Rob J. de Haan

Rates of Complications and Death After Pancreaticoduodenectomy: Risk Factors and the Impact of Hospital Volume

ObjectiveTo perform a two-part study of pancreaticoduodenectomy in the Netherlands, focusing on the effects of risk factors on outcomes in a single high-volume hospital and the effect of hospital volume on outcomes. Summary Background DataHospital volume and surgeon caseload can be related to the rates of complications and death, and the influence of risk factors can be volume-dependent. Provision of regionalized care should take this into account. MethodsIn part A, a single-institution database on 300 consecutive patients undergoing pancreaticoduodenectomy was divided into two periods with similar numbers of patients. Overall complications, deaths, hospital stay, and risk factors were analyzed in the two periods and compared with an historical reference group. In part B, Netherlands medical registry data on age and postoperative death of patients who underwent partial pancreaticoduodenectomy from 1994 to 1998 were analyzed for the influence of hospital volume on death. ResultsBetween the time periods, the institutional death rate decreased from 4.9% to 0.7%, the complication rate from 60% to 41%. Median hospital stay decreased from 24 to 15 days. The death rate was not related to patient age and did not differ between surgeons. Serum creatinine levels, need for blood transfusion, and period of resection were independent risk factors for complications. The death rate after pancreaticoduodenectomy in the Netherlands was 12.6% in 1994 and 10.1% in 1998; it was greater in patients older than age 65. During the 5-year period, 40% of the procedures were performed in hospitals performing fewer than five resections per year, and the death rate was greater than in hospitals performing more than 25 resections per year. ConclusionsThe overall death rate after pancreaticoduodenectomy did not decrease significantly during the period, and it was greater in low-volume hospitals and older patients. The lower death and complication rates in high-volume hospitals, including the single-center outcomes, were similar to those reported in other countries and may be due to better prevention and management of complications. Pancreaticoduodenectomy should be performed in centers with sufficient experience and resources for support.

Systematic review of early prediction of poor outcome in anoxic- ischaemic coma

BACKGROUND Studies to assess the prognostic value of early neurological and neurophysiological findings in patients with anoxic-ischaemic coma have not led to precise, generally accepted, prognostic rules. We did a systematic review of the relevant literature to assess whether such rules could be derived from the combined results of these studies. METHODS From Medline and Embase databases we selected studies concerning patients older than 10 years with anoxic-ischaemic coma in which findings from early neurological examination, electroencephalogram (EEG), or somatosensory evoked potentials (SSEP) were related to poor outcome--defined as death or survival in a vegetative state. We selected variables with a specificity of 100% for poor outcome in all studies, and expressed the overall prognostic accuracy of these variables as pooled positive-likelihood ratios and as 95% CIs of the pooled false-positive test rates. FINDINGS In 33 studies, 14 prognostic variables were studied, three of which had a specificity of 100%: absence of pupillary light reflexes on day 3 (pooled positive-likelihood ratio 10.5 [95% CI 2.1-52.4]; 95% CI pooled false-positive test rate 0-11.9%); absent motor response to pain on day 3 (16.8 [3.4-84.1]; 0-6.7%); and bilateral absence of early cortical SSEP within the first week (12.0 [5.3-27.6]; 0-2.0%). EEG recordings with an isoelectric or burst-suppression pattern had a specificity of 100% in five of six relevant studies (pooled positive-likelihood ratio 9.0 [2.5-33.1]; 95%CI pooled false-positive test rate 0.2-5.9%). These characteristics were present in 19%, 31%, 33%, and 33% of pooled patient populations, respectively. For the 11 SSEP studies, results did not significantly differ between studies in which the treating physicians were or were not masked from the test result, prospective and retrospective studies, studies with short and long follow-up periods, and studies with high or low overall poor outcome. INTERPRETATION SSEP has the smallest CI of its pooled positive-likelihood ratio and its pooled false-positive test rate. Because evoked potentials are also the least susceptible to metabolic changes and drugs, recording of SSEP is the most useful method to predict poor outcome.

