Active surveillance testing to reduce transmission of carbapenem-resistant, gram-negative bacteria in intensive care units: a pragmatic, randomized cross-over trial.

BACKGROUND: In intensive care unit (ICU) settings, the transmission risk of carbapenem-resistant, gram-negative bacteria (CRGNB) is high. There is a paucity of data regarding the effectiveness of interventions, including active screening, preemptive isolation, and contact precautions, to reduce transmission of CRGNB. METHODS: We conducted a pragmatic, cluster-randomized, non-blinded cross-over study in 6 adult ICUs in a tertiary care center in Seoul, South Korea. ICUs were randomly assigned to perform active surveillance testing with preemptive isolation and contact precautions (intervention) or standard precautions (control) during the initial 6-month study period, followed by a 1-month washout period. During a subsequent 6-month period, departments that used standard precautions switched to using interventional precautions and vice versa. The incidence rates of CRGNB were compared between the two periods using Poisson regression analysis. RESULTS: During the study period, there were 2268 and 2224 ICU admissions during the intervention and control periods, respectively. Because a carbapenemase-producing Enterobacterales outbreak occurred in a surgical ICU (SICU), we excluded admissions to the SICU during both the intervention and control periods and performed a modified intention-to-treat (mITT) analysis. In mITT analysis, a total of 1314 patients were included. The acquisition rate of CRGNB was 1.75 cases per 1000 person-days during the intervention period versus 3.33 cases per 1000 person-days during the control period (IRR, 0.53 [95% confidence interval (CI) 0.23-1.11]; P = 0.07). CONCLUSIONS: Although this study was underpowered and showed borderline significance, active surveillance testing and preemptive isolation could be considered in settings with high baseline prevalence of CRGNB. Trial registration Clinicaltrials.gov Identifier: NCT03980197.

Inferior Vena Cava Filter Retrieval Rates Associated With Passive and Active Surveillance Strategies Adopted by Implanting Physicians.

Importance: Inferior vena cava filters are commonly implanted and infrequently retrieved. Nonretrieval contributes to significant morbidity, motivating US Food and Drug Administration and multisociety communications emphasizing the need for improved device surveillance. Current guidelines suggest that implanting physicians and referring physicians should be responsible for device follow-up, but it is not known whether shared responsibility contributes to lower retrieval. Objective: To determine if primary responsibility for follow-up care assumed by the implanting physician team is associated with increased device retrieval. Design, Setting, and Participants: This retrospective cohort study examined a prospectively collected registry of patients with inferior vena cava filters implanted from June 2011 to September 2019. Medical record review and data analysis was completed in 2021. The study included 699 patients who underwent implantation of retrievable inferior vena cava filters at an academic quaternary care center. Exposures: Prior to 2016, implanting physicians had a passive surveillance strategy whereby letters highlighting indications for and the need for timely retrieval were mailed to patients and ordering clinicians. Starting in 2016, implanting physicians assumed active responsibility for surveillance, whereby candidacy for device retrieval was assessed periodically via phone calls and retrieval scheduled when appropriate. Main Outcomes and Measures: The main outcome was the odds of inferior vena cava filter nonretrieval. Within regression modeling of the association between the surveillance method and nonretrieval, additional covariates of patient demographics, concomitant malignant neoplasm, and presence of thromboembolic disease were included. Results: Of the 699 patients who received retrievable filter implants, 386 (55.2%) were followed up with passive surveillance, 313 (44.8%) with active surveillance, 346 (49.5%) were female, 100 (14.3%) were Black individuals, and 502 (71.8%) were White individuals. The mean (SD) age at filter implantation was 57.1 (16.0) years. Mean (SD) yearly filter retrieval increased following the adoption of active surveillance, from 190 of 386 (48.7%) to 192 of 313 (61.3%) (P < .001). Fewer filters were deemed permanent in the active group vs passive group (5 of 313 [1.6%] vs 47 of 386 [12.2%]; P < .001). Age at the time of implantation (OR, 1.02; 95% CI, 1.01-1.03), concomitant malignant neoplasm (OR, 2.18; 95% CI, 1.47-3.24), and passive contact method (OR, 1.70; 95% CI, 1.18-2.47) were associated with increased odds of filter nonretrieval. Conclusions and Relevance: The findings of this cohort study suggest that active surveillance by implanting physicians is associated with improved inferior vena cava filter retrieval. These findings support encouraging physicians who implant the filter to take primary responsibility for tracking and retrieval.

