High Use of SABAs is Associated with Higher Exacerbation Rate in Dutch Patients with Asthma.

PURPOSE: Many patients with asthma still have insufficient disease control, despite the availability of effective treatment options. A substantial proportion of patients appear to rely more on short-acting beta2-agonist (SABA) rather than on anti-inflammatory maintenance treatment. The aim of this study was to describe differences in indicators of asthma symptoms and exacerbations among patients using more or less SABA than the guideline-recommended threshold of <3 times/week. PATIENTS AND METHODS: Data from Dutch respondents in the European REcognise Asthma and LInk to Symptoms and Experience (REALISE) survey were used in this post hoc analysis. The survey included asthma patients aged 18-50 years with at least two prescriptions for their asthma in the past two years. SABA use was categorized into two groups: <3 (low-SABA users) or ≥3 (high-SABA users) times in the last week. RESULTS: Of the 736 asthma patients, 21% did not use SABA and 19% used SABA 1 to 2 times (all low SABA users) and 60% used SABA ≥3 times (high SABA users) in the last week. The majority of high and low SABA users also reported using an ICS-containing treatment. Significant differences were found for all indicators related to exacerbations (p<0.001): high SABA users more frequently used antibiotics and oral steroids, more frequently visited the emergency departments or needed an overnight hospital stay. Indicators of asthma symptoms were not significantly different between both groups. CONCLUSION: The majority of a Dutch asthmatic population reported high SABA use and had frequent moderate/severe exacerbations. More effective interventions are needed to change healthcare providers' and patients' behaviours to improve care and reduce SABA (over)use.

Prolonged release oxycodone and naloxone treatment counteracts opioid-induced constipation in patients with severe pain compared to previous analgesic treatment.

OBJECTIVE: Treatment with prolonged-release oxycodone/naloxone (PR OXN) has been shown to improve opioid induced constipation (OIC) in constipated patients. This publication reports on a real-life observational study investigating the efficacy of PR OXN with regard to bowel function in patients switching to PR OXN from WHO step 1, step 2 and step 3 opioids. METHODS: Patients with chronic pain experiencing insufficient pain relief and/or unacceptable side effects were switched to PR OXN and monitored in this observational study with respect to efficacy regarding bowel function and efficacy regarding pain relief in comparison with previous analgesic therapy. A patient was considered a responder with respect to efficacy if this assessment was "slightly better", "better" or "much better" compared with previous therapy. Bowel function index, pain intensity, quality of life, laxative medication use, and safety analgesic were also evaluated. RESULTS: A total of 1338 patients (mean [SD] age 64.3 [14.9], 63% female) were observed for 43 [3-166] days (median [range]) during treatment with PR OXN. Overall response rate regarding bowel function efficacy was 82.5%. Patients with symptoms of constipation at study entry obtained a clinically relevant improvement of the bowel function index (BFI) within the first 2 weeks of PR OXN treatment. Non-constipated patients at study entry maintained normal bowel function despite switching to treatment with the opioid PR OXN. CONCLUSION: In conclusion, treatment with PR OXN results in a significant and clinically relevant improvement of bowel function. During the observation of the treatment with PR OXN patients reported an improvement of quality of life (QoL). More interestingly, non-constipated patients maintained a normal bowel function, showing prevention of constipation despite the use of an opioid.

The efficacy of standard laxative use for the prevention and treatment of opioid induced constipation during oxycodone use: a small Dutch observational pilot study.

BACKGROUND: Dutch clinical guidelines recommend that a standard laxative treatment (SLT) should be prescribed concomitantly when starting opioid treatment to prevent opioid-induced constipation (OIC). METHODS: Clinical evidence for SLT in the treatment of OIC is lacking, therefore an observational pilot study was performed to explore the efficacy and tolerability of SLT on OIC in patients treated with the opioid oxycodone. RESULTS: Twenty-four patients (58% female, median (range) age 65 (39-92)) were included in this pilot study. The analysis showed that 9 out of 21 patients (43%) were non-responders to SLT. When also taking into consideration patients tending to develop diarrhea 75% of patients are non-responsive to SLT. CONCLUSION: This pilot study indicates that optimal laxative therapy (SLT) might not be effective and feasible for the prevention and treatment of OIC.

