31-08-2013 t/m 4-09-2013 ESC Congres 2013 Amsterdam (NH)

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Amsterdam, The Netherlands – Saturday 31 August 2013: High doses of statins prevent dementia in older people, according to research presented at the ESC Congress today by Dr Tin-Tse Lin from Taiwan. The study of nearly 58,000 patients found that high potency statins had the strongest protective effects against dementia.

Dr Lin said: “Statins are widely used in the older population to reduce the risk of cardiovascular disease. But recent reports of statin-associated cognitive impairment have led the US Food and Drug Administration (FDA) to list statin-induced cognitive changes, especially for the older population, in its safety communications.”

He added: “Previous studies had considered statin therapy to exert a beneficial effect on dementia. But few large-scale studies have focused on the impact of statins on new-onset, non-vascular dementia in the geriatric population.”

Accordingly, the current study examined whether statin use was associated with new diagnoses of dementia. The researchers used a random sample of 1 million patients covered by Taiwan’s National Health Insurance. From this they identified 57,669 patients aged >65 years who had no history of dementia in 1997 and 1998. The analysis included pre-senile and senile dementia but excluded vascular dementia.

There were 5,516 new diagnoses of dementia during approximately 4.5 years of follow-up. The remaining 52,153 patients aged >65 formed the control group. Subjects were divided into tertiles according to their mean daily equivalent1 dosage and total (across the entire follow up period) equivalent dosage.

The adjusted hazard ratios (HRs) for dementia were significantly inversely associated with increased daily or total equivalent statin dosage. The HRs for the three tertiles of mean equivalent daily dosage (lowest to highest) were 0.622, 0.697 and 0.419 vs control (p<0.001 for trend). The HRs for the three tertiles of total equivalent dosage (lowest to highest) were 0.773, 0.632 and 0.332 vs control (p<0.001 for trend). The protective effect of statins remained in different age, gender and cardiovascular risk subgroups.

Dr Lin said: “The adjusted risks for dementia were significantly inversely associated with increased total or daily equivalent statin dosage. Patients who received the highest total equivalent doses of statins had a 3-fold decrease in the risk of developing dementia. Similar results were found with the daily equivalent statin dosage.”

He added: “It was the potency of the statins rather than their solubility (lipophilic or hydrophilic) which was a major determinant in reducing dementia. High potency statins such as atorvastatin and rosuvastatin showed a significant inverse association with developing dementia in a dose-response manner. Higher doses of high potency statins gave the strongest protective effects against dementia.”

Dr Lin continued: “The results were consistent when analysing daily doses of different kinds of statins. Almost all the statins (except lovastatin) decreased the risk for new onset dementia when taken at higher daily doses. A high mean daily dosage of lovastatin was positively associated with the development of dementia, possibly because lovastatin is a lipophilic statin while the anti-inflammatory cholesterol lowering effect of lovastatin is not comparable to that of atorvastatin and simvastatin.”

Dr Lin concluded: “To the best of our knowledge, this was the first large-scale, nation-wide study which examined the effect of different statins on new onset dementia (except vascular dementia) in an elderly population. We found that high doses of statins, particularly high potency statins, prevent dementia.”

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Amsterdam, The Netherlands – Saturday 31 August 2013: Type of healthcare reimbursement system influences the achievement of cholesterol targets, reveals research presented at ESC Congress 2013 today by Dr Anselm Kai Gitt from Germany. The subanalysis of the Dyslipidemia International Study (DYSIS) found that fewer patients reached the target in countries with restrictive (e.g. Germany) compared to incentive (e.g. the UK) systems.

Dr Gitt said: “There are wide variations between European countries in the achievement of LDL-cholesterol (LDL-C) targets. However the effect of different reimbursement systems on meeting the targets was unknown.”

Between June 2008 and February 2009 DYSIS assessed the prevalence and types of persistent lipid abnormalities in patients receiving statins. Eligible patients were at high risk of a cardiovascular event, aged >45 years, and had been on chronic statin treatment for at least three months. A total of 22,063 patients were enrolled from 2,954 sites across 11 European countries and Canada.

The current subanalysis examined the possible impact of reimbursement systems on the achievement of LDL-C targets in 4,260 German patients and 540 UK patients. Germany operates a “restrictive” system in which chronic medical treatment is restricted by budget constraints. In the UK’s incentive system, reimbursement of general practitioners (GPs) is linked to achieving cholesterol targets.

