text:
- Research article
- Open Access
- Open Peer Review
Cardiovascular risk factor treatment targets and renal complications in high risk vascular patients: a cohort study
- Sharmini Selvarajah1, 2Email author,
- Yolanda vD Graaf†2,
- Frank LJ Visseren†3,
- Michiel L Bots†2 and
- the SMART study group
© Selvarajah et al; licensee BioMed Central Ltd. 2011
- Received: 11 February 2011
- Accepted: 5 July 2011
- Published: 5 July 2011
To determine if recommended treatment targets, as specified in clinical practice guidelines for the management of cardiovascular disease, reduces the risk of renal complications in high risk patient populations.
This was a cohort study. Participants in Utrecht, The Netherlands either at risk of, or had cardiovascular disease were recruited. Cardiovascular treatment targets were achievement of control in systolic and diastolic blood pressure, total and low-density cholesterol, and treatment of albuminuria. Outcome measures were time to development of end stage renal failure or symptomatic renal atherosclerotic disease requiring intervention.
The cohort consisted of 7,208 participants; 1,759 diabetics and 4,859 with clinically manifest vascular disease. The median age was 57 years and 67% were male. Overall, 29% of the cohort achieved the treatment target for systolic blood pressure, 39% for diastolic blood pressure, 28% for total cholesterol, 31% for LDL cholesterol and 78% for albuminuria. The incidence rate for end stage renal failure and renal atherosclerotic disease reduced linearly with each additional treatment target achieved (p value less than 0.001). Achievement of any two treatment targets reduced the risk of renal complications, hazard ratio 0.46 (95% CI 0.26-0.82). For patients with clinically manifest vascular disease and diabetes, the hazard ratios were 0.56 (95% CI 0.28 - 1.12) and 0.28 (95%CI 0.10 - 0.79) respectively.
Clinical guidelines for cardiovascular disease management do reduce risk of renal complications in high risk patients. Benefits are seen with attainment of any two treatment targets.
- Treatment Target
- Renal Complication
- Renal Endpoint
- Current Clinical Practice Guideline
- Diastolic Blood Pressure Target
Current clinical practice guidelines for the management of patients with diabetes, hypertension and other atherosclerotic risk factors are geared to the prevention of cardiovascular disease and its complications [1–3]. However, cardiovascular diseases are not the only complications that can arise. Renal complications such as renal atherosclerotic disease [4] and end stage renal failure (ESRF) are of equal importance [5–9] though not as common.
There are few studies looking at the effects of combined cardiovascular treatment targets on renal complications; most are aimed at cardiovascular complications for which the targets were derived for. The risk of renal complications is low [10] despite the high prevalence of diabetes and hypertension [11, 12], and is usually confined to those with a genetic predisposition [13, 14]. In clinical practice, these complications arise after a long duration of disease and/or treatment [15]. In the meantime, these patients undergo the same clinical management as those who are not predisposed to renal diseases. Studies of natural history of reno-atherosclerotic disease have shown that control of blood pressure do not necessarily prevent the progression of renal disease [16]. Therefore, it is relevant to determine whether the current clinical guidelines which have treatment targets geared for cardiovascular disease reduce the risk of renal complications.
This study will evaluate if the current 2007 European treatment guidelines for the prevention of cardiovascular disease concomitantly reduces the risk of renal complications in patients at high risk of vascular diseases. We assessed whether there is an inverse dose-response risk for renal complications by the number of treatment targets achieved or if there is an optimal number instead. We also determined if there are differences in targets to be achieved for two high risk patient groups; diabetics and those with clinically manifest vascular disease.
Study design and population
The Second Manifestations of ARTerial disease (SMART) study is a prospective cohort study that is conducted in the University Medical Centre (UMC) Utrecht. It commenced in September 1996 and is currently on-going. Patients aged 18 to 80 years with clinically manifest atherosclerotic vascular disease, newly referred to the UMC are invited to participate. Diseases that qualify for enrolment are internal carotid artery stenosis, transient ischemic attack, minor stroke, peripheral arterial disease, diabetic foot, angina pectoris, myocardial infarction, abdominal aortic aneurysm, and renal artery stenosis. Those treated for cardiovascular risk factors, including hyperlipidaemia, diabetes mellitus, hypertension and renal insufficiency are also recruited. Patients with terminal cancer, dependent in their daily activities or not fluent in Dutch are excluded. All cohort members are followed up for a minimum of three years using biannual questionnaires.
