Case-control studies are one of the major observational study designs for performing clinical research. The advantages of these study designs over other study designs are that they are relatively quick to perform, economical, and easy to design and implement. Case-control studies are particularly appropriate for studying disease outbreaks, rare diseases, or outcomes of interest. This article describes several types of case-control designs, with simple graphical displays to help understand their differences. Study design considerations are reviewed, including sample size, power, and measures associated with risk factors for clinical outcomes. Finally, we discuss the advantages and disadvantages of case-control studies and provide a checklist for authors and a framework of considerations to guide reviewers' comments.

Self-reported measures of health-related quality of life (HRQOL) are increasingly used in clinical management and evaluation of patient outcomes. HRQOL measures are used to monitor patient progress and treatment response, investigate effects of medical interventions, and provide patient-based data for quality improvement initiatives and policy decisions. Given the importance of HRQOL, it is imperative that the instruments used to assess HRQOL are precise, valid, reliable, and responsive, and that the HRQOL data are appropriately collected, analyzed, and presented. This article reviews the key attributes of studies involving HRQOL data, discusses best practices for selecting appropriate instruments, and provides guidelines for the assessment, analysis, and presentation of these data. A checklist and a reviewer guide are included to serve as templates for authors and reviewers when submitting and reviewing studies involving HRQOL.

Survival (time-to-event) analysis is commonly used in clinical research. Key features of performing a survival analysis include checking proportional hazards assumptions, reporting CIs for hazards ratios and relative risks, graphically displaying the findings, and analyzing with consideration of competing risks. This article provides a brief overview of important statistical considerations for survival analysis. Censoring schemes, different methods of survival function estimation, and ways to compare survival curves are described. We also explain competing risk and how to model survival data in the presence of it. Different kinds of bias that influence survival estimation and avenues to model the data under these circumstances are also described. Several analysis techniques are accompanied by graphical representations illustrating proper reporting strategies. We provide a list of guiding statements for researchers and reviewers.

Considerable heterogeneity persists in the conduct and reporting of statistical analyses in the medical literature. Authors submitting manuscripts to CHEST are encouraged to adhere to the following guidelines where possible.

We have entered the era of "big data" and with that the explosion of interest in prediction modeling. With this explosion comes the challenge of evaluating statistical prediction models, both from the standpoint of an author as well as a reviewer. This article provides guidance for the evaluation and critique of a statistical prediction model. Hopefully, this will improve the quality of statistical prediction modeling studies and facilitate their review.

Causal directed acyclic graphs (cDAGs) have become popular tools for researchers to better examine biases related to causal questions. DAGs comprise a series of arrows connecting nodes that represent variables and in doing so can demonstrate the causal relation between different variables. cDAGs can provide researchers with a blueprint of the exposure and outcome relation and the other variables that play a role in that causal question. cDAGs can be helpful in the design and interpretation of observational studies in pulmonary, critical care, sleep, and cardiovascular medicine. They can also help clinicians and researchers to better identify the structure of different biases that can affect the validity of observational studies. Most of the available literature on cDAGs and their function use language that might be unfamiliar to clinicians. This article explains cDAG terminology and the principles behind how they work. We use cDAGs and clinical examples that are mostly focused in the area of pulmonary medicine to describe the structure of confounding, selection bias, overadjustment bias, and detection bias. These principles are then applied to a more complex published case study on the use of statins and COPD mortality. We also introduce readers to other resources for a more in-depth discussion of causal inference principles.

Sample size determination is an essential step in planning a clinical study. It is critical to understand that different study designs need different methods of sample size estimation. Although there is a vast literature discussing sample size estimation, incorrect or improper formulas continue to be applied. This article reviews basic statistical concepts in sample size estimation, discusses statistical considerations in the choice of a sample size for randomized controlled trials and observational studies, and provides strategies for reducing sample size when planning a study. To assist clinical researchers in performing sample size calculations, we have developed an online calculator for common clinical study designs. The calculator is available at http://riskcalc.org:3838/samplesize/. Finally, we offer our recommendations on reporting sample size determination in clinical studies.

Reductions in genotyping costs and improvements in computational power have made conducting genome-wide association studies (GWAS) standard practice for many complex diseases. GWAS is the assessment of genetic variants across the genome of many individuals to determine which, if any, genetic variants are associated with a specific trait. As with any analysis, there are evolving best practices that should be followed to ensure scientific rigor and reliability in the conclusions. This article presents a brief summary for many of the key bioinformatics considerations when either planning or evaluating GWAS. This review is meant to serve as a guide to those without deep expertise in bioinformatics and GWAS and give them tools to critically evaluate this popular approach to investigating complex diseases. In addition, a checklist is provided that can be used by investigators to evaluate whether a GWAS has appropriately accounted for the many potential sources of bias and generally followed current best practices.

Medical tests are procedures intended to detect, diagnose, characterize, or monitor a specific medical condition. Understanding the accuracy of a medical test is a critical part of informed decision-making in patient management, as it allows clinicians to appreciate the types of errors a medical test might be prone to making and how often it makes them. Designing a study to assess the performance of a medical test, however, presents unique challenges, from acquiring a reference standard to dealing with the complexities that arise when the test involves an interpretation by a human reader. This article provides an overview of design considerations in this context, including common biases and how to avoid them, statistical considerations, and reporting guidelines. A short list of questions is also provided, which can serve as a quick reference for anyone designing, implementing, or reviewing a study that intends to assess the performance of a medical test.