Dr Gitt said: “The bottom line is that German doctors fear a punitive system where they could be fined if they don’t stay within budget while UK doctors get rewarded for achieving targets.”

The study found that just 42% of German patients achieved the target of LDL-C <100mg/dl compared to 79.8% of UK patients (p<0.001). Dr Gitt said: “Twice as many UK patients achieve cholesterol target levels as German patients. By definition of the study protocol all patients had been on statin treatment. As there are no differences in the availability of lipid lowering drugs between both countries, the different health care systems might have an impact on the way patients are treated.”

Atorvastatin (a potent statin) was used in 3.9% of German patients (mean dose 24.0 mg) compared to 24.8% of UK patients (mean dose 34.2 mg) (p<0.01). Simvastatin (a weaker statin) was used in 83.9% of Germans (mean dose 27.2 mg) compared to 67.6% of UK patients (mean dose 36.6 mg) (p<0.01). Daily dosages were significantly lower in Germany than in the UK, independent of the statin used.

Dr Gitt said: “We found that UK patients are treated with more potent statins and higher doses. UK doctors are treating patients aggressively with statins in response to a financial incentive to reach cholesterol targets. German doctors treat more conservatively, less often using potent statins and high doses which are more expensive.”

He added: “The quality control feedback system in the UK may also impact on the achievement of cholesterol targets. GPs have to measure cholesterol levels and this identifies which patients need more aggressive treatment to reach the target.”

Dr Gitt concluded: “Our study showed that healthcare reimbursement systems appear to impact on the achievement of cholesterol lowering targets. The German system was put in place to control costs but it remains to be seen whether it will achieve this in the long term. The UK system has higher short term costs, with more GP visits, use of potent statins and high doses, but it may ultimately be more cost effective because of fewer complications.”

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Amsterdam, The Netherlands – Saturday 31 August 2013: Aggressive treatment with statins reduces the risk of subsequent cardiovascular events in patients with coronary artery disease (CAD) even if they have very low LDL cholesterol (LDL-C) levels, reveals research presented at ESC Congress 2013 today by Dr Emi Nakano from Japan.

Dr Nakano said: “Many randomised clinical trials, such as Treating to New Targets (TNT) and PROVE IT-TIMI, have shown that aggressive cholesterol lowering with statins improves clinical outcomes in patients with CAD and high LDL-C levels.1,2 But until now it was not known whether aggressive lipid lowering with statins would also benefit CAD patients with very low LDL-C levels.”

The current study used the Ibaraki Cardiovascular Assessment Study (ICAS), a registry of 2,238 patients from 12 hospitals in the Ibaraki region of Japan, who between 0 and 1 month underwent percutaneous coronary interventions. Based on serum LDL-C levels at initial presentation participants were classified into three groups: very low (<70 mg/dl, n=214); low (71-100 mg/dl, n=669); and high (>101 mg/dl, n= 1,355). Decisions of whether to prescribe statins or not, as well as the type and dose, were left to the discretion of treating physicians.

Patients were followed up for a maximum of 3 years. The efficacy of statin treatment was analysed on the composite outcome of Major Cardiovascular Events (MACE), defined as all cause mortality, non-fatal myocardial infarction and non-fatal stroke.

Statins were prescribed in 68% of patients (143) with very low LDL-C, 67% of patients (450) with low LDL-C and 67% of patients (913) with high LDL-C. A total of 204 patients experienced MACE during the median follow-up of 404 days.

The results of a Kaplan-Meier estimate show that three years of statin treatment produced significant reductions in the incidence of MACE in all three groups (p<0.001 for all groups). A Cox regression hazard analysis adjusted for age and gender showed that statins were the main determinant of better outcome regardless of the LDL-C level (p<0.01).

Dr Nakano said: “Our study shows that CAD patients with very low LDL-C levels at initial presentation also benefit from statin treatment. We speculate that statins prevent the enlargement of atherosclerotic plaques and plaque disruption in these patients.”

She added: “Some doctors have been hesitant to prescribe statins in patients with very low LDL-C because of uncertain benefit and the risk of side effects with statins. But our findings suggest that all CAD patients should receive statins to reduce their risk of future cardiovascular events.”