The study was approved by the UMC Utrecht Institutional Review Board, which is approved by the Dutch Central Committee for research involving human subjects. The study was conducted in accordance with principles of the Declaration of Helsinki. Written informed consent was obtained from all participants. The rationale and design of the SMART study have been described elsewhere [17].
The current study selected all patients without end stage renal failure at baseline, recruited from September 1996 till February 2008. Every patient who was enrolled in the SMART study had physical examinations at baseline. Blood pressure was measured using a sphygmomanometer on both upper arms. The measurement was repeated on the arm with the highest value. The maximal value was used in this study.
Hypertension was diagnosed based on a systolic blood pressure of more or equal to 140 mm Hg and/or a diastolic blood pressure of more or equal to 90 mm Hg or being treated with two or more anti-hypertensive medications. Diabetes was determined based on self-report, hyperglycaemia at baseline (> 7.0 mmol L-1), glycated haemoglobin (HbA1c) of more than 7% or being treated with glucose lowering therapy.
Clinical measurements
Cardiovascular risk factor treatment targets
Treatment targets
Risk factor
All patients without Diabetes
Diabetes mellitus
Systolic blood pressure (mm Hg)
< 130
< 130
Diastolic blood pressure (mm Hg)
< 80
< 80
Total cholesterol (mmol L-1)
< 4.5
< 4.5
Low density lipoprotein (mmol L-1)
< 2.5
< 2.5
HbA1c (%)
< 6.5
Microalbuminuria and proteinuria
Treatment with ACEI/ARB or No proteinuria
Treatment with ACEI/ARB (Any albuminuric state)
Biochemical measurements
The biochemical assays measured in this study has been described in detail previously [17]. In summary, a venous blood sample was taken to determine lipid, glucose and creatinine levels. Plasma total cholesterol, triglycerides, glucose and creatinine were measured using a commercial enzymatic dry chemistry kit (Johnson and Johnson). HDL-cholesterol in plasma was determined using a commercial enzymatic kit (Boehringer-Mannheim) after precipitation of LDL and very low density lipoprotein (VLDL) with sodium phosphotungstate magnesium chloride. LDL-cholesterol was calculated using the Friedewald formula.
A urine sample was collected to measure micro-albuminuria and creatinine excretion. Creatinine was measured using a commercial enzymatic dry chemistry kit (Johnson and Johnson) and micro-albuminuria was determined with immunoturbidimetric assays (Boehringer-Mannheim).
Primary outcome
Renal outcomes were defined as a composite endpoint consisting of end stage renal failure requiring renal replacement therapy and reno-atherosclerotic disease requiring intervention; either arterial stenting or bypass grafting. Time to any renal endpoint was the outcome of interest.
During the follow up period, outcomes were determined through questionnaires biannually. Participants provided information on hospitalization and clinic visits. Original source documents were reviewed if a hospitalization or clinic visit was reported. All hospital discharge letters and results of related laboratory and radiological examinations were collected. Each event was classified according to a standard operating procedure. All endpoints were adjudicated by three members of the SMART Endpoint Committee, comprising of physicians from different departments.
The participants were followed up till death or refusal to participate.
Statistical analysis
Analysis was performed using SPSS version 17.0 for Windows (SPSS Inc., Chicago, IL, USA). Baseline data displayed was calculated using a general linear model for continuous variables adjusted for age and sex. P values for trends across the five treatment target groups were estimated using Mantel Haenszel's χ2. Ordinal data was tested using ordinal tests (Kendall's tau).
Confounders were selected a priori for testing based on literature. Variables selected were age, sex, waist circumference, history of coronary artery disease, cerebrovascular disease, peripheral arterial disease and renal disease, smoking status (never, former, current), alcohol consumption (never, ever, recently stopped, current), haemoglobin levels, albuminuria status (no, micro-albuminuria, overt proteinuria) and estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula. These were then determined to be included in the final model if there was a change in the hazard ratio (HR) estimate of more than 10 percent when compared to the crude estimate [23]. Medication was seen as not confounders in this study because the type and number of drugs used were primarily to achieve treatment targets. Medications which had independent action on renal function such as ACEIs and ARBs were already included as a treatment target for albuminuria.
