Humans

Background: Our ability to smell and taste is dictated by 3 chemosensory systems with distinct physiologic mechanisms - olfaction, gustation, and chemesthesis. Although often overlooked, dysfunction of these special senses may have broad implications on multiple facets of patients' lives -including safety, nutritional status, quality of life, mental health, and even cognitive function. As "loss of smell or taste" emerged as a common symptom of coronavirus disease 2019 (COVID-19), the importance of intact chemosensory function has been thrust into the spotlight. Despite the growing recognition of chemosensory dysfunction, this already highly prevalent condition will increasingly impact a larger and more diverse population, highlighting the need for improved awareness and care of these patients.

Methods: Comtemporary review of chemosensory function and assessments.

Conclusions: Although patient-reported chemosensory function measures highlight the ease of screening of chemosensory dysfunction, self-reported measures underestimate both the prevalence and degree of chemosensory dysfunction and do not adequately distinguish between olfaction, gustation, and chemesthesis. Meanwhile, psychophysical assessment tools provide opportunities for more accurate, thorough assessment of the chemosenses when appropriate. Primary care providers are uniquely situated to identify patients burdened by chemosensory dysfunction and raise patient and provider awareness about the importance of chemosensory dysfunction. Identification of chemosensory dysfunction, particularly olfactory dysfunction, may raise suspicion for many underlying medical conditions, including early detection of neurodegenerative conditions. Furthermore, identification and awareness of patients with chemosensory dysfunction may help primary care providers to identify those who may benefit from additional therapeutic and safety interventions, or consultations with specialists for more detailed evaluations and management.

Importance: The Global Initiative for Asthma (GINA) recommends 2 alternative treatments for patients receiving treatment at steps 3 to 5: single inhaler combination inhaled corticosteroid-formoterol as both maintenance and reliever (SMART) or inhaled corticosteroid-long-acting β2-agonist as maintenance plus short-acting β2-agonist as reliever.

Objective: To assess whether switching to SMART is associated with longer time to first severe asthma exacerbation compared with a step up or continuation of GINA treatment step with maintenance inhaled corticosteroid-long-acting β2-agonist plus short-acting β2-agonist reliever among patients with poorly controlled asthma.

Data sources: For this systematic review and meta-analysis, the literature, internal study databases at AstraZeneca and the Medical Research Institute of New Zealand, and references from a previous systematic review and meta-analysis on SMART were searched to identify randomized clinical trials published from January 1990 to February 2018, that compared budesonide-formoterol by SMART with maintenance inhaled corticosteroid-long-acting β2-agonist plus short-acting β2-agonist reliever.

Study selection: Trials of at least 24 weeks' duration were included if they reported baseline data on GINA treatment step, asthma control status, and efficacy measures of severe exacerbations. Included patients were adults and adolescents with asthma and baseline Asthma Control Questionnaire 5-item version scores of 1.5 or higher.

Data extraction and synthesis: Patient-level data were identified by independent extraction, and analyses were performed using a fixed-effect model. Data analysis was performed from August 2018 to November 2021.

Main outcomes and measures: The primary outcome was time to first severe asthma exacerbation associated with each treatment, analyzed by Cox proportional hazards regression.

Results: Overall, 4863 patients were included (3034 [62.4%] female; mean [SD] age, 39.8 [16.3] years). Switching patients with uncontrolled asthma at GINA step 3 (n = 1950) to SMART at either step 3 or 4 was associated with a prolonged time to first severe asthma exacerbation, with a 29% reduced risk compared with stepping up to step 4 inhaled corticosteroid-long-acting β2-agonist maintenance plus short-acting β2-agonist reliever (hazard ratio, 0.71; 95% CI, 0.52-0.97). For patients with uncontrolled asthma at step 3 and step 4 (n = 2913), switching to SMART was associated with a prolonged time to first severe asthma exacerbation and a 30% reduced risk compared with remaining at the same treatment step (hazard ratio, 0.70; 95% CI, 0.58-0.85).

Conclusions and relevance: In this systematic review and meta-analysis, for patients with poorly controlled asthma, SMART was associated with longer time to first severe asthma exacerbation compared with a step up or continuation of GINA step with maintenance inhaled corticosteroid-long-acting β2-agonist plus short-acting β2-agonist reliever. These findings suggest that if an adult or adolescent receiving treatment at GINA step 3 or 4 has poorly controlled asthma, it is preferable to switch to the SMART regimen rather than to step up or continue the GINA treatment step with maintenance inhaled corticosteroid-long-acting β2-agonist plus short-acting β2-agonist reliever therapy.

