Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Anxiety, Depression, and Stress Reaction/Adjustment Disorders and Their Associations with Healthcare Resource Utilization and Costs Among Newly Diagnosed Patients With Breast Cancer

**Background:** Breast cancer is the most common cancer among women in the United States. Newly diagnosed patients with breast cancer often experience anxiety, depression, and stress. However, the impact of psychological distress on healthcare resource utilization (HCRU) and costs has not been adequately assessed. **Objectives:** To evaluate the incidence and prevalence of anxiety, depression, and stress reaction/adjustment disorder among patients newly diagnosed with breast cancer, to examine HCRU and costs, and to assess the association of these psychiatric disorders with costs. **Methods:** This retrospective observational cohort study was conducted using a large US administrative claims database with an index date of newly diagnosed breast cancer. Demographics and comorbidities (including anxiety, depression, and stress reaction/adjustment disorder) were assessed using data collected 12 months before and after the index date. HCRU and costs were assessed using data collected 12 months after the index date. Generalized linear regressions were performed to examine the association between healthcare costs and anxiety, depression, and stress reaction/adjustment disorder. **Results:** Of 6392 patients with newly diagnosed breast cancer, 38.2% were diagnosed with psychiatric disorders including anxiety (27.7%), depression (21.9%), or stress reaction/adjustment disorder (6%). The incidence of these psychiatric disorders was 15% and the prevalence was 23.2%. Patients with anxiety, depression, or stress reaction/adjustment disorder had higher rates of several types of HCRU (_P_ < .0001) and higher total all-cause costs compared with patients without these psychiatric disorders (_P_ < .0001). Patients with incident anxiety, depression, or stress reaction/adjustment disorder incurred higher all-cause costs in the first year following breast cancer diagnosis than those with prevalent anxiety, depression, or stress reaction/adjustment disorder (_P_ < .0003), or those without these psychiatric disorders (_P_ < .0001). **Discussion:** Of patients with anxiety, depression, or stress reaction/adjustment disorder, those with incident psychiatric disorders had higher healthcare costs, suggesting that new-onset psychological distress may contribute to higher costs incurred by the payer. Timely treatment of psychiatric disorders in this population may improve clinical outcomes and reduce HCRU and costs. **Conclusions:** Anxiety, depression, and stress reaction/adjustment disorder were common among patients newly diagnosed with breast cancer and were associated with increased healthcare costs in the first year following breast cancer diagnosis

Supplemental Material - Multimorbidity and Its Associations With Anxiety and Depression Among Newly Diagnosed Patients With Breast Cancer: A Retrospective Observational Cohort Study in a US Commercially Insured and Medicare Advantage Population

Supplemental Material for Multimorbidity and Its Associations With Anxiety and Depression Among Newly Diagnosed Patients With Breast Cancer: A Retrospective Observational Cohort Study in a US Commercially Insured and Medicare Advantage Population by Dingwei Dai, Henriette Coetzer, Sean R. Zion, and Michael J. Malecki in Cancer Control</p

Multimorbidity and Its Associations With Anxiety and Depression Among Newly Diagnosed Patients With Breast Cancer: A Retrospective Observational Cohort Study in a US Commercially Insured and Medicare Advantage Population

Background Multimorbidity is common in patients with breast cancer, thus increasing the complexity of cancer care and economic burden, worsening their prognosis and quality of life. The prevalence of multimorbidity and its influence on psychological distress among patients with breast cancer have not been well characterized. Objectives To examine the prevalence of multimorbidity and its associations with anxiety and depression among newly diagnosed patients with breast cancer. Methods We conducted a retrospective observational cohort study using a large administrative claims database. Patients with breast cancer (ICD-10-CM: C50.x) were identified during the study period (1/1/2017-12/31/2020). The index date was defined as the diagnosis date of breast cancer. Demographics and comorbid conditions were assessed using data within 12 months prior to the index date. Multimorbidity was defined as the presence of ≥2 comorbid conditions. Anxiety and depression were examined using data within 12 months after the index date. Multivariable logistic regressions were performed to examine the associations between multimorbidity and anxiety and depression, adjusting for sociodemographic factors. Results Of the 6392 patients with newly diagnosed breast cancer, 86.9% had multimorbidity at the time of breast cancer diagnosis. The median number of comorbid conditions was 5. Overall, 27.7% experienced anxiety, and 21.9% experienced depression in the first year following breast cancer diagnosis. An increased number of comorbid conditions was associated with elevated prevalence of both anxiety and depression. After adjusting for possible confounding factors, number of comorbid conditions was significantly associated with risk of anxiety (adjusted odds ratio [95% confidence interval (CI)]: 1.17 [1.15-1.19]), and depression (1.24 [1.21-1.26]); all P < .0001. Conclusions Multimorbidity was highly prevalent among patients with breast cancer and was strongly associated with increased risk of anxiety and depression in the first year following breast cancer diagnosis. The presence of multimorbidity, anxiety, and depression should be considered in the context of clinical decision making to optimize cancer care and improve mental health and quality of life