Subthalamic nucleus versus globus pallidus bilateral deep brain stimulation for advanced Parkinson's disease (NSTAPS study): a randomised controlled trial

BACKGROUND Patients with advanced Parkinsons disease often have rapid swings between mobility and immobility, and many respond unsatisfactorily to adjustments in pharmacological treatment. We assessed whether globus pallidus pars interna (GPi) deep brain stimulation (DBS) gives greater functional improvement than does subthalamic nucleus (STN) DBS. METHODS We recruited patients from five centres in the Netherlands who were aged 18 years or older, had idiopathic Parkinsons disease, and had, despite optimum pharmacological treatment, at least one of the following symptoms: severe response fluctuations, dyskinesias, painful dystonias, or bradykinesia. By use of a computer-generated randomisation sequence, we randomly assigned patients to receive either GPi DBS or STN DBS (1:1), applying a minimisation procedure according to drug use (levodopa equivalent dose <1000 mg vs ≥1000 mg) and treatment centre. Patients and study assessors (but not those who assessed adverse events) were masked to treatment allocation. We had two primary outcomes: functional health as measured by the weighted Academic Medical Center Linear Disability Scale (ALDS; weighted by time spent in the off phase and on phase) and a composite score for cognitive, mood, and behavioural effects up to 1 year after surgery. Secondary outcomes were symptom scales, activities of daily living scales, a quality-of-life questionnaire, the occurrence of adverse events, and drug use. We used the intention-to-treat principle for all analyses. This trial is registered with www.controlled-trials.com, number ISRCTN85542074. FINDINGS Between Feb 1, 2007, and March 29, 2011, we enrolled 128 patients, assigning 65 to GPi DBS and 63 to STN DBS. We found no statistically significant difference in either of our primary outcomes: mean change in weighted ALDS (3·0 [SD 14·5] in the GPi group vs 7·7 [23·2] in the STN group; p=0·28) and the number of patients with cognitive, mood, and behavioural side-effects (36 [58%] of 62 patients in the GPi group vs 35 [56%] of 63 patients in the STN group; p=0·94). Secondary outcomes showed larger improvements in off-drug phase in the STN group compared with the GPi group in the mean change in unified Parkinsons disease rating scale motor examination scores (20·3 [16·3] vs 11·4 [16·1]; p=0·03), the mean change in ALDS scores (20·3 [27·1] vs 11·8 [18·9]; p=0·04), and medication (mean levodopa equivalent drug reduction: 546 [SD 561] vs 208 [521]; p=0·01). We recorded no difference in the occurrence of adverse events between the two groups. Other secondary endpoints showed no difference between the groups. INTERPRETATION Although there was no difference in our primary outcomes, our findings suggest that STN could be the preferred target for DBS in patients with advanced Parkinsons disease. FUNDING Stichting Internationaal Parkinson Fonds, Prinses Beatrix Fonds, and Parkinson Vereniging.

The development of a handicap assessment questionnaire: the Impact on Participation and Autonomy (IPA)

Objective: To report on the feasibility and psychometric properties in terms of homogeneity and construct validity of a newly developed handicap questionnaire focusing on person-perceived handicaps: the Impact on Participation and Autonomy (IPA). Design: Cross-sectional. Setting, subjects and outcome measure: One hundred consecutive individuals from the outpatient clinic of the department of rehabilitation of an academic hospital administered the new questionnaire IPA. Results: The results show good homogeneity and construct validity of the IPA. Factor analysis showed that the scale consists of four factors, explaining 68% of the total variance: social relationships, autonomy in self-care, mobility and leisure, and family role. Homogeneity of the four subscales was considered good, Cronbachs α ranged from 0.84 (family role) to 0.87 (social relationships). Feasibility in terms of the number of missing values and administration time needed was satisfactory. Conclusion: The first results suggest that the IPA promises to be a useful handicap questionnaire. Further research is needed to establish test–retest reliability, convergent validity and responsiveness to change.

Beyond disability: perceived participation in people with a chronic disabling condition

Objective: To describe the impact of a chronic disabling condition on participation and to identify variables that may explain perceived restrictions in participation. Study design: Cross-sectional. Setting: People were recruited from the outpatient clinics of two rehabilitation centres and the rehabilitation department of an academic hospital. Subjects: One hundred and twenty-six people from five diagnostic groups (neuromuscular disease, rheumatoid arthritis, spinal cord injury, stroke, fibromyalgia) participated in the study. Method: The IPA (Impact on Participation and Autonomy) questionnaire was used to describe perceived participation. Explanatory variables were studied in terms of sociodemographic factors and health status variables. Results: Some restrictions in participation seem comparable among diagnostic groups, others are specific to one or two groups. People with stroke, rheumatoid arthritis or fibromyalgia perceived more restrictions in participation than people with spinal cord injury or neuromuscular disorders. Emotional distress was the most important factor contributing to restrictions in participation. Conclusions: Perceived participation remains a complex concept in which many factors are involved. To make a contribution to meaningful participation of people with a chronic disabling condition, rehabilitation treatment should address physical, social, emotional and environmental aspects.

