammation.

PMID:34465395 | DOI:10.1186/s13075-021-02610-y

J Pharm Policy Pract. 2021 Aug 31;14(1):73. doi: 10.1186/s40545-021-00364-1.

ABSTRACT

BACKGROUND: One in four people experience a mental health problem every year and improving mental health care is an international priority. In the course of their work, pharmacists frequently encounter people with mental health problems. The experience of mental health teaching, including Mental Health First Aid (MHFA) training, in undergraduate pharmacy (MPharm) students in the UK and Ireland is not well documented. Students’ viewpoints, contextualised with curricular overviews provided by staff, were analysed to understand their experience.

METHODS: An anonymous, online questionnaire was distributed to MPharm students and staff in the UK and Ireland. Students were asked closed questions regarding their course and exposure to MHFA, which were analysed using descriptive statistics. Open questions were included to enable explanations and these data were used to contextualise the quantitative findings. One member of staff from each university was invited to answer a modified staff version of the questionnaire, to provide a curriculum overview and staff perspective.

RESULTS: 232 students and 13 staff, from 22 universities, responded. Three-quarters of students did not agree with the statement that ‘mental health was embedded throughout the MPharm’. Most students (80.6%) stated that they were taught neuropharmacology whilst 44.8% stated that their course included communicating with people about their mental health. One-third (33.2%) of students stated that their degree ‘adequately prepared them to help people with their mental health’. Twenty-six students (11.6%) had completed MHFA training of which 89% would endorse inclusion of this within the MPharm. Of those who had not completed the training, 81% expressed a desire to do so. Those who completed MHFA training self-reported greater preparedness than those who did not, but student numbers were small.

CONCLUSIONS: Mental health teaching for pharmacy undergraduates is more focussed on theoretical aspects rather than applied skills. MHFA was viewed by students as one way to enhance skill application. The association of the increased self-reported preparedness of those who completed MHFA could be confounded by a positive environmental cultural. MPharm programmes need sufficient focus on real-world skills such as communication and crisis response, to complement the fundamental science.

PMID:34465394 | DOI:10.1186/s40545-021-00364-1

BMC Musculoskelet Disord. 2021 Aug 31;22(1):750. doi: 10.1186/s12891-021-04629-3.

ABSTRACT

BACKGROUND: Reconstruction of the skeletal defects resulting from the resection of bone tumors remains a considerable challenge and one of the possibilities is the orthotopic replantation of the irradiated bone autograft. One technical option with this technique is the addition of a vital autologous fibular graft, with or without microvascular anastomosis. The aim of our study was to evaluate the clinical results of the treatment of our patient cohort with a specific view to the role of fibular augmentation.

METHODS: Twenty-one patients with 22 reconstructions were included. In all cases, the bone tumor was resected with wide margins and in 21 of them irradiated with 300 Gy. In the first case, thermal sterilization in an autoclave was used. The autograft was orthotopically replanted and stabilized with plates and screws. Fifteen patients underwent an additional fibular augmentation, 8 of which received microvascular anastomoses or, alternatively, a locally pedicled fibular interposition.

RESULTS: the most common diagnosis was a Ewing sarcoma (8 cases) and the most common location was the femur (12 cases). The mean follow-up time was 70 months (16-154 months). For our statistical analysis, the one case with autoclave sterilization and 3 patients with tumors in small bones were excluded. During follow-up of 18 cases, 55.6% of patients underwent an average of 1.56 revision surgeries. Complete bony integration of the irradiated autografts was achieved in 88.9% of cases after 13.6 months on average. In those cases with successful reintegration, the autograft was shorter (n.s.). Microvascular anastomosis in vascularized fibular strut grafts did not significantly influence the rate of pseudarthrosis.

CONCLUSIONS: the replantation of extracorporeally irradiated bone autografts is an established method for the reconstruction of bone defects after tumor resection. Our rate of complications is comparable to those of other studies and with other methods of bone reconstruction (e.g. prosthesis). In our opinion, this method is especially well suited for younger patients with extraarticular bone tumors that allow for joint preservation. However, these patients should be ready to accept longer treatment periods.

