Two-year follow-up of a dose reduction strategy trial of biologics adalimumab, etanercept, and ustekinumab in psoriasis patients in daily practice.

BACKGROUND/OBJECTIVES: Tightly-controlled dose reduction was possible during 1 year in psoriasis patients on adalimumab, etanercept or ustekinumab with low disease activity (CONDOR trial). Extended observation is needed to ensure long-term effectiveness and safety of the strategy. With prolonged follow-up, we investigated the clinical effects and safety of the strategy, the proportion of patients with successful dose reduction, and assessed if patients with a disease flare regained remission. METHODS: Two-year follow up of a subgroup of patients previously included in a randomized pragmatic study comparing usual care (UC) with stepwise dose reduction (DR). Effectiveness (Psoriasis Area and Severity Index, PASI), Dermatology Life Quality Index (DLQI), adverse events, proportion of patients with successful DR and proportion of persistent disease flares were analyzed. RESULTS: DR leads temporarily to a slightly increased PASI groupwise, but on the long-term patients regained low PASI. DLQI scores remained stable during follow-up. No serious adverse events due to DR were reported. Forty-one percent of patients remained on a low dose up to 2 years. The number of persistent flares was low in DR and UC. CONCLUSIONS: The proposed dose reduction strategy is effective for a significant part of patients and remains safe up to 2 years of follow-up.

The effect of a dermato-oncological training programme on the diagnostic skills and quality of referrals for suspicious skin lesions by general practitioners.

BACKGROUND: The rising incidence rates of skin cancer (SC) lead to an enormous burden on healthcare systems. General practitioners (GPs) might play an important part in SC care, but research has shown poor clinical recognition of SC, leading to a high rate of potentially unnecessary referrals. OBJECTIVES: The aim of this study was to evaluate if a dermato-oncological training programme (DOTP) for GPs improved their diagnostic skills and quality of referrals. METHODS: Out of 194 GPs in the Nijmegen area, 83 (42·8%) followed a DOTP on SC. Referrals from both a trained cohort (TC) and two cohorts of untrained GPs [untrained present cohort (UPC) and untrained historical cohort (UHC)] were included. Data on diagnostic skills, quality of referrals and the number of potentially unnecessary referrals were evaluated. RESULTS: A total number of 1662 referrals were analysed. The referral diagnosis was correct more often in the TC (70·3%) compared with the UPC (56·2%; P < 0·001) and the UHC (51·6%; P < 0·001). Furthermore, the TC also provided a better lesion description, mentioned a diagnosis more often in their referral letters and more often performed diagnostics before referral. In addition, fewer potentially unnecessary referrals were identified in the TC compared with the UPC (62·7% vs. 73·7%; P < 0·001) and the UHC (75·2%; P < 0·001). CONCLUSIONS: GPs who followed a DOTP had better diagnostic skills and quality of referrals than untrained GPs, leading to fewer potentially unnecessary referrals. This might enhance a more efficient use of the limited capacity in secondary dermatological care and consequently lead to lower healthcare costs.

Treatment persistence in paediatric and adolescent patients with psoriasis followed into young adulthood. From topical to systemic treatment: a prospective, longitudinal, observational cohort study of 448 patients.

BACKGROUND: Although solely topical treatment often suffices, patients with psoriasis may require more intensive treatment (phototherapy and/or systemic treatments) to control their disease. However, in paediatric, adolescent and young adult patients, little is known about persistence of topical treatment and time until switch to systemic treatment. OBJECTIVES: To determine the median time from psoriasis onset until (i) discontinuation of solely topical agents and (ii) switch to systemic treatment, and to identify patient characteristics associated with switching to systemic treatments. METHODS: Data were extracted from the Child-CAPTURE registry, a prospective, observational cohort of patients with paediatric-onset psoriasis followed into young adulthood from 2008 to 2018. Data prior to inclusion in the registry were collected retrospectively. Median times were determined through Kaplan-Meier survival analyses. Cox regression analysis was used to identify patient characteristics associated with switch to systemic treatment. RESULTS: Of 448 patients, 62·3% stayed on solely topical treatment until data lock; 14·3% switched from topicals to phototherapy, but not to systemic treatment; and 23·4% switched to systemic treatment. The median time from psoriasis onset until discontinuation of solely topical treatment was 7·3 years, and until switch to systemics was 10·8 years. Higher Psoriasis Area and Severity Index and (Children's) Dermatology Life Quality Index > 5 were independently associated with switching to systemic treatment. CONCLUSIONS: In a population of paediatric and adolescent patients with mild-to-severe psoriasis, one-third needed more intensive treatment than solely topical therapy to control their disease. We consider the median time until switching to systemics to be long.