Efficacy and Safety of Selective Serotonin Reuptake Inhibitors, Serotonin-Norepinephrine Reuptake Inhibitors, and Placebo for Common Psychiatric Disorders Among Children and Adolescents: A Systematic Review and Meta-analysis

Depressive disorders (DDs), anxiety disorders (ADs), obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD) are common mental disorders in children and adolescents.; To examine the relative efficacy and safety of selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and placebo for the treatment of DD, AD, OCD, and PTSD in children and adolescents.; PubMed, EMBASE, PsycINFO, Web of Science, and Cochrane Database from inception through August 7, 2016.; Published and unpublished randomized clinical trials of SSRIs or SNRIs in youths with DD, AD, OCD, or PTSD were included. Trials using other antidepressants (eg, tricyclic antidepressants, monoamine oxidase inhibitors) were excluded.; Effect sizes, calculated as standardized mean differences (Hedges g) and risk ratios (RRs) for adverse events, were assessed in a random-effects model.; Primary outcomes, as defined by authors on preintervention and postintervention data, mean change data, and adverse event data, were extracted independently by multiple observers following PRISMA guidelines.; Thirty-six trials were eligible, including 6778 participants (3484 [51.4%] female; mean [SD] age, 12.9 [5.1] years); 17 studies for DD, 10 for AD, 8 for OCD, and 1 for PTSD. Analysis showed that SSRIs and SNRIs were significantly more beneficial compared with placebo, yielding a small effect size (g = 0.32; 95% CI, 0.25-0.40; P &lt; .001). Anxiety disorder (g = 0.56; 95% CI, 0.40-0.72; P &lt; .001) showed significantly larger between-group effect sizes than DD (g = 0.20; 95% CI, 0.13-0.27; P &lt; .001). This difference was driven primarily by the placebo response: patients with DD exhibited significantly larger placebo responses (g = 1.57; 95% CI, 1.36-1.78; P &lt; .001) compared with those with AD (g = 1.03; 95% CI, 0.84-1.21; P &lt; .001). The SSRIs produced a relatively large effect size for ADs (g = 0.71; 95% CI, 0.45-0.97; P &lt; .001). Compared with participants receiving placebo, patients receiving an antidepressant reported significantly more treatment-emergent adverse events (RR, 1.07; 95% CI, 1.01-1.12; P = .01 or RR, 1.49; 95% CI, 1.22-1.82; P &lt; .001, depending on the reporting method), severe adverse events (RR, 1.76; 95% CI, 1.34-2.32; P &lt; .001), and study discontinuation due to adverse events (RR, 1.79; 95% CI, 1.38-2.32; P &lt; .001).; Compared with placebo, SSRIs and SNRIs are more beneficial than placebo in children and adolescents; however, the benefit is small and disorder specific, yielding a larger drug-placebo difference for AD than for other conditions. Response to placebo is large, especially in DD. Severe adverse events are significantly more common with SSRIs and SNRIs than placebo

A cognitive behavioral digital therapeutic for anxiety and depression in patients with cancer: A decentralized randomized controlled trial

