Journal scan: A review of 10 recentpapers of immediate clinical significance, harvested from major international journals
From the desk of the Editor-in-Chief
(1). Agarwal R, et al. Chlorthalidone for hypertension in advanced chronic kidney disease. NEngl J Med. 2021;385:2507-19
Abstract
Background
Little evidence has been available to support the use of thiazide diuretics to treat hypertension in patients with advanced chronic kidney disease.
Methods
We randomly assigned patients with stage 4 chronic kidney disease and poorly controlled hypertension, as confirmed by 24-hour ambulatory blood-pressure monitoring, in a 1:1 ratio to receive chlorthalidone at an initial dose of 12.5 mg per day, with increases every 4 weeks if needed to a maximum dose of 50 mg per day, or placebo; randomization was stratified according to previous use of loop diuretics. The primary outcome was the change in 24-hour ambulatory systolic blood pressure from baseline to 12 weeks. Secondary outcomes were the change from baseline to 12 weeks in the urinary albumin-to-creatinine ratio, N-terminal pro-B-type natriuretic peptide level, plasma renin and aldosterone levels, and total body volume. Safety was also assessed.
Results
A total of 160 patients underwent randomization, of whom 121 (76%) had diabetes mellitus and 96 (60%) were receiving loop diuretics. At baseline, the mean (±SD) estimated glomerular filtration rate was 23.2 ± 4.2 ml per minute per 1.73 m2 of body-surface area and the mean number of antihypertensive medications prescribed was 3.4 ± 1.4. At randomization, the mean 24 h ambulatory systolic blood pressure was 142.6 ± 8.1 mm Hg in the chlorthalidone group and 140.1 ± 8.1 mm Hg in the placebo group and the mean 24 h ambulatory diastolic blood pressure was 74.6 ± 10.1 mm Hg and 72.8 ± 9.3 mm Hg, respectively. The adjusted change in 24 h systolic blood pressure from baseline to 12 weeks was -11.0 mm Hg (95% confidence interval [CI], -13.9 to -8.1) in the chlorthalidone group and – 0.5 mm Hg (95% CI, -3.5 to 2.5) in the placebo group. The between-group difference was -10.5 mm Hg (95% CI, -14.6 to -6.4) (P < 0.001). The percent change in the urinary albumin-to-creatinine ratio from baseline to 12 weeks was lower in the chlorthalidone group than in the placebo group by 50 percentage points (95% CI, 37 to 60). Hypokalemia, reversible increases in serum creatinine level, hyperglycemia, dizziness, and hyperuricemia occurred more frequently in the chlorthalidone group than in the placebo group.
Conclusions
Among patients with advanced chronic kidney disease and poorly controlled hypertension, chlorthalidone therapy improved blood-pressure control at 12 weeks as compared with placebo.
(2). DeschS, et al. Angiography after out-of-hospital cardiac arrest without ST-segment elevation. N Engl J Med. 2021;385:2544-53
Background
Myocardial infarction is a frequent cause of out-of-hospital cardiac arrest. However, the benefits of early coronary angiography and revascularization in resuscitated patients without electrocardiographic evidence of ST-segment elevation are unclear.
Methods
In this multicenter trial, we randomly assigned 554 patients with successfully resuscitated out-of-hospital cardiac arrest of possible coronary origin to undergo either immediate coronary angiography (immediate-angiography group) or initial intensive care assessment with delayed or selective angiography (delayed-angiography group). All the patients had no evidence of ST-segment elevation on postresuscitation electrocardiography. The primary end point was death from any cause at 30 days. Secondary end points included a composite of death from any cause or severe neurologic deficit at 30 days.
Results
A total of 530 of 554 patients (95.7%) were included in the primary analysis. At 30 days, 143 of 265 patients (54.0%) in the immediate-angiography group and 122 of 265 patients (46.0%) in the delayed-angiography group had died (hazard ratio, 1.28; 95% confidence interval [CI], 1.00 to 1.63; P = 0.06). The composite of death or severe neurologic deficit occurred more frequently in the immediate-angiography group (in 164 of 255 patients [64.3%]) than in the delayed-angiography group (in 138 of 248 patients [55.6%]), for a relative risk of 1.16 (95% CI, 1.00 to 1.34). Values for peak troponin release and for the incidence of moderate or severe bleeding, stroke, and renal-replacement therapy were similar in the two groups.
