Evolving to a single inhaler extrafine LABA/LAMA/ICS - Inhalation technique and adherence at the heart of COPD patient care (TRIVOLVE).

OBJECTIVE: Incorrect inhaler use and poor treatment adherence have a negative impact on COPD outcomes. This multi-centre, single arm, non-interventional, phase IV study investigated whether inhalation technique, treatment adherence and patient outcomes change in patients who evolve from dual therapy or multiple inhaler triple therapy to single inhaler extrafine triple therapy (beclomethasone dipropionate (BDP, 87 µg), formoterol fumarate (FF, 5 µg) and glycopyrronium (G, 9 µg)) in combination with inhalation technique training. METHODS: A total of 126 COPD patients were included in the per protocol set. Inhalation technique and treatment adherence were assessed at baseline and at two visits at approximately 3 and 6 months of treatment with extrafine BDP/FF/G. In addition, lung function, symptom score, patient satisfaction and exacerbations (exploratory) were followed up. RESULTS: Before switching to single inhaler extrafine BDP/FF/G (baseline), any device errors and critical errors were detected for 28.8% and 9.6% of patients, respectively. After switching to BDP/FF/G, the percentage of patients with any device errors decreased to 14.0% (visit 2) and 16.3% (visit 3), without critical errors at the two follow-up visits. Treatment adherence increased from 67.5% at baseline to 75.8% (visit 2) and 80% (visit 3). In addition, lung function, symptom and patient satisfaction scores improved, whilst exacerbation rates substantially decreased. CONCLUSIONS: This observational study demonstrates that in eligible COPD patients in a real-life setting, the switch from dual therapy or multiple inhaler triple therapy to single inhaler extrafine BDP/FF/G in combination with inhalation technique training is associated with improved inhalation technique and adherence.

Are future medical oncologists sufficiently trained to communicate about palliative care? The medical oncology curriculum in Flanders, Belgium.

BACKGROUND: Palliative care is considered an integral part of oncology and communicating this with patients is an unavoidable task for oncologists. This contribution investigated to what extent communication skills for communicating palliative care with patients are trained in the formal academic training program in medical oncology in Flanders, Belgium. The programme is based on the recommendations for a Global Core Curriculum in Medical Oncology, developed by The American Society of Clinical Oncology (ASCO) together with the European Society for Medical Oncology (ESMO). METHODS: For this qualitative study, data were collected using document analysis from the ESMO/ASCO recommendations and the documents of the Flanders' medical oncology programme complemented with interviews with Flemish medical oncology trainees. RESULTS: Few recommendations for training communication skills to communicate about palliative care were found in the ASMO/ASCO recommendations and even less in the Flanders' programme documents. Trainees are mainly exposed to palliative care communication during the clinical practice of their training. Only very few lectures or seminars are devoted to palliative care and even less on communication about palliative care. They reported several barriers to communicate about palliative care. CONCLUSIONS: This study revealed promising developments for the training of Flemish medical oncologists to discuss palliative care. However, there is still a need for more theoretical training on palliative care complemented with communication skills trainings. Communication training in general needs to be fully integrated as a core skill within the medical curriculum at large and should be promoted as lifelong learning and competency development.

Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma.

The combination of melphalan, prednisone, and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma who are ineligible for stem cell transplantation. Long-term treatment with thalidomide is hampered by neurotoxicity. Melphalan, prednisone, and lenalidomide, followed by lenalidomide maintenance therapy, showed promising results without severe neuropathy emerging. We randomly assigned 668 patients between nine 4-week cycles of MPT followed by thalidomide maintenance until disease progression or unacceptable toxicity (MPT-T) and the same MP regimen with thalidomide being replaced by lenalidomide (MPR-R). This multicenter, open-label, randomized phase 3 trial was undertaken by Dutch-Belgium Cooperative Trial Group for Hematology Oncology and the Nordic Myeloma Study Group (the HOVON87/NMSG18 trial). The primary end point was progression-free survival (PFS). A total of 318 patients were randomly assigned to receive MPT-T, and 319 received MPR-R. After a median follow-up of 36 months, PFS with MPT-T was 20 months (95% confidence interval [CI], 18-23 months) vs 23 months (95% CI, 19-27 months) with MPR-R (hazard ratio, 0.87; 95% CI, 0.72-1.04; P = .12). Response rates were similar, with at least a very good partial response of 47% and 45%, respectively. Hematologic toxicity was more pronounced with MPR-R, especially grades 3 and 4 neutropenia: 64% vs 27%. Neuropathy of at least grade 3 was significantly higher in the MPT-T arm: 16% vs 2% in MPR-R, resulting in a significant shorter duration of maintenance therapy (5 vs 17 months in MPR-R), irrespective of age. MPR-R has no advantage over MPT-T concerning efficacy. The toxicity profile differed with clinically significant neuropathy during thalidomide maintenance vs myelosuppression with MPR.

