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Objectives The LI-RADS M (LR-M) category describes hepatic lesions probably or definitely malignant, but not specific for hepatocellular carcinoma in at-risk patients. Differentiation among LR-M entities, particularly detecting cholangiocarcinoma-containing tumors (M-CCs), is essential for treatment and prognosis. Thus, we aimed to develop diagnostic models on gadoxetate disodium–enhanced MRI comprising serum tumor markers and LI-RADS imaging features for M-CC. Methods Consecutive at-risk patients with LR-M lesions exclusively (no co-existing LR-4 and/or LR-5 lesions) were retrieved retrospectively from a prospectively collected database spanning 3 years. Intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular-cholangiocarcinoma (c-HCC-CCA) were classified together as M-CC. LI-RADS features determined by three independent radiologists and clinically relevant serum tumor markers were used to generate M-CC diagnostic models through logistic regression analysis against histology. Per-patient performance was evaluated using area under the receiver operating curve (AUC), sensitivity, and specificity. Results Forty-five patients were included, 42.2% (19/45) with hepatocellular carcinoma, 33.3% (15/45) with ICC, 13.3% (6/45) with c-HCC-CCA, and 11.1% (5/45) with other hepatic lesions. Carbohydrate antigen (CA)19-9 > 38 U/mL, α-fetoprotein (AFP) > 4.8 ng/mL, and absence of the LI-RADS feature “blood products in mass” were significant predictors of M-CC. Combining three predictors demonstrated AUC of 0.862, sensitivity of 76%, and specificity of 88%. The risk of M-CC with all three criteria fulfilled was 98% (AUC, 0.690; sensitivity, 38%; specificity, 100%). Conclusions In at-risk patients with LR-M lesions, integrating CA19-9, AFP, and the LI-RADS feature “blood products in mass” achieved high diagnostic performance for M-CC. When all three criteria were fulfilled, the specificity for M-CC was 100%. Key Points • In at-risk patients who had LR-M lesions exclusively (no concomitant LR-4/5 lesions), a model with carbohydrate antigen > 38 U/mL, α-fetoprotein > 4.8 ng/mL, and absence of the LI-RADS feature “blood products in mass” achieved high accuracy for diagnosing cholangiocarcinoma-containing tumors. • In patients of whom all three criteria were fulfilled, the specificity for M-CC was 100%, which might reduce or eliminate the need for biopsy confirmation.

Introduction: Pain is a major driver of visits to the emergency department (ED). Clinicians must consider not only the efficacy of treatment options but also subsequent healthcare utilization and patient-centered outcomes such as side effects from prescribed medications. Our goal in this study was to determine whether there was an association between acute pain treatment regimen (opioids, intranasal non-steroidal anti-inflammatory drugs [NSAIDs], or both) and unscheduled healthcare visits following ED discharge. Methods: This study was a secondary analysis of the Acute Management of Pain from the Emergency Department (AMPED) prospective, observational cohort study. We used Cox proportional hazards analysis to assess the relationship between treatment regimen and time to first unscheduled healthcare visit. Repeated measures logistic regression analyses were used to determine the relationship between treatment regimen and any unscheduled visits, and to evaluate whether this relationship was mediated by pain severity and/or medication side effects. Results: Of 831 total enrolled participants, 141 (16.9%) experienced an unplanned healthcare visit within five days of ED discharge. A majority of these visits happened one day after the ED visit. Those who were treated with intranasal NSAIDs only were less likely to have an unscheduled healthcare visit compared to those who received opioids only, with an adjusted odds ratio (AOR) of 0.63. The higher odds of unscheduled healthcare visits with opioids were mediated by both the presence of side effects and higher pain levels, with AORs of 2.24 and 1.33, respectively. Conclusion: Opioid treatment for acute pain is associated with increased unscheduled healthcare visits compared to those treated with intranasal ketorolac. This difference can be explained by higher levels of ongoing pain and greater medication side effects.

