Patient expectations, experiences and satisfaction with nintedanib and pirfenidone in idiopathic pulmonary fibrosis: a quantitative study.

BACKGROUND: Two antifibrotic drugs, nintedanib and pirfenidone, are available for treatment of idiopathic pulmonary fibrosis (IPF). Although efficacy and adverse events have been well studied, little is known about patient experiences with these drugs. We aimed to systematically and quantitatively evaluate patient expectations, experiences, and satisfaction with nintedanib and pirfenidone. Furthermore, we assessed which factors were associated with overall patient satisfaction with medication. METHODS: Outpatients with IPF prospectively completed the Patient Experiences and Satisfaction with Medication (PESaM) questionnaire before start, and after three and 6 months of antifibrotic treatment, as part of a randomized eHealth trial (NCT03420235). The PESaM questionnaire consists of an expectation module, a validated generic module evaluating patient experiences and satisfaction concerning the effectiveness, side-effects, and ease of use of a medication, and a disease-specific module about IPF. Satisfaction was scored on a scale from - 5 (very dissatisfied) to + 5 (very satisfied). RESULTS: In total, 90 patients were included, of whom 43% used nintedanib and 57% pirfenidone. After 6 months, the mean overall score for satisfaction with medication was 2.1 (SD 1.9). No differences were found in experiences and satisfaction with medication, and the number and severity of side-effects between nintedanib and pirfenidone. Perceived effectiveness of medication was rated as significantly more important than side-effects and ease of use (p = 0.001). Expectations of patients regarding effectiveness were higher than experiences after 6 months. Self-reported experience with effectiveness was the main factor associated with overall medication satisfaction. CONCLUSIONS: Patient experiences and satisfaction with antifibrotic treatment were fairly positive, and similar for nintedanib and pirfenidone. Systematic evaluation of patient expectations, experiences, and satisfaction with medication could enhance shared-decision making and guide drug treatment decisions in the future. TRIAL REGISTRATION: NCT03420235 .

Lipopolysaccharide amplifies eosinophilic inflammation after segmental challenge with house dust mite in asthmatics.

BACKGROUND: House dust contains mite allergens as well as bacterial products such as lipopolysaccharide (LPS). Asthma exacerbations are associated with the level of exposure to allergens and LPS. LPS can potentiate allergen effects in steroid-naïve patients. Long-acting ß2-agonists (LABA) were shown to inhibit LPS-induced bronchial inflammation in healthy volunteers. The aim of this study was to assess the effect of LPS on the allergen-induced eosinophilic inflammation [primary endpoints: eosinophil counts and eosinophil cationic protein (ECP)] induced by bronchial instillation of house dust mite (HDM) in patients with asthma on maintenance treatment with inhaled corticosteroids (ICS). METHODS: Thirty-two nonsmoking asthmatics with HDM allergy were treated with run-in medication (fluticasone propionate 100 µg bid) during 2 weeks before the study day. All patients underwent bronchial challenge with HDM, and half of them were randomized to receive additional LPS. Both groups were randomized to receive pretreatment with a single inhalation of 100 µg salmeterol 30 min before bronchial segmental challenge. Six hours later, bronchoalveolar lavage (BAL) was collected for leukocyte cell count, differentials, and cellular activation markers. RESULTS: Challenge with HDM/LPS induced a significant increase in eosinophil cationic protein (P = 0.036) and a trend toward an increase in BALF eosinophils as compared to HDM challenge. CONCLUSION: Lipopolysaccharide promotes eosinophilic airway inflammation in patients with asthma despite being on maintenance treatment with ICS.

Reduced risk of next exacerbation and mortality associated with antibiotic use in COPD.

The long-term risk of a subsequent exacerbation of chronic obstructive pulmonary disease (COPD) after treatment with oral corticosteroids without (OS) or with antibiotics (OSA) was compared in a historical general practice-based cohort. Eligible patients were >/=50 yrs of age, had a registered diagnosis of COPD, were on maintenance respiratory drugs, and had experienced at least one exacerbation defined as a prescription OS or OSA. Times to second and third exacerbations were assessed using Kaplan-Meier survival analysis; the risk of a subsequent exacerbation was assessed in a Cox proportional hazards analysis; and all-cause mortality was assessed using Kaplan-Meier survival and Cox proportional hazards analyses. A total of 842 patients had one or more exacerbations. The median time from first to second exacerbation was comparable for the OS and OSA groups, but the time from second to third exacerbation differed: 189 versus 258 days, respectively. The protective effect of OSA was most pronounced during the first 3 months following treatment (hazards ratio 0.72, 95% confidence interval 0.62-0.83). Exposure to antibiotics unrelated to a course of oral corticosteroids almost halved the risk of a new exacerbation. Mortality during follow-up was considerably lower in the OSA group. Adding antibiotics to oral corticosteroids was associated with: reduced risk of subsequent exacerbation, particularly in patients with recurrent exacerbations; and reduced risk of all-cause mortality.

