10957 research outputs found
Sort by
Detection and quantification of vessel morphology on retinal fundus images-challenges of retinal vasculometry at scale
Get PDFThe impact of model assumptions in interpreting cell kinetic studies
Get PDFStable isotope labelling is one of the best methods currently available for quantifying cell dynamics in vivo, particularly in humans where the absence of toxicity makes it preferable over other techniques such as CFSE or BrdU. Interpretation of stable isotope labelling data (as for BrdU and CFSE) necessitates simplifying assumptions. Here we investigate the impact of three of the most commonly used simplifying assumptions: (i) that the cell population of interest is closed, (ii) that the population of interest is kinetically homogeneous, and (iii) that the population is spatially homogeneous and suggest pragmatic ways in which the resulting errors can be reduced
Barriers to Implement Generic Medicine Prescribing and Dispensing Policies in Pakistan: Current Challenges and Future Implication
Get PDFBackground: Prescriptions comprising of generic names have made place as the norm in many countries owing to established drug regulatory regimes. Nevertheless, generics have greatly reduced worldwide pharmaceutical and healthcare spending. Objective: The current review comprehensively explores research studies focused on generic medicine in Pakistan, utilizing a variety of research methodologies. The prime objective of this review is to assess the barriers toward the implementation of generic medicine prescribing and dispensing policies in Pakistan in order to reduce the prescription cost. Methodology: The articles were filtered using databases: Google Scholar and PubMed. The research questions were developed and focused exclusively on all literature available regarding generic medicine in Pakistan. Results: Google Scholar and Pub-Med were searched for the period 2000-2023. 45 studies were included as per our criteria. The selected papers were grouped into different themes. Seven (7) papers were included regarding knowledge, attitude, perception & practice of healthcare givers regarding generic medicine in Pakistan. Seven (7) studies were related to Availability, Affordability, Pricing of Generic Medicine in Pakistan while 31 studies were included regarding percentage of generic prescribing as per WHO Core indicators. Both quantitative and qualitative research studies were eligible for inclusion. the selected papers were grouped into different themes. Conclusion: With the help of the evidence available through screening, it has been revealed that situation of generic medicine is quite alarming in Pakistan. Bioequivalence regulations as well as proper generic policy are need of the day. Educational interventions and uncompromising compliance to the drug policies of WHO may play a part in generic medication prescribing. Implementation of pricing policies is compulsory to promote rational use of drugs and to enhance availability. Presence of qualified pharmacists and electronic health system at every level of healthcare setups is need of an hour
Incidental Findings and Their Significance in Rectal MRI: UK Experience
Get PDFAbstract:
Rectal MRI studies used to stage and guide surgical or nonsurgical management of rectal cancer may harbor incidental findings (IFs) of varying significance. St George's Hospital uses a four-sequence MRI protocol which does not employ diffusion-weighted imaging (DW-MRI).
Objectives:
To determine the frequency and significance of incidental findings identified when using a rectal MRI protocol which does not employ DW-MRI.
Methods:
Retrospective analysis of rectal MRI study reports for IFs and stratifying their significance. Medical records were reviewed to clarify IFs of interest.
Results:
One hundred thirty-four studies met the inclusion criteria for the study (75 men, mean age 65). 51/134 (38%) of studies had IFs. Fifteen percent (n = 7/46) of baseline studies for a new cancer had significant IFs. The commonest IF was diverticular disease (n = 10); however, a bladder malignancy was also identified.
Conclusion:
Clinically significant IFs exist in 12% of patients undergoing rectal MRI, and any type of IFs exist in 38% of patients undergoing rectal MRI studies. The rate of significant IFs is comparable with other authors both in rectal and prostate MRI but with fewer overall IFs, possibly due to the lack of DW-MRI sequences in our local protocol. Our study is the first to assess IFs using a rectal MRI protocol which does not employ DW-MRI, and the results should be considered by centers when planning their rectal MRI protocol
The Epidemiology and Clinical Burden of Human Adenovirus Respiratory Infections Among Hospitalized Children Under 5 Years in Jordan
No full textBackground:
Human Adenovirus (HAdV) is a significant pathogen associated with severe acute respiratory infections, especially in children under 5. Despite its global impact, its epidemiological and clinical burden in Jordan, particularly post-COVID-19, is limited.
