Intravenous immunoglobulin and intravenous methylprednisolone as optimal induction treatment in chronic inflammatory demyelinating polyradiculoneuropathy: protocol of an international, randomised, double-blind, placebo-controlled trial (OPTIC).

BACKGROUND: International guidelines recommend either intravenous immunoglobulin (IVIg) or corticosteroids as first-line treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). IVIg treatment usually leads to rapid improvement and is generally safe, but does not seem to lead to long-term remissions. Corticosteroids act more slowly and are associated with more side effects, but may induce long-term remissions. The hypothesis of this study is that combined IVIg and corticosteroid induction treatment will lead to more frequent long-term remissions than IVIg treatment alone. METHODS: An international, randomised, double-blind, placebo-controlled trial, in adults with 'probable' or 'definite' CIDP according to the EFNS/PNS 2010 criteria. Three groups of patients are included: (1) treatment naïve, (2) known CIDP patients with a relapse after > 1 year without treatment, and (3) patients with CIDP who improved within 3 months after a single course of IVIg, who subsequently deteriorate at any interval without having received additional treatment. Patients are randomised to receive 7 courses of IVIg and 1000 mg intravenous methylprednisolone (IVMP) (in sodium chloride 0.9%) or IVIg and placebo (sodium chloride 0.9%), every 3 weeks for 18 weeks. IVIg treatment consists of a loading dose of 2 g/kg (over 3-5 days) followed by 6 courses of IVIg 1/g/kg (over 1-2 days). The primary outcome is remission at 1 year, defined as improvement in disability from baseline, sustained between week 18 and week 52 without further treatment. Secondary outcomes include changes in disability, impairment, pain, fatigue, quality of life, care use and costs and (long-term) safety. DISCUSSION: In case of superiority of the combined treatment, patients will experience the advantages of two proven efficacious treatments, namely rapid improvement due to IVIg and long-term remission due to corticosteroids. Long-term remission would reduce the need for maintenance IVIg treatment and may decrease health care costs. Additionally, we expect that the combined treatment leads to a higher proportion of patients with improvement as some patients who do not respond to IVIg will respond to corticosteroids. Risks of short and long-term additional adverse events of the combined treatment need to be assessed. TRIAL REGISTRATION: ISRCTN registry ISRCTN15893334 . Prospectively registered on 12 February 2018.

Improving enhanced recovery after surgery (ERAS): ERAS APPtimize study protocol, a randomized controlled trial investigating the effect of a patient-centred mobile application on patient participation in colorectal surgery.

BACKGROUND: Perioperative care in colorectal surgery is systematically defined in the Enhanced Recovery After Surgery (ERAS) protocol. The ERAS protocol improves perioperative care in a multimodal way to enhance early and safe release from the hospital. Adequate compliance to the elements of the ERAS protocol is multifactorial. There are still opportunities to improve compliance of the protocol by actively involving the patient. The main objective of this study is to investigate whether compliance of selected items in the ERAS protocol can be improved through actively involving patients in the ERAS care pathway through the use of a patient-centred mobile application. METHODS: A multicentre randomized controlled trial will be conducted. Patients undergoing elective colorectal surgery, who are 18 years or older and in possession of an eligible smartphone, will be included. Patients assigned to the intervention group will install a patient-centred mobile application to be guided through the ERAS care pathway. Patients in the control group will receive care as usual. Both groups will wear an activity tracker. The primary outcome is overall compliance to selected active elements of the ERAS protocol, as registered by the patient. Secondary outcomes include Patient Reported Outcome Measures (PROMs) such as health-related quality of life, physical activity, and patient satisfaction of received care. Care-related outcomes, such as length of hospital stay, number of complications, re-intervention, and readmission rates, will also be assessed. RESULTS: The enrolment of patients will start in the second quarter of 2019. Data collection had not begun by the time this protocol was submitted. CONCLUSION: We hypothesize that by providing patients with a patient-centred mobile application, compliance to the active elements of ERAS protocol can be improved, resulting in an increased health-related quality of life, physical activity, and patient satisfaction. TRIAL REGISTRATION: Netherlands Trial Register, NTR7314 , prospectively registered on the 9th of November 2017 ( http://www.trialregister.nl ).

Knowledge and perceived risks in couples undergoing genetic testing after recurrent miscarriage or for poor semen quality.