Importance Gallbladder disease affects approximately 20 million people in the US. Acute cholecystitis is diagnosed in approximately 200 000 people in the US each year.

Observations Gallstone-associated cystic duct obstruction is responsible for 90% to 95% of the cases of acute cholecystitis. Approximately 5% to 10% of patients with acute cholecystitis have acalculous cholecystitis, defined as acute inflammation of the gallbladder without gallstones, typically in the setting of severe critical illness. The typical presentation of acute cholecystitis consists of acute right upper quadrant pain, fever, and nausea that may be associated with eating and physical examination findings of right upper quadrant tenderness. Ultrasonography of the right upper quadrant has a sensitivity of approximately 81% and a specificity of approximately 83% for the diagnosis of acute cholecystitis. When an ultrasound result does not provide a definitive diagnosis, hepatobiliary scintigraphy (a nuclear medicine study that includes the intravenous injection of a radiotracer excreted in the bile) is the gold standard diagnostic test. Following diagnosis, early (performed within 1-3 days) vs late (performed after 3 days) laparoscopic cholecystectomy is associated with improved patient outcomes, including fewer composite postoperative complications (11.8% for early vs 34.4% for late), a shorter length of hospital stay (5.4 days vs 10.0 days), and lower hospital costs. During pregnancy, early laparoscopic cholecystectomy, compared with delayed operative management, is associated with a lower risk of maternal-fetal complications (1.6% for early vs 18.4% for delayed) and is recommended during all trimesters. In people older than 65 years of age, laparoscopic cholecystectomy is associated with lower mortality at 2-year follow-up (15.2%) compared with nonoperative management (29.3%). A percutaneous cholecystostomy tube, in which a drainage catheter is placed in the gallbladder lumen under image guidance, is an effective therapy for patients with an exceptionally high perioperative risk. However, percutaneous cholecystostomy tube placement in a randomized trial was associated with higher rates of postprocedural complications (65%) compared with laparoscopic cholecystectomy (12%). For patients with acalculous acute cholecystitis, percutaneous cholecystostomy tube should be reserved for patients who are severely ill at the time of diagnosis; all others should undergo a laparoscopic cholecystectomy.

Importance: Physical therapy and glucocorticoid injections are initial treatment options for knee osteoarthritis, but available data indicate that most patients receive one or the other, suggesting they may be competing interventions. The initial cost difference for treatment can be substantial, with physical therapy often being more expensive at the outset, and cost-effectiveness analysis can aid patients and clinicians in making decisions.

Objective: To investigate the incremental cost-effectiveness between physical therapy and intra-articular glucocorticoid injection as initial treatment strategies for knee osteoarthritis.

Design, setting, and participants: This economic evaluation is a secondary analysis of a randomized clinical trial performed from October 1, 2012, to May 4, 2017. Health economists were blinded to study outcomes and treatment allocation. A randomized sample of patients seen in primary care and physical therapy clinics with a radiographically confirmed diagnosis of knee osteoarthritis were evaluated from the clinical trial with 96.2% follow-up at 1 year.

Interventions: Physical therapy or glucocorticoid injection.

Main outcomes and measures: The main outcome was incremental cost-effectiveness between 2 alternative treatments. Acceptability curves of bootstrapped incremental cost-effectiveness ratios (ICERs) were used to identify the proportion of ICERs under the specific willingness-to-pay level ($50 000-$100 000). Health care system costs (total and knee related) and health-related quality-of-life based on quality-adjusted life-years (QALYs) were obtained.

Results: A total of 156 participants (mean [SD] age, 56.1 [8.7] years; 81 [51.9%] male) were randomized 1:1 and followed up for 1 year. Mean (SD) 1-year knee-related medical costs were $2113 ($4224) in the glucocorticoid injection group and $2131 ($1015) in the physical therapy group. The mean difference in QALY significantly favored physical therapy at 1 year (0.076; 95% CI, 0.02-0.126; P = .003). Physical therapy was the more cost-effective intervention, with an ICER of $8103 for knee-related medical costs, with a 99.2% probability that results fall below the willingness-to-pay threshold of $100 000.

Conclusions and relevance: A course of physical therapy was cost-effective compared with a course of glucocorticoid injections for patients with knee osteoarthritis. These results suggest that, although the initial cost of delivering physical therapy may be higher than an initial course of glucocorticoid injections, 1-year total knee-related costs are equivalent, and greater improvement in QALYs may justify the initial higher costs.