Methods:
We conducted a multicenter cross-sectional study across 4 hospitals in Jordan from November 2022 to April 2023. Nasopharyngeal swabs were collected from children <5 years old hospitalized with respiratory symptoms. HAdV positivity was determined using real-time polymerase chain reaction. Demographic, clinical and laboratory data were analyzed to identify predictors of HAdV positivity and complications.
Results:
Among 1000 enrolled participants (median age 9.68 months, 59% male), the HAdV positivity rate was 10.9%, highest in children 49–60 months of age. HAdV-positive cases had higher rates and longer duration of sore throat compared with HAdV-negative cases. Coinfections with respiratory syncytial viruses or influenza were present in 34.9% of HAdV-positive cases and were associated with increased rates of cough, wheezing and respiratory crackles. Logistic regression revealed lower odds of HAdV positivity in children under six months [odds ratio (OR) 0.31, P < 0.001], while invasive ventilation was associated with higher odds of positivity (OR 5.01, P < 0.001). HAdV infection without coinfection was associated with reduced odds of complications (OR 0.06, P < 0.001).
Conclusions:
This is the first comprehensive study in Jordan to document the epidemiologic and clinical burden of HAdV in children post-COVID-19. HAdV remains a major cause of respiratory morbidity, with significant coinfection rates. Further research is needed to explore the nonrespiratory manifestations, identify HAdV common local serotypes and genetic characteristics
Characterisation of chikungunya virus neutralising monoclonal antibodies expressed in tobacco plants
Get PDFChikungunya virus (CHIKV) causes a debilitating musculoskeletal disease, characterised by flu-like symptoms, rash, and severe joint pain, which can last for months, even after the resolution of infection. Although the first CHIKV vaccine was approved in the USA in 2023 for use in adults, there is currently no specific antiviral therapy for infection. While neutralising antibody-based prophylactic and therapeutic agents have been considered, affordability and accessibility are major barriers to global regions where Chikungunya disease is epidemic. Here, we expressed five anti-CHIKV neutralising IgG monoclonal antibodies (mAbs) in N. benthamiana plants to investigate the potential use of this manufacturing platform. Plants produced IgG mAbs that compared favourably to mammalian cell-expressed antibodies, including for binding kinetics to CHIKV antigens and neutralisation activity. The yields of mAbs from plants were variable, as three of the antibodies’ yields would need further expression optimisation to warrant future development. The successful expression of these antibodies in N. benthamiana plants supports the growing pipeline of Global Health product targets that could be developed using a highly transferable, low-cost, low-tech plant production platform in resource-poor countries
Hybrid in-person and internet-based pain management programs; an opportunity for improved patient experience and outcomes.
No full textIntegrative proteo-genomic profiling uncovers key biomarkers of lapatinib resistance in HER2-positive breast cancer
Get PDFIntroduction
Drug resistance is a major obstacle to the long-term effectiveness of cancer therapies. Approximately 70% of breast cancer patients relapse after 5 years of treatment, and the lack of biomarkers associated with drug resistance translates to poor prognosis in the clinic. Previous research has utilised omics approaches to uncover biomarkers driving drug resistance, with a strong emphasis on genetic mutations.
Methods
Here, we identified a nine-marker signature associated with resistance to lapatinib in a HER2-positive breast cancer model using a target discovery approach by employing an integrative multi-omics strategy, combining ATAC-seq, RNA-seq and proteomics.
Results
We found that seven markers in the drug resistance-signature had not been previously found to be implicated in HER2-positive breast cancer, some of which we further validated using an additional lung cancer model. We counterintuitively found that drug-resistant cells have restrictive chromatin accessibility with reduced gene expression associated with limited total proteome changes. However, upon closer look, we identified that the drug resistance-signature had increased chromatin accessibility near the transcriptional start sites of those seven markers and was highly differentially expressed across the three datasets. Our data show that despite the overall transcriptional and proteomic landscape showing limited changes, there are several markers that are highly expressed, which correlate with increased anchorage-independent and invasive phenotype in vitro in lapatinib-resistant cells compared to cancer cells.