Hoarseness revealing Ortner's syndrome.

Hoarseness is a common phenomenon that can be caused by uncommon pathology. One seldom cause is Ortner's syndrome, a rare cardiovocal disease that can lead to hoarseness due to left recurrent laryngeal nerve palsy induced by mechanical compression of the nerve by cardiovascular structures. This case report describes a case of a 41-year-old woman with sudden onset of hoarseness. The patient had known pulmonary hypertension and Eisenmenger's syndrome.

Serum antibody response to influenza virus vaccination during chemotherapy treatment in adult patients with solid tumours.

BACKGROUND: Higher rates of hospitalization and mortality are described in oncology patients with influenza virus infection compared to the general population. Yearly influenza vaccination is recommended for patients treated with chemotherapy. The optimal moment to administer the vaccine during a treatment cycle has not been studied extensively. PATIENTS AND METHODS: During the influenza season 2011-2012 we conducted a multicenter randomized controlled trial (OFLUVAC, NTR2858, no sponsoring) in the Netherlands. Patients receiving adjuvant chemotherapy for breast or colorectal cancer were randomized between early (day 5 after chemotherapy) and late (day 16 after chemotherapy) vaccination with the influenza virus vaccine (Influvac(®) 2011/2012-Vaxigrip(®) 2011/2012). Influenza virus-specific antibody titres were determined before, 3 and 12 weeks after vaccination by haemagglutination inhibition. RESULTS: Thirty-eight breast cancer patients (early=21; late=17) and 18 colorectal cancer patients (early=8; late=10) were analyzed. In breast cancer patients overall serologic responses were adequate. A statistically significant higher response in patients who received early compared to late vaccination in the chemotherapy cycle was observed. Geometric mean titres post vaccination on day 5 versus day 16 were 69.3 versus 27.4 (H3N2), 76.4 versus 17.5 (H1N1) and 34.4 versus 26.0 (B/Brisbane), respectively. In colorectal cancer patients overall serologic responses were adequate, no significant difference was found between early and late vaccination. Geometric mean titres post vaccination on day 5 versus day 16 were 170.1 versus 192.4 (H3N2), 233.0 versus 280.8 (H1N1) and 62.6 versus 75.9 (B/Brisbane), respectively. CONCLUSION: Overall antibody response to the influenza virus vaccine in patients treated with chemotherapy for breast or colorectal cancer patients is adequate. Breast cancer patients seem to mount the best antibody response when vaccinated early after a chemotherapy cycle (≤day 5). No difference was found between early and late vaccination in colorectal cancer patients.

[Thrombocytopenia during pregnancy]. / Trombocytopenie tijdens de zwangerschap.

Thrombocytopenia during pregnancy can be caused by a broad variety of disorders. An early diagnosis is essential for timely and adequate therapy. In cases of severe thrombocytopenia, a multidisciplinary approach by a team of obstetricians, haematologists and anaesthesiologists is needed. We describe a 30-year-old patient at a gestational age of 35 weeks who presented with preterm rupture of membranes. Coincidentally, she also had severe thrombocytopenia that proved to be due to immune thrombocytopenia (ITP). The severe thrombocytopenia persisted despite standard first-line treatment with corticosteroids and intravenous immunoglobulins. Based on this case report we discuss the differential diagnosis of thrombocytopenia during pregnancy with a focus on the management of ITP in pregnant women.

Lessons learned from microsatellite development for nonmodel organisms using 454 pyrosequencing.

Microsatellites, also known as simple sequence repeats (SSRs), are among the most commonly used marker types in evolutionary and ecological studies. Next Generation Sequencing techniques such as 454 pyrosequencing allow the rapid development of microsatellite markers in nonmodel organisms. 454 pyrosequencing is a straightforward approach to develop a high number of microsatellite markers. Therefore, developing microsatellites using 454 pyrosequencing has become the method of choice for marker development. Here, we describe a user friendly way of microsatellite development from 454 pyrosequencing data and analyse data sets of 17 nonmodel species (plants, fungi, invertebrates, birds and a mammal) for microsatellite repeats and flanking regions suitable for primer development. We then compare the numbers of successfully lab-tested microsatellite markers for the various species and furthermore describe diverse challenges that might arise in different study species, for example, large genome size or nonpure extraction of genomic DNA. Successful primer identification was feasible for all species. We found that in species for which large repeat numbers are uncommon, such as fungi, polymorphic markers can nevertheless be developed from 454 pyrosequencing reads containing small repeat numbers (five to six repeats). Furthermore, the development of microsatellite markers for species with large genomes was also with Next Generation Sequencing techniques more cost and time-consuming than for species with smaller genomes. In this study, we showed that depending on the species, a different amount of 454 pyrosequencing data might be required for successful identification of a sufficient number of microsatellite markers for ecological genetic studies.