Conclusions
Among patients with resuscitated out-of-hospital cardiac arrest without ST-segment elevation, a strategy of performing immediate angiography provided no benefit over a delayed or selective strategy with respect to the 30-day risk of death from any cause.
(3). Gahungu N. Paroxysmal atrial fibrillation. BMJ. 2021;375:e058568
What you need to know
- More than half of patients with atrial fibrillationare either asymptomatic or have mild symptoms, and none of the classic symptoms of atrial fibrillation have high diagnostic sensitivity
- Since paroxysmal atrial fibrillation cannot beexcluded by normal 12 lead ECG or short term Holter monitoring, consider prolonged monitoring in symptomatic patients with risk factors including older age, hypertension, and comorbidities
- Opportunistic radial pulse palpation has a sensitivity 94% for diagnosing silent atrial fibrillation in patients aged 65 and older
A 75-year-old man with a history of hypertension, type 2 diabetes, obesity, gout, and stage 2 chronic kidney disease presents to the emergency department with sudden onset of diplopia, left sided hemiparesis, hemisensory loss, dysarthria, and ataxic gait. He reports a 12-month history of intermittent palpitations associated with fatigue, but previous investigations with 12 lead electrocardiograms (ECGs) and 24-h Holter monitors have been normal. On arrival at the emergency department, he has an ECG which shows he is in sinus rhythm. Magnetic resonance imaging of his brain shows multifocal emboli involving the right middle cerebral artery territory, midbrain, and the cerebellum. Bilateral carotid doppler ultrasound shows no haemodynamically significant carotid stenoses. A review of his inpatient telemetry reveals several episodes of paroxysmal atrial fibrillation, and he is given apixaban for anticoagulation before he is discharged to a rehabilitation unit.
What is paroxysmal atrial fibrillation?
Atrialfibrillation is the most commonly encountered cardiac arrhythmia in clinical practice. Paroxysmal atrial fibrillation (PAF) is intermittent episodes of atrial fibrillation that terminate within seven days either spontaneously or with intervention. This excludes atrial fibrillation that is triggered by transient causes such as sepsis, cardiac surgery, pulmonary embolism, pericarditis, or other reversible causes.
(4). Besser REJ, et al. Editorials: Screening children for type 1 diabetes. BMJ.2021;375:e067937>
Insulin was discovered in 1921, turning a death sentence into a chronic condition, and 100 years later it is still the only treatment for type 1 diabetes. But new approaches are emerging that offer children with this condition a different trajectory.
Type 1 diabetes is caused by autoimmune destruction of the β cells in the pancreatic islets, resulting in insulin deficiency, and is mostly sporadic (>85% of cases). Despite clinical advances, outcomes remain suboptimal, and as many as 70% of children in some countries (25% in the UK, 40% in US) are diagnosed only after life threatening diabetic ketoacidosis.
The unexpected occurrence of type 1 diabetes causes psychological harm to both children and families, including depression, problems with adjustment, and stress. Diabetic ketoacidosis additionally requires costly and intensive hospital management and is associated with serious complications, including cerebral oedema, neurocognitive deficits, shock, and, if untreated, death.
Evidence is emerging of the benefits of diagnosing children with type 1 diabetes before they experience diabetic ketoacidosis. In an observational study of children and young people with type 1 diabetes from the US (n=3364), diabetic ketoacidosis at diagnosis was associated with worse glycaemic outcomes-a risk factor for long term complications-over 15 years of follow-up. A more recent study of young people with diabetes (n = 57000) showed that absence of diabetic ketoacidosis at diagnosis predicted fewer episodes of severe hypoglycaemia and ketoacidosis after 10 years. However, confounding by contributory factors cannot be excluded.