Perceptions and short-term experiences of newly qualified radiographers performing compulsory community service.

INTRODUCTION: Compulsory community service (CCS) is a concept that was adopted by many countries as a strategy to address the shortage of health workers. CCS was initiated in 1997 in the South African healthcare system to alleviate improper distribution of health workers in the public sector. CCS experiences of various health professions excluding radiographers were explored where debates regarding the impact, experiences and perceptions of the CCS year are ongoing. This study aimed to describe the perceptions and short-term experiences of newly qualified radiographers performing CCS in Gauteng, South Africa. METHODS: A cross sectional descriptive study was conducted using a questionnaire distributed to 81 newly qualified radiographers who had started CCS in the Gauteng province in 2017 across 11 radiology departments. A response rate of 48.1% (n = 39) was obtained. RESULTS: Newly qualified radiographers understood the objectives of CCS and felt adequately prepared for their roles as CCS radiographers in terms of education skills acquired and role expectations. Participants felt confident to commence their duties and were not intimidated by their work environments. Orientation, mentoring and supervision were identified to be the main challenges during the CCS year. CONCLUSION: The concept of CCS is widely accepted and regarded beneficial by CCS radiographers. Similar challenges emerged as reported by other health professionals despite the presence of role models. The development and implementation of structured guidelines regarding orientation and mentoring of CCS health professionals is strongly recommended to address the needs identified by this study.

Short-course antibiotic treatment in acute exacerbations of chronic bronchitis and COPD: a meta-analysis of double-blind studies.

BACKGROUND: A study was undertaken to determine whether a short course of antibiotic treatment (< or = 5 days) is as effective as the conventional longer treatment in acute exacerbations of chronic bronchitis and chronic obstructive pulmonary disease (COPD). METHODS: MEDLINE, EMBASE and the Cochrane central register of controlled trials were searched to July 2006. Studies considered eligible were double-blind randomised clinical trials including adult patients > or = 18 years of age with a clinical diagnosis of exacerbation of COPD or chronic bronchitis, no antimicrobial therapy at the time of diagnosis and random assignment to antibiotic treatment for < or = 5 days versus > 5 days. The primary outcome measure was clinical cure at early follow-up on an intention-to-treat basis. RESULTS: 21 studies with a total of 10 698 patients were included. The average quality of the studies was high: the mean (SD) Jadad score was 3.9 (0.9). At early follow-up (< 25 days), the summary odds ratio (OR) for clinical cure with short treatment versus conventional treatment was 0.99 (95% CI 0.90 to 1.08). At late follow-up the summary OR was 1.0 (95% CI 0.91 to 1.10) and the summary OR for bacteriological cure was 1.05 (95% CI 0.87 to 1.26). Similar summary ORs were observed for early cure in trials with the same antibiotic in both arms and in studies grouped by the antibiotic class used in the short-course arm. CONCLUSIONS: A short course of antibiotic treatment is as effective as the traditional longer treatment in patients with mild to moderate exacerbations of chronic bronchitis and COPD.

Antibiotic treatment is associated with reduced risk of a subsequent exacerbation in obstructive lung disease: an historical population based cohort study.

