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Background RT-qPCR is the reference test for identification of active SARS-CoV-2 infection, but is associated with diagnostic delay. Antigen detection assays can generate results within 20 min and outside of laboratory settings. Yet, their diagnostic test performance in real life settings has not been determined. Methods The diagnostic value of the Panbio™ COVID-19 Ag Rapid Test (Abbott), was determined in comparison to RT-qPCR (Seegene Allplex) in community-dwelling mildly symptomatic subjects in a medium (Utrecht, the Netherlands) and high endemic area (Aruba), using two concurrently obtained nasopharyngeal swabs. Findings: 1367 and 208 subjects were enrolled in Utrecht and Aruba, respectively. SARS-CoV-2 prevalence, based on RT-qPCR, was 10.2% (n = 139) and 30.3% (n = 63) in Utrecht and Aruba respectively. Specificity of the Panbio™ COVID-19 Ag Rapid Test was 100% (95%CI: 99.7–100%) in both settings. Test sensitivity was 72.6% (95%CI: 64.5–79.9%) in the Netherlands and 81.0% (95% CI: 69.0–89.8%) in Aruba. Probability of false negative results was associated with RT-qPCR Ct-values, but not with duration of symptoms. Restricting RT-qPCR test positivity to Ct-values

Source Citation Kalra L, Evans A, Perez I, et al. Training carers of stroke patients: randomised controlled trial. BMJ. 2004;328:1099-1103. 15130977

Cardiovascular disease (CVD) is the leading cause of death in the United States. Hypercholesterolemia is a principal modifiable risk factor for the primary prevention of CVD. In addition to lifestyle modification, statins are an important tool to reduce risk for CVD in selected patients. A useful strategy to identify candidates for statins is to estimate the 10-year risk for CVD through the use of a validated risk calculator. Commonly used calculators include the Framingham risk score and the pooled cohort equation. Multiple randomized controlled trials have shown that statins reduce the risk for CVD in patients without known CVD. Two recent guidelines have proposed an approach to the use of statins in primary prevention of CVD. The American College of Cardiology/American Heart Association and the U.S. Department of Veterans Affairs guidelines form the basis for this discussion. The guidelines differ on the use of advanced testing to modify the 10-year CVD risk estimate and on the need for low-density lipoprotein cholesterol targets to establish the efficacy of statins. Advanced testing with coronary artery calcium measurement may be helpful for patients who are potentially eligible for statin therapy but who are uncertain if they wish to take a statin. In this paper, 2 experts, a preventive cardiologist and a general internist, discuss their approach to the use of statins for primary prevention of CVD and how they would apply the guidelines to an individual patient.

We greatly appreciate Dr. Sterling’s thoughtful comment on our paper, to which we respond below. First, we would like to clarify our paper’s main findings. Our analyses suggest that lesbian women and girls aged 15–25 years who had heard of the HPV vaccine were significantly less likely to have initiated HPV vaccination compared to their heterosexual counterparts. However, we found no difference in HPV vaccination initiation between bisexual and heterosexual women and girls (1). Second, in addition to the factors mentioned by Dr. Sterling, healthcare providers’ beliefs may play an important role in shaping HPV vaccination disparities across sexual orientation groups (2, 3). Indeed, providers may erroneously believe that HPV can only be transmitted through penile-vaginal intercourse when in fact, the virus can be transmitted through any intimate skin-to-skin contact with sexual partners of any sex or gender (3, 4). Moreover, providers may not realize that the vast majority of lesbians have engaged in sex with men and are thus at risk of HPV infection from female and male sexual partners (4). Third, we did not collect the data used in this study; instead, we used 2006–2010 National Survey of Family Growth (NSFG) data, which are available from the National Center for Health Statistics. Therefore, we unfortunately had no control over the variables in the dataset. In particular, the 2006–2010 NSFG did not ask participants whether they received all three doses of the HPV vaccine. As a result, we were unable to assess disparities in HPV vaccination completion by sexual orientation among women and girls. However, new research suggests that one dose of the vaccine may confer as much protection against cervical cancer as three doses (5). Nonetheless, we are conducting additional analyses examining the association between sexual orientation identity and HPV vaccination completion. Additionally, we agree with Dr. Sterling that it would have been useful to ascertain the influence of recommendations for HPV vaccination from caregivers and providers on sexual orientation identity disparities in HPV vaccination initiation among girls and women. However, these measures were not included in the 2006–2010 NSFG. Fourth, we agree with Dr. Sterling that identifying the mechanisms that drive sexual orientation disparities in HPV vaccination among women and girls is crucial to intervening. Moreover, research is needed to assess whether disparities vary across social groups in order to inform interventions that are tailored to the needs of women and girls of diverse backgrounds.

