In the recent case of 'Re P', Newton J ordered and directed that renal replacement therapy (RRT) continue for a patient who lacked capacity. This was notwithstanding that the trust had sought a ...declaration permitting them to 'withdraw' RRT and so appears to be an instance of the Court of Protection (COP) forcing doctors to provide a treatment.
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IZUM, KILJ, NUK, PILJ, PNG, PRFLJ, SAZU, UL, UM, UPUK
Neutropenic enterocolitis is a potentially life-threatening condition of the lower gastrointestinal tract (typically the caecum, in which it is termed typhlitis), where intestinal microbes invade the ...surrounding tissue of patients with neutropenia. Prevalence of this condition is rising because of liberal use of aggressive chemotherapy agents that damage the intestinal mucosa, and it is being increasingly recognised as a complication of stem-cell transplantation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Triazoles remain first-line agents for antifungal prophylaxis in high-risk haemato-oncology patients, but their use is increasingly contraindicated due to drug-drug interactions and additive ...toxicities with novel treatments. In this retrospective, single-centre, observational study, we present our eight-year experience of antifungal prophylaxis using intermittent high-dose liposomal Amphotericin B (L-AmB). All adults identified through our Antifungal Stewardship Programme as receiving L-AmB prophylaxis at 7.5 mg/kg once-weekly between February 2012 and January 2020 were included. Adverse reactions, including infusion reactions, electrolyte loss, and nephrotoxicity, were recorded. 'Breakthrough' invasive fungal infection (IFI) occurring within four weeks of L-AmB was classified using European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. Moreover, 114 courses of intermittent high-dose L-AmB prophylaxis administered to 92 unique patients were analysed. Hypokalaemia was the most common grade 3-4 adverse event, with 26 (23%) courses. Grade 3 nephrotoxicity occurred in 8 (7%) and reversed in all six patients surviving to 90 days. There were two (1.8%) episodes of breakthrough IFI, one 'probable' and one 'possible'. In this study, the largest evaluation of intermittent high-dose L-AmB prophylaxis conducted to date, toxicity was manageable and reversible and breakthrough IFI was rare. L-AmB prophylaxis represents a viable alternative for patients with a contraindication to triazoles.
Background: The cartridge-based nucleic acid amplification test (CBNAAT) Xpert MTB/RIF is more sensitive than smear microscopy for the diagnosis of tuberculosis (TB). It is also more expensive, ...costing 1450 INR as compared to 10 INR per smear. Objectives: We conducted a prospective study to evaluate the impact of CBNAAT results on patient management in our low-resource, high-burden Indian rural setting. Materials and Method: Between February and July 2017, clinicians were asked to complete one questionnaire at the time of CBNAAT request and another when reviewing the result. The first questionnaire, "Form 1," concerned pretest treatment status and asked clinicians to rate their confidence in the diagnosis. "Form 2" concerned postresult treatment and investigation plan. Results: Over the study period, 206 CBNAATs were requested. Form 1 was not completed for 85 patients and 21 were excluded leaving 100 in the main analysis. MTB was detected (MTB-D) in 60 of 100 (60%) of samples tested. At the time of CBNAAT request, 56 of 100 (56%) of patients were already on treatment, this being empirical in 34 of 100 (34%). Despite this, 17 of 60 (28.3%) of MTB-D results occurred in patients not yet started on treatment. Postresult treatment status was available for 94 of 100 CBNAATs (55 MTB-D and 39 MTB-ND). Following an MTB-D result, all 17 patients not on treatment started and all 38 on so already continued. Following an MTB Not Detected (MTB-ND) result, 26 of 27 (96.3%) of patients not yet on treatment remained so, but only 2 of 12 (16.7%) already on treatment stopped. Even where the clinician's pretest confidence in TB was low, 9of 30 (30%) of CBNAAT results were MTB-D. Conclusion: In a low-resource high-burden setting, CBNAAT may have greatest impact where the clinician's pretest confidence in TB is low and empirical treatment has not been started. This is because MTB-D results will lead to appropriate initiation of treatment and MTB-ND results may enable clinicians to hold-off treatment.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Marked reductions in serum iron concentrations are commonly induced during the acute phase of infection. This phenomenon, termed hypoferremia of inflammation, leads to inflammatory anemia, but could ...also have broader pathophysiological implications. In patients with coronavirus disease 2019 (COVID-19), hypoferremia is associated with disease severity and poorer outcomes, although there are few reported cohorts.
In this study, we leverage a well characterised prospective cohort of hospitalised COVID-19 patients and perform a set of analyses focussing on iron and related biomarkers and both acute severity of COVID-19 and longer-term symptomatology.