Geriatric Conditions in Acutely Hospitalized Older Patients: Prevalence and One-Year Survival and Functional Decline

Background To study the prevalence of eighteen geriatric conditions in older patients at admission, their reporting rate in discharge summaries and the impact of these conditions on mortality and functional decline one year after admission. Method A prospective multicenter cohort study conducted between 2006 and 2008 in two tertiary university teaching hospitals and one regional teaching hospital in the Netherlands. Patients of 65 years and older, acutely admitted and hospitalized for at least 48 hours, were invited to participate. Eighteen geriatric conditions were assessed at hospital admission, and outcomes (mortality, functional decline) were assessed one year after admission. Results 639 patients were included, with a mean age of 78 years. IADL impairment (83%), polypharmacy (61%), mobility difficulty (59%), high levels of primary caregiver burden (53%), and malnutrition (52%) were most prevalent. Except for polypharmacy and cognitive impairment, the reporting rate of the geriatric conditions in discharge summaries was less than 50%. One year after admission, 35% had died and 33% suffered from functional decline. A high Charlson comorbidity index score, presence of malnutrition, high fall risk, presence of delirium and premorbid IADL impairment were associated with mortality and overall poor outcome (mortality or functional decline). Obesity lowered the risk for mortality. Conclusion Geriatric conditions were highly prevalent and associated with poor health outcomes after admission. Early recognition of these conditions in acutely hospitalized older patients and improving the handover to the general practitioner could lead to better health outcomes and reduce the burden of hospital admission for older patients.

Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial

BACKGROUND Platelet transfusion after acute spontaneous primary intracerebral haemorrhage in people taking antiplatelet therapy might reduce death or dependence by reducing the extent of the haemorrhage. We aimed to investigate whether platelet transfusion with standard care, compared with standard care alone, reduced death or dependence after intracerebral haemorrhage associated with antiplatelet therapy use. METHODS We did this multicentre, open-label, masked-endpoint, randomised trial at 60 hospitals in the Netherlands, UK, and France. We enrolled adults within 6 h of supratentorial intracerebral haemorrhage symptom onset if they had used antiplatelet therapy for at least 7 days beforehand and had a Glasgow Coma Scale score of at least 8. With use of a secure web-based system that concealed allocation and used biased coin randomisation, study collaborators randomly assigned participants (1:1; stratified by hospital and type of antiplatelet therapy) to receive either standard care or standard care with platelet transfusion within 90 min of diagnostic brain imaging. Participants and local investigators giving interventions were not masked to treatment allocation, but allocation was concealed from outcome assessors and investigators analysing data. The primary outcome was shift towards death or dependence rated on the modified Rankin Scale (mRS) at 3 months, and analysed by ordinal logistic regression, adjusted for stratification variables and the Intracerebral Haemorrhage Score. The primary analysis was done in the intention-to-treat population and safety analyses were done in the intention-to-treat and as-treated populations. This trial is registered with the Netherlands Trial Register, number NTR1303, and is now closed. FINDINGS Between Feb 4, 2009, and Oct 8, 2015, 41 sites enrolled 190 participants. 97 participants were randomly assigned to platelet transfusion and 93 to standard care. The odds of death or dependence at 3 months were higher in the platelet transfusion group than in the standard care group (adjusted common odds ratio 2·05, 95% CI 1·18-3·56; p=0·0114). 40 (42%) participants who received platelet transfusion had a serious adverse event during their hospital stay, as did 28 (29%) who received standard care. 23 (24%) participants assigned to platelet transfusion and 16 (17%) assigned to standard care died during hospital stay. INTERPRETATION Platelet transfusion seems inferior to standard care for people taking antiplatelet therapy before intracerebral haemorrhage. Platelet transfusion cannot be recommended for this indication in clinical practice. FUNDING The Netherlands Organisation for Health Research and Development, Sanquin Blood Supply, Chest Heart and Stroke Scotland, French Ministry of Health.

