HER2 fluorescent in situ hybridization signal degradation: a 10-year retrospective study.

CONTEXT: Fluorescence in situ hybridization (FISH) analysis is recommended for invasive breast carcinomas with equivocal (2+) immunohistochemical expression of human epidermal growth factor receptor 2 (HER2). However, existing guidelines for the retention and storage requirements for HER2 FISH slides vary widely among countries and laboratories. OBJECTIVE: To determine the degradation rate of HER2 FISH signals, and the optimal retention time and storage conditions for HER2 FISH slides. DESIGN: Dual-probe HER2 FISH slides from March 2009 to June 2019 were retrieved from the archive to assess the presence, intensity and quantity of the green chromosome enumeration probe 17 (CEP 17) and orange HER2 signals. Per the institutional policy, FISH slides are placed in slide boxes and stored in - 80 °C freezers for up to 4 years, whereas older slides are stored at room temperature. RESULTS: After excluding HER2 FISH slides that were deemed uninterpretable due to technical issues, a total of 6255 slides were assessed. Slides from 2009 to 2014 were stored at room temperature, while slides from 2015 to 2019 were stored in - 80 °C freezers. Slides stored in freezers showed retention of both the green and the orange signals. Slide stored at room temperature demonstrated significant decrease in the signal retention rate and the loss of signal did not progress in a linear fashion. The CEP17 signal was quenched much faster than the HER2 signal. CONCLUSION: Our study is the first to demonstrate HER2 FISH signal degradation with time and slide storage conditions. Storing HER2 FISH slides in a -80 °C freezer allows for retention of both HER2 and CEP17 signals. At room temperature, the signals start to degrade with CEP17 signals lost at a faster rate. The results of the study may be used in official guidelines for storage conditions and retention time for HER2 FISH slides.

Neuroleptic strategies for terminal agitation in patients with cancer and delirium at an acute palliative care unit: a single-centre, double-blind, parallel-group, randomised trial.

BACKGROUND: The role of neuroleptics for terminal agitated delirium is controversial. We assessed the effect of three neuroleptic strategies on refractory agitation in patients with cancer with terminal delirium. METHODS: In this single-centre, double-blind, parallel-group, randomised trial, patients with advanced cancer, aged at least 18 years, admitted to the palliative and supportive care unit at the University of Texas MD Anderson Cancer Center (Houston, TX, USA), with refractory agitation, despite low-dose haloperidol, were randomly assigned to receive intravenous haloperidol dose escalation at 2 mg every 4 h, neuroleptic rotation with chlorpromazine at 25 mg every 4 h, or combined haloperidol at 1 mg and chlorpromazine at 12·5 mg every 4 h, until death or discharge. Rescue doses identical to the scheduled doses were administered at inception, and then hourly as needed. Permuted block randomisation (block size six; 1:1:1) was done, stratified by baseline Richmond Agitation Sedation Scale (RASS) scores. Research staff, clinicians, patients, and caregivers were masked to group assignment. The primary outcome was change in RASS score from time 0 to 24 h. Comparisons among group were done by modified intention-to-treat analysis. This completed study is registered with ClinicalTrials.gov, NCT03021486. FINDINGS: Between July 5, 2017, and July 1, 2019, 998 patients were screened for eligibility, with 68 being enrolled and randomly assigned to treatment; 45 received the masked study interventions (escalation n=15, rotation n=16, combination n=14). RASS score decreased significantly within 30 min and remained low at 24 h in the escalation group (n=10, mean RASS score change between 0 h and 24 h -3·6 [95% CI -5·0 to -2·2]), rotation group (n=11, -3·3 [-4·4 to -2·2]), and combination group (n=10, -3·0 [-4·6 to -1·4]), with no difference among groups (p=0·71). The most common serious toxicity was hypotension (escalation n=6 [40%], rotation n=5 [31%], combination n=3 [21%]); there were no treatment-related deaths. INTERPRETATION: Our data provide preliminary evidence that the three strategies of neuroleptics might reduce agitation in patients with terminal agitation. These findings are in the context of the single-centre design, small sample size, and lack of a placebo-only group. FUNDING: National Institute of Nursing Research.

Effect of Lorazepam With Haloperidol vs Haloperidol Alone on Agitated Delirium in Patients With Advanced Cancer Receiving Palliative Care: A Randomized Clinical Trial.

