Vaccine effectiveness against SARS-CoV-2 infection or COVID-19 hospitalization with the Alpha, Delta, or Omicron SARS-CoV-2 variant: A nationwide Danish cohort study.

BACKGROUND: The continued occurrence of more contagious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants and waning immunity over time require ongoing reevaluation of the vaccine effectiveness (VE). This study aimed to estimate the effectiveness in 2 age groups (12 to 59 and 60 years or above) of 2 or 3 vaccine doses (BNT162b2 mRNA or mRNA-1273) by time since vaccination against SARS-CoV-2 infection and Coronavirus Disease 2019 (COVID-19) hospitalization in an Alpha-, Delta-, or Omicron-dominated period. METHODS AND FINDINGS: A Danish nationwide cohort study design was used to estimate VE against SARS-CoV-2 infection and COVID-19 hospitalization with the Alpha, Delta, or Omicron variant. Information was obtained from nationwide registries and linked using a unique personal identification number. The study included all previously uninfected residents in Denmark aged 12 years or above (18 years or above for the analysis of 3 doses) in the Alpha (February 20 to June 15, 2021), Delta (July 4 to November 20, 2021), and Omicron (December 21, 2021 to January 31, 2022) dominated periods. VE estimates including 95% confidence intervals (CIs) were calculated (1-hazard ratio∙100) using Cox proportional hazard regression models with underlying calendar time and adjustments for age, sex, comorbidity, and geographical region. Vaccination status was included as a time-varying exposure. In the oldest age group, VE against infection after 2 doses was 90.7% (95% CI: 88.2; 92.7) for the Alpha variant, 82.3% (95% CI: 75.5; 87.2) for the Delta variant, and 39.9% (95% CI: 26.3; 50.9) for the Omicron variant 14 to 30 days since vaccination. The VE waned over time and was 73.2% (Alpha, 95% CI: 57.1; 83.3), 50.0% (Delta, 95% CI: 46.7; 53.0), and 4.4% (Omicron, 95% CI: -0.1; 8.7) >120 days since vaccination. Higher estimates were observed after the third dose with VE estimates against infection of 86.1% (Delta, 95% CI: 83.3; 88.4) and 57.7% (Omicron, 95% CI: 55.9; 59.5) 14 to 30 days since vaccination. Among both age groups, VE against COVID-19 hospitalization 14 to 30 days since vaccination with 2 or 3 doses was 98.1% or above for the Alpha and Delta variants. Among both age groups, VE against COVID-19 hospitalization 14 to 30 days since vaccination with 2 or 3 doses was 95.5% or above for the Omicron variant. The main limitation of this study is the nonrandomized study design including potential differences between the unvaccinated (reference group) and vaccinated individuals. CONCLUSIONS: Two vaccine doses provided high protection against SARS-CoV-2 infection and COVID-19 hospitalization with the Alpha and Delta variants with protection, notably against infection, waning over time. Two vaccine doses provided only limited and short-lived protection against SARS-CoV-2 infection with Omicron. However, the protection against COVID-19 hospitalization following Omicron SARS-CoV-2 infection was higher. The third vaccine dose substantially increased the level and duration of protection against infection with the Omicron variant and provided a high level of sustained protection against COVID-19 hospitalization among the +60-year-olds.

Using practical wisdom to facilitate ethical decision-making: a major empirical study of phronesis in the decision narratives of doctors.