Active surveillance of atypical cartilaginous tumours of bone: short term quality of life measurements.

BACKGROUND: In the recent years active surveillance has been introduced for atypical cartilaginous tumours (ACT). This is the first study on the impact of this new treatment approach on patients' quality-of-life. We evaluated general health-related quality of life (HRQL) in patients diagnosed with enchondroma or ACT. METHODS: In this prospective study, patients recently diagnosed with enchondroma and ACT of the long bones were asked to participate. Health-related quality of life (HRQL) was assessed at diagnosis and at six month follow-up, using the 36-item Short Form Health Survey (SF-36) and Numeric Pain Rating Scale (NRS). HRQL of the active surveillance group was compared to the Dutch population and a Dutch sample with locoregional cancer. RESULTS: In total, 45 patients were included in the study, of which four patients underwent curettage and cryosurgery, 41 patients were under active surveillance. The HRQL of the active surveillance group seemed lower compared to the Dutch population, but similar to patients suffering locoregional cancers. No comparison between the surgery and the active surveillance group could be made. In the active surveillance group no statistical difference was found between baseline and six months follow-up regarding HRQL and pain during rest and activities. CONCLUSION: Patients diagnosed with non-malignant chondroid tumours have lower HRQL compared to the healthy population. Active surveillance had no adverse effect on patients well-being, after six months active surveillance the HRQL remained unchanged. Interestingly, in our study no impact on mental health was seen, implicating that diagnosed but untreated chondroid tumours do not seem to influence patients anxiety.

Time Trends and Variation in the Use of Active Surveillance for Management of Low-risk Prostate Cancer in the US.

Importance: Active surveillance (AS) is endorsed by clinical guidelines as the preferred management strategy for low-risk prostate cancer, but its use in contemporary clinical practice remains incompletely defined. Objective: To characterize trends over time and practice- and practitioner-level variation in the use of AS in a large, national disease registry. Design, Setting, and Participants: This retrospective analysis of a prospective cohort study included men with low-risk prostate cancer, defined as prostate-specific antigen (PSA) less than 10 ng/mL, Gleason grade group 1, and clinical stage T1c or T2a, newly diagnosed between January 1, 2014, and June 1, 2021. Patients were identified in the American Urological Association (AUA) Quality (AQUA) Registry, a large quality reporting registry including data from 1945 urology practitioners at 349 practices across 48 US states and territories, comprising more than 8.5 million unique patients. Data are collected automatically from electronic health record systems at participating practices. Exposures: Exposures of interest included patient age, race, and PSA level, as well as urology practice and individual urology practitioners. Main Outcomes and Measures: The outcome of interest was the use of AS as primary treatment. Treatment was determined through analysis of electronic health record structured and unstructured clinical data and determination of surveillance based on follow-up testing with at least 1 PSA level remaining greater than 1.0 ng/mL. Results: A total of 20 809 patients in AQUA were diagnosed with low-risk prostate cancer and had known primary treatment. The median age was 65 (IQR, 59-70) years; 31 (0.1%) were American Indian or Alaska Native; 148 (0.7%) were Asian or Pacific Islander; 1855 (8.9%) were Black; 8351 (40.1%) were White; 169 (0.8%) were of other race or ethnicity; and 10 255 (49.3%) were missing information on race or ethnicity. Rates of AS increased sharply and consistently from 26.5% in 2014 to 59.6% in 2021. However, use of AS varied from 4.0% to 78.0% at the urology practice level and from 0% to 100% at the practitioner level. On multivariable analysis, year of diagnosis was the variable most strongly associated with AS; age, race, and PSA value at diagnosis were all also associated with odds of surveillance. Conclusions and Relevance: This cohort study of AS rates in the AQUA Registry found that national, community-based rates of AS have increased but remain suboptimal, and wide variation persists across practices and practitioners. Continued progress on this critical quality indicator is essential to minimize overtreatment of low-risk prostate cancer and by extension to improve the benefit-to-harm ratio of national prostate cancer early detection efforts.