Female patients are less satisfied with biological treatment for psoriasis and experience more side-effects than male patients: results from the prospective BioCAPTURE registry.

BACKGROUND: Female sex has been reported as a predictor for treatment discontinuation with biological therapies for psoriasis, although reasons remain unclear. It can be hypothesized that lower satisfaction with biological treatment in women might add to the lower drug survival rates. OBJECTIVES: To identify possible differences in satisfaction with biological treatment between female and male patients using the Treatment Satisfaction Questionnaire for Medication (TSQM). METHODS: Data of psoriasis patients treated with biologics were obtained from the prospective, multicentre, daily-practice BioCAPTURE registry. Longitudinal TSQM data were analysed by linear mixed models. Relevant patient characteristics were incorporated as possible confounding factors. Post hoc analysis of adverse events was performed in order to investigate differences between sexes. RESULTS: We included 315 patients with 396 corresponding treatment episodes (137 adalimumab, 90 etanercept, 137 ustekinumab, 24 secukinumab and 8 infliximab). Almost forty per cent of the patients were female. Women had significantly lower baseline PASI scores (P = 0.01). Longitudinal analyses demonstrated lower TSQM scores for 'side-effects' (P = 0.05) and 'global satisfaction' (P = 0.01) in female patients compared with male patients over 1 year of treatment. Women reported more relevant adverse events in the context of biologic treatment compared to men (rate ratio 1.79; P < 0.001), with more fungal (rate ratio 2.20; P = 0.001) and herpes simplex infections (rate ratio 3.25; P = 0.005). CONCLUSIONS: This study provides a prospective, longitudinal analysis of treatment satisfaction with biologics in female and male patients with psoriasis. Women were slightly less satisfied with treatment regarding side-effects and global satisfaction. Differences in treatment satisfaction and side-effects might add to the fact that women discontinue biological treatments more often.

Comparison of the 1- and 5-year effectiveness of adalimumab, etanercept and ustekinumab in patients with psoriasis in daily clinical practice: results from the prospective BioCAPTURE registry.

BACKGROUND: The efficacy of etanercept and ustekinumab in psoriasis has been compared in one randomized controlled trial. Comparison of the long-term effectiveness of biologics in daily-practice psoriasis treatment is currently lacking. OBJECTIVES: To compare the effectiveness between the three widely used outpatient biologics adalimumab, etanercept and ustekinumab in daily-practice psoriasis treatment and to correct for confounders. METHODS: Data were extracted from the prospective, multicentre BioCAPTURE registry. Multilevel linear regression analyses (MLRAs) and generalized estimating equation (GEE) analyses were performed on the course of mean Psoriasis Area and Severity Index (PASI) and PASI 75 (≥ 75% reduction vs. baseline). Both models were corrected for confounders. Subgroup analyses for biological dose were performed. RESULTS: We included 356 patients with 513 treatment episodes: 178 adalimumab, 245 etanercept and 90 ustekinumab. MLRA showed a similar effectiveness between adalimumab, etanercept and ustekinumab after 1 year, but the highest effectiveness for ustekinumab during 5 years of treatment (P = 0·047; ustekinumab vs. etanercept, P = 0·019). GEE analysis revealed a higher chance of attaining PASI 75 with adalimumab and ustekinumab than with etanercept at 1 year of treatment. A higher than label dose was more often used in patients treated with etanercept (adalimumab, etanercept and ustekinumab: respectively 31·5%, 55·1% and 17% after 1 year, P < 0·001; 39·3%, 71·4% and 24% after 5 years, P < 0·001). CONCLUSIONS: Compared with etanercept, ustekinumab had the highest effectiveness during 5 years of treatment. Patients receiving adalimumab and ustekinumab more often reached PASI 75 than those on etanercept at 1 year of treatment. Dose escalation was more frequent in etanercept and adalimumab than in ustekinumab.

Central line bloodstream infections can be reduced in newborn infants using the modified Seldinger technique and care bundles of preventative measures.