BACKGROUND: Medical ethics has recently seen a drive away from multiple prescriptive approaches, where physicians are inundated with guidelines and principles, towards alternative, less deontological perspectives. This represents a clear call for theory building that does not produce more guidelines. Phronesis (practical wisdom) offers an alternative approach for ethical decision-making based on an application of accumulated wisdom gained through previous practice dilemmas and decisions experienced by practitioners. Phronesis, as an 'executive virtue', offers a way to navigate the practice virtues for any given case to reach a final decision on the way forward. However, very limited empirical data exist to support the theory of phronesis-based medical decision-making, and what does exist tends to focus on individual practitioners rather than practice-based communities of physicians. METHODS: The primary research question was: What does it mean to medical practitioners to make ethically wise decisions for patients and their communities? A three-year ethnographic study explored the practical wisdom of doctors (n = 131) and used their narratives to develop theoretical understanding of the concepts of ethical decision-making. Data collection included narrative interviews and observations with hospital doctors and General Practitioners at all stages in career progression. The analysis draws on neo-Aristotelian, MacIntyrean concepts of practice- based virtue ethics and was supported by an arts-based film production process. RESULTS: We found that individually doctors conveyed many different practice virtues and those were consolidated into fifteen virtue continua that convey the participants' 'collective practical wisdom', including the phronesis virtue. This study advances the existing theory and practice on phronesis as a decision-making approach due to the availability of these continua. CONCLUSION: Given the arguments that doctors feel professionally and personally vulnerable in the context of ethical decision-making, the continua in the form of a video series and app based moral debating resource can support before, during and after decision-making reflection. The potential implications are that these theoretical findings can be used by educators and practitioners as a non-prescriptive alternative to improve ethical decision-making, thereby addressing the call in the literature, and benefit patients and their communities, as well.

Checklists in community care: reducing differences in care delivery between regular and relief staff to improve consistency and client experience.

BACKGROUND: Today, healthcare is more complex than just ensuring clients receive quality care; it also involves consistently delivering excellent client experience. A non-profit community support services agency conducted an extensive diagnostic journey to determine root causes of inconsistent care delivery between regular and relief frontline staff. LOCAL PROBLEM: Clients and family caregivers noted lower satisfaction in care delivery when a relief staff (ie, internal staff or an external agency that is covering a shift) provided service in comparison with their regular staff. The diagnostic journey discovered that the shift exchange process-when outgoing staff transfers critical knowledge to incoming staff for continuing care-varied significantly between the 11 service locations, leading to a lack of consistent service delivery, thereby impacting client experience. METHODS: A working group consisting of Supervisors of Client Services, Personal Support Workers (PSW) and management were tasked with process mapping the current state, highlighting gaps and outlining the ideal state of the shift exchange process. INTERVENTIONS: Using best practices from the aviation industry, a checklist was developed that encapsulated all the critical steps needed to be undertaken for a successful, consistent shift exchange. The theory was that the utilisation of the checklist would enable consistency and improve client satisfaction with care delivery, especially when care is delivered by a staff unfamiliar with clients. RESULTS: Prior to the checklist implementation, 74% of clients were satisfied or very satisfied with their relief staff, and post checklist implementation client satisfaction improved to 90%. Staff self-assessments also indicated that PSWs agreed that the checklist helped provide consistent care. CONCLUSION: The use of checklists can transform the way care is delivered in the community support sector and other service delivery agencies alike to bring greater standardisation of care between providers, thus significantly improving client experience across the healthcare sector.

Phronesis in Medical Ethics: Courage and Motivation to Keep on the Track of Rightness in Decision-Making.

Ethical decision making in medicine has recently seen calls to move towards less prescriptive- based approaches that consider the particularities of each case. The main alternative call from the literature is for better understanding of phronesis (practical wisdom) concepts applied to decision making. A well-cited phronesis-based approach is Kaldjian's five-stage theoretical framework: goals, concrete circumstances, virtues, deliberation and motivation to act. We build on Kaldjian's theory after using his framework to analyse data collected from a three-year empirical study of phronesis and the medical community. The data are a set of narratives collected in response to asking a medical community (131 doctors at various stages of their careers) what making ethically wise decisions means to them. We found that Kaldjian's five concepts are present in the accounts to some extent but that one of the elements, motivation, is constructed as playing a different, though still crucial role. Rather than being an end-stage of the process as Kaldjian's framework suggests, motivation was constructed as initiating the process and maintaining the momentum of taking a phronesis-based approach. The implications for medical ethics decision-making education are significant as motivation itself is a highly complex concept. We therefore theorise that motivation is required for leading in, continuing and completing the actions of the ethical decision taken. Appreciating the central importance of motivation through the whole of Kaldjian's framework has implications for cultivating the virtues of phronesis and courage to take the right course of action.