Dr Nakano concluded: “The next step should now be to initiate a randomised controlled trial of statin use in patients with CAD and very low LDL-C levels. This trial should be designed to confirm the benefits of statins for preventing future cardiovascular events in these patients, and to identify which type and dose of statins are most beneficial.”

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Amsterdam, The Netherlands – Saturday 31 August 2013: Patients with five or more risk factors have the same stroke risk as patients with atrial fibrillation, according to research presented at the ESC Congress today by Dr Christine Benn Christiansen from Denmark. The study included data on more than 4 million patients from Danish registries over a 10 year period.

Dr Benn Christiansen said: “We know that atrial fibrillation increases the risk of ischemic stroke. And in patients with atrial fibrillation or previous ischemic stroke, the risk of stroke increases with the number of risk factors. But until now, little attention has been paid to the association between stroke risk and risk factors in patients without prior stroke or atrial fibrillation. We wanted to explore that association and to quantify if stroke risk was of comparable size in patients with numerous risk factors.”

The study included 4,198,119 people aged 18 to 90 years with no history of stroke from nationwide Danish registries during 2000 to 2010. Of these, 161,651 (3.85%) had atrial fibrillation. The investigators compared the risk of stroke in patients with and without atrial fibrillation according to the number of risk factors.

The risk factors included in the study were myocardial infarction, peripheral artery disease, arterial embolism, excessive alcohol consumption, heart failure, carotid stenosis, retinal occlusion, chronic systemic inflammation, chronic kidney disease, venous thromboembolism, epilepsy, migraine, diabetes mellitus, hypertension and age >75 years.

The rate of stroke was calculated per 100 person-years (see figure). Patients with 0 risk factors and no atrial fibrillation had a stroke rate of 0.32 (95% confidence interval [CI] 0.31-0.32) per 100 person-years vs. 2.55 (CI=2.47-2.64) in patients with atrial fibrillation. With 1-2 risk factors present the stroke rate was 1.77 (CI=1.76-1.78) (no atrial fibrillation) and 5.69 (CI=5.61-5.78) (with atrial fibrillation).

For patients with 3-4 risk factors the stroke rates were 4.88 (CI=4.80-4.96) without atrial fibrillation vs. 6.96 (CI=6.79-7.14) with atrial fibrillation. In the presence of 5 or more risk factors stroke rates were 7.27 (CI=6.82-7.74) without atrial fibrillation vs. 8.00 (CI=7.34-8.71) with atrial fibrillation.

Dr Benn Christiansen said: “These results indicate that in patients with three or more risk factors, the risk of stroke is high regardless of the presence of atrial fibrillation. In fact, with five or more risk factors such as diabetes, hypertension, myocardial infarction, heart failure and age above 75 years, the risk associated with atrial fibrillation is eliminated.”

She continued: “Our findings suggest that patients without atrial fibrillation or prior stroke may have a stroke risk that is comparable to patients with atrial fibrillation if they have three or more risk factors.”

Dr Benn Christiansen concluded: “More research is needed on the effect of multiple risk factors on the risk of stroke in patients without atrial fibrillation. Stroke prevention measures may need to be tailored according to the number of risk factors.”

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Amsterdam, The Netherlands – Saturday 31 August 2013: General practitioners (GPs) undertreat women with atrial fibrillation (AF), according to research presented at ESC Congress 2013 today by Dr Pierre Sabouret from France. The analysis of more than 15,000 patients showed that women were undertreated with antithrombotic medications compared to men regardless of their stroke risk and comorbidities.

Dr Sabouret said: “Gender-related differences among outpatients with stable coronary artery disease are well known.1-6 Heart diseases are one of the most important causes of death among women worldwide.5 Therefore, it’s crucial that women benefit from optimal treatments according to guidelines.”

In France both the prevalence (600,000 to 1 million patients) and incidence (110,000 to 230,000 new cases per year) of AF are dramatically increasing.7 ESC AF guidelines recommend the CHA2DS2-VASc score to determine stroke risk and the need for anticoagulation to prevent stroke.8 Female gender is a specific risk and adds one point to the stroke risk score. However no antithrombotic treatment is required if the patient is female, <65 years old and has lone AF.

Dr Sabouret said: “To improve the cardiovascular prognosis of women with AF it’s important to know if there are any gender differences in management. Many AF patients are treated by GPs so we studied their practise.”