In comparative studies, the treatment effect is often assessed using a binary outcome that indicates response to the therapy. Commonly used summary measures for response include the cumulative and the current response rate at a specific time point. The current response rate is sometimes referred to as the “probability-of-being-in-response” (PBIR), which regards a patient as a responder only if he/she has achieved and remains in response at present. The methods utilized in practice for estimating these rates, however, may not be appropriate. Moreover, while an effective treatment is expected to achieve a rapid and sustained response, the response at a fixed time point does not provide information about the duration of response. As an alternative, one may consider a curve constructed from the current response rates over the entire study period, which can be used for visualizing how rapidly patients responded to therapy, and how long responses were sustained. The area under the probability-of-being-in-response curve is the mean duration of response. This connection between response and duration of response makes this curve attractive for assessing the treatment effect. In contrast to the conventional method for analyzing the duration of response data, which uses responders only, the above procedure includes all comers in the study. Though discussed extensively in the statistical literature, estimation of the current response rate curve has garnered little attention in the medical literature. In this paper, we illustrate how to construct and analyze such a curve using data from a recent study for treating renal cell carcinoma. We encourage clinical trialists to consider this robust and clinically interpretable procedure as an additional tool for evaluating treatment effects in clinical studies.

Clinical workflow is the enactment of a series of steps to perform a clinical activity. The transition from paper to electronic health records (EHRs) over the past decade has been characterized by profound challenges supporting clinical workflow, impeding frontline clinicians' ability to deliver safe, efficient, and effective care. In response, there has been substantial effort to study clinical workflow as well as workarounds-exceptions to routine workflow-in order to identify opportunities for improvement. This article describes predominant methods of studying workflow and workarounds and provides examples of the applications of these methods along with the resulting insights. Challenges to studying workflow and workarounds are described, and recommendations for how to approach such studies are given. Although there is not yet a set of standard approaches, this article helps advance workflow research that ultimately serves to inform how to coevolve the design of EHR systems and organizational decisions about processes, roles, and responsibilities in order to support clinical workflow that more consistently delivers on the potential benefits of a digitized health care system.

Psychological distress often causes suffering in terminally ill patients and their families and poses challenges in diagnosis and treatment. Increased attention to diagnosis and treatment of depression can improve the coping mechanisms of patients and families. This paper reviews the clinical characteristics of normal grief and clinical depression and explains strategies for differential diagnosis. Although some literature discusses the psychological issues facing elderly patients and terminally ill patients with cancer, less is known about patients with end-stage pulmonary, cardiac, renal, and neurologic disease. Data on the effectiveness of interventions in terminally ill patients are lacking. Treatment recommendations in this paper represent extrapolations from existing literature and expert opinion. Diagnosing and treating depression in terminally ill patients involve unique challenges. Evidence of hopelessness, helplessness, worthlessness, guilt, and suicidal ideation are better indicators of depression in this context than neurovegetative symptoms. Although terminally ill patients often have suicidal thoughts, they are usually fleeting. Sustained suicidal ideation should prompt a comprehensive evaluation. Clinicians should have a low threshold for treating depression in terminally ill patients. Psychostimulants, because of their rapid onset of action, are useful agents and are generally well tolerated. Selective serotonin reuptake inhibitors and tricyclic antidepressants may also be used. Psychological interventions-including eliciting concerns and conveying the potential for connection, meaning, reconciliation, and closure in the dying process-can also facilitate coping.

A critical mass of Internet users will soon enable wide diffusion of electronic communication within medical practice. E-mail between physicians and patients offers important opportunities for better communication. Linking patients and physicians through e-mail may increase the involvement of patients in supervising and documenting their own health care, processes that may activate patients and contribute to improved health. These new linkages may have profound implications for the patient-physician relationship. Although the federal government proposes regulation of telemedicine technologies and medical software, communications technologies are evolving under less scrutiny. Unless these technologies are implemented with substantial forethought, they may disturb delicate balances in the patient-physician relationship, widen social disparities in health outcomes, and create barriers to access to health care. This paper seeks to identify the promise and pitfalls of electronic patient-physician communication before such technology becomes widely distributed. A research agenda is proposed that would provide data that are useful for careful shaping of the communications infrastructure. The paper addresses the need to 1) define appropriate use of the various modes of patient-physician communication, 2) ensure the security and confidentiality of patient information, 3) create user interfaces that guide patients in effective use of the technology, 4) proactively assess medicolegal liability, and 5) ensure access to the technology by a multicultural, multilingual population with varying degrees of literacy.