We report the clinical history, laboratory findings, and imaging features of coronavirus disease 2019 (COVID-19) in a neonate whose mother was also a patient. The newborn was the youngest patient with COVID-19 in the world at the time he was diagnosed. This case has brought more attention and understanding to the epidemic and mode of transmission of the disease.

A 72-year-old woman with diabetes mellitus was admitted to our hospital because of dyspnea on exertion. Sputum cytologic evaluation revealed intranuclear inclusion bodies in the cells; we therefore considered viral pneumonia and performed a bronchoscopy. The bronchial washing fluid was positive for immunoperoxidase staining of herpes simplex virus type 1 (HSV1) and HSV1 polymerase chain reaction. The patient was diagnosed as having pneumonia due to HSV1 and was successfully treated with acyclovir.

A 50-year-old woman with a medical history significant for limited scleroderma (SSc) complicated by interstitial lung disease (ILD) and pulmonary arterial hypertension presented to our institution with acute on chronic shortness of breath. Ten years before presentation, she was diagnosed with SSc. Two years before presentation, she was found to have ILD, for which she was started on mycophenolate mofetil and low-dose prednisone. One year before presentation, she noted worsening dyspnea on exertion (New York Heart Association Functional Class III) and required supplemental oxygen, up to 5 L, despite findings of stable ILD on a maintenance dose of mycophenolate mofetil. A subsequent right heart catheterization showed findings consistent with severe pulmonary arterial hypertension: right atrial pressure of 19 mm Hg, pulmonary arterial pressure of 98/39 mm Hg with a mean pulmonary arterial pressure of 58 mm Hg, right ventricular pressure of 59/6 mm Hg, pulmonary arterial wedge pressure of 10 mm Hg, cardiac output of 4.2 L/min with a cardiac index of 2.7 L/min/m2, and a calculated pulmonary vascular resistance of 11.43 Wood units. She had no significant vasoreactivity on inhaled nitric oxide challenge. She was started on IV treprostinil that had been up-titrated over the course of 6 months before presentation. On admission, she denied any cough, fevers, chills, chest pains, palpitations, or lower extremity edema. She denied any sick contacts or any recent travel. She denied any periods of prolonged immobility.

A 68-year-old man developed an erythematous, papular, pruritic rash on his right thigh 1 month prior to presentation. It subsequently spread to his other extremities and trunk. He also endorsed fevers of > 38.3°C, night sweats, fatigue, shortness of breath, and a dry cough. He was prescribed triamcinolone 0.1% cream for his rash and azithromycin for presumed community-acquired pneumonia, with no improvement in symptoms. He had a history of relapsing polychondritis for which he was prescribed infliximab and low-dose prednisone. He had never smoked tobacco, did not use alcohol or illicit substances, and had no significant travel history.

A 71-year-old ex-bus driver (ex-smoker, 20 pack-years) was admitted for the first time to the respiratory department because of chronic dry cough and progressive exertional dyspnea with insidious onset 8 years ago. The patient also reported weight loss of about 20 kg in 3 years and proximal muscle weakness. A decade ago, he was diagnosed with gastric adenocarcinoma and subjected to partial gastrectomy and splenectomy, followed by an unspecified chemotherapy regimen. Additionally, the patient has coronary disease and underwent coronary bypass graft surgery 7 years ago. In the course of his disease, many diagnostic procedures have been performed including Mantoux tests, five CT scans, a CT-guided biopsy, two bronchoscopies, and an 18F-fluorodeoxyglucose PET scan with inconclusive results. The patient was referred to the hospital to have his long-lasting condition diagnosed and treated.

A 57-year-old woman with a history of mantle cell lymphoma presented to the ED with complaints of vomiting, bleeding per rectum, and leg cramps, that started 6 h prior to her arrival. She had received chemotherapy a week prior. Her leg cramps were not associated with pain or swelling of the legs; she also denied any trauma to the legs. She did complain of mild lower abdominal pain at presentation. Review of systems was negative for fever, chills, diarrhea, chest pain, and dizziness. She denied using alcohol or nonsteroidal anti-inflammatory drugs. The patient was tachycardic with a systolic BP (SBP) of 85 mm Hg and was administered 1-L normal saline, with improvement in her SBP to 90 mm Hg. The hematocrit level was 24%, the WBC count was 0.3 × 109/L, and the platelet count was 6 × 109/L in the ED. On arrival in the ICU, she was noted to have an SBP of 70 mm Hg. Resuscitation with IV fluids was initiated, followed by transfusion of packed RBCs and platelets, based on the blood counts. Despite aggressive fluid resuscitation and improvement in her hemoglobin, the patient remained persistently hypotensive. The diagnosis of underlying septic shock because of neutropenia was considered; the patient was started on vasopressors and empirical broad-spectrum antibiotics, with improvement in her BP. After this, the patient was sent to radiology for a CT scan of the abdomen and pelvis with contrast to evaluate for mesenteric infarction, enteric or colonic bleeding, and the need for arterial embolization.

A 70-year-old woman presented with hemorrhagic shock secondary to hemoperitoneum following a paracentesis. On hospital day 3, she developed respiratory alkalosis and increased respiratory rates observed on the ventilator despite no spontaneous inspiratory effort. Converting to pressure support mode uncovered a cardiogenic oscillatory flow that had been auto-triggering the ventilator. This cardiogenic auto-triggering resolved with large-volume paracentesis. Cardiogenic auto-triggering leads to patient-ventilator dyssynchrony, respiratory alkalosis, lung distension, and difficulty with weaning from the ventilator, and it may be unrecognized in ICUs.