Double sigmoid atresia with meconium pseudocyst masquerading as a mesenteric cyst

Sigmoid atresia is one of the rarest cause of neonatal intestinal obstruction. We report an antenatally diagnosed mesenteric cyst in a neonate that was subsequently diagnosed as a meconium pseudocyst with double sigmoid atresia. A localized type 4 atresia or a colonic atresia associated with meconium pseudocyst has not been reported in the literature to date.Keywords: atresia, obstruction, pseudocyst, sigmoid colo

Recent scenario on psychotropic drug usage pattern among patients attending psychiatric outpatient department of a tertiary care teaching hospital in Nepal

Background: Due to increasing burden of psychiatric illnesses, it is essential to study the psychotropic drug utilization pattern in actual clinical practice. The objective of the study was to study the psychotropic drug usage pattern among patients attending psychiatric OPD of a tertiary care teaching hospital in Nepal.Methods: This observational retrospective study was conducted in Nepal Gunj Medical College, Nepal for a period of 6 months from January 2016 to June 2016. A total of 282 prescriptions from Psychiatric OPD were analysed for drug usage pattern. Prescriptions containing at least one psychotropic drug were included. Data was measured for number and percentage of prescriptions or drugs, using selected World Health Organization (WHO) drug use indicators.Results: A total of 282 prescriptions from Psychiatric OPD were analysed. Patients had a mean age of 35.01±1.17 years. Male and Female %age was 41.49% and 58.51% respectively. Majority of the patients (47.52%) were in 31-45 years age group. 70.57% patients were literate. Depression was the leading psychiatric illness seen in 144 (51.06%) patients followed by Anxiety disorders which were seen in 60 (21.28%) patients. A total of 2463 drugs were prescribed which included 591 (23.99%) antipsychotic drugs followed by 462 (18.76%) antidepressants, 390 (15.83%) antiepileptics, 312 (12.67%) supplements, 276 (11.21%) antianxiety, 171 (6.94%) antacids, 165 (6.7%) anticholinergics, 96 (3.9%) drugs in miscellaneous category. Drugs prescribed per prescription were 8.73 and psychotropic drugs per prescription were 6.09. Number of oral and injectable drugs were 2313 (93.91%) and 150 (6.09%) respectively. 87 fixed dose combinations (FDCs) of psychotropic drugs were prescribed. 903 (36.66%) drugs were prescribed from WHO’s 18th List of Essential Medicines.Conclusions: Depression was the most common psychiatric illness and antipsychotics were the most commonly prescribed medicines in psychiatry OPD. Majority of the prescriptions revealed polypharmacy

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (antispike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group).Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose

The ethical dimensions of nanomedicine

Medical practice is about to enter a new era focused on the nanoscale and the practice of nanomedicine, defined as the monitoring, control, construction, repair, defense, and improvement of human biologic systems via engineered nanodevices and nanomaterials. The potential impact of nanomedicine on society is expected to be huge as the nanopharma market grows significantly in the coming years. Given this backdrop, nanomedicine is poised to add a profound and complex set of ethical and societal questions. Some of these are recurring themes in bioethics while others will be discussed in slightly new ways due to nanomedicine's interdisciplinary nature: privacy, confidentiality, risks and benefits, defining disease, and enhancement

Human Clinical Relevance of the Porcine Model of Pseudoallergic Infusion Reactions

Pigs provide a highly sensitive animal model for pseudoallergic infusion reactions, which are mild-to-severe hypersensitivity reactions (HSRs) that arise following intravenous administration of certain nanoparticulate drugs (nanomedicines) and other macromolecular structures. This model has been used in research for three decades and was also proposed by regulatory bodies for preclinical assessment of the risk of HSRs in the clinical stages of nano-drug development. However, there are views challenging the human relevance of the model and its utility in preclinical safety evaluation of nanomedicines. The argument challenging the model refers to the “global response” of pulmonary intravascular macrophages (PIM cells) in the lung of pigs, preventing the distinction of reactogenic from non-reactogenic particles, therefore overestimating the risk of HSRs relative to its occurrence in the normal human population. The goal of this review is to present the large body of experimental and clinical evidence negating the “global response” claim, while also showing the concordance of symptoms caused by different reactogenic nanoparticles in pigs and hypersensitive man. Contrary to the model’s demotion, we propose that the above features, together with the high reproducibility of quantifiable physiological endpoints, validate the porcine “complement activation-related pseudoallergy” (CARPA) model for safety evaluations. However, it needs to be kept in mind that the model is a disease model in the context of hypersensitivity to certain nanomedicines. Rather than toxicity screening, its main purpose is specific identification of HSR hazard, also enabling studies on the mechanism and mitigation of potentially serious HSRs

