Predictors of long-term cancer-related distress among female BRCA1 and BRCA2 mutation carriers without a cancer diagnosis: an international analysis.

BACKGROUND: Women with a BRCA1 or BRCA2 mutation have high lifetime risks of developing breast and ovarian cancers. We sought to estimate the prevalence of cancer-related distress and to identify predictors of distress in an international sample of unaffected women with a BRCA mutation. METHODS: Women with a BRCA1/2 mutation and no previous cancer diagnosis were recruited from the United States, Canada, the United Kingdom, Australia and from a national advocacy group. Using an online survey, we asked about cancer risk reduction options and screening, and we measured cancer-related distress using the Impact of Event Scale. RESULTS: Among 576 respondents, mean age was 40.8 years (SD = 8.1). On average 4.9 years after a positive test result, 16.3% of women reported moderate-to-severe cancer-related distress. Women who had undergone risk-reducing breast and ovarian surgery were less likely to have (moderate or severe) cancer-related distress compared to other women (22.0% versus 11.4%, P value = 0.007). Women recruited from the advocacy group were more likely to have cancer-related distress than other women (21.6% versus 5.3%, P value = 0.002). CONCLUSIONS: Approximately 16% of women with a BRCA1 or BRCA2 mutation experience distress levels comparable to those of women after a cancer diagnosis. Distress was lower for women who had risk-reducing surgery.

International survey of androgen deprivation therapy (ADT) for non-metastatic prostate cancer in 19 countries.

BACKGROUND: Continuous androgen deprivation therapy (CADT) is commonly used for patients with non-metastatic prostate cancer as primary therapy for high-risk disease, adjuvant therapy together with radiation or for recurrence after initial local therapy. Intermittent ADT (IADT), a recently developed alternative strategy for providing ADT, is thought to potentially reduce adverse effects, but little is known about practice patterns relating to it. We aimed to describe factors related to physicians' ADT use and modality for patients with non-metastatic prostate cancer. METHODS: A 45 min online survey was completed by urologists and oncologists responsible for treatment decisions for non-metastatic prostate cancer from 19 countries with high or increasing prevalence of non-metastatic prostate cancer. RESULTS: There were 441 treating physicians who completed the survey which represented 99 177 patients with prostate cancer under their care, of which 76 386 (77%) had non-metastatic prostate cancer. Of patients with non-metastatic prostate cancer, 38% received ADT (37% gonadotropin-releasing hormone (GnRH), 2% orchiectomy); among patients on GnRH, 54% received CADT (≥6 without >3 months interruption), 23% IADT and 23% <6 months. Highest rates of ADT were reported among oncologists (62%) and in Eastern Europe (Czech Republic, Hungary and Poland). Prostate-specific antigen (PSA) levels (65%), Gleason score (52%) and treatment guidelines (48%) were the most common reasons for CADT whereas PSA levels (54%), patient request (48%), desire to maintain sexual function (40%), patient age and comorbidities (38%) were cited most frequently as reasons for IADT. CONCLUSIONS: This international survey with 441 treating physicians from 19 countries showed that ADT is commonly used in treating patients with non-metastatic prostate cancer, and type of ADT is influenced by high-risk criteria (PSA and Gleason), treatment guidelines and patient preferences. IADT use was primarily driven by PSA levels, patient request and patient age/comorbidities, likely reflecting an attempt to minimise adverse effects of ADT in patients with lower risk tumours.

High values of the pulmonary artery wedge pressure in patients with acute lung injury and acute respiratory distress syndrome.