An exploration of patient safety culture in Kuwait hospitals: a qualitative study of healthcare professionals' perspectives.

OBJECTIVE: Patient safety culture (PSC) represents a key component of the quality of care offered by healthcare professionals. Therefore, it is crucial to understand the factors that influence the implementation of a safe culture. This study explored the knowledge and attitudes of healthcare professionals in Kuwait towards the factors that might affect the PSC. METHODS: A qualitative study using semi-structured interviews with healthcare professionals was conducted between February and June 2018 at two major hospitals in Kuwait. Both hospitals had been accredited and have been applying the safety programmes recommended by the Kuwaiti Ministry of Health. Participants were purposively selected where 20 healthcare professionals were interviewed. The interviewees comprised of six physicians, six clinical pharmacists, six nurses and two members of the patient safety committee. Inclusion criteria involved healthcare professionals who had more than 1-year clinical experience, have interest in patient safety and had a good level of English. Interviews were audio-recorded and transcribed verbatim. Thematic analysis of the interview transcripts was conducted to identify the emergent themes. KEY FINDINGS: Thematic analysis of the interviews yielded three major themes related to 'management', 'regulations and policies' and 'healthcare professionals'. Management issues included managerial support, resources, safety environment and staff training. Regulations and policies highlighted issues related to policies and procedures and incident reporting system. Healthcare professionals' theme covered factors related to knowledge, communication and teamwork among healthcare professionals. CONCLUSIONS: This study gave insight into how healthcare professionals perceive the current PSC in Kuwait. Despite their positive attitudes and knowledge towards patient safety, various barriers were reported that hinder optimal PSC. These barriers were related to support, staffing, resources and response to error.

Successful pregnancy outcome after septum resection and use of amnion graft in patient with high transverse vaginal septum.

A 20-year-old woman recently married presented to the outpatient department of the hospital, with primary amenorrhea and difficulty in having coitus. Her height was 155 cm, breast development was normal for age, and other secondary sexual characters seemed normal. On local examination, external genitalia was normal looking, and there was no vaginal discharge. She had a blind vagina of 2 cm length. The ultrasound showed a normal-sized uterus and ovaries seemingly normal. Hormonal profile comprising serum follicle-stimulating hormone, luteinising hormone, prolactin and thyroid stimulating hormone were all within normal limits. Karyotyping was done, which showed a 46,XX pattern. The patient underwent vaginal surgery during which septum resection was done, and amnion grafting was performed to prevent stricture formation. The patient resumed successful coitus 3 months after surgery. There was no discomfort on coitus. She conceived 7 months later. Following this, the patient delivered a healthy baby boy through caesarean section at term.

The revised Declaration of Helsinki: cosmetic or real change?

The Declaration of Helsinki, adopted by the World Medical Association's General Assembly in 1964, is the most important set of guidelines about research on human participants. It both reflects and shapes the ethos of international research ethics. It is a living instrument and is reviewed and revised regularly. Its latest revision was in 2013. There are four substantial changes, reflected in the new Paragraph 15 (which deals with compensation for trial related injuries), Paragraph 33 (relating to placebos), Paragraph 20 (relating to vulnerable groups) and the new Paragraph 34 (relating to post-trial provisions). This article analyses these changes, and asks whether they indicate any shift in the overall philosophy of the Declaration. We conclude that these changes, though significant, are not tectonic. They accord with the spirit that has motivated the Declaration through all its iterations, and indicate a steady, incremental evolution towards a holistic code of research ethics for research on human participants. Patient autonomy, though crucial, is no longer the only concern of the Declaration; distributive justice and beneficence are motivating forces too. While the Declaration is aware of the need to facilitate research, it is equally aware of the need to protect the vulnerable, and of the practical difficulties involved in that protection.

