Evaluation of financial incentives as a quality improvement strategy in the public hospital context : clinician attitudes, design variables, and economic costs

In 2008, a three-year pilot ‘pay for performance’ (P4P) program, known as ‘Clinical Practice Improvement Payment’ (CPIP) was introduced into Queensland Health (QHealth). QHealth is a large public health sector provider of acute, community, and public health services in Queensland, Australia. The organisation has recently embarked on a significant reform agenda including a review of existing funding arrangements (Duckett et al., 2008). Partly in response to this reform agenda, a casemix funding model has been implemented to reconnect health care funding with outcomes. CPIP was conceptualised as a performance-based scheme that rewarded quality with financial incentives. This is the first time such a scheme has been implemented into the public health sector in Australia with a focus on rewarding quality, and it is unique in that it has a large state-wide focus and includes 15 Districts. CPIP initially targeted five acute and community clinical areas including Mental Health, Discharge Medication, Emergency Department, Chronic Obstructive Pulmonary Disease, and Stroke. The CPIP scheme was designed around key concepts including the identification of clinical indicators that met the set criteria of: high disease burden, a well defined single diagnostic group or intervention, significant variations in clinical outcomes and/or practices, a good evidence, and clinician control and support (Ward, Daniels, Walker & Duckett, 2007). This evaluative research targeted Phase One of implementation of the CPIP scheme from January 2008 to March 2009. A formative evaluation utilising a mixed methodology and complementarity analysis was undertaken. The research involved three research questions and aimed to determine the knowledge, understanding, and attitudes of clinicians; identify improvements to the design, administration, and monitoring of CPIP; and determine the financial and economic costs of the scheme. Three key studies were undertaken to ascertain responses to the key research questions. Firstly, a survey of clinicians was undertaken to examine levels of knowledge and understanding and their attitudes to the scheme. Secondly, the study sought to apply Statistical Process Control (SPC) to the process indicators to assess if this enhanced the scheme and a third study examined a simple economic cost analysis. The CPIP Survey of clinicians elicited 192 clinician respondents. Over 70% of these respondents were supportive of the continuation of the CPIP scheme. This finding was also supported by the results of a quantitative altitude survey that identified positive attitudes in 6 of the 7 domains-including impact, awareness and understanding and clinical relevance, all being scored positive across the combined respondent group. SPC as a trending tool may play an important role in the early identification of indicator weakness for the CPIP scheme. This evaluative research study supports a previously identified need in the literature for a phased introduction of Pay for Performance (P4P) type programs. It further highlights the value of undertaking a formal risk assessment of clinician, management, and systemic levels of literacy and competency with measurement and monitoring of quality prior to a phased implementation. This phasing can then be guided by a P4P Design Variable Matrix which provides a selection of program design options such as indicator target and payment mechanisms. It became evident that a clear process is required to standardise how clinical indicators evolve over time and direct movement towards more rigorous ‘pay for performance’ targets and the development of an optimal funding model. Use of this matrix will enable the scheme to mature and build the literacy and competency of clinicians and the organisation as implementation progresses. Furthermore, the research identified that CPIP created a spotlight on clinical indicators and incentive payments of over five million from a potential ten million was secured across the five clinical areas in the first 15 months of the scheme. This indicates that quality was rewarded in the new QHealth funding model, and despite issues being identified with the payment mechanism, funding was distributed. The economic model used identified a relative low cost of reporting (under $8,000) as opposed to funds secured of over $300,000 for mental health as an example. Movement to a full cost effectiveness study of CPIP is supported. Overall the introduction of the CPIP scheme into QHealth has been a positive and effective strategy for engaging clinicians in quality and has been the catalyst for the identification and monitoring of valuable clinical process indicators. This research has highlighted that clinicians are supportive of the scheme in general; however, there are some significant risks that include the functioning of the CPIP payment mechanism. Given clinician support for the use of a pay–for-performance methodology in QHealth, the CPIP scheme has the potential to be a powerful addition to a multi-faceted suite of quality improvement initiatives within QHealth.