1507 Background: Patients with cancer often experience clinically elevated levels of distress, including anxiety and depression. Psychological interventions, such as Cognitive Behavioral Stress Management (CBSM), have evidenced benefits on distress, quality of life, and long-term health outcomes, however, they are not widely available or easily accessible. Digitizing these interventions may be a means of democratizing access to cancer-focused and empirically-supported mental health care. Methods: This double-blind randomized controlled trial (RCT) compared the impact of a 10-module digitized CBSM app [attune] vs. a health education control app [cerena] on anxiety and depression symptoms in patients with cancer (n=449). Patients with non-metastatic (stage I-III) and hematological cancers who were receiving or recently (≤6 months) completed systemic treatment and reported a PROMIS-A T-Score >60 were recruited to participate in this decentralized clinical trial through a nationwide online advertising campaign. The pre-specified primary outcome was change in anxiety symptoms (PROMIS-A) across conditions over time (week 0, 4, 8, and 12) in the intention-to-treat population analyzed using a linear mixed effects model with repeated measures. Secondary outcomes included change in depression symptoms (PROMIS-D) and global impression of change in anxiety and depression (PGI-C). Results: Patients in the study were 80.6% female, 76.5% white, and the mean (SD; range) age was 52.44 (11.46; 25-80) years. Compared to the control, attune participants showed significantly greater reductions in anxiety (β=-0.03; p=0.019) and depression (β=-0.02; p=0.042) symptoms over 12-weeks, and at end-of-study (week 12) there was a greater proportion of attune participants in the PROMIS-A (χ 2 =7.13; p=0.004) and PROMIS-D (χ 2 =3.53; p=0.035) mild-none symptom severity category. There were also significant group differences in PGI-C, with attune participants more likely to report ‘much’ or ‘very much’ improvement in their anxiety (χ 2 =31.76; p<0.001) and depression symptoms (χ 2 =19.70; p<0.001). Conclusions: Digital therapeutics have the potential to improve access to empirically supported psychological treatments for symptoms of anxiety and depression in patients with cancer. In this decentralized, double-blind RCT, we show that compared with a visually and functionally similar sham app, patients who used attune had significantly greater reductions in anxiety and depression symptoms over time. Moreover, at the end of the study, participants who used attune were significantly more likely to report their anxiety and depression symptoms were ‘much’ or ‘very much’ improved, indicating clinically meaningful change. Future work aims to explore implementation strategies to maximize benefit and accessibility of this cancer-specific digital therapeutic. Clinical trial information: NCT05227898

Effects of a Cognitive Behavioral Digital Therapeutic on Anxiety and Depression Symptoms in Patients With Cancer:A Randomized Controlled Trial

Results from a clinical trial of a new cognitive behavioral stress management (CBSM) app show a significant benefit for patients with cancer with symptoms of anxiety and depression. The double-blind, randomized controlled trial compared the cancer-specific app with a health education sham app in 449 patients diagnosed with nonmetastatic cancers. Patients who received the cancer-specific app showed significantly greater reductions in symptoms of anxiety and depression over 12 weeks and were significantly more likely to report their symptoms as much or very much improved at the end of the study. Self-reported adverse events were also collected to inform benefit-risk. PURPOSE Patients with cancer often experience elevated levels of distress. This double-blind, randomized controlled trial compared the impact of an app-based version of cognitive behavioral stress management (CBSM) versus a health education sham app on anxiety and depression symptoms. METHODS Patients with nonmetastatic (stage I-III) cancer who were receiving or recently completed (≤6 months) systemic treatment were recruited nationwide. The primary outcome of change in anxiety symptoms (PROMIS-Anxiety) over 12 weeks and the top secondary outcome of change in depression symptoms (PROMIS-Depression) over 12 weeks were analyzed using mixed-effects modeling with repeated measures (weeks 0, 4, 8, 12). Patient global impressions of change in anxiety and depression were reported at weeks 4, 8, and 12. In addition, self-reported adverse events were collected throughout the study and adjudicated by the site principal investigator. RESULTS Four hundred forty-nine patients were enrolled in the trial (age M [standard deviation] = 52.44 [11.46]; 81% female; 76% White; 53% breast cancer). Patients randomly assigned to digitized CBSM showed significantly greater reductions in anxiety ( B = –0.03; P = .019) and depression ( B = –0.02; P = .042) symptoms over 12 weeks. Patients who received digitized CBSM were also significantly more likely to perceive much or very much improvement ( v no/minimal change or much/very much worse) in their symptoms of anxiety (χ 2 = 31.76; P < .001) and depression (χ 2 = 19.70; P < .001) compared with the control. CONCLUSION The use of digitized CBSM led to significant improvements in anxiety and depression outcomes compared with the sham app