Couples with recurrent miscarriage (RM) and men with poor semen quality may undergo genetic testing as part of the diagnostic work-up. This study explored their knowledge and perception of genetic testing, evaluated psychological wellbeing and identified associated variables. A prospective questionnaire study was conducted in seven clinical genetics centres and referring gynaecological departments in couples with RM or poor semen quality. Questionnaires were completed before disclosure of genetic test results. Main outcome measures were knowledge, perceived risk, anxiety and depression. Of 439 participants, 256 were not aware genetic testing was part of the diagnostic work-up. One-third (36% RM, 33% poor semen quality) indicated they had not received information about the genetic test from their doctor. Perceived risk of receiving an abnormal genetic test result was higher than objective risk. Anxiety was highly correlated with perceived risk. Women with RM were more anxious than women in the poor semen quality group or men (P<0.01). These couples undergoing genetic testing have a suboptimal understanding of the nature of testing, overestimate the risks of receiving an abnormal result and some show high levels of anxiety. The results of this study can be used to improve patient counselling before genetic testing.

The psychological impact of testing for thrombophilia: a systematic review.

BACKGROUND: Nowadays, large numbers of patients are tested for thrombophilia, even though the benefits of this strategy remain unclear. A potential disadvantage of this predominantly genetic testing is the psychological impact, including fear, depression and worry. OBJECTIVES: To systematically review studies that determined the nature and extent of the psychological impact of testing for thrombophilia. PATIENTS/METHODS: We searched the MEDLINE data base (1966-2008), the EMBASE data base (1985-2008) and the PsychInfo data base (1806-2008) for relevant trials, without language restrictions. Bibliographies of relevant articles were scanned for additional articles. We reviewed all relevant studies that focused on the psychological impact of testing for thrombophilia. Only full papers of studies that included 15 patients or more were considered eligible for this review. Two reviewers independently extracted data and assessed quality. RESULTS: Six studies fulfilled the eligibility criteria. As these studies varied appreciably in methodology, the pooling of data was not possible. Studies of psychological impact of genetic testing for thrombophilia report few negative results, although most assessments were limited to short-term follow-up, or lacked methodological accuracy. CONCLUSIONS: No valid conclusions can be drawn about the psychological impact of genetic testing in patients based on the current available literature. Given the large number of patients that are being exposed to testing for thrombophilia, and the uncertain benefits, there is an urgent need for more uniformity in the measurement of the psychological impact of thrombophilia testing.

Costs associated with shorter duration of antibiotic therapy in hospitalized patients with mild-to-moderate severe community-acquired pneumonia.

OBJECTIVES: The optimal duration of antibiotic therapy in patients with uncomplicated pneumonia may be shorter than that recommended in the current guidelines. A shorter duration will probably also lead to a cost reduction. This study evaluates the costs associated with 3 versus 8 day antibiotic therapy and subsequent follow-up in patients hospitalized with mild-to-moderate-severe community-acquired pneumonia. PATIENTS AND METHODS: The economic evaluation was based on primary resource utilization data collected within the framework of a randomized, double blind, placebo-controlled trial. As 3 day therapy was shown to be clinically not inferior to 8 day therapy, the cost-minimization analysis was performed based on direct medical and indirect non-medical costs, estimated from a societal perspective for the 28 days following hospital admission. RESULTS: Lower costs of shorter therapy during hospital admission (euro 209 lower) were partially offset by higher costs for primary healthcare providers (euro 66 higher). The average costs generated per patient by resource utilization during admission and follow-up were estimated as euro 3,959 in the 3 day group versus euro 4,102 in the 8 day group (difference euro 143 in favour of shorter therapy). The difference was affected by changes in assumptions concerning the unit costs for hospital stay but was consistently in favour of shorter therapy. CONCLUSIONS: Shorter duration of antibiotic therapy in hospitalized patients with uncomplicated pneumonia does not result in a substantial substitution of resource utilization to primary healthcare providers. As 3 day antibiotic therapy does not lead to inferior clinical results, these findings support a 3 day therapy as a more efficient strategy.

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.

Development and validation of a short questionnaire in community acquired pneumonia.

BACKGROUND: A short but sensitive questionnaire evaluating changes in respiratory symptoms and well being during the treatment of community acquired pneumonia (CAP) is needed. We have developed a measurement and evaluated its psychometric properties in 67 patients admitted with CAP. METHODS: The patients were asked to indicate the presence and severity of dyspnoea, coughing, coughing up sputum, coughing up sputum with ease, the colour of the sputum, fatigue, fitness, and their state of health. The item fatigue showed substantial overlap with fitness and was therefore excluded. The response of the patients to the remaining eight items was used to calculate a CAP score. RESULTS: The percentage of missing data (0.2-1.7%), floor and ceiling effects (0.2/5.5%), internal consistency (Cronbach alpha = 0.87), and the intraclass correlation coefficient for test-retest reproducibility (0.83) met predefined criteria, indicating good acceptability and reliability. Face and clinical validity were satisfactory. Effect sizes under treatment were large, indicating high responsiveness. CONCLUSION: The newly developed CAP score is a simple, reliable, valid, and highly responsive instrument. This makes it scientifically sound and clinically relevant for measuring outcome when evaluating treatment strategies in CAP.