PMID:34465336 | DOI:10.1186/s12891-021-04629-3

Allergy Asthma Clin Immunol. 2021 Aug 31;17(1):86. doi: 10.1186/s13223-021-00586-7.

ABSTRACT

BACKGROUND: Increased intestinal permeability, either due to the exposure to antigens in asthmatic patients or due to a barrier defect, plays a critical role in susceptibility to environmental allergens. House dust mite allergy occurs more commonly than any other type of allergy among Egyptian asthmatic patients.

AIM: To assess the relation between serum zonulin level as a marker of increased intestinal permeability and the severity of house dust mite allergic asthma.

METHODS: A case-control study which included 48 patients with house dust mite allergic asthma and 48 healthy control subjects attending the Allergy and Immunology Unit, Microbiology and Immunology Department, Faculty of Medicine, Zagazig University.

RESULTS: A statistically significant difference was detected between the two studied groups with respect to serum IgE and serum zonulin levels (p ˂ 0.001 and ˂ 0.001, respectively). The mean serum zonulin was equal to 258.3 ± 153.01 ng/ml in the asthmatic group and 80 ± 13 ng/ml in the control group. Serum zonulin level significantly increased with the increase of asthma severity (p ˂ 0.001). The cut off value of serum zonulin was ≥ 198 ng/ml, and the area under the curve was 0.76. It displayed sensitivity equal to 80% and specificity equal to 71.4%. Its negative predictive value was equal to 83.3%.

CONCLUSION: Intestinal barrier dysfunction contributes to the pathogenesis of allergic asthma. Serum zonulin level reflects an increase in intestinal permeability. Zonulin acts as prognostic factor of severity in asthma. Correction of the gut barrier defect may have a potential positive prognostic effect in asthma.

PMID:34465387 | DOI:10.1186/s13223-021-00586-7

BMC Infect Dis. 2021 Aug 31;21(1):894. doi: 10.1186/s12879-021-06622-6.

ABSTRACT

BACKGROUND: Primary care and frontline healthcare providers are often the first point of contact for patients experiencing tick-borne disease (TBD) but face challenges when recognizing and diagnosing these diseases. The specific aim of this study was to gain a qualitative understanding of frontline and primary care providers’ knowledge and practices for identifying TBDs in patients.

METHODS: From fall 2018 to spring 2019, three focus groups were conducted with primary care providers practicing in a small-town community endemic to Lyme disease (LD) and with emerging incidence of additional TBDs. A follow up online survey was distributed to urgent and emergency care providers in the small-town community and an academic medical center within the referral network of the local clinical community in spring and summer 2019. Qualitative analysis of focus group data was performed following a grounded theory approach and survey responses were analyzed through the calculation of descriptive statistics.

RESULTS: Fourteen clinicians from three primary care practices participated in focus groups, and 24 urgent and emergency care clinicians completed the survey questionnaire. Four overarching themes emerged from focus group data which were corroborated by survey data. Themes highlighted a moderate level of awareness on diagnosis and treatment of LD among participants and limited knowledge of diagnosis and treatment for two other regionally relevant TBDs, anaplasmosis and babesiosis. Providers described challenges and frustrations in counseling patients with strong preconceptions of LD diagnosis and treatment in the context of chronic infection. Providers desired additional point-of-care resources to facilitate patient education and correct misinformation on the diagnosis and treatment of TBDs.

CONCLUSIONS: Through this small study, it appears that clinicians in the small-town and academic medical center settings are experiencing uncertainties related to TBD recognition, diagnosis, and patient communication. These findings can inform the development of point-of-care resources to aid in patient-provider communication regarding TBDs and inform the development of continuing medical education programs for frontline and primary care providers.

PMID:34465298 | DOI:10.1186/s12879-021-06622-6

BMC Health Serv Res. 2021 Aug 31;21(1):897. doi: 10.1186/s12913-021-06871-w.

ABSTRACT

BACKGROUND: Urinary catheters are useful among hospital patients for allowing urinary flows and preparing patients for surgery. However, urinary infections associated with catheters cause significant patient discomfort and burden hospital resources. A nurse led intervention aiming to reduce inpatient catheterisation rates was recently trialled among adult overnight patients in four New South Wales hospitals. It included: ‘train-the trainer’ workshops, site champions, compliance audits and promotional materials. This study is the ‘in-trial’ cost-effectiveness analysis, conducted from the perspective of the New South Wales Ministry of Health.