AIM: There has been no evidence to show whether care bundles of preventive measures reduce central line-associated bloodstream infection (CLABSI) in peripherally inserted central catheters using the modified Seldinger technique, which requires more specific skills than the traditional technique. The aim of this study was to address that gap in our knowledge and to determine whether other variables influenced the outcome. METHODS: This prospective observational study was conducted on a neonatal intensive care unit. We observed the incidence of CLABSI in 45 newborn infants with peripheral catheters before the introduction of bundles of preventative measures and 88 infants after the introduction. RESULTS: Laboratory-confirmed CLABSI decreased after the introduction of the bundles, from 12.9 per 1000 days to 4.7/1000 days (p = 0.09). When we combined the rates for laboratory-confirmed CLABSI and clinical CLABSI in a survival analysis, the incidence reduced significantly after introduction of the bundles (p = 0.02). There were no other variables that affected the outcome. CONCLUSION: Cost-effective care bundles reduced CLABSI in peripherally inserted central catheters using the modified Seldinger technique, despite the specific insertion skills that were required. The bundles of preventative measures may increase healthcare professionals' awareness of the need to care for central catheters and reduce CLABSI infections.

Evaluation of long-term function, complications, quality of life and health status after restorative proctocolectomy with ileo neo rectal and with ileal pouch anal anastomosis for ulcerative colitis.

AIM: Restorative surgery after (procto)colectomy with ileo-neorectal anastomosis (INRA) or restorative proctocolectomy with ileal pouch anal anastomosis (RPC) combines cure of ulcerative colitis (UC) with restoration of intestinal continuity. This study aimed to evaluate these two operations. METHOD: Patients having INRA and RPC were matched according to sex, age at onset of UC, age at restorative surgery and duration of follow-up. Patients were included if they were over 18 years of age, had UC confirmed histopathologically and had undergone either operation. Long-term function, anal and neorectal physiology, complications, quality of life (QoL) and health status (HS) were determined. RESULTS: Seventy-one consecutive patients underwent surgery with the intention of having an INRA procedure. This was successfully carried out in 50, and 21 underwent intra-operative conversion to RPC. Median defaecation frequency was 6/24 h. In 11/71 patients reservoir failure occurred and 13/71 developed pouchitis. QoL and HS were comparable to the healthy population. Median follow-up was 6.2 years. These patients were matched with 71 patients who underwent RPC. RPC was successful in all patients. Median defaecation frequency was 8/24 h. Failure occurred in 7/71 patients and 13/71 developed pouchitis. QoL and HS were comparable with the healthy population. Median follow-up was 6.9 years. CONCLUSION: Comparison of INRA and RPC on an intention to treat basis was not considered to be realistic due to the high intra-operative conversion rate and the failures in the INRA group. RPC remains the procedure of choice for restoring intestinal continuity after proctocolectomy for UC.

Predictive value of POSSUM and ACPGBI scoring in mortality and morbidity of colorectal resection: a case-control study.

BACKGROUND: Preoperative risk prediction to assess mortality and morbidity may be helpful to surgical decision making. The aim of this study was to compare mortality and morbidity of colorectal resections performed in a tertiary referral center with mortality and morbidity as predicted with physiological and operative score for enumeration of mortality and morbidity (POSSUM), Portsmouth POSSUM (P-POSSUM), and colorectal POSSUM (CR-POSSUM). The second aim of this study was to analyze the accuracy of different POSSUM scores in surgery performed for malignancy, inflammatory bowel diseases, and diverticulitis. POSSUM scoring was also evaluated in colorectal resection in acute vs. elective setting. In procedures performed for malignancy, the Association of Coloproctology of Great Britain and Ireland (ACPGBI) score was assessed in the same way for comparison. METHODS: POSSUM, P-POSSUM, and CR-POSSUM predictor equations for mortality were applied in a retrospective case-control study to 734 patients who had undergone colorectal resection. The total group was assessed first. Second, the predictive value of outcome after surgery was assessed for malignancy (n = 386), inflammatory bowel diseases (n = 113), diverticulitis (n = 91), and other indications, e.g., trauma, endometriosis, volvulus, or ischemia (n = 144). Third, all subgroups were assessed in relation to the setting in which surgery was performed: acute or elective. In patients with malignancy, the ACPGBI score was calculated as well. In all groups, receiver operating characteristic (ROC) curves were constructed. RESULTS: POSSUM, P-POSSUM, and CR-POSSUM have a significant predictive value for outcome after colorectal surgery. Within the total population as well as in all four subgroups, there is no difference in the area under the curve between the POSSUM, P-POSSUM, and CR-POSSUM scores. In the subgroup analysis, smallest areas under the ROC curve are seen in operations performed for malignancy, which is significantly worse than for diverticulitis and in operations performed for other indications. For elective procedures, P-POSSUM and CR-POSSUM predict outcome significantly worse in patients operated for carcinoma than in patients with diverticulitis. In acute surgical interventions, CR-POSSUM predicts mortality better in diverticulitis than in patients operated for other indications. The ACPGBI score has a larger area under the curve than any of the POSSUM scores. Morbidity as predicted by POSSUM is most accurate in procedures for diverticulitis and worst when the indication is malignancy. CONCLUSION: The POSSUM scores predict outcome significantly better than can be expected by chance alone. Regarding the indication for surgery, each POSSUM score predicts outcome in patients operated for diverticulitis or other indications more accurately than for malignancy. The ACPGBI score is found to be superior to the various POSSUM scores in patients who have (elective) resection of colorectal malignancy.