A multivariate Cox proportional hazards model was used to determine the association between the number of treatment targets achieved and the risk of renal complications. Hazard ratios and the 95% confidence intervals were calculated for each number of treatment targets achieved, with the category of one or less targets achieved as reference. The likelihood ratio test was used to determine the significance of the variables included in the model. A p value of less than 0.05 (two tailed) was considered to be statistically significant. Analysis was performed with two adjustments; 1) adjustment for statistically significant confounders 2) adjustment for statistically significant confounders, age and sex. For participants from the whole cohort, the significant confounders were hypertension, albuminuria, eGFR and haemoglobin levels. For those with clinically manifest vascular disease, the confounders were hypertension, albuminuria and eGFR levels. Only eGFR and haemoglobin were significant confounders for participants with diabetes. The Wald test was used to determine if treatment targets were significant as a linear variable. A p value of less than 0.05 was considered to be statistically significant.
The assessment of hazard ratios for individual treatment targets was done at a quantitative level. There was a statistically significant correlation between systolic and diastolic blood pressure. Pearson's correlation coefficient r was 0.68 with a p value of less than 0.001 (two tailed). There was stronger correlation between total cholesterol and LDL levels, Spearman's correlation coefficient rho 0.88 was statistically significant at a p value of less than 0.001 (two tailed). When testing the hazard ratios at the risk factor level, due to the high correlation between these variables, only one from each set of these factors was chosen; systolic blood pressure and LDL. Both systolic blood pressure and LDL cholesterol levels are the more important treatment targets for the prevention of cardiovascular disease [24, 25]. Cox proportional hazards assumptions were tested visually using hazard and Log Minus Log (LML) plots.
Incidence rates were calculated using the number of events, divided by the total person time in years. The time period is calculated from baseline till event, death or loss to follow up.
Missing data was reviewed to determine if it was Missing At Random. Those missing at less than one percent were imputed using mean or median values where applicable. Single imputation using a linear regression with an error term was done for other variables. This was done for four variables; albuminuria (6.2% missing), LDL (6.9% missing), waist circumference (17.6% missing) and HbA1c for diabetics (38.1% missing).
Between September 1996 and February 2008, 7,292 participants were enrolled in the SMART study cohort. Of these, the 84 participants who had end stage renal failure at baseline were excluded from this study. At the end of the study period, 670 had died and 253 were lost to follow up. The median duration for follow up was 4.21 years (IQR 2.08 - 7.11).
Characteristics of the participants
The cohort consisted of 7,208 participants. There were 4,859 (67.4%) with clinically manifest vascular disease and 1,759 (24.4%) diabetics, both conditions not mutually exclusive. Other participants had risk factors without clinical evidence of atherosclerotic disease. The median age was 57 years (IQR 48 - 66) and 67.2% were male. Overall, 29.1% of the cohort fulfilled the treatment target for systolic blood pressure, 38.5% for diastolic blood pressure, 28.2% for total cholesterol, 30.7% for LDL cholesterol and 77.9% for albuminuria. About 47% of those prescribed beta blockers had ischaemic heart disease. Only 12% of those prescribed beta blockers were due to hypertension.
Clinical profile and end points of study population according to number of cardiovascular risk factor treatment targets achieved at baseline
Treatment Targets Achieved
≤ 1
≥ 5
p value for trends
Age (years)a
57 (49,66)
57 (48,66)