The current study investigated the management of AF patients by GPs in France with a focus on gender differences. The aim was to identify potential factors in the choice of prescription (vitamin K antagonist [VKA] alone, aspirin alone or no oral anticoagulants), particularly patient characteristics, disease characteristics, medical history and concomitant medications.

A total of 15,623 AF patients aged ≥18 years were identified from the Longitudinal Patient Database (LPD) during 1 July 2010 to 30 June 2011. The LPD (set up in 1994) contains information on medical history, comorbidities and concomitant medication in 1.6 million active patients from a representative sample of 1,200 active GPs in France. The multivariate analyses included 14,274 patients after excluding those on clopidogrel. Median age was 77 years old, 41.6% were women and 93.2% had a CHA2DS2-VASc score >1.

After excluding women ineligible for anticoagulation (CHA2DS2-VASc score of 1 and age <65 years) the researchers found that women were significantly less treated than men. Just 48.1% of women received VKA (vs 52.6% men) (p<0.0001) and 30.5% received no prevention at all (vs 25.4% men) (p<0.0001). More than 21% received only aspirin despite guideline recommendations that they should receive VKA.

Dr Sabouret said: “Women with AF receive less anticoagulation treatment than men despite the fact that they are at greater risk of stroke. The new CHA2DS2-VASc score should be used more stringently, especially in women, to optimise their treatment. Treatment of all women with AF should be reviewed to ensure they are receiving anticoagulation if appropriate according to the CHA2DS2-VASc score.”

Age-stratified multivariate analysis* of VKA prescription in patients <75 years found women were half as likely to be treated as men (odds ratio [OR]=0.56, 95% confidence interval [CI]=0.48-0.65) (p<0.0001). In the >75 years subgroup women were 33% less likely to be treated than men (OR=0.67, 95% CI=0.60-0.75) (p<0.0001).

Dr Sabouret concluded: “Women with AF are undertreated compared with men regardless of their stroke risk and comorbidities. This study has revealed a significant gap between guidelines and practice and requires GPs and cardiologists to work together to optimise treatment for women.”

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Amsterdam, The Netherlands – Saturday 31 August 2013: The risk of ischemic stroke after acute myocardial infarction (AMI) in diabetics has dropped over a 10 year period, according to a study of more than 173,000 AMI patients in the Swedish RIKS-HIA register. The findings were presented at the ESC Congress today by Ms Stina Jakobsson from Sweden. They reveal that reperfusion therapy and secondary prevention drugs produced the decline and brought stroke risk after AMI closer to that of non-diabetics.

Ms Jakobsson said: “Ischemic stroke following an acute myocardial infarction is a fairly uncommon but devastating event with high mortality. It has long been recognized that patients with diabetes mellitus are at a particularly high risk of complications after an AMI but until now, the risk of ischemic stroke after an AMI in patients with diabetes has been uncertain.”

The study included 173,233 patients registered as having their first AMI during 1998-2008 in the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA). RIKS-HIA contains data on all patients admitted to Sweden’s 74 coronary care units.

During 1998-2008, of the 33,503 (19%) patients in the register who had a previous diagnosis of diabetes, 5.5% had an ischemic stroke within one year after the AMI. This compared to a stroke rate of 3.5% in patients on the register who did not have diabetes and 0.3% in the Swedish general population (who were not on the register and had no history of AMI). Ms Jakobsson said: “We believe that an important mechanism behind the increased risk for ischemic stroke after an AMI, especially in diabetic patients, may be increased inflammation and platelet reactivity seen with an AMI.”

Ischemic stroke rate decreased over time (see figure 1). During 1998-2000, 7.1% of diabetic patients had an ischemic stroke within one year after their first AMI, compared to 4.7% during 2007-2008. A smaller decline was observed in non-diabetic patients, from 4.2% in 1998-2000 to 3.7% in 2007-2008.

In the diabetics, prior reperfusion therapy with coronary angioplasty, coronary angioplasty during the AMI hospital stay, and prescription of the secondary preventive medications acetylsalicylic acid, P2Y12-inhibitors and statins when leaving hospital were independently associated with the reduced stroke risk over time.