The Nanotechnology Patent ‘Gold Rush’

426-433During the past decade, a swarm of patent applications pertaining to nanotechnology has been arriving at all the major patent offices of the world, including the US Patent and Trademark Office (USPTO). As companies develop products and processes and begin to seek commercial applications for their inventions, securing valid and defensible patent protection will be vital to their long-term survival. In the decades to come, with nanotechnology further maturing and the promised breakthroughs accruing, patents will generate licensing revenue, provide leverage in deals and mergers, and reduce the like-lihood of infringement. Because development of nanotech-related products is extremely research intensive, without the mar-ket exclusivity offered by a US patent, development of these products and their commercial viability in the marketplace will be significantly hampered. In this paper, effects of ‘nanopatent gold rush’ that is underway by ‘patent prospectors’ as start-ups are highlighted whereby corporations compete to lock up broad patents in these critical early days. In fact, the entire US patent system is under greater scrutiny and strain, with the USPTO continuing to struggle with evaluating nanotech-related patent applications. It is unclear whether the nanotech industry will thrive like the information technology (IT) industry or get bogged down like the radio patent deadlock

Recent scenario on psychotropic drug usage pattern among patients attending psychiatric outpatient department of a tertiary care teaching hospital in Nepal

Background: Due to increasing burden of psychiatric illnesses, it is essential to study the psychotropic drug utilization pattern in actual clinical practice. The objective of the study was to study the psychotropic drug usage pattern among patients attending psychiatric OPD of a tertiary care teaching hospital in Nepal.Methods: This observational retrospective study was conducted in Nepal Gunj Medical College, Nepal for a period of 6 months from January 2016 to June 2016. A total of 282 prescriptions from Psychiatric OPD were analysed for drug usage pattern. Prescriptions containing at least one psychotropic drug were included. Data was measured for number and percentage of prescriptions or drugs, using selected World Health Organization (WHO) drug use indicators.Results: A total of 282 prescriptions from Psychiatric OPD were analysed. Patients had a mean age of 35.01±1.17 years. Male and Female %age was 41.49% and 58.51% respectively. Majority of the patients (47.52%) were in 31-45 years age group. 70.57% patients were literate. Depression was the leading psychiatric illness seen in 144 (51.06%) patients followed by Anxiety disorders which were seen in 60 (21.28%) patients. A total of 2463 drugs were prescribed which included 591 (23.99%) antipsychotic drugs followed by 462 (18.76%) antidepressants, 390 (15.83%) antiepileptics, 312 (12.67%) supplements, 276 (11.21%) antianxiety, 171 (6.94%) antacids, 165 (6.7%) anticholinergics, 96 (3.9%) drugs in miscellaneous category. Drugs prescribed per prescription were 8.73 and psychotropic drugs per prescription were 6.09. Number of oral and injectable drugs were 2313 (93.91%) and 150 (6.09%) respectively. 87 fixed dose combinations (FDCs) of psychotropic drugs were prescribed. 903 (36.66%) drugs were prescribed from WHO’s 18th List of Essential Medicines.Conclusions: Depression was the most common psychiatric illness and antipsychotics were the most commonly prescribed medicines in psychiatry OPD. Majority of the prescriptions revealed polypharmacy

Nanomedicines: addressing the scientific and regulatory gap

Nanomedicine is the application of nanotechnology to the discipline of medicine: the use of nanoscale materials for the diagnosis, monitoring, control, prevention, and treatment of disease. Nanomedicine holds tremendous promise to revolutionize medicine across disciplines and specialties, but this promise has yet to be fully realized. Beyond the typical complications associated with drug development, the fundamentally different and novel physical and chemical properties of some nanomaterials compared to materials on a larger scale (i.e., their bulk counterparts) can create a unique set of opportunities as well as safety concerns, which have only begun to be explored. As the research community continues to investigate nanomedicines, their efficacy, and the associated safety issues, it is critical to work to close the scientific and regulatory gaps to assure that nanomedicine drives the next generation of biomedical innovation