56 (47,64)
58 (50,66)
55 (46,64)
Male sex
65.6 (1845)
65.9 (1088)
67.3 (1202)
73.9 (438)
75.1 (274)
32.1 (902)
33.7 (556)
30.3 (541)
29.3 (174)
30.7 (112)
41.7 (1174)
42.3 (698)
45.2 (806)
43.8 (260)
46.3 (169)
26.2 (737)
24.1 (398)
24.5 (438)
26.8 (159)
23 (84)
18 ± 0.36
19 ± 0.46
18 ± 0.45
18 ± 0.77
17 ± 0.99
Alcohol consumption
20.8 (584)
21.7 (358)
19.9 (355)
18.2 (108)
18.1 (66)
9.7 (273)
9 (148)
9.8 (175)
10.8 (64)
12.9 (47)
Recently stopped
29.5 (831)
28.5 (470)
23.1 (412)
16.5 (98)
14.2 (52)
40 (1125)
40.9 (676)
47.2 (843)
54.5 (323)
54.8 (200)
History of:
Coronary artery disease
26.5 (745)
36.7 (607)
49 (875)
63.4 (376)
71 (259)
Cerebrovascular disease
19.9 (561)
20.8 (343)
17.9 (319)
18.4 (109)
15.6 (57)
Peripheral arterial disease
16.8 (472)
17.1 (283)
13 (232)
8.4 (50)
7.9 (29)
Previous kidney disease
2.6 (74)
2.7 (44)
2.7 (48)
4.9 (29)
3.6 (13)
Any of the above
56.7 (1595)
64.5 (1065)
71.8 (1281)
82.1 (487)
87.1 (318)
BMI (kg m-2)
27 ± 0.08
27 ± 0.11
27 ± 0.10
27 ± 0.18
26 ± 0.23
Waist circumference (cm)
95 ± 0.22
94 ± 0.29
93 ± 0.28
94 ± 0.49
92 ± 0.62
Systolic BP (mm Hg)
154 ± 0.34
141 ± 0.44
135 ± 0.43
130 ± 0.74
119 ± 0.95
Diastolic BP (mm Hg)
91 ± 0.20
82 ± 0.26
79 ± 0.25
75 ± 0.44
71 ± 0.56
S. Glucose (mmol L-1)
6.5 ± 0.04
6.6 ± 0.06
6.1 ± 0.05
6.6 ± 0.09
5.9 ± 0.12
HbA1c (%)
6.1 ± 0.02
6.2 ± 0.03
5.9 ± 0.03
6.1 ± 0.05
5.8 ± 0.06
Total cholesterol (mmol L-1)
5.95 ± 0.02
5.45 ± 0.03
4.87 ± 0.03
4.02 ± 0.05
3.76 ± 0.06
HDL cholesterol (mmol L-1)
1.28 ± 0.01
1.25 ± 0.01
1.25 ± 0.01
1.24 ± 0.02
1.20 ± 0.02
LDL cholesterol (mmol L-1)
3.75 ± 0.02
3.23 ± 0.03
2.84 ± 0.03
2.04 ± 0.05
1.95 ± 0.06
Triglycerides (mmol L-1)
2.05 ± 0.04
2.16 ± 0.05
1.74 ± 0.05
1.65 ± 0.09
1.38 ± 0.11
Creatinine (μmol L-1)
92.3 ± 0.87
93.9 ± 1.13
92.1 ± 1.09
91.6 ± 1.88
93.1 ± 2.40
21.9 (616)
16.5 (272)
9.7 (174)
13.8 (82)
7.9 (29)
3.6 (102)
2.8 (46)
1.4 (25)
1.9 (11)
0.8 (3)
eGFR (mL min-1 1.73 m-2)
78.1 ± 0.33
77.6 ± 0.43
77.9 ± 0.41
78.7 ± 0.71
78.1 ± 0.91
Haemoglobin (mmol L-1)
9.0 ± 0.01
8.8 ± 0.02
8.8 ± 0.02
8.7 ± 0.03
8.6 ± 0.04
Patients with Hypertension
84.9 (2387)
62.3 (1029)
54.2 (968)
55.3 (328)
41.4 (151)
Duration of hypertension (years)
6.0 ± 0.19
5.1 ± 0.24
4.8 ± 0.23
5.5 ± 0.40
4.5 ± 0.51
Use of BP lowering drugs
62.2 (1749)
61.8 (1021)
64.8 (1157)
75.9 (450)
79.2 (289)
Type of BP lowering drugs
29.6 (834)
36 (594)
42.7 (762)
50.9 (302)
60.8 (222)
18.3 (516)
16.6 (274)
16.6 (296)
22.8 (135)
16.4 (60)
ACE inhibitors
20.5 (576)
22.8 (377)
26.8 (478)
33.1 (196)
32.3 (118)
7.2 (203)
6.6 (109)
7.1 (126)
11.5 (68)
8.5 (31)
Calcium channel blockers
15.2 (428)
15.7 (260)
16.1 (288)
20.2 (120)
18.1 (66)
Number of BP lowering drugs
27.3 (768)
26.8 (443)
26.3 (470)
28.8 (171)
37.5 (137)
18.3 (515)
18.9 (313)
22.7 (406)
27 (160)
24.7 (90)
7.6 (214)
9.1 (151)
10.2 (182)
13.8 (82)
14.8 (54)
≥ 4
1.8 (51)
2.1 (33)
2.1 (36)
3.9 (23)
1.4 (5)
Use of Lipid lowering drugs
32.7 (920)
43.6 (721)
57 (1017)
72.7 (431)
77.3 (282)
Patients with Diabetes
24.4 (686)
28.8 (475)
17.8 (318)
34.7 (206)
20.3 (74)
Duration of diabetes (years)
1.4 ± 0.09
1.8 ± 0.12
1.3 ± 0.12
2.2 ± 0.21
1.3 ± 0.26
Use of oral anticoagulants
43.1 (1211)
51.7 (854)
60 (1071)
74.5 (442)
77.3 (282)
End stage renal failure
Reno-atherosclerotic disease
Number of total events
Total person years
Incidence rate per 1000 population
< 0.001
Among those with clinically manifest vascular disease, 29.2% achieved the systolic blood pressure treatment target, 43.3% the diastolic blood pressure target, 33.7% the total cholesterol target, 34.8% the LDL target and 78.9% the appropriate treatment target for albuminuria. Among the diabetic participants, 24.6% achieved the systolic blood pressure treatment target, 38.1% the diastolic blood pressure target, 33.9% the total cholesterol target, 38.2% the LDL target, 41% achieved appropriate treatment of albuminuria and 26.9% achieved the HbA1c target. The diabetics had poorer control of blood pressure and less use of RAS inhibitors for the treatment of albuminuria than the general cohort.
