Nevin Manimala

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 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 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

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

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

Cancer Sci. 2021 Aug 31. doi: 10.1111/cas.15126. Online ahead of print.

ABSTRACT

Fusobacterium nucleatum has been detected in 8-13% of human colorectal cancer, and shown to inhibit immune responses against primary colorectal tumours in animal models. Thus, we hypothesised that the presence of F. nucleatum might be associated with reduced T-cell density in colorectal cancer liver metastases (CRLMs). We quantified F. nucleatum DNA in 181 CRLM specimens using quantitative polymerase chain reaction assay. The densities of CD8⁺ T cells, CD33⁺ cells (marker for myeloid-derived suppressor cells (MDSCs)), and CD163⁺ cells (marker for tumour-associated macrophages (TAMs)) in CRLM tissue were determined by immunohistochemical staining. F. nucleatum was detected in eight (4.4%) of 181 CRLM specimens. Compared with F. nucleatum-negative CRLMs, F. nucleatum-positive CRLMs exhibited significantly lower density of CD8⁺ T cells (P = 0.033) and higher density of MDSCs (P = 0.001). The association of F. nucleatum with the density of TAMs was not statistically significant (P = 0.70). The presence of F. nucleatum is associated with a lower density of CD8⁺ T cells and a higher density of MDSCs in CRLM tissue. Upon validation, our findings may provide insights to develop strategies that involve targeting microbiota and immune cells for the prevention and treatment of CRLMs.

PMID:34464993 | DOI:10.1111/cas.15126

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

Mol Biol Evol. 2021 Aug 31:msab243. doi: 10.1093/molbev/msab243. Online ahead of print.

ABSTRACT

A nonsense allele at rs1343879 in human MAGEE2 on chromosome X has previously been reported as a strong candidate for positive selection in East Asia. This premature stop codon causing ∼80% protein truncation is characterized by a striking geographical pattern of high population differentiation: common in Asia and the Americas (up to 84% in the 1000 Genomes Project East Asians) but rare elsewhere. Here, we generated a Magee2 mouse knockout mimicking the human loss-of-function mutation to study its functional consequences. The Magee2 null mice did not exhibit gross abnormalities apart from enlarged brain structures (13% increased total brain area, P = 0.0022) in hemizygous males. The area of the granular retrosplenial cortex responsible for memory, navigation and spatial information processing was the most severely affected, exhibiting an enlargement of 34% (P = 3.4×10-6). The brain size in homozygous females showed the opposite trend of reduced brain size, although this did not reach statistical significance. With these insights, we performed human association analyses between brain size measurements and rs1343879 genotypes in 141 Chinese volunteers with brain MRI scans, replicating the sexual dimorphism seen in the knockout mouse model. The derived stop gain allele was significantly associated with a larger volume of grey matter in males (P = 0.00094), and smaller volumes of grey (P = 0.00021) and white (P = 0.0015) matter in females. It is unclear whether or not the observed neuroanatomical phenotypes affect behaviour or cognition, but it might have been the driving force underlying the positive selection in humans.

PMID:34464968 | DOI:10.1093/molbev/msab243

J Stroke Cerebrovasc Dis. 2021 Jun 18;30(11):105953. doi: 10.1016/j.jstrokecerebrovasdis.2021.105953. Online ahead of print.

ABSTRACT

Background and purpose; Chile has been one of the most affected countries by the COVID-19 pandemic, with one of the highest case rates per population. This has affected the epidemiological behaviour of various pathologies. We analyze the impact of the pandemic on the number of admissions due to stroke, its severity and mortality in Santiago, Chile.

METHODS: a multicenter observational study based on the records of the 3 hospitals of the South East health service in Santiago, Chile. We recorded the number of patients admitted for ischemic stroke between 01 January 2020 and 30 June 2020. We grouped the cases into two periods, pre-pandemic and pandemic, according to the setting of the state of emergency in Chile.

RESULTS: 431 patients were admitted with ischemic stroke during the study period. There was a non-significant decrease in weekly admissions (17 vs 15 patients per week). No differences were observed in the proportion of patients with medical treatment (p = 0.810), IVT (p = 0.638), EVT (p = 0.503) or IVT + EVT (p = 0.501). There was a statistically significant increase in the NIHSS on admission (7.23 vs 8.78, p = 0.009) and mortality (5.2% vs 12.4%, p = 0.012). In a multivariate analysis the NIHSS on admission was associated with the increased mortality (RR 1.11, CI 1.04-1.19, p = 0.003).

CONCLUSION: We found an increase in the severity of ischemic stroke on admission and in-hospital mortality during the pandemic period. The main factor to increase in-hospital mortality was the NIHSS on admission.

PMID:34464928 | DOI:10.1016/j.jstrokecerebrovasdis.2021.105953

J Infect Public Health. 2021 Aug 24;14(9):1247-1253. doi: 10.1016/j.jiph.2021.08.022. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the efficacy of Favipiravir compared to the standard therapy in treating patients with severe COVID-19 infection.

METHODS: This is a retrospective cohort of patients with COVID-19 pneumonia who were treated with favipiravir, versus comparison group that received the standard of care.

RESULTS: A total of 226 patients were included; 110 patients received favipiravir and 116 patients received standard of care. Patients who received favipiravir had longer time to recovery (14.2 ± 8.8 versus 12.8 ± 5.2, p = 0.17). Favipiravir was associated with an improved early day 14 mortality (4 [3.6%] versus 11 [9.5%]), p = 0.008), but was associated with a higher day 28 mortality (26 [23.6%] versus 11 [9.5%], p = 0.02). The overall mortality was higher in the favipiravir versus the standard of care group but difference was not statistically significant (33 [30.0%] versus 24 [20.7%], p = 0.10).

CONCLUSION: The addition of favipiravir to standard of care was not associated with any improvement in clinical outcomes or mortality. Larger randomized controlled clinical trials are needed to further assess the efficacy of favipiravir.

PMID:34464921 | DOI:10.1016/j.jiph.2021.08.022