METHODS: The primary outcome variable was catheterisation rates. Catheterisation and procedure/treatment data were collected in three point prevalence patient surveys: pre-intervention (n = 1630), 4-months (n = 1677), and 9-months post-intervention (n = 1551). Intervention costs were based on trial records while labour costs were gathered from wage awards. Incremental cost effectiveness ratios were calculated for 4- and 9-months post-intervention and tested with non-parametric bootstrapping. Sensitivity scenarios recalculated results after adjusting costs and parameters.

RESULTS: The trial found reductions in catheterisations across the four hospitals between preintervention (12.0 % (10.4 – 13.5 %), n = 195) and the 4- (9.9 % (8.5 – 11.3 %), n = 166 ) and 9- months (10.2 % (8.7 – 11.7 %) n = 158) post-intervention points. The trend was statistically non-significant (p = 0.1). Only one diagnosed CAUTI case was observed across the surveys. However, statistically and clinically significant decreases in catheterisation rates occurred for medical and critical care wards, and among female patients and short-term catheterisations. Incremental cost effectiveness ratios at 4-months and 9-months post-intervention were $188 and $264. Bootstrapping found reductions in catheterisations at positive costs over at least 72 % of iterations. Sensitivity scenarios showed that cost effectiveness was most responsive to changes in catheterisation rates.

CONCLUSIONS: Analysis showed that the association between the intervention and changes in catheterisation rates was not statistically significant. However, the intervention resulted in statistically significant reductions for subgroups including among short-term catheterisations and female patients. Cost-effectiveness analysis showed that reductions in catheterisations were most likely achieved at positive cost.

TRIAL REGISTRATION: Registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000090314). First hospital enrolment, 15/11/2016; last hospital enrolment, 8/12/2016.

PMID:34465324 | DOI:10.1186/s12913-021-06871-w

BMC Mol Cell Biol. 2021 Aug 31;22(1):44. doi: 10.1186/s12860-021-00382-6.

ABSTRACT

Sequence-specific transcription factors (TFs) recognize motifs of related nucleotide sequences at their DNA binding sites. Upon binding at these sites, TFs regulate critical molecular processes such as gene expression. It is widely assumed that a TF recognizes a single “canonical” motif, although recent studies have identified additional “non-canonical” motifs for some TFs. A comprehensive approach to identify non-canonical DNA binding motifs and the functional importance of those motifs’ matches in the human genome is necessary for fully understanding the mechanisms of TF-regulated molecular processes in human cells. To address this need, we developed a statistical pipeline for in vitro HT-SELEX data that identifies and characterizes the distributions of non-canonical TF motifs in a stringent manner. Analyzing ~170 human TFs’ HT-SELEX data, we found non-canonical motifs for 19 TFs (11%). These non-canonical motifs occur independently of the TFs’ canonical motifs. Non-canonical motif occurrences in the human genome show similar evolutionary conservation to canonical motif occurrences, explain TF binding in locations without canonical motifs, and occur within gene promoters and epigenetically marked regulatory sequences in human cell lines and tissues. Our approach and collection of non-canonical motifs expand current understanding of functionally relevant DNA binding sites for human TFs.

PMID:34465294 | DOI:10.1186/s12860-021-00382-6

BMC Med Res Methodol. 2021 Aug 31;21(1):182. doi: 10.1186/s12874-021-01359-x.

ABSTRACT

BACKGROUND: Healthcare decisions are ideally based on clinical trial results, published in study registries, as journal articles or summarized in secondary research articles. In this research project, we investigated the impact of academically and commercially sponsored clinical trials on medical practice by measuring the proportion of trials published and cited by systematic reviews and clinical guidelines.

METHODS: We examined 691 multicenter, randomized controlled trials that started in 2005 or later and were completed by the end of 2016. To determine whether sponsorship/funding and place of conduct influence a trial’s impact, we created four sub-cohorts of investigator initiated trials (IITs) and industry sponsored trials (ISTs): 120 IITs and 171 ISTs with German contribution compared to 200 IITs and 200 ISTs without German contribution. We balanced the groups for study phase and place of conduct. German IITs were funded by the German Research Foundation (DFG), the Federal Ministry of Education and Research (BMBF), or by another non-commercial research organization. All other trials were drawn from the German Clinical Trials Register or ClinicalTrials.gov. We investigated, to what extent study characteristics were associated with publication and impact using multivariable logistic regressions.