Conclusions
Our results demonstrate that disease aggressiveness can be related to reduced chromatin and gene expression dynamics. We anticipate that the resistant signature identified here using an integrative target discovery approach can be applied to complex, more representative models and validated before they can be targeted by suitable therapeutic agents
The impact of the COVID-19 pandemic on maternal healthcare costs: a time series analysis of pregnancies of multi-ethnic mothers in South London, United Kingdom
Get PDFBACKGROUND: Due to the COVID-19 pandemic, maternity care reconfigurations disrupted in-person care, which shifted towards virtual care and self-monitoring. We assessed the impact of these changes on maternity service provision costs. METHODS: Data from October 2018 to April 2023 were used from the population-based early-LIfe data cross-LInkage in Research, Born in South London (eLIXIR-BiSL) platform linking maternity, neonatal, and mental healthcare data from three National Health Service (NHS) hospitals in South London, United Kingdom. Maternity costs were generated from the NHS perspective, using national unit costs and individual-level use of maternity, mental health, and primary care services. Interrupted time series analysis estimated the pandemic impact on monthly mother-newborn costs over time. Cross-sectional pre-pregnancy cost models isolated the impact of virtual care and gestational diabetes (GDM) self-monitoring using the GDm-Health app. Ethnic inequalities in the impact of the pandemic on maternity costs were assessed via interaction terms. RESULTS: Among 36,895 pregnancies, the monthly cost time series level dropped by 4% (£ - 38, 95% confidence interval: [£ - 65 to - 10]), during the first pandemic lockdown, and by 7.6% (£ - 72 [£ - 108 to - 36]), when lockdowns were lifted compared with the pre-pandemic period. However, the pre-pandemic slightly upward timeseries slope of costs (£4 per month, [£0.30 to £6.83]) was unchanged during the pandemic (£0.46 [£ - 2.93 to 3.84]). Monthly costs increased with first lockdown for Black (£103 [£26 to 181]) and Asian women (£128 [£38 to 218]) and increased more slowly during post-lockdown (£ - 12 [£ - 23 to - 2]), for Asian women, remaining higher throughout the pandemic for Black and Asian women compared with White women. A 1% increase in virtual care was associated with a £7 (£3 to 10) increase in maternity costs. GDM self-monitoring via GDm-Health was cost-neutral (£140 [£ - 68 to 348]). CONCLUSIONS: The pandemic was associated with temporary reductions in maternity costs due to lower healthcare utilisation. Ongoing, rising maternity costs were unchanged. The pandemic had differential effects on Black and Asian women compared with White women. Further research is needed into clinical outcomes of virtual care (associated with higher costs) and use of GDm-Health (cost-neutral)
Pharmacokinetics of Dexamethasone in Tuberculous Meningitis
Get PDFBackground
Dexamethasone is recommended as adjunctive therapy for tuberculous meningitis (TBM). Co-administration with rifampicin is expected to reduce dexamethasone exposure in TBM, an effect that may be more pronounced with the higher rifampicin doses currently being evaluated in clinical trials.
Methods
This pharmacokinetic study was nested in a randomized controlled trial comparing the safety of high-dose rifampicin (oral, 35 mg/kg; intravenous, 20 mg/kg) plus linezolid, with or without aspirin, versus standard-dose rifampicin (10 mg/kg) for adults with HIV-associated TBM. All participants received adjunctive oral dexamethasone every 12 hours starting at a dose of 0.4 mg/kg/day. Dexamethasone concentrations were measured on intensively sampled plasma on day 3 after study enrollment and analysed using nonlinear mixed-effects modeling.
Results
In total, 261 dexamethasone concentrations from 43 participants were available for model development. Eight (18%) participants were on efavirenz-based ART and five (11%) were on a lopinavir/ritonavir-based regimen. The median duration of rifampicin therapy at the time of pharmacokinetic sampling was 4 days (range: 0–7). Dexamethasone pharmacokinetics was best described by a one-compartment disposition model with first-order absorption and elimination. Typical oral clearance (CL/F) was 131 L/h, reduced to 11.5 L/h with concomitant lopinavir/ritonavir. High-dose rifampicin had no significant additional effect on dexamethasone pharmacokinetic parameters compared with the standard-dose.
Conclusions
In adults with HIV-associated TBM, there was high dexamethasone clearance, likely related to a drug-drug interaction with rifampicin. High-dose rifampicin had no additional effect on dexamethasone exposure
Access Repository Dashboard
Do you manage St George's Online Research Archive? Access insider analytics, issue reports and manage access to outputs from your repository in the CORE Repository Dashboard!