[Progress in active surveillance for adult low-risk papillary thyroid microcarcinoma].

The incidence of papillary thyroid microcarcinoma （PTMC） increases rapidly. However, epidemiological and autopsy studies show that the prevalence of low-risk papillary thyroid microcarcinoma （LR-PTMC） is very high, but the mortality is very low. There is over-diagnosis and over-treatment for LR-PTMC. Active surveillance （AS） was adopted for LR-PTMCs instead of immediate surgery, and more than 70% of the lesions remained stable or shrank in clinical observation. Therefore, AS is recommended for LR-PTMCs in clinical guidelines of several academic organizations around the world. However, PTMC is not equal to low-risk cancer. The implementation of AS strategy requires a strict grasp of indications and full consideration of population characteristics to ensure the maximum benefit of patients. This paper summarizes the present clinical progress of active surveillance for adult LR-PTMC.

Expectant management of advanced abdominal pregnancies: Is it justifiable?

OBJECTIVE: To evaluate the outcome of a case series of women with advanced abdominal pregnancies (AAP) who underwent expectant management. STUDY DESIGN: A retrospective study that utilized prospective data of 46 women who were admitted for expectant management at a tertiary hospital in Durban, South Africa. All data was analyzed descriptively and presented in percentages. RESULTS: The average period of expectant management was 27 days; thirty-three (72 %) of the 46 women were discharged from the hospital with live babies. There were 11 (24 %) neonatal deaths and two cases of stillbirths. There were no maternal deaths and morbidity was minimal. CONCLUSION: When diagnosed after the 24th week of gestation, an option is expectant management which includes careful patient selection, prolonged hospitalization, and close antenatal fetal and maternal surveillance to achieve fetal viability. Management by experienced clinicians and a multidisciplinary team in a tertiary institution is recommended. Informed consent needs to take into consideration the risks with interventional laparotomy, social separation from family and friends, and the guarded perinatal outcome.

Pathological Effects of Apalutamide in Lower-risk Prostate Cancer: Results From a Phase II Clinical Trial.

PURPOSE: Active surveillance is a safe and effective strategy for men with lower-risk prostate cancer who want to avoid local therapy; however, many patients on active surveillance progress to active treatment (eg, prostatectomy or radiation). We hypothesized that apalutamide would decrease active surveillance attrition rates through downstaging low-grade tumors. MATERIALS AND METHODS: This was an open-label, single-arm, phase II study testing 90 days of oral apalutamide 240 mg daily in men with low- to intermediate-risk prostate cancer on active surveillance. The primary objective was to determine the percentage of patients with a negative biopsy immediately following treatment. Secondary objectives were to assess long-term clinical outcomes, quality of life, safety, and biomarkers of response/resistance. RESULTS: Twenty-three patients enrolled and 22 completed 90 days of apalutamide with post-treatment biopsy. Fifteen (65%) had Grade Group 1 disease, and all others had Grade Group 2 disease. Seven (30%) had favorable- to intermediate-risk disease. Of 22 evaluable patients, 13 (59%) had no residual cancer on post-treatment biopsy. The median time to first positive biopsy was 364 days (95% CI: 91-742 days). The impact of apalutamide on quality of life was minimal and transient. Decipher risk classifier revealed a greater number of negative post-treatment biopsies in those with higher baseline genomic risk score (P = .01). CONCLUSIONS: The negative repeat biopsy rate following 90 days of apalutamide was high in men with prostate cancer followed on active surveillance. Apalutamide was safe, well tolerated, and had minimal impact on quality of life. Randomized studies evaluating the effects of apalutamide in men enrolled on active surveillance are warranted.