Background Risk-versus-benefit optimization required a quantitative comparison of the two. The latter, directly related to effective diagnosis, can be associated to clinical risk. While many strategies have been developed to ascertain radiation risk, there has been a paucity of studies assessing clinical risk, thus limiting the optimization reach to achieve a minimum total risk to patients undergoing imaging examinations. In this study, we developed a mathematical framework for an imaging procedure total risk index considering both radiation and clinical risks based on specific tasks and investigated diseases. Methods The proposed model characterized total risk as the sum of radiation and clinical risks defined as functions of radiation burden, disease prevalence, false-positive rate, expected life-expectancy loss for misdiagnosis, and radiologist interpretative performance (i.e., AUC). The proposed total risk model was applied to a population of one million cases simulating a liver cancer scenario. Results For all demographics, the clinical risk outweighs radiation risk by at least 400%. The optimization application indicates that optimizing typical abdominal CT exams should involve a radiation dose increase in over 90% of the cases, with the highest risk optimization potential in Asian population (24% total risk reduction; 306% C T D I v o l increase) and lowest in Hispanic population (5% total risk reduction; 89% C T D I v o l increase). Conclusions Framing risk-to-benefit assessment as a risk-versus-risk question, calculating both clinical and radiation risk using comparable units, allows a quantitative optimization of total risks in CT. The results highlight the dominance of clinical risk at typical CT examination dose levels, and that exaggerated dose reductions can even harm patients. Plain language summary The proper practice of radiology (using imaging technology to diagnose and treat diseases) should take into consideration both the risk and benefit to a patient. Such a comparison can be hard because risk and benefit are measured in different ways. The risk includes some amount of radiation exposure to patients which can cause harm, but the benefit could be identifying a medical problem that needs attention. To overcome this obstacle, we developed a mathematical model describing the risk-to-benefit of a medical imaging study. Our modeling exercise found that the clinical benefit outweighs the radiation risk. The finding that benefit of detecting a problem is worth the risk of imaging is contrary to common belief. This study shows that so much emphasis could be put on radiation safety in imaging that avoiding imaging could negatively impact patients’ path of care. Ria et al. develop a mathematical framework for estimating total risk of an imaging procedure that accounts for both radiation and clinical risks. The authors propose a model that accounts for a variety of factors including disease prevalence, false positive rate, and expected life-expectancy loss.

Background For patients and their intimate partners, advanced cancer poses significant challenges that can negatively impact both individuals and their relationship. Prior studies have found evidence that couple-based communication skills interventions can to be beneficial for patients and partners. However, these studies have been limited by reliance on in-person treatment delivery and have not targeted couples at high risk for poor outcomes. This study tests the efficacy of a Couples Communication Skills Training (CCST) intervention delivered via videoconference for couples reporting high levels of holding back from discussing cancer-related concerns, a variable associated with poorer psychological and relationship functioning. Methods This RCT is designed to evaluate the efficacy of CCST in improving patient and partner relationship functioning (primary outcome). Secondary outcomes include patient and partner psychological functioning and patient symptoms and health care use. We also examine the role of objective and self-reported communication behaviors as mediators of treatment effects. Two hundred thirty patients with advanced lung, gastrointestinal, genitourinary, and breast cancer and their partners will be randomized to CCST or an education control intervention. Participants in both conditions complete self-reported outcome measures at baseline, mid-treatment, post-treatment, and 3 months post-treatment. Objective measures of communication are derived from video-recorded couple conversations collected at baseline and post-treatment. An implementation-related process evaluation (assessing implementation outcomes and potential barriers to/facilitators of implementation) will be conducted to inform future efforts to implement CCST in real-world settings. Discussion This trial can yield important new knowledge about effective ways to improve patient and partner adjustment to advanced cancer. Trial registration This study trial is registered at clinicaltrials.gov (Trial # NCT04590885); registration date: October 19, 2020.