Long-evans rats acquire operant self-administration of 20% ethanol without sucrose fading

A major obstacle in the development of new medications for the treatment of alcohol use disorders (AUDs) has been the lack of preclinical, oral ethanol consumption paradigms that elicit high consumption. We have previously shown that rats exposed to 20% ethanol intermittently in a two-bottle choice paradigm will consume two times more ethanol than those given continuous access without the use of water deprivation or sucrose fading (5-6 g/kg every 24 h vs 2-3 g/kg every 24 h, respectively). In this study, we have adapted the model to an operant self-administration paradigm. Long-Evans rats were given access to 20% ethanol in overnight sessions on one of two schedules: (1) intermittent (Monday, Wednesday, and Friday) or (2) daily (Monday through Friday). With the progression of the overnight sessions, both groups showed a steady escalation in drinking (3-6 g/kg every 14 h) without the use of a sucrose-fading procedure. Following the acquisition phase, the 20% ethanol groups consumed significantly more ethanol than did animals trained to consume 10% ethanol with a sucrose fade (1.5 vs 0.7 g/kg every 30 min) and reached significantly higher blood ethanol concentrations. In addition, training history (20% ethanol vs 10% ethanol with sucrose fade) had a significant effect on the subsequent self-administration of higher concentrations of ethanol. Administration of the pharmacological stressor yohimbine following extinction caused a significant reinstatement of ethanol-seeking behavior. Both 20% ethanol models show promise and are amenable to the study of maintenance, motivation, and reinstatement. Furthermore, training animals to lever press for ethanol without the use of sucrose fading removes a potential confound from self-administration studies. © 2010 Nature Publishing Group All rights reserved.

Representational change and strategy use in children's number line estimation during the first years of primary school

Background: The objective of this study was to scrutinize number line estimation behaviors displayed by children in mathematics classrooms during the first three years of schooling. We extend existing research by not only mapping potential logarithmic-linear shifts but also provide a new perspective by studying in detail the estimation strategies of individual target digits within a number range familiar to children. Methods: Typically developing children (n = 67) from Years 1 – 3 completed a number-to-position numerical estimation task (0-20 number line). Estimation behaviors were first analyzed via logarithmic and linear regression modeling. Subsequently, using an analysis of variance we compared the estimation accuracy of each digit, thus identifying target digits that were estimated with the assistance of arithmetic strategy. Results: Our results further confirm a developmental logarithmic-linear shift when utilizing regression modeling; however, uniquely we have identified that children employ variable strategies when completing numerical estimation, with levels of strategy advancing with development. Conclusion: In terms of the existing cognitive research, this strategy factor highlights the limitations of any regression modeling approach, or alternatively, it could underpin the developmental time course of the logarithmic-linear shift. Future studies need to systematically investigate this relationship and also consider the implications for educational practice.

Preliminary evaluation of a primary care intervention for cry-fuss behaviours in the first 3-4 months of life (‘The Possums Approach’) : effects on cry-fuss behaviours and maternal mood

Problem crying in the first few months of life is both common and complex, arising out of multiple interacting and co-evolving factors. Parents whose babies cry and fuss a lot receive conflicting advice as they seek help from multiple health providers and emergency departments, and may be admitted into tertiary residential services. Conflicting advice is costly, and arises out of discipline-specific interpretations of evidence. An integrated, interdisciplinary primary care intervention (‘The Possums Approach’) for cry-fuss problems in the first months of life was developed from available peer-reviewed evidence. This study reports on preliminary evaluation of delivery of the intervention. A total of 20 mothers who had crying babies under 16 weeks of age (average age 6.15 weeks) completed questionnaires, including the Crying Patterns Questionnaire and the Edinburgh Postnatal Depression Scale, before and 3-4 weeks after their first consultation with trained primary care practitioners. Preliminary evaluation is promising. The Crying Patterns Questionnaire showed a significant decrease in crying and fussing duration, by 1 h in the evening (P = 0.001) and 30 min at night (P = 0.009). The median total amount of crying and fussing in a 24-h period was reduced from 6.12 to 3 h. The Edinburgh Postnatal Depression Scale showed a significant improvement in depressive symptoms, with the median score decreasing from 11 to 6 (P = 0.005). These findings are corroborated by an analysis of results for the subset of 16 participants whose babies were under 12 weeks of age (average age 4.71 weeks). These preliminary results demonstrate significantly decreased infant crying in the evening and during the night and improved maternal mood, validating an innovative interdisciplinary clinical intervention for cry-fuss problems in the first few months of life. This intervention, delivered by trained health professionals, has the potential to mitigate the costly problem of health professionals giving discipline-specific and conflicting advice post-birth.