[Re]considering Respect for Persons in a Globalizing World.

Contemporary clinical ethics was founded on principlism, and the four principles: respect for autonomy, nonmaleficence, beneficence and justice, remain dominant in medical ethics discourse and practice. These principles are held to be expansive enough to provide the basis for the ethical practice of medicine across cultures. Although principlism remains subject to critique and revision, the four-principle model continues to be taught and applied across the world. As the practice of medicine globalizes, it remains critical to examine the extent to which both the four-principle framework, and individual principles among the four, suffice patients and practitioners in different social and cultural contexts. Using the four-principle model we analyze two accounts of surrogate decision making - one from the developed and one from the developing world - in which the clinician undertakes medical decision-making with apparently little input from the patient and/or family. The purpose of this analysis is to highlight challenges in assessing ethical behaviour according to the principlist model. We next describe cultural expectations and mores that inform both patient and clinician behaviors in these scenarios in order to argue that the principle of respect for persons informed by culture-specific ideas of personhood may offer an improved ethical construct for analyzing and guiding medical practice in a globalized and plural world.

A case-control study of the role of human papillomavirus in oesophageal squamous cell carcinoma in australia.

Objective. We investigate the prevalence of human papillomavirus (HPV) in oesophageal squamous cell carcinoma (OSCC) tissues compared to oesophageal tissue from healthy controls, in an Australian cohort. Methods. We conducted a hospital-based case-control study of 99 patients with OSCC and 100 healthy controls to examine the presence of HPV DNA. Paraffin tissues were tested using the PapType high-risk HPV detection and genotyping kit and with INNO-LiPA HPV Genotyping Extra. The biopsy samples were tested for HPV using a PCR-ELISA method based on the L1 consensus primer set PGMY09-PGMY11. Results. HPV DNA of the oncogenic genotype 16 was detected in 1/99 case specimens, a rate of 1010 per 100,000 (95% CI: 30-5500). All control specimens were negative for HPV. Significantly higher rates of smoking, other aerodigestive cancers, and mortality were seen among cases than controls. A pooled analysis of this study and the only other Australian case-control study found that 9/321 cases and 0/155 controls were positive for HPV. The pooled odds ratio for HPV being a risk factor for OSCC was 9.35 (95% CI: 0.47-190.33). Conclusion. Our results suggest that in this multifactorial cancer HPV may be an additional risk factor; although a larger, better powered study is needed.

From informed consent to informed request: strengthening shared decisionmaking.

Obtaining valid consent is regarded as essential before there can be an ethically or legally appropriate medical intervention. The justification is, simply, that patient autonomy should be respected. The patient's body is hers, and she has a right to do with it what she chooses. In order for that choice to be real, it has to be a choice made by a patient who is competent to make it. That competence has two elements. First, the patient must have the cognitive hardware and software necessary to receive, retain and process the information, weighing the benefits and the burdens of the proposed treatment against each other. Second, the inputs must be the relevant ones: the information to be processed must be (i) accurate and (ii) sufficient.

Radial contrast enhancement on brain magnetic resonance imaging diagnostic of primary angiitis of the central nervous system: a case report and review of the literature.