[Drug related problems pharmacists encounter when a patient is discharged from hospital]. / Problématique des médicaments à prendre par les patients sortant de l'hôpital: etude réalisée auprès de pharmaciens d'officine flamands.

AIMS: To explore drug related problems a community pharmacist encounters when a patient is discharged from hospital. The study also investigates which information from the hospital reaches the community pharmacy. METHODS: A validated survey was presented, by community pharmacists, to patients or their family after hospital discharge, between the 1st of December 2007 and the 29th of February 2008. The survey contained questions on 4 items: patient characteristics--discharge medication--information received from the hospital--drug related problems and pharmacists interventions. Analyses were done with SPSS 16.0. MAIN RESULTS: 82 community pharmacists participated. 261 patients were included. Only 25% of the patients collected their medication from the pharmacy themselves. On discharge, patients on average received two additional drugs, compared to the pre-hospital situation. 69% received a medication chart, but less than half of them brought this chart along when visiting the pharmacy. Only 9% got computer-generated prescriptions from the hospital and < 3% received a letter of referral addressed to their pharmacist. In 33% of the cases the pharmacists noticed one or more problems concerning the medication prescribed after hospital discharge. The chance to detect a problem increased significantly when the chart was brought to the pharmacy (p=0.033). In case of observed problems, the community pharmacist succeeded to reach the treating specialist by phone in less than one third of those cases. CONCLUSION: The results foster the discussion on the need for a better seamless care and the role clinical and community pharmacists could play in this care model.

Novel CDH3 mutations in hypotrichosis with juvenile macular dystrophy.

BACKGROUND: Hypotrichosis with juvenile macular dystrophy (HJMD) is a rare autosomal recessive disorder characterized by sparse and short hair, heralding progressive degeneration of the retinal pigment epithelium, which leads to blindness by the second decade of life. The disorder is caused by mutations in CDH3, a gene encoding P-cadherin, a major component of adherens junctions. Most HJMD cases reported to date have been shown to be caused by homozygous CDH3 mutations segregating in consanguineous families. AIM AND METHODS: To elucidate the genetic basis of HJMD in two nonconsanguineous families, we established the coding sequence of CDH3 in four patients and their healthy siblings. RESULTS: The four patients demonstrated markedly variable degrees of visual acuity impairment. Novel biallelic recessive mutations were identified in all affected individuals. One patient in the first family was found to carry two heterozygous mutations, IVS2 + 1G-->A and p.E504K; the other three patients in the second family were compound heterozygous for a missense mutation, p.H575R, and a nonsense mutation, p.R221X. CONCLUSION: This paper expands the spectrum of known mutations in CDH3 and points to the existence of clinical heterogeneity in this syndrome.

A phase II study of raltitrexed and gemcitabine in patients with advanced pancreatic carcinoma.

Advanced adenocarcinoma of the pancreas has a very poor prognosis. The aim of this study was to assess the efficacy and tolerability of a combination of the chemotherapeutic agents gemcitabine and raltitrexed. Chemonaive patients with advanced adenocarcinoma of the pancreas were treated with a combination of raltitrexed (3.5 mg m(-2) on day 1 of a 21-day treatment cycle) and gemcitabine (800 mg m(-2) intravenously (i.v.) on days 1 and 8 of a 21-day cycle). Between April 2000 and February 2003, 27 patients were enrolled onto the study. The mean duration of treatment was 11 weeks. Four of 27 patients experienced at least one episode of grade 3 or 4 neutropenia. One patient with grade 4 neutropenia died due to sepsis. Four of 27 patients experienced grade 4 diarrhoea. There was one partial remission (4%) and 12 patients experienced disease stabilisation (44%). The 6-month and 1-year survival rates were 37 and 11%, respectively. Symptomatic benefit occurred in seven (26%) patients. We conclude that a combination of raltitrexed and gemcitabine, using the schedule and doses in this study, cannot be recommended for patients with advanced pancreatic cancer.

Progressive cone dystrophy and sensorineural hearing loss.