Outcomes of an early feeding practices intervention to prevent childhood obesity

Objective Use a randomised controlled trial (RCT) to evaluate outcomes of a universal intervention to promote protective feeding practices, which commenced in infancy and aimed to prevent childhood obesity Subjects and Methods The NOURISH RCT enrolled 698 first-time mothers (mean age 30.1 years, SD=5.3) with healthy term infants (51% female) aged 4.3 (SD=1.0) months at baseline. Mothers were randomly allocated to self-directed access to usual care or to attend two 6-session interactive group education modules that provided anticipatory guidance on early feeding practices. Outcomes were assessed six months after completion of the second information module, 20 months from baseline and when the children were two years old. Maternal feeding practices were self-reported using validated questionnaires and study-developed items. Study-measured child height and weight were used to calculate BMI Z-score. Results Retention at follow-up was 78%. Mothers in the intervention group reported using responsive feeding more frequently on 6/9 subscales and 8/8 items (Ps ≤.03) and overall less ‘controlling feeding practices’ (P<.001). They also more frequently used feeding practices (3/4 items; Ps <.01) likely to enhance food acceptance. No statistically significant differences were noted in anthropometric outcomes (BMI Z-score: P=.11), nor in prevalence of overweight/obesity (control 17.9% vs. intervention 13.8%, P=.23). Conclusions Evaluation of NOURISH at child age two years found that anticipatory guidance on complementary feeding, tailored to developmental stage, increased use by first-time mothers of 'protective' feeding practices that potentially support the development of healthy eating and growth patterns in young children.

Phase III trial comparing paclitaxel poliglumex (CT-2103, PPX) in combination with carboplatin versus standard paclitaxel and carboplatin in the treatment of PS 2 patients with chemotherapy-naïve advanced non-small cell lung cancer

INTRODUCTION: Performance status (PS) 2 patients with non-small cell lung cancer (NSCLC) experience more toxicity, lower response rates, and shorter survival times than healthier patients treated with standard chemotherapy. Paclitaxel poliglumex (PPX), a macromolecule drug conjugate of paclitaxel and polyglutamic acid, reduces systemic exposure to peak concentrations of free paclitaxel and may lead to increased concentrations in tumors due to enhanced vascular permeability. METHODS: Chemotherapy-naive PS 2 patients with advanced NSCLC were randomized to receive carboplatin (area under the curve = 6) and either PPX (210 mg/m/10 min without routine steroid premedication) or paclitaxel (225 mg/m/3 h with standard premedication) every 3 weeks. The primary end point was overall survival. RESULTS: A total of 400 patients were enrolled. Alopecia, arthralgias/myalgias, and cardiac events were significantly less frequent with PPX/carboplatin, whereas grade ≥3 neutropenia and grade 3 neuropathy showed a trend of worsening. There was no significant difference in the incidence of hypersensitivity reactions despite the absence of routine premedication in the PPX arm. Overall survival was similar between treatment arms (hazard ratio, 0.97; log rank p = 0.769). Median and 1-year survival rates were 7.9 months and 31%, for PPX versus 8 months and 31% for paclitaxel. Disease control rates were 64% and 69% for PPX and paclitaxel, respectively. Time to progression was similar: 3.9 months for PPX/carboplatin versus 4.6 months for paclitaxel/carboplatin (p = 0.210). CONCLUSION: PPX/carboplatin failed to provide superior survival compared with paclitaxel/carboplatin in the first-line treatment of PS 2 patients with NSCLC, but the results with respect to progression-free survival and overall survival were comparable and the PPX regimen was more convenient. © 2008International Association for the Study of Lung Cancer.