OBJECTIVE: To determine the incidence and severity of pulmonary artery wedge pressure (PAWP) elevation in patients with ALI/ARDS. In addition, to examine the effects of clinical variables on the presence of a high PAWP (>18 mmHg) and the effect of an elevated PAWP on mortality. DESIGN AND PATIENTS: Post hoc analysis of 120 patients with or at high risk of ARDS, enrolled in a randomized controlled trial of pressure- and volume-limited ventilation. Patients with or at high risk of congestive heart failure were excluded from the original study. SETTING: Eight tertiary intensive care units. MEASUREMENTS AND RESULTS: Pulmonary artery catheters were inserted at the discretion of the attending physician, and PAWP was collected every 8 h when present. Of 120 subjects 71 (59%) had a pulmonary artery catheter (44 at randomization, 27 later). The mean maximum PAWP reading among patients was 22.5 mmHg (95% CI 21.2-23.8) and mean median was 16.6 mmHg (95% CI 15.6-17.5). Patients who met standard criteria for ARDS were more likely to develop a high PAWP. In a multivariate stepwise logistic regression model a persistently elevated PAWP (median >18 mmHg) was a strong predictor of mortality after correction for baseline differences (OR estimate 6.82; 95% CI 1.66-37.81). CONCLUSIONS: We conclude that in this group of patients a PAWP higher than 18 mmHg is common. Mandating a PAWP of 18 mmHg or less may negatively impact clinical trials in which ARDS is an inclusion/exclusion criteria or an endpoint.

Screening of ARDS patients using standardized ventilator settings: influence on enrollment in a clinical trial.

OBJECTIVES: The American-European consensus conference (AECC) definition for acute respiratory distress syndrome (ARDS) requires a PaO(2)/F(I)O(2)< or =200 mmHg, regardless of ventilator settings. We report the results of using standardized ventilator settings to screen and enroll ARDS patients in a clinical trial of high-frequency oscillatory ventilation (HFOV), including the impact on study enrollment, and potential effects on study outcome. DESIGN: Prospective cohort study. SETTING: Intensive care units in two teaching hospitals. PARTICIPANTS. A consecutive sample of 41 patients with early ARDS by AECC criteria (baseline PaO(2)/F(I)O(2)< or =200) who met all other inclusion/exclusion criteria for the HFOV trial. INTERVENTIONS: Patients were placed on standardized ventilator settings (tidal volume 7-8 ml/kg, PEEP 10 cmH(2)O, F(I)O(2) 1.0), and the PaO(2)/F(I)O(2) was reassessed after 30 min. RESULTS: Seventeen patients (41.5%) had PaO(2)/F(I)O(2) ratios that remained < or =200 mmHg [Persistent ARDS; PaO(2)/F(I)O(2)=94+/-36 (mean+/-SD)] and went on to inclusion in the HFOV study; however, in 24 patients (58.5%) the PaO(2)/F(I)O(2) was >200 mmHg [Transient ARDS; PaO(2)/F(I)O(2)=310+/-74] and these patients were ineligible for the HFOV study. The ICU mortality was significantly greater (52.9 vs 12.5%; p=0.01) in the Persistent ARDS patients. CONCLUSIONS: The use of these standardized ventilatory significantly impacted the PaO(2)/F(I)O(2) ratio and therefore the ARDS prevalence and trial enrollment. These results have effects on the evaluation of the current ARDS literature and conduct of clinical trials in ARDS and hence consideration should be given to the use of standardized ventilatory settings in future ARDS trials.

Combining high-frequency oscillatory ventilation and recruitment maneuvers in adults with early acute respiratory distress syndrome: the Treatment with Oscillation and an Open Lung Strategy (TOOLS) Trial pilot study.