INTRODUCTION: Primary angiitis of the central nervous system is a rare disease of unclear etiology. There is no single test diagnostic of primary angiitis of the central nervous system. We report an unusual pattern on brain magnetic resonance imaging that might be specific for primary angiitis of the central nervous system. CASE PRESENTATION: A 47-year-old Caucasian man developed progressive bilateral hand tremor, difficulty walking, cognitive slowing and headache. A physical examination showed bilateral hand tremor with dysmetria, hyperreflexia and abnormal gait. Magnetic resonance imaging of his brain showed bilateral, symmetrical, increased intensity on T2-weighted images concurrent with linear contrast enhancement in a radial distribution throughout his white matter, sparing subcortical regions in his centrum semiovale, corona radiata, basal ganglia and brainstem. Magnetic resonance spectroscopy demonstrated elevated choline and decreased N-acetyl aspartate. Except for elevated protein and lymphocytic pleocytosis, examination of his cerebrospinal fluid showed no abnormalities. Serological tests for rheumatologic, vasculitic, paraneoplastic, infectious and peroxisomal disorders were negative. A brain biopsy revealed primary angiitis of the central nervous system. Our patient was treated with steroids and intravenous cyclophosphamide, with improvement in signs and symptoms as well as changes on magnetic resonance imaging. CONCLUSION: Bilateral, symmetrical, increased intensity on T2-weighted images concurrent with linear contrast enhancement in a radial distribution throughout the white matter on magnetic resonance imaging of the brain should be recognized as a feature of primary angiitis of the central nervous system, and might avoid the need for a brain biopsy to diagnose primary angiitis of the central nervous system.

Knowledge and attitude regarding euthanasia among medical students in the public and private medical schools of Karachi.

OBJECTIVE: To assess the awareness about and perception of euthanasia among medical students of Karachi. METHOD: The cross-sectional study was conducted from December 2011 to March 2012 among students of private-sector and one public-sector medical college in Karachi. Data was analysed using SPSS version 17, and associations were worked out using chi-square test. RESULTS: Out of the 493 students, 226 (46%) were from the matriculation system and 194 (39%) from the Cambridge system, while the remaining 15% were from the American High School. The male-female ratio was 1:3. There were 284 (58%) students from the private medical college. Majority of the private medical school students (n = 284; 99.6%) knew about euthanasia, compared to the public-sector facility where only 161 (77%) knew of it. Of the total, 405 (82%) students agreed that it is physician-assisted suicide; 255 (52%) agreed to the idea of palliative care, claiming it was sufficient to maintain life; 226 (54%) disagreed that a doctor should not be allowed to administer a lethal dose while only 162 (33%) agreed to the idea of it; 285 (58%) disagreed that a law regarding the practice of euthanasia should not be introduced, whereas 134 (27%) agreed to it; 70 (14%) agreed to the practice of euthanasia, while 311 (63%) disagreed, mostly for religious reasons. CONCLUSION: The awareness of euthanasia was high, but a very small proportion of students approved of it. There is need to include palliative care and euthanasia in the Behavioural Science module in the under-graduation programme of both public and private medical schools.

Role of human papillomaviruses in esophageal squamous cell carcinoma.

Esophageal cancer (EC) is responsible for almost half a million deaths worldwide annually and has a multifactorial etiology, which may account for its geographical variation in incidence. In the last 30 years the potential of human papillomaviruses (HPV) as oncogenes or co-factors in the tumorigenic process of esophageal squamous cell carcinoma (ESCC) has been widely studied. While the etiology of HPV in cervical and certain other anogenital and aerodigestive cancers has been established, results regarding its role in EC have been largely inconclusive. A causal association can be evaluated only with a case-control study, where normal controls are compared to ESCC cases for the presence of HPV. We reviewed all studies investigating ESCC tissue for HPV DNA and identified 139 that met our inclusion criteria, of which only 22 were case-control studies. Our results support previous findings of higher levels of HPV detection in high-risk ESCC regions than in areas of low risk. In addition, we confirm that the role of HPV in ESCC remains unclear, despite an accumulation of studies on the subject. The variations in investigative technique, study design and sample types tested may account for the lack of consistency in results. There is a need for a meta-analysis of all case-control studies to date, and for large, well-designed case-control studies with adequate power to investigate the association. The potential benefits of prophylactic HPV vaccines could be evaluated if HPV is identified as an etiological factor in EC, highlighting the need for further research in this area.

Physician-Researchers' Experiences of the Consent Process in the Sociocultural Context of a Developing Country.

