This article summarizes the top 20 research studies of 2022 identified as POEMs (patient-oriented evidence that matters), excluding COVID-19. Statins for primary prevention of cardiovascular disease produce only a small absolute reduction in a person's likelihood of dying (0.6%), having a myocardial infarction (0.7%), or having a stroke (0.3%) over three to six years. Supplemental vitamin D does not reduce the risk of a fragility fracture, even in people with low baseline vitamin D levels or a previous fracture. Selective serotonin reuptake inhibitors are preferred medical therapy for panic disorder, and patients who discontinue antidepressants are more likely to relapse (number needed to harm = 6) compared with those who continue. Combination therapy using a selective serotonin reuptake inhibitor, serotonin-norepinephrine reuptake inhibitor, or tricyclic antidepressant with mirtazapine or trazodone is more effective than monotherapy for first-line treatment of acute severe depression and when monotherapy fails. Using hypnotic agents for insomnia in adults comes with a significant trade-off between effectiveness and tolerability. In patients with moderate to severe asthma, using a combination of albuterol and glucocorticoid inhalers as rescue therapy reduces exacerbations and need for systemic steroids. Observational research shows an increased risk of gastric cancer in patients taking proton pump inhibitors (number needed to harm = 1,191 over 10 years). The American College of Gastroenterology updated its guideline for gastroesophageal reflux disease, and a new guideline provides sound advice for the evaluation and management of irritable bowel syndrome. Adults older than 60 years with prediabetes are more likely to become normoglycemic than to develop diabetes mellitus or die. Treatment of prediabetes via intensive lifestyle intervention or metformin has no impact on long-term cardiovascular outcomes. Persons with painful diabetic peripheral neuropathy have similar degrees of improvement with monotherapy using amitriptyline, duloxetine, or pregabalin and greater improvement with combination therapy. When communicating with patients about disease risk, most patients prefer numbers over words because people overestimate word-based probabilities. In terms of drug therapy, the duration of an initial varenicline prescription should be 12 weeks. Many drugs can interact with cannabidiol. No important difference was found among ibuprofen, ketorolac, and diclofenac for treatment of acute nonradicular low back pain in adults.