Primary objective
At the end of the follow up period, there were 81 renal endpoints (Table 2). The unadjusted incidence rate for renal endpoints was 2.41 per 1,000 person-years. There were 57 renal endpoints for end stage renal failure with an incidence rate of 1.7 per 1,000 person-years. For renal atherosclerotic disease, there were 24 events with an incidence rate of 0.71 per 1,000 person-years. There was a statistically significant linear trend (p value less than 0.001) for incidence rate reduction with increasing target achievement.
Hazard ratios of renal endpoints by number of cardiovascular risk factor treatment targets achieved
Clinically Manifest Vascular Disease
p for trends
p for trends
p for trends
number of events
Renal endpoint
Model 1 (crude)
Targets achieved
≤ 1
(0.34, 1.02)
(0.26, 1.00)
(0.27, 1.81)
(0.18, 0.71)
(0.09, 0.59)
(0.39, 3.05)
(0.12, 1.19)
(0.07, 1.22)
(0.29, 3.47)
≥ 5
(0.03, 1.59)
Model 2 adjusted
Targets achieved
≤ 1
(0.28, 0.86)
(0.29, 1.14)
(0.13, 1.00)
(0.27, 1.09)
(0.15, 0.99)
(0.22, 1.80)
(0.14, 1.51)
(0.15, 2.69)
(0.15, 1.99)
≥ 5
(0.06, 3.11)
Model 3 adjusted d
Targets achieved
≤ 1
(0.26, 0.82)
(0.28, 1.12)
(0.10, 0.79)
(0.26, 1.03)
(0.14, 0.95)
(0.12, 1.26)
(0.15, 1.60)
(0.15, 2.67)
(0.16, 2.01)
≥ 5
(0.05, 2.76)
Risk factors e
SBP (per mmHg)
(1.01, 1.03)
(1.01, 1.03)
(1.01, 1.05)
LDL (per mmol/L)
(1.04, 1.53)
(1.02, 1.68)
(0.83, 1.75)
Treatment for albuminuria
(0.57, 1.43)
(0.55, 1.70)
(0.24, 1.39)
HbA1c (per %)
(1.01, 1.38)
(0.96, 1.49)
(1.12, 1.84)
Secondary objective
When individual cardiovascular risk factors were compared, there was an increased risk of developing any renal endpoint for each increase in unit of systolic blood pressure, LDL and HbA1c levels. The hazard ratios for all risk factors were similar for all subgroups of patients, except for the hazard ratio of HbA1c among diabetics. Each unit increase in HbA1c levels suggests a higher rate of increase in the hazard ratio for renal complications in diabetics, than in the general cohort or in those with clinically manifest vascular disease.
In this cohort study, we studied whether the attainment of treatment targets established for the prevention of cardiovascular disease would concomitantly reduce the rate of renal complications. Based on the current 2007 European clinical practice guidelines, we observed that the achievement of any two or more treatment targets at baseline do reduce the rates of renal complications, for patients at high risk of atherosclerotic disease and for those with clinically manifest vascular disease. Although this observation was not statistically significant for diabetics, it may be clinically beneficial. A previous study of diabetics showed a decline in renal complications if three or more treatment targets were achieved [26]. With increasing treatment targets achieved, a lower haemoglobin concentration level was seen. However, it was not associated with poorer outcomes. This may be a result of more liberal use of RAS inhibitors, which decreases erythropoiesis [27]. There was no optimal number of cardiovascular risk factor treatment targets to achieve. The risk of renal complications decreased linearly as more targets were attained; consistent with the notion that no J-curve exists for renal outcomes.