Inappropriateness of using opioids for end-stage palliative sedation: a Dutch study.

To be able to distinguish end-stage palliative sedation from euthanasia without having to refer to intentions that are difficult to verify, physicians must be able to manage palliative sedation appropriately (i.e., see that death is not hastened as a result of disproportionate medication). In the present study, we assessed whether or not this requirement is met in the Netherlands. We sent a retrospective questionnaire to 1,464 medical specialists, general practitioners, and nursing home physicians in the Netherlands. Furthermore, we held two sets of 20 and 22 semi-structured in-depth interviews with general practitioners, internists, lung specialists, and nursing home physicians. Although most guidelines discourage the administration of opioids alone for purposes of palliative sedation, opioids alone were administered for 22% of all the patients reported upon. Those physicians who were more experienced, general practitioners, and physicians who had consulted a palliative care expert administered only opioids significantly less often than the other physicians. The interviewees reported difficulties in assessing the appropriateness of medication, feeling uncertain about the pharmacokinetics of drugs used in moribund patients. Given that no more than 2% of the respondents perceived palliative sedation to be used as a form of euthanasia and that the use of opioids alone was not associated with shorter survival rates, the inappropriate use of opioids can only be attributed to a lack of knowledge or skill and/or a tradition of alleviating refractory dyspnoea with the use of opioids and not as an intentional means of hastening death.

Long-term evaluation of bilateral cleft lip and palate patients after early secondary closure and premaxilla repositioning.

The aim of this retrospective, mixed longitudinal study was to assess the long-term outcome of early secondary closure and premaxilla osteotomy in 40 bilateral cleft lip and palate patients who underwent early secondary osteotomy of the premaxilla and bone grafting at the age of 8-12 years. Clinical and cephalometric evaluations of profile, lip relation, nasolabial angle and position of the maxilla preoperatively, postoperatively and at adolescence were compared to normal values of non-cleft individuals and the reported data of 90 bilateral cleft lip and palate patients treated in Oslo. In 68% of patients the profile was considered acceptable, but in 26 maxillary growth appeared to be impaired by cephalometric standards. In four patients a Le Fort I osteotomy was carried out and nine patients would have benefited from such a procedure. This study reveals a trend towards maxillary growth retardation partially compensated by orthodontic and dental treatment. Since the results are comparable to those reported for the Oslo group with regard to maxillary growth, the surgical protocol followed does not require revision. Considering the benefits, i.e. closure of alveolo-palatal cleft, continuity of dental arch, eruption of canine in the graft and closure of oro-nasal communications, this mode of treatment should be continued.

Risk calculation for hyperkalaemia in heart failure patients.

BACKGROUND: We aimed to develop a model to estimate the risk of hyperkalaemia in patients treated for heart failure in a tertiary reference hospital and to identify precipitating factors. METHODS: 125 congestive heart failure (CHF) patients were studied retrospectively. Thirty of these patients developed episodes of hyperkalaemia (K>or=5.5 mmol/l). Both groups were compared for possible risk factors for hyperkalaemia (age, glomerular filtration rate (GFR), New York Heart Association (NYHA) class, diabetes mellitus (DM), ejection fraction and medication use (ACE inhibitors, angiotensin receptor blockers, aldosterone antagonists). RESULTS: On multivariate logistic regression analysis DM (OR 2.9, 95% CI=1.05 to 8.3, p=0.041), GFR<45 ml/min (OR 4.1, 95% CI=1.6 to 10.5. p=0.004) and NYHA class III-IV (OR 2.4, 95% CI=0.9 to 6.3, p=0.086) were independently associated with hyperkalaemia, whereas age, ejection fraction and medication sort and dose were not. Of the episodes of hyperkalaemia, 38% were precipitated by periods of dehydration (diarrhoea, fever) or change of medication. CONCLUSION: We identified kidney function, diabetes mellitus and heart failure class as independent risk factors of hyperkalaemia. The majority of the hyperkalaemic episodes develop without a precipitating factor. This implies that heart failure patients in a tertiary reference hospital should be very closely monitored to minimize the risk for hyperkalaemia.