Greater integration of medication-assisted treatment (MAT) for opioid use disorder (OUD) in U.S. primary care settings would expand access to treatment for this condition. Models for integrating MAT in primary care vary in how they are structured. This paper summarizes findings of a technical report for the Agency for Healthcare Research and Quality (AHRQ) describing OUD MAT models of care, based on a literature review and interviews with key informants in the field. The report describes 12 representative models of care for integrating MAT in primary care settings that could be considered for adaptation across diverse healthcare settings. Common components of existing care models include (1) pharmacotherapy with buprenorphine or naltrexone, (2) provider and community education, (3) coordination/integration of OUD with other medical/psychological needs, and (4) psychosocial services/interventions. Models varied with respect to how each component is implemented. Decisions about adopting MAT models of care should be individualized to address the unique milieu of each implementation setting.

Further evidence is presented, in addition to that of our previous papers, that the intestinal tract is, under ordinary circumstances, the sole place of origin of urobilin. So long as the biliary tract remains sterile the presence of the pigment in bile and urine is entirely dependent upon the passage of bile to the intestine. Animals rendered urobilin-free by the collection of all the bile from the intubated, uninfected common duct, remain urobilin-free during and after extensive blood destruction caused by intravenous injections of distilled water, as also after reinjections of the animal's own blood, hemolyzed in vitro. No urobilin appears in the bile, urine, or feces of animals so intubated when blood destruction has been caused by sodium oleate, or by an agent, toluylenediamine, which damages the liver as well as the blood. On the other hand, when bile flow into the intestine is uninterrupted, urobilinuria occurs during blood destruction caused in any of the ways mentioned and it parallels, both in severity and duration, the destructive process. Merely increasing the amount of bilirubin within the intestines of healthy dogs by feeding urobilin-free bile, will lead to marked urobilinuria. The extravasation of blood into the tissues, resulting from the trauma of an operation for intubation of a bile duct, does not lead to urobilinuria in animals losing all of the bile after this operation, but may do so when only a small fraction of the bile is drained, while the remainder reaches the intestine as usual. The production of artificial hematomas, without operation, is not followed by urobilinuria, under the circumstances last mentioned, but merely by an increase in the bilirubin of the bile. The effect on the liver of the anesthetic employed during the intubation may be responsible for the difference in the two cases. During the course of certain intercurrent infections affecting some of the intubated animals, notably distemper, there was a drop in the hemoglobin percentage of the circulating blood, accompanied by an increased output of bile pigment or further by urobilinuria, when the conditions were such that bile still reached the intestine. The findings pointed to increased blood destruction as a factor in the urobilinuria. The evidence presented, taken with that of our previous papers, suffices to demonstrate, that urobilinuria, occurring during blood destruction, is primarily the result of an increased excretion of bilirubin from which, in turn, an unusually large quantity of urobilin is formed within the intestine. The liver fails to remove from the portal blood all of the latter pigment which is resorbed and consequently some of it reaches the kidneys and urine. Our work has been carried out on animals with uninfected biliary tracts and livers, save for one case which has special mention. The influence of infection of the biliary tract on the place of formation of urobilin and the development of urobilinuria will be discussed in a succeeding communication.

Two papers in this issue address mammography screening for women aged 40 to 49 years. van Ravesteyn and colleagues' comparative modeling study found that screening women in their 40s who have a 2-f...

Do we really need another paper on socioeconomic inequalities in health? Alter and colleagues have added to our knowledge, but the assumption that we can reduce socioeconomic inequalities in surviv...

More patients with opioid addiction are receiving opioid agonist therapy (OAT) with methadone and buprenorphine. As a result, physicians will more frequently encounter patients receiving OAT who develop acutely painful conditions, requiring effective treatment strategies. Undertreatment of acute pain is suboptimal medical treatment, and patients receiving long-term OAT are at particular risk. This paper acknowledges the complex interplay among addictive disease, OAT, and acute pain management and describes 4 common misconceptions resulting in suboptimal treatment of acute pain. Clinical recommendations for providing analgesia for patients with acute pain who are receiving OAT are presented. Although challenging, acute pain in patients receiving this type of therapy can effectively be managed.