Children who develop type 1 diabetes have more frequent contact with health services in the year before diagnosis, yet the condition is often missed. Campaigns to increase public and professional awareness have had minimal success. A different strategy is needed, and we believe that nationwide screening should be considered, with robust clinical trials to evaluate potential benefits, harms, and costs.
Antibodies
Diabetes associated islet autoantibodies could be a useful screening tool, since a positive result in an asymptomatic child is strongly associated with later development of diabetes. In an analysis of data from three prospective cohort studies, 84% of children with two or more islet autoantibodies developed diabetes over 15 years of follow-up.
A more recent study from Bavaria screened 906328 children for islet autoantibodies at a median age of 3.1, followed by education, metabolic staging, and clinical follow-up for the 280 (0.3%) children with positive results. Of the 62 antibody positive children who developed diabetes either at the time of screening (n = 26) or after 2.4 years of follow-up (n = 36), only two had ketoacidosis (3.2%). This compares with an incidence above 20% among unscreened children who develop diabetes.
Islet autoantibody testing is now commercially available in the US,9 and the possibility of preventive intervention for people with positive results is emerging. In one placebo controlled trial (n = 76; 55 aged ≤ 18 years), the anti-CD3 monoclonal antibody tepluzimab delayed diagnosis of diabetes by a median of 24 months (48.4 months to diagnosis v 24.4 months) in participants who were positive for islet autoantibodies and had raised glucose levels below the threshold for diabetes.
Type 1 diabetes meets several of Wilson and Jungner’s criteria for screening: it is an important condition, and incidence is increasing by 4% worldwide each year. Data from Bavaria, as well as observational studies such as Teddy (The Environmental Determinants of Diabetes in the Young), suggest that screening can be acceptable to families. In Teddy, children identified through a screening and monitoring strategy that combined genetic risk with islet autoantibody testing reported significantly better diabetes specific quality of life over the first year after diagnosis than matched community controls diagnosed without screening. Their parents reported significantly lower parenting stress.
Age 3-4 years has been suggested as the best time to screen children using islet autoantibody testing, allowing time for interventions such as parental education and monitoring to reduce the risk of diabetic ketoacidosis in those with positive results. However, this strategy would miss the youngest, and often sickest, children who develop diabetes, as well as those who develop autoantibodies later in childhood. Adding genetic data to autoantibody screening may increase the proportion of children identified as high risk, including the youngest children. But many children considered genetically high risk will never develop type 1 diabetes, raising concerns about the acceptability of genetic screening.
The time lag between screening for islet autoantibodies and diagnosis is a further concern. Evidence is needed on how best to follow up children with antibodies, and when to retest those with only one type of antibody, who have a relatively low risk (10-15%) of diabetes. More precise predictors of diabetes onset are needed to support clinical pathways and allow fully informed shared decision making with families.
More research is required to identify the most effective and cost-effective screening strategies, and most importantly to quantify the balance of benefits and harms, which include raised anxiety for children and parents and the burden associated with a follow-up programme for children found to be at risk. Trials should include rate of hospital admission at diagnosis as an outcome, as well as short and long term psychological and metabolic outcomes. A hundred years after the discovery of insulin, the evaluation of screening should be a research priority.
(5). Bachtiger P, et al. Point-of-care screening for heart failure with reduced ejection fraction using artificial intelligence during ECG-enabled stethoscope examination in London, UK: a prospective, observational, multicentre study. 2022
Summary
Background
Most patients who have heart failure with a reduced ejection fraction, when left ventricular ejection fraction (LVEF) is 40% or lower, are diagnosed in hospital. This is despite previous presentations to primary care with symptoms. We aimed to test an artificial intelligence (AI) algorithm applied to a single-lead ECG, recorded during ECG-enabled stethoscope examination, to validate a potential point-of-care screening tool for LVEF of 40% or lower.