Active Surveillance of Differentiated Thyroid Cancer Metastatic Cervical Lymph Nodes: A Retrospective Single-Center Cohort Study.

Background: The most frequent site of recurrence of differentiated thyroid cancer (DTC) is cervical lymph nodes (LNs), which often necessitates repeated surgical interventions and morbidity in a generally indolent disease. Data on active surveillance (AS) of small cervical nodal metastasis are still scarce, particularly in real-world clinical settings. In this study, we evaluated the DTC outcomes of AS of metastatic cervical LNs and explored factors associated with disease progression. Methods: We conducted a retrospective cohort study, including DTC patients with biopsy-proven metastatic cervical LNs, who were followed on AS in a tertiary care, university-based institution in Brazil. The inclusion criteria were cervical metastasis ≤2.0 cm and an AS duration of at least 6 months. We excluded lesions with aggressive histology, those in close proximity to or invading local structures. The primary outcome was disease progression (enlargement ≥3 mm in any diameter or a new cervical metastasis). Results: Data from 40 patients were analyzed. Most were female (77.5%) and had papillary thyroid cancer (97.5%). The mean age was 47.0 (± standard deviation 15.8) years. The 8th edition of the tumor, node, metastasis stage (TNM8) staging for DTC was as follows: 29 in stage I (74.4%), 8 in stage II (20.5%), and 2 in stage IV (5.0%). The median maximum LN diameter was 0.9 (interquartile range [IQR], 0.8-1.3) cm, and the median AS follow-up duration was 27.5 (IQR, 16.5-47.3) months. Disease progression occurred in 14 (35%) patients: 7 (17.5%) due to enlargement ≥3 mm, and 7 (17.5%) had new cervical metastasis. The cervical progression-free survival was 51.0 (confidence interval, 47.0-55.0) months. No demographic, oncological, or biochemical factors were associated with disease progression. Of the 14 patients with disease progression, 8 were referred for surgery. No permanent surgical complications were reported. Of the six patients who remained on AS despite disease progression, five showed no further progression during subsequent follow-up (range 6-40 months). Conclusions: We observed that most small metastatic cervical LNs remained stable and were safely managed with AS. Nevertheless, these observations are limited by the retrospective design, small sample size, and short follow-up. Further prospective and long-term studies are warranted.

Low-volume grade group 2 prostate cancer candidates for active surveillance: a radical prostatectomy retrospective analysis.

OBJECTIVE: Guidelines support considering selected men with ISUP grade group (GG) 2 prostate cancer for active surveillance (AS). We assessed the association of clinical variables with unfavorable pathology at radical prostatectomy in low-volume GG 2 prostate cancer on biopsy in a retrospective cohort. MATERIALS AND METHODS: This was a retrospective analysis of 378 men with low-volume (≤ 2 cores) GG 2 localized prostate cancer who underwent prostatectomy at a single tertiary cancer center. Multivariable logistic regression of unfavorable pathology, upgrading to ≥ T3, or GG ≥ 3 was performed in relation to clinical factors, common variables used in AS in GG 1 and percentage Gleason 4 at biopsy. We compared the performance of potential variables with commonly used combined AS restrictions in GG 1 prostate cancer. RESULTS: In total, 128/378 (34%) men had unfavorable pathology at radical prostatectomy. On multivariable analysis, > 5% Gleason pattern 4 was independently associated with an increased risk of GG ≥ 3. A maximum percentage core involvement > 50% was independently associated with an increased risk of pT-stage ≥ 3 and unfavorable pathology. Restriction to patients with ≤ 5% Gleason 4 decreased the upgrading of both unfavorable pathology (OR = 0.62, p = 0.041) and GG ≥ 3 (OR = 0.17, p = 0.0007) compared to the full cohort, while restriction to those with ≤ 50% of max core involvement did not. CONCLUSION: In low-volume GG 2, the percentage of Gleason 4 of ≤ 5% was the strongest predictor in reducing upgrading at final pathology. This easily available pathological descriptor could be used to guide urologists and patients when considering AS in this setting.