We observed no associations between acute serum iron and long-term outcomes (including fatigue, breathlessness or quality of life); however, lower haemoglobin was associated with poorer quality of life. We also quantified iron homeostasis associated parameters, demonstrating that among 50 circulating mediators of inflammation IL-6 concentrations were strongly associated with serum iron, consistent with its central role in inflammatory control of iron homeostasis. Surprisingly, we observed no association between serum hepcidin and serum iron concentrations. We also observed elevated erythroferrone concentrations in COVID-19 patients with anaemia of inflammation.
These results enhance our understanding of the regulation and pathophysiological consequences of disturbed iron homeostasis during SARS-CoV-2 infection.
The immunocompetent defence against infection comprises a multifaceted and coordinated armoury of physical barriers, and innate and adaptive immunity. Certain medical conditions and treatments can ...compromise either single or multiple components of this defence and provoke susceptibility to pathogens rarely encountered in immunocompetent hosts. When evaluating such patients, it can be helpful to consider things from both a ‘pathogen-focused’ and a ‘host-focused’ perspective. Understanding geographical and healthcare contact can help inform which bacterial, viral, fungal and parasitic pathogens the patient has been exposed to, and screening swabs/serological tests can further clarify this risk. The specific clinical scenario at hand always dictates which infections should be considered but no pathogen is linked to a single clinical syndrome. Both the likely infection and its severity are contingent upon which component of immunity has been compromised, to what degree and for how long. The time that has elapsed since transplantation has a strong influence over which infections are plausible in the recipient, whereas for patients with HIV, it their CD4+ count. The overall host vulnerability to infection, however, results from an interplay between these direct causes of immunodeficiency, other co-morbidities and iatrogenic factors such as catheters and surgical interventions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In April 2015, the first legally approved HIV self-testing kit went on sale in the UK—except Northern Ireland where they remain illegal. These tests allow individuals to test their HIV status and ...read the result in the privacy of their own home, much like a home pregnancy test. This paper explores the ethical implications of HIV self-testing. We conclude that there are no strong ethical objections to self-testing being made widely available in the UK. Pretest counselling for an HIV test is not an ethical necessity, and self-testing has the potential to increase early diagnosis of HIV infection and thus improve prognosis and reduce ongoing transmission. Self-testing kits might also empower people and promote autonomy by allowing people to dictate the terms on which they test their HIV status. We accept that there are some potential areas of concern. These include the possibility of user error with the tests, and the concern that individuals may not present to health services following a reactive result. False negatives have the potential to cause harm if the ‘window period’ is not understood, and false positives might produce psychological distress. There is, however, little evidence to suggest that self-testing kits will cause widespread harm, and we argue that the only way to properly evaluate whether they do cause significant harm is to carefully evaluate their use, now that they are available on the market.
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BFBNIB, CMK, NMLJ, NUK, ODKLJ, PNG, SAZU, UL, UM, UPUK
9.
HIV and the right not to know Youngs, Jonathan; Simmonds, Joshua
Journal of medical ethics,
02/2016, Volume:
42, Issue:
2
Journal Article
Peer reviewed
Open access
It is a tenet of the prevailing ethic in medicine that competent adults have the ‘right to know’ information necessary to make informed decisions about their healthcare. Whether there is a ‘right not ...to know’ unwanted information is more hotly debated. When deciding whether or not to override a competent adult's desire not to know his/her HIV result, a desire to respect patient autonomy can be seen to pull in both directions. We thus conclude that there is not a very strong presumption on the side of non-disclosure but rather the adult's interest in not knowing must be weighed against the potential harms and benefits of disclosure for both the individual and others. This does not, however, negate the fact that patients retain a right to refuse an HIV test and this is so even where issues of bodily integrity are not at stake. This implies that explicit consent should still be sought for HIV testing, at least where there is some possibility that the patient may refuse, or want more information, if given the chance.
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BFBNIB, CMK, NMLJ, NUK, ODKLJ, PNG, SAZU, UL, UM, UPUK
Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description of specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for ...patients with varying COVID-19 severity in an integrated comparison with influenza and sepsis patients versus healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity involved cells, their inflammatory mediators and networks, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism, and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Systems-based integrative analyses including tensor and matrix decomposition of all modalities revealed feature groupings linked with severity and specificity compared to influenza and sepsis. Our approach and blood atlas will support future drug development, clinical trial design, and personalized medicine approaches for COVID-19.
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•Blood atlas delineating innate and adaptive immune dysregulation in COVID-19•Shared and specific immune signatures of COVID-19, influenza and all cause sepsis•Multi-omic immune profiling differentiates hospitalized patient severity in COVID-19•Immune activation and proliferation involving AP-1/p38MAPK associated with COVID-19
A multi-omic analysis of patient blood samples reveals both similarities and specific features of COVID-19 when compared with samples obtained from sepsis or influenza patients, which could yield better targeted therapies for severe COVID-19.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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