Methods
We conducted an observational, prospective, multicentre study of a convolutional neural network (known as AI-ECG) that was previously validated for the detection of reduced LVEF using 12-lead ECG as input. We used AI-ECG retrained to interpret single-lead ECG input alone. Patients (aged ≥18 years) attending for transthoracic echocardiogram in London (UK) were recruited. All participants had 15 s of supine, single-lead ECG recorded at the four standard anatomical positions for cardiac auscultation, plus one handheld position, using an ECG-enabled stethoscope. Transthoracic echocardiogram-derived percentage LVEF was used as ground truth. The primary outcome was performance of AI-ECG at classifying reduced LVEF (LVEF ≤ 40%), measured using metrics including the area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity, with two-sided 95% CIs. The primary outcome was reported for each position individually and with an optimal combination of AI-ECG outputs (interval range 0-1) from two positions using a rule-based approach and several classification models. This study is registered with ClinicalTrials.gov, NCT04601415.
Findings
Between Feb 6 and May 27, 2021, we recruited 1050 patients (mean age 62 years [SD 17.4], 535 [51%] male, 432 [41%] non-White). 945 (90%) had an ejection fraction of at least 40%, and 105 (10%) had an ejection fraction of 40% or lower. Across all positions, ECGs were most frequently of adequate quality for AI-ECG interpretation at the pulmonary position (979 [93.3%] of 1050). Quality was lowest for the aortic position (846 [80.6%]). AI-ECG performed best at the pulmonary valve position (p = 0.02), with an AUROC of 0.85 (95% CI 0.81-0.89), sensitivity of 84.8% (76.2-91.3), and specificity of 69.5% (66.4-72.6). Diagnostic odds ratios did not differ by age, sex, or non-White ethnicity. Taking the optimal combination of two positions (pulmonary and handheld positions), the rule-based approach resulted in an AUROC of 0.85 (0·81-0.89), sensitivity of 82.7% (72.7-90.2), and specificity of 79.9% (77.0-82.6). Using AI-ECG outputs from these two positions, a weighted logistic regression with l2 regularisation resulted in an AUROC of 0.91 (0.88-0.95), sensitivity of 91.9% (78.1-98.3), and specificity of 80.2% (75.5-84.3).
Interpretation
A deep learning system applied to single-lead ECGs acquired during a routine examination with an ECG-enabled stethoscope can detect LVEF of 40% or lower. These findings highlight the potential for inexpensive, non-invasive, workflow-adapted, point-of-care screening, for earlier diagnosis and prognostically beneficial treatment.
(6). Latour RP, et al. Eltrombopag added to immunosuppression in severe aplastic anemia. N Engl J Med 2022; 386:11-23.
Abstract
Background
A single-group, phase 1-2 study indicated that eltrombopag improved the efficacy of standard immunosuppressive therapy that entailed horse antithymocyte globulin (ATG) plus cyclosporine in patients with severe aplastic anemia.
Methods
In this prospective, investigator-led, open-label, multicenter, randomized, phase 3 trial, we compared the efficacy and safety of horse ATG plus cyclosporine with or without eltrombopag as front-line therapy in previously untreated patients with severe aplastic anemia. The primary end point was a hematologic complete response at 3 months.
Results
Patients were assigned to receive immunosuppressive therapy (Group A, 101 patients) or immunosuppressive therapy plus eltrombopag (Group B, 96 patients). The percentage of patients who had a complete response at 3 months was 10% in Group A and 22% in Group B (odds ratio, 3.2; 95% confidence interval [CI], 1.3 to 7.8; P = 0.01). At 6 months, the overall response rate (the percentage of patients who had a complete or partial response) was 41% in Group A and 68% in Group B. The median times to the first response were 8.8 months (Group A) and 3.0 months (Group B). The incidence of severe adverse events was similar in the two groups. With a median follow-up of 24 months, a karyotypic abnormality that was classified as myelodysplastic syndrome developed in 1 patient (Group A) and 2 patients (Group B); event-free survival was 34 and 46%, respectively. Somatic mutations were detected in 29% (Group A) and 31% (Group Î’) of the patients at baseline; these percentages increased to 66% and 55%, respectively, at 6 months, without affecting the hematologic response and 2-year outcome.