Validating the total cancer location density metric for stratifying patients with low-risk localized prostate cancer at higher risk of grade group reclassification while on active surveillance.

PURPOSE: To validate a previously proposed prognostic metric, Total Cancer Location (TCLo) density, in a contemporary cohort of men with grade group (GG) 1 prostate cancer (PCa) on active surveillance (AS). METHODS: We evaluated 123 patients who entered AS with maximum GG1 PCa at diagnostic and/or confirmatory biopsy. TCLo was defined as the total number of PCa locations identified on both biopsy sessions. TCLo density was calculated as TCLo / prostate volume [ml]. Primary endpoint was progression-free survival (PFS), defined as time from confirmatory biopsy to grade group reclassification (GGR) on repeat biopsy or prostatectomy. Optimal cut-point for TCLo density was predefined in a previously reported cohort and applied to this contemporary cohort. Kaplan-Meier and multivariable Cox regression analysis were used to estimate the association of predictors with PFS. RESULTS: During median follow-up of 7.8 years, (IQR 7.3-8.2) 34 men had GGR. Using previously defined cut-points, PFS at 5-years was 60% (95% CI: 44%-81%) vs. 89% (95% CI: 83%-96%) in men with high (≥0.06 ml-1) vs. low (<0.06 ml-1) TCLo density, and 63% (95% CI: 48%-82%) vs. 90% (95% CI: 83%-96%) in men with high (≥3) vs. low (≤2) TCLo (log-rank test: P < 0.0001, respectively). Adjusting for age, prostate volume, percent of positive cores and PSA, both higher TCLo density (HR [per 0.01 ml-1 increase]: 1.18, 95% CI: 1.05-1.33, P = 0.005) and TCLo (HR: 1.69, 95% CI: 1.20-2.38, P = 0.002) were associated with shorter PFS. CONCLUSION: The previously suggested prognostic value of TCLo density was confirmed in this validation cohort. TCLo alone performed similarly well. Patients with high TCLo density (≥0.06 ml-1) or TCLo (>2) were at greater risk of GGR while on AS. With external validation, these metric may help guide risk-adapted surveillance protocols.

No difference in renal function outcomes for patients with oncocytoma managed with active surveillance vs. partial nephrectomy.

OBJECTIVES: To investigate the difference in renal function outcomes for patients with oncocytomas undergoing active surveillance (AS) vs. partial nephrectomy (PN). METHODS: We reviewed our institutional database for patients with biopsy/surgically confirmed oncocytoma from 2000-2020. The primary outcome was to assess for differences in renal function outcomes in patients undergoing AS vs. PN. We fit two generalized estimating equation (GEE) with an interaction term between follow up time and management strategy to predict 1) mean eGFR for patients managed with AS and PN and 2) the probability of progression to CKD stage III or greater. RESULTS: We identified 114 eligible patients, of which 32 were managed with AS. Median follow-up was 21 months vs. 44 months for PN vs. AS patients. AS patients tended to be older (median: 72 years vs. 65 years, P<0.001) and have lower baseline renal function (median: eGFR: 71 mL/min/1.73m2 vs. 82 mL/min/1.73m2, P<0.001) compared with PN patients. Renal mass size from baseline imaging was similar between patients undergoing PN vs. AS (2.8 cm vs. 2.9 cm, P=0.634). For patients undergoing PN vs. AS, there was not a significant difference in predicted longitudinal eGFR (-0.079, 95% CI -0.18-0.023, P=0.129) or predicted probability of progression to CKD stage III or greater (OR: 0.61, 95% CI: 0.16-2.33, P=0.47). CONCLUSIONS: In our institutional dataset, patients undergoing AS or PN with an oncocytoma had similar long-term renal function outcomes. Given similar renal function outcomes in patients undergoing AS and PN, surgery should remain reserved for select patients with oncocytomas.