Background: International guidelines for medical research involving human subjects maintain the primacy of informed consent while recognizing cultural diversity. Methods: This article draws on empirical data obtained from interviews with physician-researchers in teaching hospitals of Lahore, Pakistan, to identify social and cultural factors that affect the consent process for participants in research. Results: This article presents variable findings with regards to communication, comprehension, and decision making. While some physicians consider that social factors such as lack of education, a patriarchal family system, and skepticism about research can make patients dependent on either the physician-researcher or the family, others believe that patients do make independent decisions. Conclusions: In light of the findings, the article ends with a recommendation for communication and decision making that is sensitive to the local sociocultural environment while at the same time meeting the ethical imperative of respect for persons.

Cytokines in the placenta of Pakistani newborns with and without intrauterine growth retardation.

Although intrauterine growth retardation (IUGR) is a major risk factor for increased neonatal mortality and morbidity, the mechanisms behind it are not clear. We analyzed cytokine gene expression and gene polymorphisms in infants with and without IUGR in Pakistan, where IUGR is very common. 45 IUGR and 55 control mother/infant pairs were studied. mRNA for IL-10, IL-8, TNF-alpha, TGF-beta, IL-6, IL-4, IL-1beta, IL-12, IFN-gamma and GAPDH was quantified with RT-PCR from placenta. Cytokine and cytokine receptor gene polymorphisms for -1087IL10, -308TNFA, -174IL6, +915TGFB1, intron 2 IL1RN, +36TNFR1, 150V IL4RA and -159CD14 were determined from genomic DNA. The serum levels of IL-1beta, IL-6, IL-8, IL-10, IL-12, TNF-alpha and TGF-beta were measured. There was a significant decrease of IL-10 and IL-12, but increase of TGF-beta in the decidua and similarly decrease of IL-10, but increase of TGF-beta in the trophoblasts of the IUGR placentas compared with the non-IUGR placentas. We found significantly lower levels of IL-1beta in serum from the mothers of the IUGR infants and of TGF-beta in serum of the infants with IUGR compared with the non-IUGR infants. We note that the IL-10 mRNA expression in the decidua was down-regulated, but the TGF-beta mRNA up-regulated in IUGR placentas of mothers from a population with multiple risk factors for IUGR. We propose that the low IL-10 in the placenta may be involved in the pathogenesis of IUGR and might possibly be treatable.

Folate, vitamin B12, and homocysteine levels in South Asian women with growth-retarded fetuses.

OBJECTIVE: To investigate whether intrauterine growth retardation (IUGR) and preterm delivery in a poor population of South Asia was associated with altered maternal and fetal levels of folate, vitamin B12, and homocysteine. SUBJECTS AND METHODS: Hundred and twenty-eight pregnant women from a low socio-economic strata in the city of Lahore, Pakistan were followed with ultrasound of fetal growth from the 12th week of pregnancy. Blood samples were drawn from the woman and the cord at delivery. Serum was analyzed by a chemiluminescent immunoassay for folate and vitamin B12 and by fluorescence polarization immunoassay for total homocysteine (tHcy). RESULTS: Fourty-six infants showed IUGR. In term, but not preterm, deliveries with IUGR, maternal and cord blood folate levels were half of those in deliveries of normal birth weight infants (P=0.004 and P=0.005). The risk of IUGR was reduced among women with folate levels in the highest quartile (OR 0.31, 95% CI 0.10--0.84). There was no association between vitamin B12 and IUGR. Total homocysteine levels were higher in women delivering IUGR infants (P=0.02). There was an inverse correlation between cord blood folate and tHcy levels (r=-0.26, P=0.006). We also found increased risks for hypertensive illness (OR 3.5, 95% CI 1.4--8.6) and premature delivery (OR 2.5, 95% CI 1.1--6.2) in women in the highest quartile of tHcy. CONCLUSIONS: The occurrence of IUGR increased with low maternal and cord concentrations of folate and high maternal levels of tHcy. Further studies on the effects of vitamin B supplementation through pregnancy are warranted.