Higher age, prior ischemic stroke, a specific type of myocardial infarction (ST-elevation MI) and atrial fibrillation during the hospitalization were found to be risk factors for an ischemic stroke within one year after AMI in patients with diabetes.

The study found that despite the greater improvements in stroke risk seen in diabetic patients, they were treated to a lesser extent than non-diabetic patients with reperfusion therapies during their initial hospital stay. They also left hospital with less standard medication for secondary prevention after an AMI. During the entire study period, the prescription of secondary preventive medication increased in both diabetic and non-diabetic patients.

Ms Jakobsson said: “The decreased ischemic stroke rate in both patient groups over time may be explained by a reduction in established risk factors for stroke and increased use of secondary preventive treatments after AMI. The larger reduction in stroke risk seen in diabetic patients may indicate that they gained more from the greater use of secondary preventive medication. But secondary preventive treatments are still underutilized in diabetic patients and there is room for increased use.”

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Amsterdam, The Netherlands – Saturday 31 August 2013: Mass screening in more than 25,000 Swedish residents has identified untreated atrial fibrillation in 5% of 75-76 year olds, putting them at increased stroke risk. The preliminary findings of the STROKESTOP trial were presented at the ESC Congress today by Dr Emma Svennberg from Sweden.

Stroke is the second cause of death worldwide. Atrial fibrillation is the most common clinically relevant cardiac arrhythmia in Europe, affecting approximately 1.5–2% of the general population.1 Prevalence is estimated to double in the next 50 years as the population ages.

Patients with atrial fibrillation have a five-fold increased risk of ischaemic stroke even though around 30% have no symptoms. As blood is less adequately shifted from the heart during atrial fibrillation, blood clots can form and cause large ischaemic strokes. Strokes that occur in association with atrial fibrillation are often fatal, and survivors are left more disabled and at a high risk of a recurrent stroke.

Dr Svennberg said: “There is hope, however, as oral anticoagulant medication reduces the risk of atrial fibrillation related stroke by 64-70%. But more than 50% of high-risk patients with atrial fibrillation do not receive any treatment.2 We are looking at an epidemic of atrial fibrillation related strokes if nothing is done to improve treatment levels.”

The STROKESTOP trial is a mass screening programme of all 75-76 year olds in Stockholm County and Region Halland in Sweden. It aims to identify patients with undiagnosed atrial fibrillation and find out if oral anticoagulation (OAC) therapy reduces their risk of ischaemic stroke.

For the trial, more than 25,000 people born in 1936 and 1937 were randomised 1:1 to screening for atrial fibrillation or a control group. Screening is done at home with a handheld ECG device and takes 1 minute per day for 2 weeks. When atrial fibrillation is diagnosed, patients are offered OAC treatment. Both screening and control groups will be followed prospectively for 5 years for thromboembolic events, bleeding and mortality.

Preliminary results from STROKESTOP are presented today. A year into the trial, 6,496 (50%) of the 13,000 inhabitants in the screening arm agreed to screening for atrial fibrillation. A lower proportion of patients agreed to screening in Stockholm (49%) than in rural areas (65%). Dr Svennberg said: “We will investigate factors related to participation, in an effort to increase uptake.”

More than 11% of the screening group had atrial fibrillation. Of these, previously undiagnosed atrial fibrillation was found in 192 (3%) of patients while in 129 (2%) of patients, atrial fibrillation had been diagnosed but they were not on OAC. More than 90% of the patients with undiagnosed atrial fibrillation were started on OAC.

Dr Svennberg said: “We found that 5% of patients in the screening arm had untreated atrial fibrillation. We successfully started oral anticoagulation treatment in more than 90% of the patients with newly diagnosed atrial fibrillation. This should reduce their risk of a stroke by up to 70%. We are still collecting data on patients with known atrial fibrillation but not on OAC.”

Professor Mårten Rosenqvist, chair of the STROKESTOP steering committee, said: “Without appropriate treatment atrial fibrillation is a ticking bomb. We hope the STROKESTOP study will show that screening for atrial fibrillation reduces the risk of stroke. Our final results should be available by November 2018.”

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Amsterdam, The Netherlands – Saturday 31 August 2013: The CHADS2 stroke risk scores 0 or 1 assign more than one-third of patients in atrial fibrillation (AF) with stroke to low or intermediate risk not mandating oral anticoagulation, according to research presented at ESC Congress 2013 today by Professor Michael Nabauer from Germany. In contrast, a CHA2DS2-VASc score of 0 identifies a subgroup of patients with very low stroke risk unlikely to benefit from anticoagulation treatment.