OBJECTIVES: The risk of a subsequent exacerbation after treatment of an exacerbation with oral corticosteroids without (OS) or with (OSA) antibiotics was evaluated in a historical population based cohort study comprising patients using maintenance medication for obstructive lung disease. METHODS: The Pharmo database includes drug dispensing records of more than 2 million subjects in The Netherlands. Eligible were patients >or=50 years who in 2003 were dispensed >or=2 prescriptions of daily used inhaled beta(2) agonists, anticholinergics and/or corticosteroids, and experienced at least one exacerbation before 1 January 2006. Exacerbation was defined as a prescription of OS or OSA. The times to the second and third exacerbations were compared using Kaplan-Meier survival analysis. Independent determinants of new exacerbations were identified using multivariable Cox recurrent event survival analysis. RESULTS: Of 49,599 patients using maintenance medication, 18 928 had at least one exacerbation; in 52%, antibiotics had been added. The OS and OSA groups were comparable for potential confounding factors. Median time to the second exacerbation was 321 days in the OS group and 418 days in the OSA group (p<0.001); and between the second and third exacerbation 127 vs 240 days (p<0.001). The protective effect of OSA was most pronounced during the first 3 months following treatment (hazard ratio (HR) 0.62; 99% CI 0.60 to 0.65). In the OSA group, mortality during follow-up was lower (HR 0.82; 99% CI 0.66 to 0.98). CONCLUSION: Treatment with antibiotics in addition to oral corticosteroids was associated with a longer time to the next exacerbation, and a decreased risk of developing a new exacerbation.

Who is prone to high levels of distress after prophylactic mastectomy and/or salpingo-ovariectomy?

BACKGROUND: The present study aimed to assess predictors of distress after 'prophylactic mastectomy (PM) and salpingo-ovariectomy (PSO), in order to enable the early identification of patients who could benefit from psychological support. PATIENTS AND METHODS: General distress and cancer-related distress were assessed in 82 women at increased risk of hereditary breast and/or ovarian cancer undergoing PM and/or PSO, before and 6 and 12 months after prophylactic surgery. Neurotic lability and coping were assessed before surgery. RESULTS: Cancer-related distress and general distress at both follow-up moments were best explained by the level of cancer-related and general distress at baseline. Being a mutation carrier was predictive of increased cancer-related distress at 6-month follow-up (but not at 12 months), and of lower general distress 12 months after prophylactic surgery. Also, coping by having comforting thoughts was predictive of less cancer-related distress at 6-month follow-up. CONCLUSIONS: Genetically predisposed women who are at risk of post-surgical distress can be identified using one or more of the predictors found in this study. Exploration of and/or attention to cancer-related distress and coping style before prophylactic surgery may help physicians and psychosocial workers to identify women who might benefit from additional post-surgical support.

The course of distress in women at increased risk of breast and ovarian cancer due to an (identified) genetic susceptibility who opt for prophylactic mastectomy and/or salpingo-oophorectomy.

The levels and course of psychological distress before and after prophylactic mastectomy (PM) and/or prophylactic salpingo-oophorectomy (PSO) were studied in a group of 78 women. General distress was measured through the hospital anxiety and depression scale (HADS), cancer-related distress using the impact of events scale (IES). Measurement moments were baseline (2-4 weeks prior to prophylactic surgery), and 6 and 12 months post-surgery. After PM, anxiety and cancer-related distress were significantly reduced, whereas no significant changes in distress scores were observed after PSO. At one year after prophylactic surgery, a substantial amount of women remained at clinically relevant increased levels of cancer-related distress and anxiety. We conclude that most women can undergo PM and/or PSO without developing major emotional distress. More research is needed to further define the characteristics of the women who continue to have clinically relevant increased scores after surgery, in order to offer them additional counselling.

Three vs. 10 days of amoxycillin-clavulanic acid for type 1 acute exacerbations of chronic obstructive pulmonary disease: a randomised, double-blind study.

The optimal duration of antibiotic treatment for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is unknown. This study compared the outcome of treatment for 3 vs. 10 days with amoxycillin-clavulanic acid of hospitalised patients with AECOPD who had improved substantially after initial therapy for 3 days. Between November 2000 and December 2003, 56 patients with AECOPD were enrolled in the study. Unfortunately, because of the low inclusion rate, the trial was discontinued prematurely. Patients were treated with oral or intravenous amoxycillin-clavulanic acid. Patients who showed improvement after 72 h were randomised to receive oral amoxycillin-clavulanic acid 625 mg or placebo, four times daily for 7 days. The primary outcome measure of the study was clinical cure after 3 weeks and 3 months. Of 46 patients included in the final analysis, 21 were in the 3-day treatment group and 25 were in the 10-day treatment group. After 3 weeks, 16 (76%) of 21 patients in the 3-day treatment group were cured, compared with 20 (80%) of 25 in the 10-day treatment group (difference -3.8%; 95% CI -28 to 20). After 3 months, 13 (62%) of 21 patients were cured, compared with 14 (56%) of 25 (difference 5.9%; 95% CI -23 to 34). Microbiological success, symptom recovery, the use of corticosteroids, the duration of oxygen therapy and the length of hospital stay were comparable for both treatment groups. It was concluded that 3-day treatment with amoxycillin-clavulanic acid can be a safe and effective alternative to the standard 10-day treatment for hospitalised patients with AECOPD who have improved after initial therapy for 3 days.