Importance: The use of benzodiazepines to control agitation in delirium in the last days of life is controversial. Objective: To compare the effect of lorazepam vs placebo as an adjuvant to haloperidol for persistent agitation in patients with delirium in the setting of advanced cancer. Design, Setting, and Participants: Single-center, double-blind, parallel-group, randomized clinical trial conducted at an acute palliative care unit at MD Anderson Cancer Center, Texas, enrolling 93 patients with advanced cancer and agitated delirium despite scheduled haloperidol from February 11, 2014, to June 30, 2016, with data collection completed in October 2016. Interventions: Lorazepam (3 mg) intravenously (n = 47) or placebo (n = 43) in addition to haloperidol (2 mg) intravenously upon the onset of an agitation episode. Main Outcomes and Measures: The primary outcome was change in Richmond Agitation-Sedation Scale (RASS) score (range, -5 [unarousable] to 4 [very agitated or combative]) from baseline to 8 hours after treatment administration. Secondary end points were rescue neuroleptic use, delirium recall, comfort (perceived by caregivers and nurses), communication capacity, delirium severity, adverse effects, discharge outcomes, and overall survival. Results: Among 90 randomized patients (mean age, 62 years; women, 42 [47%]), 58 (64%) received the study medication and 52 (90%) completed the trial. Lorazepam + haloperidol resulted in a significantly greater reduction of RASS score at 8 hours (-4.1 points) than placebo + haloperidol (-2.3 points) (mean difference, -1.9 points [95% CI, -2.8 to -0.9]; P < .001). The lorazepam + haloperidol group required less median rescue neuroleptics (2.0 mg) than the placebo + haloperidol group (4.0 mg) (median difference, -1.0 mg [95% CI, -2.0 to 0]; P = .009) and was perceived to be more comfortable by both blinded caregivers and nurses (caregivers: 84% for the lorazepam + haloperidol group vs 37% for the placebo + haloperidol group; mean difference, 47% [95% CI, 14% to 73%], P = .007; nurses: 77% for the lorazepam + haloperidol group vs 30% for the placebo + haloperidol group; mean difference, 47% [95% CI, 17% to 71%], P = .005). No significant between-group differences were found in delirium-related distress and survival. The most common adverse effect was hypokinesia (3 patients in the lorazepam + haloperidol group [19%] and 4 patients in the placebo + haloperidol group [27%]). Conclusions and Relevance: In this preliminary trial of hospitalized patients with agitated delirium in the setting of advanced cancer, the addition of lorazepam to haloperidol compared with haloperidol alone resulted in a significantly greater reduction in agitation at 8 hours. Further research is needed to assess generalizability and adverse effects. Trial Registration: clinicaltrials.gov Identifier: NCT01949662.

Purchasing condoms near a college campus: environmental barriers.

UNLABELLED: Background Given the propensity for college students to engage in sexual activity and the subsequent lack of consistent condom use, there is a need to determine environmental factors that may be motivating or deterring factors for college students to access condoms. This study aimed to determine the number of businesses available to purchase condoms from near a large, south-eastern college campus and investigate environmental differences between types of businesses. METHODS: Environmental factors (e.g. distance from campus, barriers to purchasing, selection availability and price) were collected among businesses within a 2-mile radius of the campus. Both χ(2) and ANOVA determined significant differences between types of businesses (P≤0.05). RESULTS: Forty-two businesses sold condoms, 66.7% of which were convenience-type stores. The average distance from the campus was 1.33 miles (s.d.=0.58). The average unit price of male condoms was significantly higher in drug store/pharmacies (M=1.68) compared with convenience-type stores (M=1.22) and grocery stores (M=0.97); P=0.005. Assistance was needed to purchase condoms in 25% of businesses. Barriers to purchasing condoms were significantly higher in convenience stores/gas stations (P<0.05). CONCLUSION: Environmental barriers related to purchasing condoms exist and must be considered when targeting sexual health promotion on college campuses.

Evaluation of different methods for measuring lateral tibial slope using magnetic resonance imaging.

BACKGROUND: Since lateral tibial slope (LTS) affects the amount of anterior tibial translation and anterior cruciate ligament (ACL) strain during a dynamic maneuver, accurate measurements of LTS may be beneficial in screening people at a higher risk for ACL injury. Methods for measuring LTS on magnetic resonance imaging (MRI) scans of the proximal tibia include the midpoint and circle methods. No current studies have validated different LTS measurement methods using a proximal tibia MRI scan. HYPOTHESIS: We tested the null hypotheses that (1) LTS measurements were independent of the length of tibia imaged using the midpoint method, and (2) LTS measurements calculated from different methods (midpoint, circle, and full tibia) would not differ significantly. STUDY DESIGN: Controlled laboratory study. METHODS: Blinded observers measured LTS from 3-tesla, 3-dimensional MRIs from 40 size-matched donors according to 1 circle method and 3 midpoint methods. Outcomes were then compared with the full-tibial anatomic axis (line connecting the center of 2 circles fit within the proximal and distal tibia) in 11 donors. Bonferroni-corrected paired t tests (significance, P < .005) were used to compare the 5 methods. RESULTS: The circle and full-tibia methods had the lowest interobserver and intraobserver variability, whereas the midpoint method with 10-cm tibia was the most variable. The midpoint method with 10-cm and 15-cm proximal tibia closely resembled LTS measurements with the full-tibial anatomic axis. The circle method, although repeatable, provided smaller numerical LTS measurements than the full-tibia and midpoint methods. CONCLUSION: Although LTS measurements using the midpoint method can resemble measurements made using the full tibia, the reliability of the midpoint method depends on the length of proximal tibia used. The circle method may be the preferred method for future studies since it was the most repeatable method and is independent of proximal tibial length. CLINICAL RELEVANCE: LTS measurements vary depending on the method used.