Conclusions
The addition of eltrombopag to standard immunosuppressive therapy improved the rate, rapidity, and strength of hematologic response among previously untreated patients with severe aplastic anemia, without additional toxic effects.
(7). Seifert SA. Snake Envenomation. N Engl J Med. 2022;386:68-78.
Snake envenomation represents an important health problem in much of the world. In 2009, it was recognized by the World Health Organization (WHO) as a neglected tropical disease, and in 2017, it was elevated into Category A of the Neglected Tropical Diseases list, further expanding access to funding for research and antivenoms. However, snake envenomation occurs in both tropical and temperate climates and on all continents except Antarctica. Worldwide, the estimated number of annual deaths due to snake envenomation (80,000 to 130,000) is similar to the estimate for drug-resistant tuberculosis and for multiple myeloma. In countries with adequate resources, deaths are infrequent (e.g., < 6 deaths per year in the United States, despite the occurrence of 7000 to 8000 bites), but in countries without adequate resources, deaths may number in the tens of thousands. Venomous snakes kept as pets are not rare, and physicians anywhere might be called on to manage envenomation by a nonnative snake. Important advances have occurred in our understanding of the biology of venom and the management of snake envenomation since this topic was last addressed in the Journal two decades ago. For the general provider, it is important to understand the spectrum of snake envenomation effects and approaches to management and to obtain specific guidance, when needed.
Note: The PDF is available on request
(8). Geng EH. The doctor’s oldest tool. N Engl J Med. 2022;386:7-9
I first came across Mr. B. while reviewing charts for new patients in my primary care HIV clinic. Even in a public hospital where many patients were down-and-out, his case struck me. He lived in a single-room-occupancy hotel and had a history of homelessness. He’d received an HIV diagnosis years before and had managed occasional contact with the health care system but had never started HIV treatment. He adamantly maintained that HIV was not the cause of AIDS and that the medications were useless at best and toxic at worst. He’d been hospitalized several times recently with life-threatening diagnoses, pneumocystis pneumonia and pneumococcal sepsis among them. He’d come to the clinic for urgent care and postdischarge visits, but never developed a lasting bond with any clinician.
Mr. B. looked thin and worn when we met. After discussing his recent hospitalization, I fell into a common trap. I brought up HIV treatment, and he confidently declared that HIV does not cause AIDS. I mentioned robust research, but he quoted early reports on HIV – citing journal, date, and author – and pointed out subtle inconsistencies. He asked me whether I knew a seminal paper from the 1980s, and I had to admit I’d never read it in detail. Asked why he thought he was sick, he sounded somewhat fearful but largely resigned: “I don’t know.” When the encounter ended, I put in a prescription for antiretrovirals and said, “If you change your mind, they are there for you to pick up.” He chuckled.
Two weeks later, he didn’t show for his follow-up visit, and the social worker said she would call him. Several months later, an inpatient team emailed me saying he’d been admitted with an advanced systemic malignant condition. The oncologists believed chemotherapy would be futile without HIV treatment, so he was being discharged to hospice. The life events documented in his chart suggested a difficult time: marginal housing, no clear relationships, psychiatric encounters but no diagnosis, a history of trauma, limited schooling, trouble with the law. I was amazed that he’d perused so many scientific journals.
AIDS denialism has always been part of the HIV crisis. In the 1990s, virologist Peter Duesberg vociferously denied that HIV causes AIDS. Playing to homophobic tropes, he suggested that elements of the “gay lifestyle,” such as drug use, led to immunodeficiency. The medical establishment shunned Duesberg, but his theories spread widely. When HIV raged through South Africa, former President Thabo Mbeki subscribed to Duesberg’s views and delayed public health treatment, costing hundreds of thousands of lives. Prominent U.S. acolytes of Duesberg died of AIDS, and some let their children die rather than take proven treatments. Duesberg wasn’t the sole source of dissent. The Black American community’s justified mistrust of the medical establishment led some to believe that the Central Intelligence Agency had created HIV. But although I’d encountered many patients who were skeptical of HIV medications to varying degrees and for various reasons, none had taken this skepticism as far as Mr. B.