Interstitial lung disease as the first manifestation of systemic sclerosis.

We describe three patients with progressive fibrosing interstitial lung disease (ILD) as the first and only manifestation of systemic sclerosis. In one patient the presence of anti-Scl-70 autoantibodies suggested systemic sclerosis to be the underlying cause of the disease. In the two other subjects, however, anti-Scl-70 antibodies were negative. In these patients the lung disease preceded other manifestations of systemic sclerosis by several years. Diagnosis, prognosis and treatment of systemic sclerosisassociated ILD is discussed.

Chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rapidly progressive and deadly disease, resulting from incomplete resolution of acute pulmonary embolism. Historically, the incidence of CTEPH was significantly underestimated but it may be as high as 3.8% following acute pulmonary embolism. Although the medical management of CTEPH may be supportive, the only curative treatment is pulmonary endarterectomy (PEA). However, a careful screening programme is mandatory to select CTEPH patients who are likely to benefit from PEA. In this review we discuss the pathophysiology, clinical and diagnostic pitfalls, surgical treatment, outcome after surgery, and the potential benefit of medical treatment in inoperable CTEPH patients.

Applicability of bosentan in Dutch patients with Eisenmenger syndrome: preliminary results on safety and exercise capacity.

BACKGROUND: The purpose of this study was to investigate the applicability of bosentan treatment in a broad selection of patients with Eisenmenger syndrome. METHODS: Dutch patients with Eisenmenger syndrome in New York Heart Association functional class III, 9 (41%) male and 13 (59%) female, including 11 patients with Down syndrome (50%), aged 20 to 61 years (median 37 years), were screened for an open-label, standardised treatment protocol. Patients underwent clinical examinations, six-minute walk test (6-MWT), resting oxygen saturation measurements, cardiac MRI, Doppler echocardiography, lung function tests and exercise capacity testing by peak oxygen consumption at baseline. At 12 weeks of treatment 6-MWT and at 26 weeks 6-MWT and Doppler echocardiography were repeated. RESULTS: Median follow-up of the patients who started bosentan treatment was five months (range 0.5 to 9.6 months). Oxygen saturation at baseline was 83% (range 76 to 91%) and did not decrease during treatment. Compared with baseline, 6-MWT increased after 12 weeks from 333±93 m to 384±89 m. None of the patients discontinued medication and no liver function abnormalities were observed. Of all Doppler echocardiographic and MRI parameters measured for right ventricular function, tricuspid annular peak systolic velocities using tissue Doppler imaging (TDI-S) was the only independent predictor for six-minute walk test (ß=0.8, p=0.001). CONCLUSION: Bosentan may be safely applied in patients with Eisenmenger syndrome combined with complex congenital heart disease or with Down syndrome. Our preliminary results suggest that exercise tolerance improves during the first months of bosentan treatment.

[Tumour lysis syndrome in small-cell lung cancer]. / Tumorlysissyndroom bij kleincellig longcarcinoom.

BACKGROUND: Small-cell lung cancer (SCLC) is a rapidly proliferating malignancy. Dramatic response to chemotherapy can therefore be expected. Unfortunately, tumour lysis prophylaxis is not mentioned in the current Dutch guidelines on SCLC treatment. CASE DESCRIPTION: A 64-year-old female was diagnosed with extensive SCLC and metastases. Shortly after diagnosis, chemotherapy was initiated. Based on Dutch guidelines, no tumour lysis prophylaxis was given. In addition to paraplegia, the patient also developed a clinical tumour lysis syndrome (TLS), and she passed away 5 days after start of treatment. CONCLUSION: Although tumour lysis prophylaxis is not mentioned in SCLC guidelines, tumour lysis in SCLC can occur as reported previously. Retrospectively, based on parameters applied to haematological malignancies, our patient was assessed as being at high risk of developing TLS.

Abnormal radiological findings and a decreased carbon monoxide transfer factor can persist long after the acute phase of Legionella pneumophila pneumonia.