Objective To determine the rate of development of clinically significant liver nodules (LR-4, LR-5, LR-M) after a negative MRI in an HCC screening population. Methods This retrospective study included patients at risk of developing HCC requiring imaging surveillance who had undergone multiphase Gadobenate dimeglumine-enhanced MRI that was negative and had follow up LI-RADS compliant multiphase CTs or MRIs for at least 12 months or positive follow-up within 12 months. Follow-up examinations were classified as negative (no nodules or only LR-1 nodules) or positive (nodule other than LR-1). Time-to-first positive examination, types of nodules, and cumulative incidence of nodule development were recorded. Results 204 patients (mean age 58.9 ± 10.2 years, 128 women), including 172 with cirrhosis, were included. Based CT/MRI follow-up (median 35 months, range 12–80 months), the overall cumulative incidence of developing a nodule was 10.5%. Cumulative incidence of nodule development was: 0.5% at 6–9 months and 2.1% at 12 ± 3 months, including one LR-4 nodule, one LR-M nodule, and two LR-3 nodules. The cumulative incidence of clinically significant nodule development was 1.1% at 9–15 months. 70% (143/204) of patients also underwent at least one US follow-up, and no patient developed a positive US examination following index negative MRI. Conclusion Clinically significant liver nodules develop in 1.1% of at-risk patients in the first year following negative MRI. While ongoing surveillance is necessary for at-risk patients, our study suggests than longer surveillance intervals after a negative MRI may be reasonable and that further research is needed to explore this possibility.

The COVID-19 pandemic led to widespread college campus closures in the months of March to June 2020, endangering students' access to on-campus health resources, including reproductive health services. To assess contraceptive access and use among undergraduate and graduate students in North Carolina during the COVID-19 pandemic. We conducted a cross-sectional web-based survey of undergraduate and graduate students enrolled at degree-granting institutions in North Carolina. Participants were recruited using targeted Instagram advertisements. The survey queried several aspects of participants' sexual behavior, including sex drive, level of sexual experience, number of sexual partners, digital sexual experience, dating patterns, and types of contraception used. Participants were asked to compare many of these behaviors before and after the pandemic. The survey also assessed several sociodemographic factors that we hypothesized would be associated with contraceptive use based on prior data, including educational background, sexual orientation and gender minority status (ie, lesbian, gay, bisexual, transgender, queer), health insurance status, race, ethnicity, degree of sensation seeking, religiosity, and desire to become pregnant. Over 10 days, 2035 Instagram users began our survey, of whom 1002 met eligibility criteria. Of these 1002 eligible participants, 934 completed the survey, for a 93% completion rate. Our respondents were mostly female (665/934, 71%), cisgender (877/934, 94%), heterosexual (592/934, 64%), white (695/934 75%), not Hispanic (835/934, 89%), and enrolled at a 4-year college (618/934, 66%). Over 95% (895/934) of respondents reported that they maintained access to their preferred contraception during the COVID-19 pandemic. In a multivariable analysis, participants who were enrolled in a 4-year college or graduate program were less likely to lose contraceptive access when compared to participants enrolled in a 2-year college (risk ratio [RR] 0.34, 95% CI 0.16-0.71); in addition, when compared to cisgender participants, nonbinary and transgender participants were more likely to lose contraceptive access (RR 2.43, 95% CI 1.01-5.87). Respondents reported that they were more interested in using telehealth to access contraception during the pandemic. The contraceptive methods most commonly used by our participants were, in order, condoms (331/934, 35.4%), oral contraception (303/934, 32.4%), and long-acting reversible contraception (LARC; 221/934, 23.7%). The rate of LARC use among our participants was higher than the national average for this age group (14%). Emergency contraception was uncommonly used (25/934, 2.7%). Undergraduate and graduate students in North Carolina overwhelmingly reported that they maintained access to their preferred contraceptive methods during the COVID-19 pandemic and through changing patterns of health care access, including telehealth. Gender nonbinary and transgender students and 2-year college students may have been at greater risk of losing access to contraception during the first year of the COVID-19 pandemic.