That Saturday, Mr. B. was on my mind. Discovering that his hospice facility happened to be nearby, I decided to visit. When I arrived, his room was quiet except for the tinkling sounds of a water sculpture. Mr. B. looked peaceful and seemed neither especially happy nor annoyed to see me.
“I thought I’d come by and see how you’re doing,” I said. Then I cut to the chase: ‘I didn’t think you were looking to die. You don’t want to be here, do you?”
“I don’t,” he replied, “but I don’t know what can be done for me.”
I told him that HIV medications could still work despite his severe illness. He reiterated calmly that HIV doesn’t cause AIDS and that HIV medications are useless. I argued that science is an imperfect system but that work is peer reviewed, fake data get exposed, and dozens of rigorous studies with similar results could not all be wrong. His counterarguments contained more than a grain of truth: the pharmaceutical industry influences science, profits dictate medical practice, desire for scientific prestige corrupts researchers. We’d reached a stalemate. “Well,” I said, “I don’t know if there is anything else I can do for you.” The usual departing niceties felt unserviceable. “See you later” seemed false, “Take care” absurd. I finally mumbled “Bye” as I slipped out of the room.
Leaving the hospice, I felt that something remained unsaid, though I didn’t know what. Mr. B. was dying. He was not psychotic – he was reasonable. He was not ignorant – he was rather well informed. He didn’t want to die but seemed willing to die for his beliefs. I tried to genuinely consider his point of view. How could I be certain that HIV causes AIDS? Had I conducted the experiments myself? Could I even fully understand them?
The truth is that I believe HIV causes AIDS because I trust the people – professors, editors, scientists – who have told me so, not because I can independently evaluate and confirm the science. I am part of what anthropologist Heidi Larson calls a “chain of trust” in a social system that has treated me fairly and generously – a chain that did not reach Mr. B. I realized that the chain’s links consist of lived experiences and relationships, not data in scientific journals. I believe what my colleagues say because of my proximity to their experience: I work with people like the scientists who conducted the earliest studies, and I know them to be generally honorable and credible. Mr. B. did not believe – ultimately, not because of quibbles with the scientific method, but because the sum of what society, and “expert” professionals like me, had offered him in life seemed more like lies than the truth. Instead of arguing about the veracity of science, perhaps I could simply bear witness, as one human to another. It was worth a shot.
I returned to Mr. B. and began, “I was thinking that you might feel that the world has lied to you many times. I admit that I’m not well versed enough in laboratory science to verify the experiments, but I do know this: I’ve seen many people who have the same condition you have, and I’ve given them these medications, and today they are healthy, doing the things they want to in life, even if I cannot be certain exactly why or how. I have seen them for years. I am asking you to trust me on this one.”
Mr. B. was silent. I was surprised, and pressing what might be an advantage, I asked, “Would you be willing to try the medications?” I was stunned when he said yes.
I asked a nurse for a spare dose of antiretroviral medications, which I watched Mr. B. swallow. Now he was on treatment, and I could more easily send him to the emergency department. Over the next few weeks, with inpatient treatment, he recovered remarkably quickly – a phenomenon that was dubbed the ‘Lazarus effect’ early in the HIV-treatment era. Over the subsequent months, he came to my clinic for monitoring. His CD4 levels climbed rapidly. We didn’t discuss the medications, but he’d been discharged with them, and his viral loads were undetectable. When his monthly prescriptions ran low, I renewed them. Over the years, he rarely came to the clinic, yet the pharmacy confirmed he was picking up his medications. In our brief conversations, we focused on how he was feeling: his chronic edema, his weight gain, his housing. We never spoke about that day in the hospice. Years later, I moved and he was assigned to a new clinician.
I’ve been remembering Mr. B. during the Covid pandemic, as public health and medicine have struggled with public dissent over social distancing, masking, and now vaccination. Covid denialism, like AIDS denialism, reveals that many of doctors’ assumptions are incorrect. We overestimate the value of reasoning and facts. We believe in our clinical authority. We expect patients to behave rationally. But we all develop our beliefs through interactions with other people – what you believe depends on whom you trust. In a life where Mr. B. had struggled, I have been rewarded. He was dying, while I was thriving. No wonder the conventional truths that were self-evident to me would seem otherwise to him.
