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To the Editor: Greinacher et al. (April 9) 1 report on the development of platelet-activating antibodies against platelet factor 4 (PF4) after ChAdOx1 nCoV-19 vaccination in patients without previous exposure to heparin. These patients had clinical features that mimicked autoimmune heparin-induced thrombocytopenia. In serum samples obtained from these patients, platelets were shown to be activated in the absence of heparin. Platelet activation was shown to be inhibited when high doses of heparin were added to the serum samples. Thrombocytopenia after the administration of adenoviral gene transfer vectors has been reported. Platelet activation with the formation of adenovirus–platelet–leukocyte complexes leading to accelerated . . .

Background. Experience from treating patients with Spanish influenza and influenza A(H5N1) suggested that convalescent plasma therapy might be beneficial. However, its efficacy in patients with severe pandemic influenza A(H1N1) 2009 virus (H1N1 2009) infection remained unknown. Methods. During the period from 1 September 2009 through 30 June 2010, we conducted a prospective cohort study by recruiting patients aged ≥ 18 years with severe H1N1 2009 infection requiring intensive care. Patients were offered treatment with convalescent plasma with a neutralizing antibody titer of ≥1:160, harvested by apheresis from patients recovering from H1N1 2009 infection. Clinical outcome was compared with that of patients who declined plasma treatment as the untreated controls. Results. Ninety-three patients with severe H1N1 2009 infection requiring intensive care were recruited. Twenty patients (21.5%) received plasma treatment. The treatment and control groups were matched by age, sex, and disease severity scores. Mortality in the treatment group was significantly lower than in the nontreatment group (20.0% vs 54.8%; P = .01). Multivariate analysis showed that plasma treatment reduced mortality (odds ratio [OR], .20; 95% confidence interval [CI], .06-.69; P = .011), whereas complication of acute renal failure was independently associated with death (OR, 3.79; 95% CI, 1.15-12.4; P = .028). Subgroup analysis of 44 patients with serial respiratory tract viral load and cytokine level demonstrated that plasma treatment was associated with significantly lower day 3, 5, and 7 viral load, compared with the control group (P < .05). The corresponding temporal levels of interleukin 6, interleukin 10, and tumor necrosis factor α (P < .05) were also lower in the treatment group. Conclusions. Treatment of severe H1N1 2009 infection with convalescent plasma reduced respiratory tract viral load, serum cytokine response, and mortality.

Background. Infections caused by the pandemic H1N1 2009 influenza virus range from mild upper respiratory tract syndromes to fatal diseases. However, studies comparing virological and immunological profile of different clinical severity are lacking. Methods. We conducted a retrospective cohort study of 74 patients with pandemic H1N1 infection, including 23 patients who either developed acute respiratory distress syndrome (ARDS) or died (ARDS-death group), 14 patients with desaturation requiring oxygen supplementation and who survived without ARDS (survived-without-ARDS group), and 37 patients with mild disease without desaturation (mild-disease group). We compared their pattern of clinical disease, viral load, and immunological profile. Results. Patients with severe disease were older, more likely to be obese or having underlying diseases, and had lower respiratory tract symptoms, especially dyspnea at presentation. The ARDS-death group had a slower decline in nasopharyngeal viral loads, had higher plasma levels of proinflammatory cytokines and chemokines, and were more likely to have bacterial coinfections (30.4%), myocarditis (21.7%), or viremia (13.0%) than patients in the survived-without-ARDS or the mild-disease groups. Reactive hemophagocytosis, thrombotic phenomena, lymphoid atrophy, diffuse alveolar damage, and multiorgan dysfunction similar to fatal avian influenza A H5N1 infection were found at postmortem examinations. Conclusions. The slower control of viral load and immunodysregulation in severe cases mandate the search for more effective antiviral and immunomodulatory regimens to stop the excessive cytokine activation resulting in ARDS and death.

