Fecal Occult Blood Test (FOBT) efficacy in hospitalized patients

Introduction:Fecal occult blood test (FOBT) is one of the most popular diagnostic tools for screening colorectal cancer in the inpatient setting. Despite that, its outpatient use has been largely replaced by more advanced tools that decrease cost and increase sensitivity/specificity. This is essential when factors including diet and medications contribute to the low sensitivity and elevated false positive results FOBT demonstrate when detecting gastrointestinal (GI) bleeds

Active Screening for Tuberculosis Among Street Sweepers in Ahmedabad City

Background & Aims: Primary aim of Active Case Finding (ACF) is to ensure that active TB is detected early to reduce the risk of adverse outcomes as well as help in reducing TB transmission. There is a paucity of literature about prevalence of Tuberculosis among street sweepers. WHO described a high risk group for TB but it doesn’t include street sweepers though we are considering them at risk of TB due to their occupational exposure. Hence, active case finding among street sweepers is done. Materials and Methods: Cross-sectional study was conducted for active case finding of TB among street sweepers of North zone Ahmedabad. Symptomatic screening of all sweepers done and sweepers having any of the symptoms was investigated further by Chest X-ray and Sputum Microscopy. Sweeper who was diagnosed positive for TB, treatment was initiated as per NTEP guidelines. Results: Total 1200 sweepers were there in the north zone. At stage 1 43.5 % dropped out. 56 (8.25%, CI: 6.15-10.35) were having Presumptive TB. 28 sweepers participated for further testing. 50% (56-28=28) dropped out at the second stage. One Confirmed TB patient was identified and put on Treatment. Conclusion: We could reach approximately 50% of the total sweepers and the reason behind the low turnout could be the unprecedented event of covid19. Huge drops out at different stages of the screening process indicates poor health seeking behaviour, fear etc so further work to be done in this direction. Emphasis on usage of personal protective gears need to be given

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The genetics of the mood disorder spectrum:genome-wide association analyses of over 185,000 cases and 439,000 controls

Background Mood disorders (including major depressive disorder and bipolar disorder) affect 10-20% of the population. They range from brief, mild episodes to severe, incapacitating conditions that markedly impact lives. Despite their diagnostic distinction, multiple approaches have shown considerable sharing of risk factors across the mood disorders. Methods To clarify their shared molecular genetic basis, and to highlight disorder-specific associations, we meta-analysed data from the latest Psychiatric Genomics Consortium (PGC) genome-wide association studies of major depression (including data from 23andMe) and bipolar disorder, and an additional major depressive disorder cohort from UK Biobank (total: 185,285 cases, 439,741 controls; non-overlapping N = 609,424). Results Seventy-three loci reached genome-wide significance in the meta-analysis, including 15 that are novel for mood disorders. More genome-wide significant loci from the PGC analysis of major depression than bipolar disorder reached genome-wide significance. Genetic correlations revealed that type 2 bipolar disorder correlates strongly with recurrent and single episode major depressive disorder. Systems biology analyses highlight both similarities and differences between the mood disorders, particularly in the mouse brain cell-types implicated by the expression patterns of associated genes. The mood disorders also differ in their genetic correlation with educational attainment – positive in bipolar disorder but negative in major depressive disorder. Conclusions The mood disorders share several genetic associations, and can be combined effectively to increase variant discovery. However, we demonstrate several differences between these disorders. Analysing subtypes of major depressive disorder and bipolar disorder provides evidence for a genetic mood disorders spectrum

Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders.

Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The engineering and control of cell-toxic nanoparticles

In this project, native and functionalised mesoporous silica nanoparticles (MSNs) are synthesised and explored for their use as antibacterial delivery vehicles. These antibacterial loaded MSNs contribute significantly to the developing field of nanomedicine. This work broadly entails nanoparticle generation, characterisation, functionalisation, nanoparticle-bacteria cell viability studies and cell confocal imaging. Silica nanoparticles possess tunable surface chemistry, are thermally stable up to 800°C and are suitable for cell-study due to their low toxicity at sub-100 μg/ml concentrations. The preparation of silica nanoparticles with mesopores offers great potential for their use in a variety of applications; by loading or doping them with drugs, dyes, and imaging agents. In the present study, mesoporous silica nanoparticles with amino, carboxyl, PEG and lactose functionalities are prepared and characterised to determine their size, surface charge, surface area and purity using techniques including transmission electron microscope, dynamic light scattering, zeta potential, nitrogen adsorption-desorption and thermo gravimetric analysis. These particles are subsequently loaded with hydrophobic and volatile antibacterial oils- allyl isothiocyanate and cinnamaldehyde to determine the delivery dosage, release kinetics and need for capping. The silica surface is functionalised with lactose as a capping agent due to its inherent biocompatibility and potential for bio-triggering of hydrolysis in bacterial cells such as Escherichia coli. It is hoped that lactose acts as a suitable stopper via cross-linking the surface with intramolecular hydrogen bonding. Cell viability assays are carried out with antibacterial loaded MSNs to demonstrate bacterial cell killing and its killing efficiency. Thus the mesoporous nanoparticles are envisaged as efficient and colloidally stable antibacterial delivery systems