Single-agent versus combination chemotherapy in patients with advanced non-small cell lung cancer and a performance status of 2 : prognostic factors and treatment selection based on two large randomized clinical trials

Purpose: Data from two randomized phase III trials were analyzed to evaluate prognostic factors and treatment selection in the first-line management of advanced non-small cell lung cancer patients with performance status (PS) 2. Patients and Methods: Patients randomized to combination chemotherapy (carboplatin and paclitaxel) in one trial and single-agent therapy (gemcitabine or vinorelbine) in the second were included in these analyses. Both studies had identical eligibility criteria and were conducted simultaneously. Comparison of efficacy and safety was performed between the two cohorts. A regression analysis identified prognostic factors and subgroups of patients that may benefit from combination or single-agent therapy. Results: Two hundred one patients were treated with combination and 190 with single-agent therapy. Objective responses were 37 and 15%, respectively. Median time to progression was 4.6 months in the combination arm and 3.5 months in the single-agent arm (p < 0.001). Median survival imes were 8.0 and 6.6 months, and 1-year survival rates were 31 and 26%, respectively. Albumin <3.5 g, extrathoracic metastases, lactate dehydrogenase ≥200 IU, and 2 comorbid conditions predicted outcome. Patients with 0-2 risk factors had similar outcomes independent of treatment, whereas patients with 3-4 factors had a nonsignificant improvement in median survival with combination chemotherapy. Conclusion: Our results show that PS2 non-small cell lung cancer patients are a heterogeneous group who have significantly different outcomes. Patients treated with first-line combination chemotherapy had a higher response and longer time to progression, whereas overall survival did not appear significantly different. A prognostic model may be helpful in selecting PS 2 patients for either treatment strategy. © 2009 by the International Association for the Study of Lung Cancer.

Molecular biomarkers in non-small-cell lung cancer : a retrospective analysis of data from the phase 3 FLEX study

Background: Findings from the phase 3 FLEX study showed that the addition of cetuximab to cisplatin and vinorelbine significantly improved overall survival, compared with cisplatin and vinorelbine alone, in the first-line treatment of EGFR-expressing, advanced non-small-cell lung cancer (NSCLC). We investigated whether candidate biomarkers were predictive for the efficacy of chemotherapy plus cetuximab in this setting. Methods: Genomic DNA extracted from formalin-fixed paraffin-embedded (FFPE) tumour tissue of patients enrolled in the FLEX study was screened for KRAS codon 12 and 13 and EGFR kinase domain mutations with PCR-based assays. In FFPE tissue sections, EGFR copy number was assessed by dual-colour fluorescence in-situ hybridisation and PTEN expression by immunohistochemistry. Treatment outcome was investigated according to biomarker status in all available samples from patients in the intention-to-treat population. The primary endpoint in the FLEX study was overall survival. The FLEX study, which is ongoing but not recruiting participants, is registered with ClinicalTrials.gov, number NCT00148798. Findings: KRAS mutations were detected in 75 of 395 (19%) tumours and activating EGFR mutations in 64 of 436 (15%). EGFR copy number was scored as increased in 102 of 279 (37%) tumours and PTEN expression as negative in 107 of 303 (35%). Comparisons of treatment outcome between the two groups (chemotherapy plus cetuximab vs chemotherapy alone) according to biomarker status provided no indication that these biomarkers were of predictive value. Activating EGFR mutations were identified as indicators of good prognosis, with patients in both treatment groups whose tumours carried such mutations having improved survival compared with those whose tumours did not (chemotherapy plus cetuximab: median 17·5 months [95% CI 11·7-23·4] vs 8·5 months [7·1-10·8], hazard ratio [HR] 0·52 [0·32-0·84], p=0·0063; chemotherapy alone: 23·8 months [15·2-not reached] vs 10·0 months [8·7-11·0], HR 0·35 [0·21-0·59], p<0·0001). Expression of PTEN seemed to be a potential indicator of good prognosis, with patients whose tumours expressed PTEN having improved survival compared with those whose tumours did not, although this finding was not significant (chemotherapy plus cetuximab: median 11·4 months [8·6-13·6] vs 6·8 months [5·9-12·7], HR 0·80 [0·55-1·16], p=0·24; chemotherapy alone: 11·0 months [9·2-12·6] vs 9·3 months [7·6-11·9], HR 0·77 [0·54-1·10], p=0·16). Interpretation: The efficacy of chemotherapy plus cetuximab in the first-line treatment of advanced NSCLC seems to be independent of each of the biomarkers assessed. Funding: Merck KGaA. © 2011 Elsevier Ltd.

