Primary Care Physicians’ Experiences With and Adaptations to Time Constraints

Importance The primary care workforce shortage is significant and persistent, with organizational and policy leaders urgently seeking interventions to enhance retention and recruitment. Time constraints are a valuable focus for action; however, designing effective interventions requires deeper understanding of how time constraints shape employees’ experiences and outcomes of work. Objective To examine how time constraints affect primary care physicians’ work experiences and careers. Design, Setting, and Participants Between May 1, 2021, and September 31, 2022, US-based primary care physicians who trained in family or internal medicine were interviewed. Using qualitative analysis of in-depth interviews, this study examined how participants experience and adapt to time constraints during a typical clinic day, taking account of their professional and personal responsibilities. It also incorporates physicians’ reflections on implications for their careers. Main Outcomes and Measures Thematic analysis of in-depth interviews and a measure of well-being (American Medical Association Mini-Z survey). Results Interviews with 25 primary care physicians (14 [56%] female and 11 [44%] male; median [range] age, 43 [34-63] years) practicing in 11 US states were analyzed. Two physicians owned their own practice, whereas the rest worked as employees. The participants represented a wide range of years in practice (range, 1 to ≥21), with 11 participants (44%) in their first 5 years. Physicians described that the structure of their work hours did not match the work that was expected of them. This structural mismatch between time allocation and work expectations created a constant experience of time scarcity. Physicians described having to make tradeoffs between maintaining high-quality patient care and having their work overflow into their personal lives. These experiences led to feelings of guilt, disillusionment, and dissatisfaction. To attempt to sustain long-term careers in primary care, many sought ways to see fewer patients. Conclusions and Relevance These findings suggest that organizational leaders must align schedules with work expectations for primary care physicians to mitigate physicians’ withdrawal from work as a coping mechanism. Specific strategies are needed to achieve this realignment, including incorporating more slack into schedules and establishing realistic work expectations for physicians

Raman Spectroscopy of Lymphocytes for the Identification of Prostate Cancer Patients with Late Radiation Toxicity Following Radiotherapy

The success of radiotherapy in tumour control depends on the total dose given. However, the tolerance of the normal tissues surrounding the tumour limits this dose. It is not known why some patients develop radiation toxicity and, currently, it is not possible to predict before treatment which patients will experience adverse effects. Thus, there is an unmet clinical need for a new test to identify patients at risk of radiation toxicity. Here, we report a new approach based on Raman spectroscopy.Blood samples were collected from 42 patients who had undergone radiotherapy for prostate cancer and had shown either severe or no/minimal late radiation toxicity in follow up. Radiation response was assessed following in vitro irradiation using Raman spectroscopy in addition to the G2 chromosomal radiosensitivity assay and the H2AX DNA damage assay.A Partial Least Squares Discriminant Analysis model was developed to classify patients using known radiation toxicity scores. A sensitivity of 95%, specificity of 92% and overall accuracy of 93% was achieved. In the future, this technology may have potential to lead to individualised patient radiotherapy by identifying which patients are at risk of radiation toxicity

Vibrational Spectroscopy of Liquid Biopsies for Prostate Cancer Diagnosis

Background: Screening for prostate cancer with prostate specific antigen and digital rectal examination allows early diagnosis of prostate malignancy but has been associated with poor sensitivity and specificity. There is also a considerable risk of over-diagnosis and overtreatment, which highlights the need for better tools for diagnosis of prostate cancer. This study investigates the potential of high throughput Raman and Fourier Transform Infrared (FTIR) spectroscopy of liquid biopsies for rapid and accurate diagnosis of prostate cancer. Methods: Blood samples (plasma and lymphocytes) were obtained from healthy control subjects and prostate cancer patients. FTIR and Raman spectra were recorded from plasma samples, while Raman spectra were recorded from the lymphocytes. The acquired spectral data was analysed with various multivariate statistical methods, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and classical least squares (CLS) fitting analysis. Results: Discrimination was observed between the infrared and Raman spectra of plasma and lymphocytes from healthy donors and prostate cancer patients using PCA. In addition, plasma and lymphocytes displayed differentiating signatures in patients exhibiting different Gleason scores. A PLS-DA model was able to discriminate these groups with sensitivity and specificity rates ranging from 90% to 99%. CLS fitting analysis identified key analytes that are involved in the development and progression of prostate cancer. Conclusions: This technology may have potential as an alternative first stage diagnostic triage for prostate cancer. This technology can be easily adaptable to many other bodily fluids and could be useful for translation of liquid biopsy-based diagnostics into the clinic