RESULTS: For 80% of the 691 trials, results were published as result articles in a medical journal and/or study registry, 52% were cited by a systematic review, and 26% reached impact in a clinical guideline. Drug trials and larger trials were associated with a higher probability to be published and to have an impact than non-drug trials and smaller trials. Results of IITs were more often published as a journal article while results of ISTs were more often published in study registries. International ISTs less often gained impact by inclusion in systematic reviews or guidelines than IITs.

CONCLUSION: An encouraging high proportion of the clinical trials were published, and a considerable proportion gained impact on clinical practice. However, there is still room for improvement. For publishing study results, study registries have become an alternative or complement to journal articles, especially for ISTs. IITs funded by governmental bodies in Germany reached an impact that is comparable to international IITs and ISTs.

PMID:34465296 | DOI:10.1186/s12874-021-01359-x

Oral Dis. 2021 Aug 31. doi: 10.1111/odi.14014. Online ahead of print.

ABSTRACT

OBJECTIVE: To preliminary evaluate the clinical effects of probiotics in individuals with symptomatic oral lichen planus, and the possible mechanisms of action.

SUBJECTS AND METHODS: 30 individuals with symptomatic oral lichen planus were recruited in a double-blind parallel group randomised controlled (1:1) proof-of-concept pilot trial of probiotic VSL#3 vs placebo. Efficacy outcomes included changes in pain numeric rating scale, oral disease severity score and the chronic oral mucosal disease questionnaire. Adverse effects, home diary, and withdrawals were assessed as feasibility outcomes. Mechanistic outcomes included changes in salivary and serum levels of CXCL10 and IFN-γ and in oral microbial composition.

RESULTS: The probiotic VSL#3 was safe and well tolerated. We observed no statistically significant change in pain, disease activity, quality of life, serum/salivary CXCL10 or oral microbial composition with respect to placebo. Salivary IFN-γ levels demonstrate a trend for a reduced level in the active group (p=0.082) after 30 days of probiotic consumption.

CONCLUSIONS: The present proof-of-concept study provides some weak not convincing indication of biological and clinical effects of probiotic VSL#3 in individuals with painful oral lichen planus. Further research in this field is needed, with the current study providing useful information to the design of future clinical trials.

PMID:34464996 | DOI:10.1111/odi.14014

J Viral Hepat. 2021 Aug 31. doi: 10.1111/jvh.13606. Online ahead of print.

ABSTRACT

Hepatitis B viral (HBV) load and hepatic enzymes play a critical role in hepatocellular carcinoma (HCC) development. The clinical significance of both in HBV-related HCC patients after hepatectomy remains unclear. This study analyzed 1940 HBV-related HCC patients who underwent hepatectomy from four hospitals in west China. Risk classification was constructed based on baseline HBV-DNA level and AST/ALT ratio. Based on the HBV-DNA and AST/ALT ratio classification, four types with distinguishable prognosis were established. Type 1 patients had best prognosis with 69.8% 5-year overall survival (OS), while the type 4 patients had worst prognosis with 42.7% 5-year OS, type 3 and type 2 patients followed. Similarly, the four subgroups had statistically different recurrence free survival (RFS). This classification was significantly associated with HCC recurrence (hazard ratio [HR]:1.492, p<0.001) and long-term survival (HR:1.574, p=0.001). Pathologically, Type 4 correlated with more advanced tumors, such as tumor size and microvascular invasion (vs. type 1/2/3). Moreover, type 4 patients had more severe hepatic inflammation in underlying liver. Conversely, type 1 had active tumor immune microenvironment indicated by more CD8+ T cell infiltration and less PD-L1 expression. In conclusion, baseline HBV-DNA and AST/ALT ratio classification could effectively stratify HBV-related HCC patients with distinguishable prognosis after hepatectomy.

PMID:34464991 | DOI:10.1111/jvh.13606