A phase II study of the modulation of 5-fluorouracil and folinic acid with high-dose infusional hydroxyurea in metastatic colorectal carcinoma

Background: Hydroxyurea (HU), an inhibitor of ribonucleotide reductase, may potentiate the activity of 5-fluorouracil (5-FU) and folinic acid (FA) by reducing the deoxyribonucleotide pool available for DNA synthesis and repair. However as HU may inhibit the formation of 5-fluoro-2-deoxyuridine-5- monophosphate (FdUMP), one of the principal active metabolites of 5-FU, the scheduling of HU may be critical. In vitro experiments suggest that administration of HU following 5-FU, maintaining the concentration in the region of I mM for six or more hours, significantly enhances the efficacy of 5-FU. Patients and methods: 5-FU/FA was given as follows: days 1 and 2 - FA 250 mg/m 2 (max. 350 mg) over two hours followed by 5-FU 400 mg/m 2 by intravenous bolus (ivb) over 15 minutes and subsequently 5-FU 400 mg/m 2 infusion (ivi) over 22 hours. HU was administered on day 3 immediately after the 5-FU with 3 g ivb over 15 minutes followed by 12 g ivi over 12 hours. Results: Thirty patients were entered into the study. Median survival was nine months (range 1-51 + months). There were eight partial responses (28%, 95% CI: 13%-47%). The median duration of response was 6.5 (range 4-9 months). Grade 3-4 toxicities included neutropenia (grade 3 in eight patients and grade 4 in five), anaemia (grade 3 in one patient) and diarrhoea (grade 3 in two patients). Neutropenia was associated with pyrexia in two patients. Phlebitis at the infusion site occurred in five patients. The treatment was complicated by pulmonary embolism in one patient and deep venous thrombosis in another. Conclusion: HU administered in this schedule is well tolerated. Based on these results and those of other phase II studies, a randomised phase III study of 5-FU, FA and HU versus 5-FU and FA using the standard de Gramont schedule is recommended.

Safety and efficacy of the combination of trastuzumab with docetaxel for HER2-positive women with advanced breast cancer : a review of the existing clinical trials and results of the expanded access programme in the UK

Trastuzumab is a humanised monoclonal antibody against the extracellular domain of HER2 (human epidermal growth factor receptor-2) that is overexpressed in about 25% of human breast cancers. It has shown clinical benefit in HER2-positive breast cancer cases when used alone or in combination with chemotherapy. Trastuzumab increases the response rate to chemotherapy and prolongs survival when used in combination with taxanes. In this article, we review the clinical trials where trastuzumab has been administered together with docetaxel, and we present the results of the trastuzumab expanded access programme (EAP) in the UK. Combination of trastuzumab with docetaxel results in similar response rates and time-to-progression with the trastuzumab/paclitaxel combinations. The toxicity of the combination and the risk of heart failure are low. The clinical data for the docetaxel/trastuzumab combination indicate a favourable profile from both the efficacy and the safety point of view and confirm the feasibility and safety of trastuzumab administration both as monotherapy and in combination with docetaxel. © 2004 Blackwell Publishing Ltd.

The efficacy of Aloe vera, tea tree oil and saliva as first aid treatment for partial thickness burn injuries

Many alternative therapies are used as first aid treatment for burns, despite limited evidence supporting their use. In this study, Aloe vera, saliva and a tea tree oil impregnated dressing (Burnaid) were applied as first aid to a porcine deep dermal contact burn, compared to a control of nothing. After burn creation, the treatments were applied for 20 min and the wounds observed at weekly dressing changes for 6 weeks. Results showed that the alternative treatments did significantly decrease subdermal temperature within the skin during the treatment period. However, they did not decrease the microflora or improve re-epithelialisation, scar strength, scar depth or cosmetic appearance of the scar and cannot be recommended for the first aid treatment of partial thickness burns.

The optimal temperature of first aid treatment for partial thickness burn injuries

Using our porcine model of deep dermal partial thickness burn injury, various cooling techniques (15 degrees C running water, 2 degrees C running water, ice) of first aid were applied for 20 minutes compared with a control (ambient temperature). The subdermal temperatures were monitored during the treatment and wounds observed and photographed weekly for 6 weeks, observing reepithelialization, wound surface area and cosmetic appearance. Tissue histology and scar tensile strength were examined 6 weeks after burn. The 2 degrees C and ice treatments decreased the subdermal temperature the fastest and lowest, however, generally the 15 and 2 degrees C treated wounds had better outcomes in terms of reepithelialization, scar histology, and scar appearance. These findings provide evidence to support the current first aid guidelines of cold tap water (approximately 15 degrees C) for 20 minutes as being beneficial in helping to heal the burn wound. Colder water at 2 degrees C is also beneficial. Ice should not be used.