Effect of hemolysis on Fourier transform infrared and Raman spectra of blood plasma

Hemolysis is a very common phenomenon and is referred as the release of intracellular components from red blood cells to the extracellular fluid. Hemolyzed samples are often rejected in clinics due to the interference of hemoglobin and intracellular components in laboratory measurements. Plasma and serum based vibrational spectroscopy studies are extensively applied to generate spectral biomarkers for various diseases. However, no studies have reported the effect of hemolysis in blood based vibrational spectroscopy studies. This study was undertaken to evaluate the effect of hemolysis on infrared and Raman spectra of blood plasma. In this study, prostate cancer plasma samples (n = 30) were divided into three groups (nonhemolyzed, mildly hemolyzed, and moderately hemolyzed) based on the degree of hemolysis and FTIR and Raman spectra were recorded using high throughput (HT)-FTIR and HT-Raman spectroscopy. Discrimination was observed between the infrared and Raman spectra of nonhemolyzed and hemolyzed plasma samples using principal component analysis. A classical least square fitting analysis showed differences in the weighting of pure components in nonhemolyzed and hemolyzed plasma samples. Therefore, it is worth to consider the changes in spectral features due to hemolysis when comparing the results within and between experiments

Prediction of DNA Damage and G2 Chromosomal Radio-Sensitivity Ex-vivo in Peripheral Blood Mononuclear Cells with Label-Free Raman Microspectroscopy

Liquid biopsies are a potentially rich store of biochemical information that can be linked to an individual’s response to therapeutic treatments, including radiotherapy, and which may ultimately play a role in the individualization of treatment regimens. Peripheral blood mononuclear cells (PBMCs) can be used for the biochemical profiling of the individual, but also, being living cells, can provide insights into the individuals response to ionizing radiation exposure

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

“Good Care Is Slow Enough to Be Able to Pay Attention”: Primary Care Time Scarcity and Patient Safety

Background: There is growing, widespread recognition that expectations of US primary care vastly exceed the time and resources allocated to it. Little research has directly examined how time scarcity contributes to harm or patient safety incidents not readily capturable by population-based quality metrics. Objective: To examine near-miss events identified by primary care physicians in which taking additional time improved patient care or prevented harm. Design: Qualitative study based on semi-structured interviews. Participants: Twenty-five primary care physicians practicing in the USA. Approach: Participants completed a survey that included demographic questions, the Ballard Organizational Temporality Scale and the Mini-Z scale, followed by a one hour qualitative interview over video-conference (Zoom). Iterative thematic qualitative data analysis was conducted. Key Results: Primary care physicians identified several types of near-miss events in which taking extra time during visits changed their clinical management. These were evident in five types of patient care episodes: high-risk social situations, high-risk medication regimens requiring patient education, high acuity conditions requiring immediate workup or treatment, interactions of physical and mental health, and investigating more subtle clinical suspicions. These near-miss events highlight the ways in which unreasonably large patient panels and packed schedules impede adequate responses to patient care episodes that are time sensitive and intensive or require flexibility. Conclusions: Primary care physicians identify and address patient safety issues and high-risk situations by spending more time than allotted for a given patient encounter. Current quality metrics do not account for this critical aspect of primary care work. Current healthcare policy and organization create time scarcity. Interventions to address time scarcity and to measure its prevalence and implications for care quality and safety are urgently needed