Pulmonary abnormalities may persist long after the acute phase of legionnaires disease (LD). In a cohort of 122 survivors of an outbreak of LD, 57% were still experiencing an increased number of symptoms associated with dyspnea at a mean of 16 months after recovery from acute-phase LD. For 86 of these patients, additional evaluation involving high-resolution computed tomography (HRCT) of the lung revealed pulmonary abnormalities in 21 (24%); abnormal HRCT findings generally presented as discrete and multiple radiodensities. Residual pulmonary abnormalities were associated with a mean reduction of 20% in the gas transport capacity of the lung. This latter sign could not be used to explain the increased symptoms of dyspnea reported by patients. Receipt of mechanical ventilation during the acute phase of LD, delayed initiation of adequate antibiotic therapy, and chronic obstructive pulmonary disease were identified as risk factors for the persistence of lung abnormalities.

Chylous pleural effusion associated with primary lymphedema and lymphangioma-like malformations.

We describe a patient with a chylous pleural effusion associated with primary lymphedema of his right leg and abdominal wall. On evaluation a generalized, severe hypoplasia of the lymphatic system turned out to be associated with hyperplastic, lymphangioma-like malformations.

Interaction of clinical isolates of nonencapsulated Haemophilus influenzae with mammalian extracellular matrix proteins.

The adherence of clinical isolates of nonencapsulated Haemophilus influenzae strains from patients with chronic bronchitis to distinct immobilized extracellular matrix components was determined. With selected strains the induction of plasmin formation by these isolates was studied. The strains could be divided into two groups: strains that showed a very high level of adherence to laminin and type I collagen, as well as adhesion to fibronectin and strains that showed only a moderate level of adhesion to laminin and a low level of adhesion to fibronectin. Plasmin formation was demonstrated for three out of eight isolates. Persisting and nonpersisting strains did not differ quantitatively or qualitatively with respect to the level of adhesiveness to the distinct matrix proteins and in their ability to induce plasmin formation.

Idiopathic retroperitoneal fibrosis of the bladder.

A patient is described with isolated idiopathic retroperitoneal fibrosis (IRPF) of the bladder causing overhydration due to postrenal oliguria. IRPF is known to spread to the bladder; restriction of the bladder, however, is extremely rare. The patient was successfully treated with corticosteroids. The potential role of corticosteroids in the management of IRPF is discussed.

[Current developments in the diagnosis and therapy of cytomegalovirus infections]. / Nieuwe ontwikkelingen in diagnostiek en therapie van cytomegalovirusinfectie.

We describe the case history of a 40-year-old, negroid woman with systemic lupus erythematosus who acquired a severe cytomegalovirus infection on immunosuppression; this infection was successfully treated with ganciclovir. New ideas in the management of CMV infections in immuno-compromised hosts are discussed. The traditional diagnostics are unsatisfactory, antibody detection being very insensitive and culture techniques too slow. A new diagnostic approach by detection of the immediate early antigens of the cytomegalovirus (CMV-IEA) using monoclonal antibodies is fast and reliable (sensitivity 93%, specificity 92%), even in case of immuno-deficiency. Finally we discuss the efficacy of the antiviral agent ganciclovir in the management of severe CMV infections.

Cardiac sarcoidosis: Case-studies and a brief review of the literature.

Sarcoidosis is a multi-system granulomatous disorder of unknown aetiology. Symptomatic cardiac involvement occurs in approximately 5% of patients. The prevalence of sarcoidosis in the Netherlands is unknown, but estimated to be approximately 20 per 100,000 population (3200 patients). We report on five patients who presented with different manifestations of cardiac sarcoidosis, and give a brief review on the current management of this condition. Magnetic Resonance Imaging (MRI) can be of great help in diagnosing this condition as well as in the follow-up of the response to therapy.

[Is gambling a disease in the sense of section 169 of the federal insurance law?]. / Ist Spielsucht eine Erkrankung im Sinne des Section 169 VVG?

The socalled gambling addiction expresses itself as an exaggerated form of the gambling passion. The act of becoming fixed on or addicted to this (or another) behaviour pattern is always proceded by tentative situations man is succumbing to. The stimulant becomes increasingly more attractive. Regarding such a process, there is not criterion to determine a point when the addiction (which is not linked to a certain matter) becomes a disease. At all events, it is a legal matter to decide whether an extremely defective development that has obviously resulted into social ruin is to be regarded as a disease. The whole range of medical and educational requirements, however, has to be dealt with separately.