A 39-year old man presented 13 years ago with a history of progressive loss of vision and photophobia. A full ophthalmological and ENT work-up during several years of follow-up, including psychophysical as well as electrophysiological tests, revealed a progressive cone dystrophy in combination with sensorineural hearing loss. His younger sister presented with very similar features and underwent the same work-up. A novel syndrome of progressive cone dystrophy and sensorineural hearing loss is described in both siblings. Both also suffered from non-ocular disease possibly related to ciliary dysfunction. The condition is likely to be inherited as an autosomal recessive trait.

A large field Panel D-15 test for low vision patients.

A large surface Panel D-15 Test, specially designed for low vision patients, is presented. The value of the test is compared to the one of other standard colour vision tests in such patients.

Parallel pathways, noise masking and glaucoma detection: behavioral and electrophysiological measures.

PURPOSE: We tested the hypothesis that because of their reduced neural efficiency, glaucoma patients should have increasingly impaired thresholds as external noise is added to a stimulus. METHOD: We compared the performance of 20 normals (mean age = 39 years) with that of 15 patients with early glaucoma or at very high risk for glaucoma (mean age 45 years). All patients had normal visual acuity. Contrast thresholds were measured on two sets of tasks: (1) behavioral and (2) sweep visually evoked potentials (VEPs). Two stimuli were used (a) 7.5 Hz reversing gratings of 0.69 cpd, and (b) 5.5 cpd gratings. Noise was binary and contrast varied from 0 to 80%. Psychophysical thresholds were determined using a staircase which employed a spatial four alternative forced choice procedure (4AFC) and converged on 50% correct. Sweep VEP thresholds were determined by extrapolation to zero volts as a function of log contrast. RESULTS: Differences between normal subjects and patients with early glaucoma were not significant without noise. Both the absolute size of the difference and its significance increased as noise level increased. For the behavioral thresholds these trends were clearer with the 5.5 cpd grating, while for the sweep VEPs they were more clear for the 0.69 cpd grating. CONCLUSION: The performance deficit of glaucoma patients which may be minimal under normal testing conditions is magnified when external noise is added to the stimulus. VEPs and psychophysical thresholds show interesting differences in their sensitivity to this effect. Implications for the early detection of glaucoma are discussed.

Acetazolamide affects performance on the Nagel II anomaloscope.

BACKGROUND: Recent reports have indicated that acetazolamide alters human electroretinograms. We wished to determine the effects of administering acetazolamide on performance on the Nagel II anomaloscope. METHODS: We tested 15 subjects matches of blue-green light to a mixture of blue and green lights (luminance match) on a Nagel type II anomaloscope 2.5 h after ingesting 500 mg of acetazolamide or a placebo. RESULTS: The mean of the luminance settings for the subjects was 54.4 for the placebo condition and 58.5 for the acetazolamide condition. The mean difference of 4.1 was statistically significant, indicating that following ingestion of acetazolamide subjects were less sensitive to a blue-green light. In two supplementary experiments we tested (1) a second group of four normal subjects using the Nagel type II anomaloscope and (2) the previously untreated eyes of four patients with primary open-angle glaucoma before and after placing them on acetazolamide therapy. In both groups, more blue-green light was needed to make the match after ingestion of acetazolamide. CONCLUSIONS: Acetazolamide alters the sensitivity of one or more cone populations, probably the carbonic anhydrase-containing cones. The sensitivity loss is reversible and does not appear to be clinically significant. However, the results suggest that patients administered acetazolamide should be excluded from studies which compare the color vision of glaucomatous patients to that of normals.

Myelinated nerve fibers and retinal vascular abnormalities.

BACKGROUND/PURPOSE: Abnormal retinal vessels may develop in a region of myelinated nerve fibers, and these vessels may cause vitreous hemorrhages. METHODS: The clinical histories of seven patients with retinovascular abnormalities in a patch of myelinated nerve fibers are presented. None of the reported patients had other evidence of systemic disease. The cases were traced by a multicentric retrospective study. RESULTS: Retinal vascular abnormalities ranged from mild telangiectasis to frank neovascularization, with or without obstruction of the capillary network and signs of branch artery and vein occlusion. Age at diagnosis ranged from 15 to 68 years. Vitreous hemorrhages occurred in the four youngest patients and occurred at 15, 27, 27, and 43 years of age. Laser photocoagulation was applied in three patients and vitrectomy was performed in one. CONCLUSION: The authors' findings suggest that the abnormal structure of the myelinated nerve fibers and the thickened nerve fiber layer of the affected portions of retina may play a role in the onset of retinal vascular abnormalities and eventually cause telangiectasis, branch artery and vein occlusion, neovascularization, and vitreous hemorrhages. This suggestion is based on the absence of other causes of neovascularization or vitreous hemorrhage in all seven patients, and on the relatively young age of four of the patients with this association.