Treatment with prolonged-release oxycodone/naloxone improves pain relief and opioid-induced constipation compared with prolonged-release oxycodone in patients with chronic severe pain and laxative-refractory constipation.

PURPOSE: Laxative-refractory opioid-induced constipation (OIC) is defined as OIC despite using 2 laxatives with a different mechanism of action (based on the Anatomical Therapeutic Chemical Classification System level 4 term [contact laxatives, osmotically acting laxatives, softeners/emollients, enemas, and others]). OIC has a significant impact on the treatment and quality of life of patients with severe chronic pain. This noninterventional, observational, real-life study in Belgium investigated the efficacy of prolonged-release oxycodone/naloxone combination (PR OXN) treatment regarding pain relief and OIC compared with previous prolonged-release oxycodone (PR OXY) treatment for laxative-refractory OIC in daily clinical practice. METHODS: Laxative-refractory OIC patients with severe chronic pain were treated with PR OXN for 12 weeks (3 visits). Pain relief (assessed on a numerical rating scale) and OIC (assessed by using the Bowel Function Index [BFI]) were evaluated at each visit. A responder was defined as a patient who had: (1) no worsening of pain at the last visit compared with visit 1 or a numerical rating scale ≤4 at visit 3/last visit; and (2) a reduction in BFI ≥12 units at visit 3/last visit compared with visit 1; or (3) a BFI ≤28.8 at visit 3/last visit. FINDINGS: Sixty-eight laxative-refractory OIC patients with severe chronic pain (mean (sd) age 59.8 (13.3) years, 67.6% female and 91.2% non-malignant pain) were treated for 91 days with PR OXN (median daily dose, 20 mg). Treatment with PR OXN resulted in a significant and clinically relevant decrease of pain of 2.1 units (P < 0.001; 95% CI, 1.66-2.54) and of BFI by 48.5 units (P < 0.001; 95% CI, 44.4-52.7) compared with PR OXY treatment; use of laxatives was also significantly reduced (P < 0.001). Approximately 95% of patients were responders, and quality of life (as measured by using the EQ-5D) improved significantly. Adverse events were opioid related, and PR OXN treatment was well tolerated. IMPLICATIONS: Treatment with PR OXN resulted in a significant and clinically relevant reduction in OIC compared with previous PR OXY treatment for these patients with severe chronic pain and laxative-refractory OIC. Treatment with PR OXN also resulted in a significant improvement in pain relief and quality of life. ClinicalTrials.gov identifier: NCT01710917.

High acute myeloid leukemia derived VEGFA levels are associated with a specific vascular morphology in the leukemic bone marrow.

BACKGROUND: Acute Myeloid Leukemia (AML) bone marrow biopsies at diagnosis display enhanced angiogenesis and increased VEGFA expression. In a xenograft mouse model it was described that availability of free VEGFA versus bound VEGFA is related to different vascular morphology. In this study we investigate the relationship between vascular morphology within AML bone marrow biopsies and AML derived VEGFA levels. METHODS: Vessel count and surface area (Chalkley count) were calculated in AML bone marrow biopsies at diagnosis (n = 32), at remission (n = 8) and Normal Bone Marrow (n = 32) using immunohistochemical staining for FVIII, CD31, CTIV, SMA and VEGFA. VEGFA protein levels were measured. RESULTS: High vessel count was associated with an immature vessel status. Combining vessel count and Chalkley count different vessel morphology patterns were quantified within AML bone marrow biopsies. Three different subgroups could be distinguished. The subgroup (37.5% of the samples) exhibiting a high vessel count and vessels with predominantly large lumen (normal Chalkley count) was associated with high secreted VEGFA protein levels. CONCLUSION: Different vasculature patterns are seen in AML bone marrow biopsies, defined by combining number and size of vessel. These quantified morphology patterns, combined with VEGFA levels, might be of value in the success of VEGF/VEGFR-signaling interference approaches.