Prognostic factors for the progression of Parkinson's disease: a systematic review.

The purpose of this systematic review is to summarize studies that describe the course of Parkinsons disease (PD) and to identify factors that predict change in motor impairment, disability, and quality of life. A literature search was conducted in MEDLINE, EMBASE, CINAHL, and Web of Science limited to the English, French, German, Spanish, and Dutch language. Reports were selected if the study involved subjects with PD, the outcome measures described impairment, disability, or quality of life and follow‐up was at least 6 months. All included studies were scored for methodological quality. Data were extracted and summarized in a best evidence synthesis. We screened 1,535 titles and abstracts, of which 27 fulfilled our inclusion criteria. A meta‐analysis to quantitatively aggregate progression scores of motor impairment and disability was not possible because of the wide variety of outcome measures used and the heterogeneous study populations. Limited evidence is found for lower UPDRS‐ME at baseline, dementia and SE < 70% as prognostic factors for future motor impairment. There is strong evidence for higher age at onset and higher PIGD‐score; and limited evidence for higher bradykinesia‐score, non‐tremor dominant subtype, symmetrical disease at baseline, and depression as prognostic factors for progression of disability. Prognostic factors were identified for impairment and disability. The literature on prognosis in PD is not fulfilling the high methodological standards applied nowadays. There is a need for prospective cohorts of PD patients assembled at a common early point in the disease with long time follow‐up.

Statin Treatment and the Occurrence of Hemorrhagic Stroke in Patients With a History of Cerebrovascular Disease

Background and Purpose— The recently published Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study showed that statins exert a marginally beneficial effect on stroke prevention in patients with a history of cerebrovascular disease. Interestingly, the magnitude of the beneficial effect shown in this study is smaller than in similar studies, which included patients without a history of cerebrovascular disease. In SPARCL, an increased occurrence of hemorrhagic strokes in patients on statin treatment was observed, an effect that was also earlier described in the Heart Protection Study in a subgroup of patients with a history of cerebrovascular disease. The purpose of this systematic review was therefore to investigate the effect of statin treatment on the occurrence of ischemic and hemorrhagic strokes in patients with a history of cerebrovascular disease. Methods— We systematically searched the PUBMED database for the combination of the variables “statin” AND “stroke.” Furthermore, we searched for relevant studies in the Cochrane Library and Cochrane Central Register of Controlled Trials and handsearched citations. Pooled effect sizes were expressed in relative risk estimates with corresponding 95% CIs. Results— Four studies were included investigating the effect of statins in 8832 patients with a history of cerebrovascular disease. The pooled relative risk for statin users of overall stroke during follow-up was 0.88 (95% CI: 0.78 to 0.99). The pooled relative risk of ischemic stroke was 0.80 (95% CI: 0.70 to 0.92) and of hemorrhagic stroke 1.73 (95% CI: 1.19 to 2.50). Conclusion— In patients with a history of cerebrovascular disease, statins clearly decrease the risk of ischemic stroke. However, this beneficial effect is partly lost by an increased risk of hemorrhagic stroke.

Prevalence of orthostatic hypotension in Parkinson's disease: a systematic review and meta-analysis.

BACKGROUND Although orthostatic hypotension (OH) is recognized as one of the main non-motor symptoms of Parkinsons disease (PD), there is inconsistent evidence about the prevalence of OH in PD. To estimate the prevalence of OH in PD more precisely we conducted a systematic review of the literature. METHODS From PubMed and Embase searches with predefined inclusion criteria, we identified studies published up till December 2009. Prevalence numbers from studies were pooled using a non-linear random-effects meta-analysis. RESULTS We found 25 studies from which the prevalence of OH could be calculated. The pooled estimate of the point prevalence of OH in PD was 30.1% (95% CI: 22.9% to 38.4%). We found a large statistical heterogeneity between studies which could not be reduced by several subgroup analyses. CONCLUSIONS The estimated prevalence of OH in PD is 30%. However, due to the large heterogeneity between studies this pooled estimate should be interpreted with caution. More data from unselected population-based cohorts are needed.