I never ventured to ask Mr. B. why he’d changed his mind. But if acceptance of Covid vaccines and other evidence-based interventions depends on trust, then doctors have one important card to play. Primary care doctors in particular can know our patients as people, their needs and wants, their preferences and idiosyncrasies, sometimes their fears and hopes. But even hospitalists who round on a patient for several days form a bond. No disembodied message (even if crafted by marketing experts) can compete with someone you know who will pull up a chair. Even though the pandemic has pushed those in our profession to our emotional and professional limits, one of our oldest tools may turn out to be one of our best: talking with patients. By getting to know patients’ stories, and perhaps letting them know ours, we might be able to add a link to the chain of trust, even if it is a single one, and collectively these conversations may be one potential remedy for the afflicted social fabric of our times.
(9). Ahmed H, et al. Respiratory tract infection and risk of bleeding in oral anticoagulantusers: self-controlled case series. BMJ 2021;375:e068037
Abstract
Objective: To estimate the association between untreated,community acquired, respiratory tract infections and bleeding in oral anticoagulant users.
Design: Self-controlled case series.
Setting: General practices in England contributing data to the Clinical PracticeResearch Datalink GOLD.
Participants: 1208 adult users of warfarin or direct oralanticoagulants with a general practice or hospital admission record of a bleeding event between January 2010 and December 2019, and a general practice record of a consultation for a community acquired respiratory tract infection for which immediate antibiotics were not prescribed (that is, untreated).
Main outcome measures: Relative incidence of major bleeding and clinicallyrelevant non-major bleeding in the 0-14 days after an untreated respiratory tract infection, compared to unexposed time periods.
Results: Of 1208 study participants, 58% (n = 701) were male, median age at timeof first bleed was 79 years (interquartile range 72-85), with a median observation period of 2.4 years (interquartile range 1.3-3.8). 292 major bleeds occurred during unexposed time periods and 41 in the 0-14 days after consultation for a respiratory tract infection. 1003 clinically relevant non-major bleeds occurred during unexposed time periods and 81 in the 0-14 days after consultation for a respiratory tract infection. After adjustment for age, season, and calendar year, the relative incidence of major bleeding (incidence rate ratio 2.68, 95% confidence interval 1.83 to 3.93) and clinically relevant non-major bleeding (2.32, 1.82 to 2.94) increased in the 0-14 days after an untreated respiratory tract infection. Findings were robust to several sensitivity analyses and did not differ by sex or type of oral anticoagulant.
Conclusions: This study observed a greater than twofold increasein the risk of bleeding during the 0-14 days after an untreated respiratory tract infection. These findings have potential implications for how patients and clinicians manage oral anticoagulant use during an acute intercurrent illness and warrant further investigation into the potential risks and how they might be mitigated.
(10). Cillóniz C, et al. Management of pneumonia in critically ill patients. BMJ2021;375:e065871
Severe pneumonia is associated with high mortality (short and long term), as well as pulmonary and extrapulmonary complications. Appropriate diagnosis and early initiation of adequate antimicrobial treatment for severe pneumonia are crucial in improving survival among critically ill patients. Identifying the underlying causative pathogen is also critical for antimicrobial stewardship. However, establishing an etiological diagnosis is challenging in most patients, especially in those with chronic underlying disease; those who received previous antibiotic treatment; and those treated with mechanical ventilation. Furthermore, as antimicrobial therapy must be empiric, national and international guidelines recommend initial antimicrobial treatment according to the location’s epidemiology; for patients admitted to the intensive care unit, specific recommendations on disease management are available. Adherence to pneumonia guidelines is associated with better outcomes in severe pneumonia. Yet, the continuing and necessary research on severe pneumonia is expansive, inviting different perspectives on host immunological responses, assessment of illness severity, microbial causes, risk factors for multidrug resistant pathogens, diagnostic tests, and therapeutic options.
Note: The PDF is available on request