A review of first aid treatments for burn injuries

Throughout history there have been many different and sometimes bizarre treatments prescribed for burns. Unfortunately many of these treatments still persist today, although they often do not have sufficient evidence to support their use. This paper reviews common first aid and pre-hospital treatments for burns (water--cold or warm, ice, oils, powders and natural plant therapies), possible mechanisms whereby they might work and the literature which supports their use. From the published work to date, the current recommendations for the first aid treatment of burn injuries should be to use cold running tap water (between 2 and 15 degrees C) on the burn, not ice or alternative plant therapies.

Determination of urinary thymidine glycol using affinity chromatography, HPLC and post-column reaction detection : a biomarker of oxidative DNA damage upon kidney transplantation

Reactive oxygen species are generated during ischaemia-reperfusion of tissue. Oxidation of thymidine by hydroxyl radicals (HO) leads to the formation of 5,6-dihydroxy-5,6-dihydrothymidine (thymidine glycol). Thymidine glycol is excreted in urine and can be used as biomarker of oxidative DNA damage. Time dependent changes in urinary excretion rates of thymidine glycol were determined in six patients after kidney transplantation and in six healthy controls. A new analytical method was developed involving affinity chromatography and subsequent reverse-phase high-performance liquid chromatography (RP-HPLC) with a post-column chemical reaction detector and endpoint fluorescence detection. The detection limit of this fluorimetric assay was 1.6 ng thymidine glycol per ml urine, which corresponds to about half of the physiological excretion level in healthy control persons. After kidney transplantation the urinary excretion rate of thymidine glycol increased gradually reaching a maximum around 48 h. The excretion rate remained elevated until the end of the observation period of 10 days. Severe proteinuria with an excretion rate of up to 7.2 g of total protein per mmol creatinine was also observed immediately after transplantation and declined within the first 24 h of allograft function (0.35 + 0.26 g/mmol creatinine). The protein excretion pattern, based on separation of urinary proteins on sodium dodecyl sulphate-polyacrylamide gel electrophorosis (SDS-PAGE), as well as excretion of individual biomarker proteins, indicated nonselective glomerular and tubular damage. The increased excretion of thymidine glycol after kidney transplantation may be explained by ischaemia-reperfusion induced oxidative DNA damage of the transplanted kidney.

Initial burden of disease estimates for South Africa, 2000

BACKGROUND This paper describes the first national burden of disease study for South Africa. The main focus is the burden due to premature mortality, i.e. years of life lost (YLLs). In addition, estimates of the burden contributed by morbidity, i.e. the years lived with disability (YLDs), are obtained to calculate disability-adjusted life years (DALYs); and the impact of AIDS on premature mortality in the year 2010 is assessed. METHOD Owing to the rapid mortality transition and the lack of timely data, a modelling approach has been adopted. The total mortality for the year 2000 is estimated using a demographic and AIDS model. The non-AIDS cause-of-death profile is estimated using three sources of data: Statistics South Africa, the National Department of Home Affairs, and the National Injury Mortality Surveillance System. A ratio method is used to estimate the YLDs from the YLL estimates. RESULTS The top single cause of mortality burden was HIV/AIDS followed by homicide, tuberculosis, road traffic accidents and diarrhoea. HIV/AIDS accounted for 38% of total YLLs, which is proportionately higher for females (47%) than for males (33%). Pre-transitional diseases, usually associated with poverty and underdevelopment, accounted for 25%, non-communicable diseases 21% and injuries 16% of YLLs. The DALY estimates highlight the fact that mortality alone underestimates the burden of disease, especially with regard to unintentional injuries, respiratory disease, and nervous system, mental and sense organ disorders. The impact of HIV/AIDS is expected to more than double the burden of premature mortality by the year 2010. CONCLUSION This study has drawn together data from a range of sources to develop coherent estimates of premature mortality by cause. South Africa is experiencing a quadruple burden of disease comprising the pre-transitional diseases, the emerging chronic diseases, injuries, and HIV/AIDS. Unless interventions that reduce morbidity and delay morbidity become widely available, the burden due to HIV/AIDS can be expected to grow very rapidly in the next few years. An improved base of information is needed to assess the morbidity impact more accurately.