OBJECTIVE: To determine the safety, feasibility, and lung-recruitment efficacy of an explicit ventilation protocol combining high-frequency oscillatory ventilation and recruitment maneuvers. DESIGN: Prospective, multiple-center, single-intervention pilot study. SETTING: Four university-affiliated intensive care units. PATIENTS: Twenty-five patients with early acute respiratory distress syndrome and severe oxygenation failure. INTERVENTIONS: Patients were transitioned from standardized conventional ventilation to high-frequency oscillatory ventilation beginning with an initial cycle of up to three sustained inflation recruitment maneuvers (40 cm H2O x 40 secs), followed by a decremental titration of Fio2 and then mean airway pressure. Recruitment maneuvers were repeated for hypoxemia and routinely at least twice daily if the Fio2 was >0.4. A specific protocol was used for weaning high-frequency oscillatory ventilation, for transitioning to conventional ventilation, and for judging intolerance of conventional ventilation whereby patients should be put back on high-frequency oscillatory ventilation. MEASUREMENTS AND MAIN RESULTS: Patients (median [interquartile range] Acute Physiology and Chronic Health Evaluation II, 24 [19-32]; age, 50 [41-64]) were enrolled after 13 (range, 6-51) hrs of conventional ventilation. Following the initial cycle of recruitment, the mean (+/-sd) Pao2/Fio2 increased significantly compared with standardized conventional ventilation (200 +/- 117 vs. 92 +/- 36 mm Hg, p < .001). After a mean of 12 hrs of high-frequency oscillatory ventilation, the mean Fio2 was significantly reduced compared with prestudy levels (0.5 +/- 0.2 vs. 0.9 +/- 0.1, p < .001). A median of seven (four to 11) recruitment maneuvers was performed per patient over the study period, with only eight of 244 (3.3%) being aborted. Six of 19 patients transitioned to conventional ventilation (32%) were deemed intolerant and were switched back to high-frequency oscillatory ventilation. Protocol adherence was excellent with documented rates >90%. CONCLUSIONS: The combination of high-frequency oscillatory ventilation and recruitment maneuvers resulted in rapid and sustained improvement in oxygenation, likely through lung recruitment. This explicit high-frequency oscillatory ventilation protocol appears well tolerated, feasible, and physiologically sound.

Acute oxygenation response to inhaled nitric oxide when combined with high-frequency oscillatory ventilation in adults with acute respiratory distress syndrome.

OBJECTIVE: To prospectively evaluate the oxygenation effect of inhaled nitric oxide (INO) delivered during high-frequency oscillatory ventilation in adult patients with the acute respiratory distress syndrome and oxygenation failure. DESIGN Prospective, clinical study. SETTING: Intensive care unit of a university teaching hospital. PATIENTS: A total of 23 adults (14 women, 9 men, 44.9 +/- 17.5 yrs, Acute Physiology and Chronic Health Evaluation II score of 28.6 +/- 7.1) with acute respiratory distress syndrome (lung injury score, 3.5 +/- 0.4) with Fio2 of > or = 0.6 and mean airway pressure of >or=28 cm H2O. INTERVENTIONS: INO was initiated at a dose of 5 ppm, and subsequently titrated according to a protocol, to determine the dose (5, 10, or 20 ppm) resulting in the greatest increase in Pao2/Fio2. Blood gas measurements were obtained 10-15 mins after initiation or any increase in INO dosage to assess the effect on Pao2/Fio2. MEASUREMENTS AND MAIN RESULTS: Arterial blood gases and ventilator settings were recorded at four time points: during conventional ventilation just before initiating high-frequency oscillatory ventilation, during high-frequency oscillatory ventilation just before initiating INO, after 30 mins on the optimal dose of INO, and 8-12 hrs after starting INO. Oxygenation index ([Fio2 x mean airway pressure x 100]/Pao2) and Pao2/Fio2 ratios were calculated at the same time intervals. At 30 mins after INO initiation, 83% of patients had a significant increase in blood oxygen tension, defined as > or = 20% increase in Pao2/Fio2. The mean change in Pao2/Fio2 at 30 mins was 38%. In these 19 patients, Pao2/Fio2 was highest at 20 ppm in four patients, at 10 ppm in eight patients, and at 5 ppm in seven patients. Compared with baseline measurements, Pao2/Fio2 improved significantly at both 30 mins (112 +/- 59 vs. 75 +/- 32, p=.01) and 8-12 hrs after INO initiation (146 +/- 52 vs. 75 +/- 32, p<.0001). In addition, oxygenation index was reduced at 8-12 hrs compared with baseline measurements (26 +/- 13 vs. 40 +/- 17, p=.08). CONCLUSIONS: INO delivered at doses of 5 to 20 ppm during high-frequency oscillatory ventilation increases Pao2/Fio2 and may be a safe and effective rescue therapy for patients with severe oxygenation failure.