BACKGROUND: Inhaled corticosteroids (ICS) form the basis of maintenance therapy in asthma and their efficacy is well established. However, the optimal starting dose of ICS is not clearly established. Recent reviews demonstrate a relatively flat efficacy curve for ICS and increasing side effects with increasing ICS doses. High doses are frequently prescribed and there are now reports of significant side effects occurring with high dose ICS use. These issues demonstrate the need to establish the optimal starting dose of ICS in asthma. OBJECTIVES: To establish the optimal starting dose of ICS by evaluating the efficacy of initial high dose ICS with low dose ICS in subjects with asthma, not currently on ICS. SEARCH METHODS: We searched the Cochrane Airways Group trials register and reference lists of articles.Date of last search: January 2003 SELECTION CRITERIA: Randomised controlled trials of two different doses of the same ICS in adults and children with asthma with no concomitant ICS or OCS. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted independently by two reviewers. Study authors were contacted for confirmation. Trials were analysed according to the following ICS dose comparisons: step down vs constant dose ICS (n=7); high vs moderate (n=11); high vs low (n=9); moderate vs low (n=11); fold change in dose (all studies). MAIN RESULTS: 31 papers reporting the results of 26 trials were included in the review. For studies that compared a step down approach to a constant moderate/low ICS dose, there were no significant differences in lung function, symptoms, rescue medications or asthma control between the two treatment approaches. Significant but clinically small improvements in percent predicted FEV1 ( WMD 5.32, 95% CI 0.65 to 9.99) and non significant improvements in the change in morning PEF were found for high dose ICS compared to moderate dose ICS. There were no significant differences in efficacy between high and low dose ICS. For moderate dose ICS, compared to low dose ICS, there were significant improvements in the change in morning PEF L/min from baseline (WMD 11.14, 95% CI 1.34 to 20.93) and nocturnal symptoms (SMD ‐0.29, 95% CI ‐0.53 to ‐0.06 ) . Commencing ICS at double or quadruple a base moderate or low dose had no greater effect than commencing with the base dose. Several studies reported greater improvement in airway hyperresponsiveness for high dose ICS. AUTHORS' CONCLUSIONS: For patients with asthma who require ICS, commencing with a moderate dose ICS is equivalent to commencing with a high dose ICS and down‐titrating. The small significant benefits of commencing with a high ICS dose are not of sufficient clinical benefit to warrant its use when compared to moderate or low dose ICS. Initial moderate ICS dose appears to be more effective than initial low ICS dose. High dose ICS may be more effective than moderate or low dose ICS for airway hyperresponsiveness. There is no benefit in doubling or quadrupling ICS in subjects with stable asthma.

To comprehend the results of a randomized, controlled trial (RCT), readers must understand its design, conduct, analysis, and interpretation. That goal can be achieved only through complete transparency from authors. Despite several decades of educational efforts, the reporting of RCTs needs improvement. Investigators and editors developed the original CONSORT (Con solidated S tandards o f R eporting T rials) statement to help authors improve reporting by using a checklist and flow diagram. The revised CONSORT statement presented in this paper incorporates new evidence and addresses some criticisms of the original statement. The checklist items pertain to the content of the Title, Abstract, Introduction, Methods, Results, and Discussion. The revised checklist includes 22 items selected because empirical evidence indicates that not reporting the information is associated with biased estimates of treatment effect or because the information is essential to judge the reliability or relevance of the findings. We intended the flow diagram to depict the passage of participants through an RCT. The revised flow diagram depicts information from four stages of a trial (enrollment, intervention allocation, follow-up, and analysis). The diagram explicitly includes the number of participants, for each intervention group, that are included in the primary data analysis. Inclusion of these numbers allows the reader to judge whether the authors have performed an intention-to-treat analysis. In sum, the CONSORT statement is intended to improve the reporting of an RCT, enabling readers to understand a trial's conduct and to assess the validity of its results.

Excerpt The title of my paper is: "The Nature, Qualities, and Varieties of Medical Research." I hasten to assure you that this title was not composed by me, and that, while it permits almost limitl...

Excerpt Listeriamonocytogeneswas described as a new species in 1926 by Murray et al.,1and human infection caused by this microorganism was first reported in 1936 by Burn.2, 3Several recent papers h...