ObjectivesDespite growing recognition of the importance of speaking up to protect patient safety in critical care, little research has been performed in this area in an intensive care unit (ICU) context. This study explored the communication openness perceptions of Chinese doctors and nurses and identified their perceptions of issues in ICU communication, their reasons for speaking up and the possible factors and strategies involved in promoting the practice of speaking up.DesignA mixed-methods design with quantitative and sequential qualitative components was used.Setting and participantsEighty ICU staff members from a large public hospital in Hong Kong completed a questionnaire regarding their perceptions of communication openness. Ten clinicians whose survey responses indicated support for open communication were then interviewed about their speak-up practices.ResultsThe participating ICU staff members had similar perceptions of their openness to communication. However, the doctors responded more positively than the nurses to many aspects of communication openness. The two groups also had different perceptions of speaking up. The interviewed ICU staff members who indicated a high level of communication openness reported that their primary reasons for speaking up were to seek and clarify information, which was achieved by asking questions. Other factors perceived to influence the motivation to speak up included seniority, relationships and familiarity with patient cases.ConclusionsCreating an atmosphere of safety and equality in which team members feel confident in expressing their personal views without fear of reprisal or embarrassment is necessary to encourage ICU staff members, regardless of their position, to speak up. Because harmony and saving face is valued in Chinese culture, training nurses and doctors to speak up by focusing on human factors and values rather than simply addressing conflict management is desirable in this context.

{Table 1} Patients admitted to Intensive Care Unit (ICU) of Queen Elizabeth Hospital in Hong Kong between January 2011 and December 2015 were included in the retrospective study if they met the following criteria: (1) metformin as usual treatment or overdose; (2) peak lactate> 5 mmol/L; (3) pH < 7.35 and bicarbonate < 22 mmol/L. {Table 2} Compared with the 54 survivors, the 5 nonsurvivors had higher Acute Physiology and Chronic Health Evaluation IV (APACHE IV) scores (P = 0.005), APACHE IV predicted mortality risk (P = 0.003), temperature (P = 0.032), heart rate (P = 0.035), and PaCO2 (P = 0.002); and lower first 24-h urine volume (P = 0.013) and serum albumin (P = 0.012). {Figure 1} When comparing patients with other precipitating factors, patients with sepsis were found to have higher heart rates (P = 0.016), PaCO2 levels (P = 0.017), APACHE IV risk (P = 0.02), sequential organ failure assessment score (P = 0.001), and maximum nor-adrenaline infusion dosages (P = 0.001), with higher rates of mechanical ventilation (P = 0.013) and ICU mortality (P = 0.001).

China is undergoing a recent outbreak of a novel H7N9 avian influenza virus (nH7N9) infection that has thus far involved 132 human patients, including 37 deaths. The nH7N9 virus is a reassortant virus originating from the H7N3, H7N9 and H9N2 avian influenza viruses. nH7N9 isolated from humans contains features related to adaptation to humans, including a Q226L mutation in the hemagglutinin cleavage site and E627K and D701N mutations in the PB2 protein. Live poultry markets provide an environment for the emergence, spread and maintenance of nH7N9 as well as for the selection of mutants that facilitate nH7N9 binding to and replication in the human upper respiratory tract. Innate immune suppression conferred by the internal genes of H9N2 may contribute to the virulence of nH7N9. The quail may serve as the intermediate host during the adaptation of avian influenza viruses from domestic waterfowl to gallinaceous poultry, such as chickens and related terrestrial-based species, due to the selection of viral mutants with a short neuraminidase stalk. Infections in chickens, common quails, red-legged partridges and turkeys may select for mutants with human receptor specificity. Infection in Ratitae species may lead to the selection of PB2-E627K and PB2-D701N mutants and the conversion of nH7N9 to a highly pathogenic avian influenza virus.

China is undergoing a recent outbreak of a novel H7N9 avian influenza virus (nH7N9)infection that has thus far involved 132 human patients, including 37 deaths. The nH7N9virus is a reassortant virus originating from the H7N3, H7N9 and H9N2 avian influenzaviruses. nH7N9 isolated from humans contains features related to adaptation to humans,including a Q226L mutation in the hemagglutinin cleavage site and E627K and D701Nmutations in the PB2 protein. Live poultry markets provide an environment for theemergence, spread and maintenance of nH7N9 as well as for the selection of mutants thatfacilitate nH7N9 binding to and replication in the human upper respiratory tract. Innateimmune suppression conferred by the internal genes of H9N2 may contribute to the virulenceof nH7N9. The quail may serve as the intermediate host during the adaptation of avianinfluenza viruses from domestic waterfowl to gallinaceous poultry, such as chickens andrelated terrestrial-based species, due to the selection of viral mutants with a shortneuraminidase stalk. Infections in chickens, common quails, red-legged partridges andturkeys may select for mutants with human receptor specificity. Infection inRatitae species may lead to the selection of PB2-E627K and PB2-D701Nmutants and the conversion of nH7N9 to a highly pathogenic avian influenza virus.

[This corrects the article DOI: 10.1038/emi.2013.48.].

I refer to the article ''Making an incision into local health care'' (South, China Morning Post, February 5), in which Director of Health Margaret...