A rapid heuristic ratiometric analysis for estimating tissue hemoglobin concentration and oxygen saturation from measured tissue diffuse reflectance spectra is presented. The analysis was validated in tissue-mimicking phantoms and applied to clinical measurements in head and neck, cervical and breast tissues. The analysis works in two steps. First, a linear equation that translates the ratio of the diffuse reflectance at 584 nm and 545 nm to estimate the tissue hemoglobin concentration using a Monte Carlo-based lookup table was developed. This equation is independent of tissue scattering and oxygen saturation. Second, the oxygen saturation was estimated using non-linear logistic equations that translate the ratio of the diffuse reflectance spectra at 539 nm to 545 nm into the tissue oxygen saturation. Correlations coefficients of 0.89 (0.86), 0.77 (0.71) and 0.69 (0.43) were obtained for the tissue hemoglobin concentration (oxygen saturation) values extracted using the full spectral Monte Carlo and the ratiometric analysis, for clinical measurements in head and neck, breast and cervical tissues, respectively. The ratiometric analysis was more than 4000 times faster than the inverse Monte Carlo analysis for estimating tissue hemoglobin concentration and oxygen saturation in simulated phantom experiments. In addition, the discriminatory power of the two analyses was similar. These results show the potential of such empirical tools to rapidly estimate tissue hemoglobin in real-time spectral imaging applications.

With limited data quantifying opioid requirements based on substance use history, including buprenorphine/naloxone use, optimal pain management for mechanically ventilated patients remains unknown. To compare opioid requirements in mechanically ventilated adults admitted to the intensive care unit (ICU) taking buprenorphine/naloxone prior to admission compared to those who do not. This multicenter, retrospective study included adults admitted to a medical ICU and mechanically ventilated for at least 12 h. The primary endpoint was mean hourly opioid rate (fentanyl equivalents [FE], μg FE/h) from intubation until extubation or up to 72 h. Secondary endpoints included sedative requirements and time with pain and depth of sedation scores within goal. To adjust for confounders, a negative binomial model was performed. Of 176 patients, 47 took buprenorphine/naloxone, 69 were opioid-naïve, and 60 were opioid-tolerant. There was no difference in mean hourly opioid rate between buprenorphine/naloxone (40.8 ± 37.1 μg FE/h) and opioid-naïve (31.7 ± 32.5 μg FE/h; p = 0.17) and opioid-tolerant patients (51 ± 46 μg FE/h; p = 0.22). Multivariable regression demonstrated similar hourly rates in buprenorphine/naloxone and opioid-naïve patients, but opioid-tolerant patients had 50 % higher rates (estimated rate ratio 1.5, 95 % CI [1.01, 2.23]). Time spent with pain scores at goal was similar. Time spent with sedation scores at goal was similar between buprenorphine/naloxone and opioid-naïve patients, but was lower than opioid-tolerant patients. Patients taking buprenorphine/naloxone prior to admission who are mechanically ventilated for at least 12 h may have opioid requirements similar to opioid-naïve patients and lower than opioid-tolerant patients. •Opioid rates during mechanical ventilation were similar for patients taking buprenorphine/naloxone prior to admission and opioid-naïve patients.•Patients taking buprenorphine/naloxone prior to admission had significantly lower mean hourly opioid rates compared to opioid-tolerant patients.•Time spent with RASS -2 to +1 was similar between buprenorphine/naloxone and opioid-naïve patients, but was lower than opioid-tolerant patients.•Buprenorphine/naloxone resumption during mechanical ventilation was uncommon.

Despite research indicating that stressful life events are associated with subsequent suicidal ideation (SI) and behavior, there is a lack of clarity regarding whether specific types of life events are differentially related to SI and attempts. The current prospective study examines whether social rejection related life events are proximally related to SI and suicide attempts in a clinically acute sample of adolescents. Adolescents aged 12 to 18 (n = 219) were followed for 6 months after discharge from inpatient hospitalization. A contextual threat interview of stressful life events between index admission and 6-month follow-up was administered. Participants were also assessed for current SI and suicide attempts at baseline and 6-month follow-up. Results from a multiple linear regression model indicated a significant prospective association between number of social rejection stressors and SI, even after controlling for baseline depressive symptoms, SI at study entry, gender, age, and number of non-social rejections stressors. An Anderson-Gill recurrent events model was conducted to examine the relationship between SR stressors and suicide attempts. Results demonstrated that the 31 days following a major social rejection stressor were associated with heightened risk for prospective suicide attempts. However, social rejection stressors were not more strongly related to risk for suicide attempt than non-social rejection stressors. These findings help clarify the role of social rejection as a precipitant of suicidal crises and have potential to inform more accurate, targeted risk assessment.