Professor Nabauer said: “AF is the most frequent cardiac arrhythmia requiring hospitalisation and has a 1-2% prevalence in the general population. AF is associated with a significant risk of stroke with frequently disabling consequences. While oral anticoagulation is very effective in preventing ischaemic strokes in AF, it increases bleeding risk. Identification of patients with low risk of stroke not requiring oral anticoagulation is important to maximise anticoagulation benefit while avoiding the cost, hassle, and bleeding risk of oral anticoagulation.”

The present study tested stroke risk stratification schemes for identifying patients with very low stroke risk who may not benefit from oral anticoagulation. The analysis was based on the prospective registry of the German Competence Network on Atrial Fibrillation (AFNET) which started in 2004-2006 and includes 9,575 patients with AF. Follow-up was for a mean of 5.1 years, and stroke events were adjudicated by a critical event committee.

On enrolment, 47.7% of patients with non-valvular AF (n=8,847) in the AFNET registry were assigned a CHADS2 score of 0 (16.2%) or 1 (31.5%) indicating that oral anticoagulation was not definitively recommended. Surprisingly, 35.8% (145 out of 405) of strokes and other thromboembolic events (transient ischaemic attack, systemic embolism) during follow-up occurred in this patient subgroup initially classified by CHADS2 to have low or intermediate stroke risk (CHADS2=0: 45, CHADS2=1: 100 events).

Professor Nabauer said: “This finding suggests that classes CHADS2 0 and 1 contain subgroups of patients with significant stroke risk that may be identified by refined stroke risk stratification.”

The CHA2DS2-VASc score, which adds age 65-74 years, vascular disease and female gender as stroke risk factors to the CHADS2 score, has been put forward to improve risk stratification in patients with low stroke risk and is the recommended risk stratification scheme in the ESC Guidelines on atrial fibrillation.1,2

In the current study, application of the CHA2DS2-VASc score reclassified 53.8% of patients with CHADS2 scores 0 or 1 to a CHA2DS2-VASc score of 2 and higher, where oral anticoagulation is the recommended treatment. Conversely, CHA2DS2-VASc assigned a very low stroke risk score of 0 to 55.6% of patients previously classified as CHADS2=0 (9.0% of all patients).

Professor Nabauer said: “Only 8 strokes and other thromboembolic events were observed in these patients classified as CHA2DS2-VASc=0 during the follow-up period (strokes occurring in association with cardioversion or ablation were excluded). This finding supports the use of CHA2DS2-VASc stroke risk stratification to identify patients at very low stroke risk who may not benefit from oral anticoagulation for ischaemic stroke prevention.”

He concluded: “A CHADS2 score of 0 or 1 does not appear to be suitable to identify patients with AF at low risk for stroke while CHA2DS2-VASc picks up these patients. The risk of stroke in patients with a CHA2DS2-VASc score of 0 over a mean follow up of 5.1 years was very low. Our data support the current recommendation that oral anticoagulation is not beneficial in patients with ‘lone AF’ or a CHA2DS2-VASc score of 0.”

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http://www.escardio.org/Pages/index.aspx

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ESC President Prof Panos Vardas asks delegates to support European Heart for Children.

http://www.europeanheartforchildren.org/

Meer info:

EHC - Helping children with congenital heart disease - First Mission in Syria (short version)

Children born with congenital heart disease do not have equal access to appropriate care and, in some cases, the range of disparity is important. To help remedy to that situation, the European Society of Cardiology is supporting European Heart for Children, a project to help children with congenital heart disease.

First mission: Syria, Damascus - 17th-21st April 2009
Actions: 82 children examined, 5 operated on and 2 transferred to Italy for more complex surgery:

Lin -- operated for Fallot tetralogy
Fatima -- operated for PDA closure
Telenaz -- operated for Arterial switch
Ali -- operated for Pulmonary arteries
Yusra -- operated for Fallot tetralogy
Marie -- transferred to Italy for more complex surgery
Jamal -- transferred to Italy for more complex surgery

Forumleden mogen uiteraard ook doneren, http://www.europeanheartforchildren.org/donate.php