Expectant Management or Early Ibuprofen for Patent Ductus Arteriosus.

BACKGROUND: Cyclooxygenase inhibitors are commonly used in infants with patent ductus arteriosus (PDA), but the benefit of these drugs is uncertain. METHODS: In this multicenter, noninferiority trial, we randomly assigned infants with echocardiographically confirmed PDA (diameter, >1.5 mm, with left-to-right shunting) who were extremely preterm (<28 weeks' gestational age) to receive either expectant management or early ibuprofen treatment. The composite primary outcome included necrotizing enterocolitis (Bell's stage IIa or higher), moderate to severe bronchopulmonary dysplasia, or death at 36 weeks' postmenstrual age. The noninferiority of expectant management as compared with early ibuprofen treatment was defined as an absolute risk difference with an upper boundary of the one-sided 95% confidence interval of less than 10 percentage points. RESULTS: A total of 273 infants underwent randomization. The median gestational age was 26 weeks, and the median birth weight was 845 g. A primary-outcome event occurred in 63 of 136 infants (46.3%) in the expectant-management group and in 87 of 137 (63.5%) in the early-ibuprofen group (absolute risk difference, -17.2 percentage points; upper boundary of the one-sided 95% confidence interval [CI], -7.4; P<0.001 for noninferiority). Necrotizing enterocolitis occurred in 24 of 136 infants (17.6%) in the expectant-management group and in 21 of 137 (15.3%) in the early-ibuprofen group (absolute risk difference, 2.3 percentage points; two-sided 95% CI, -6.5 to 11.1); bronchopulmonary dysplasia occurred in 39 of 117 infants (33.3%) and in 57 of 112 (50.9%), respectively (absolute risk difference, -17.6 percentage points; two-sided 95% CI, -30.2 to -5.0). Death occurred in 19 of 136 infants (14.0%) and in 25 of 137 (18.2%), respectively (absolute risk difference, -4.3 percentage points; two-sided 95% CI, -13.0 to 4.4). Rates of other adverse outcomes were similar in the two groups. CONCLUSIONS: Expectant management for PDA in extremely premature infants was noninferior to early ibuprofen treatment with respect to necrotizing enterocolitis, bronchopulmonary dysplasia, or death at 36 weeks' postmenstrual age. (Funded by the Netherlands Organization for Health Research and Development and the Belgian Health Care Knowledge Center; BeNeDuctus ClinicalTrials.gov number, NCT02884219; EudraCT number, 2017-001376-28.).

Mindfulness-based stress reduction for men on active surveillance for prostate cancer and their spouses: Design and methodology of a randomized controlled trial.

BACKGROUND: Although active surveillance (AS) is an increasingly adopted treatment paradigm for management of very low risk prostate cancer, many men and their partners face a variety of AS-related psychosocial stressors. Stressors may include anxiety and fear of progression, which may negatively affect short- and long-term psychosocial adjustment and influence early withdrawal from AS in order to seek definitive therapies such as surgery or radiation. Here we describe the protocol for an NCI-funded trial, which seeks to examine the efficacy of mindfulness training compared with a time/attention-matched health promotion control condition in a geographically generalizable sample of men on AS and their spouses. METHODS: Using a randomized, controlled, partially double-blinded study design, this study involves the delivery of 8 weeks of standardized mindfulness training (MBSR; mindfulness-based stress reduction) and patient reported outcomes over a 12-month period (proposed enrollment of 80 men on AS and spouses), compared with a health promotion control (proposed enrollment of 80 men on AS and spouses) that has been matched for time and attention. Baseline (T1) measures (e.g., anxiety, fear of progression, quality of life) are administered just prior to randomization to the two study arms, followed by repeated assessments at 2 months (T2), 6 months (T3) and 12 months (T4). CONCLUSION: This study has the potential to offer men and their partners on AS with important educational and self-regulatory skills to better cope and adjust with known stressors related to being placed on this protocol.