There are distinct differences between the diabetic and clinically manifest vascular disease population cohorts. Primarily, the decreased hazard ratios for renal outcomes in diabetics were only observed after the model was adjusted for renal confounders such as eGFR and haemoglobin levels. This may be because once chronic renal disease has set in, achievement of treatment targets alone is insufficient to reduce or retard the rate of complications in diabetics. This was not the case for those with manifest vascular disease, where there was a consistent reduced risk of renal complications even with non-adjustment for renal confounders. The second distinct difference is, there does not appear to be a gradient decreased hazard ratio for diabetics as the number of treatment targets achieved increased. A previous study of treatment targets and cardiovascular outcomes in diabetics showed a graded response [28].
The low percentage of participants achieving treatment targets is consistent with other countries. In a Swedish study, only 17% of their hypertensive population had achieved a systolic blood pressure target of less than 140 mmHg and 64% achieved the diastolic blood pressure target of less than 90 mmHg [29]. In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, which was a multi country randomized control trial, only 16.3% had achieved the total cholesterol target of less than 5.0 mmol/l at baseline [30]. In the United Kingdom, only 19.7% and 26.9% achieved blood pressure and cholesterol targets respectively [31]. More patients achieving the target for diastolic blood pressure than for systolic blood pressure is also consistent with other studies [29]. This is probably reflective of older, stiffer arteries which is expected in high risk patients, and not because therapies used were more effective in lowering diastolic blood pressure.
Looking at the individual cardiovascular risk factor levels, the findings amongst the study population is consistent with current literature. With increasing systolic blood pressure [32], LDL and HbA1c, the risk for renal complications increases statistically significantly. Considering the similar risks for renal complications in all cohort groups with increasing systolic blood pressure and LDL levels, the treatment of HbA1c levels is crucial in diabetics. The non-significant decreased hazard ratio seen in all patient groups for the treatment of albuminuria may be due to two reasons; suboptimal dosing or discontinuation of medication due to non-response to blood pressure lowering with ACEI or ARB use. Inadequate dosing of ACEI or ARB's causes less anti-albuminuric activity thus there is suboptimal reduction in albuminuria. Aside from this, non-response to blood pressure reduction does not mitigate the effects of anti-albuminuric activity; therefore discontinuation of these drugs increases the risk of renal endpoints [33].
This study has a few limitations. The number of treatment targets achieved was determined only at baseline. Over the entire duration of follow up, patients may fluctuate between different categories of targets achieved, depending on clinical management received.
The duration of follow up may be insufficient for ESRF development in many patients. In the UKPDS study, development of renal endpoints occurred in only 0.8% after a median of 10 years [34]. Aside from this, the number of events that occurred was small, 81 in total and in diabetics 28. This may explain the lack of power in proving statistical significance, except for the tests for trends. A longer follow up duration would provide more accurate estimates and therefore stronger evidence. Nevertheless, this study had a total sample size of 7,208 participants with a sum of 33, 593 person-years of follow up. This is sizable.
Another key strength of this study is the use of hard endpoints; end stage renal failure and symptomatic renal vascular disease requiring intervention. We did not use surrogate endpoints such as rate of GFR decline because in diabetics and in other patient populations, the calculated GFR using the MDRD formula underestimates the rate of renal function loss [35–37]. It also becomes inaccurate as renal function improves; real GFR can fluctuate between 35 to 90 mL min-1 1.73 m-2 for an eGFR of 60 mL min-1 1.73 m-2 [38]. Aside from this, stabilization or regression of renal function decline has been known to occur in patients treated with ACEI despite having severe GFRs [39]. In this study, the maximum survival time for an eGFR of less than 15 mL min-1 1.73 m-2 was 6.27 years.
These hard endpoints reflect different pathophysiological mechanisms. End stage renal failure may be caused by both micro and macrovascular changes whereas renal vascular disease is caused by macrovascular changes. Despite these differing pathophysiological mechanisms, these findings are suggestive that the same treatment targets reduce their risk of development.
This study shows that current clinical practice guideline targets for the prevention of cardiovascular disease are useful in concomitantly reducing the risk of renal complications; in any patient population at high risk for vascular diseases. If more patients can be adequately treated to achieve the cardiovascular risk factor treatment targets, there will be important reductions in renal complications.
SMART Study Group
Members of the SMART Study Group are Ale Algra, MD, PhD, Pieter A. Doevendans, MD, PhD, Yolanda van der Graaf, MD, PhD, Diederick E. Grobbee, MD, PhD, L. Jaap Kappelle, MD, PhD, Willem P. Th. M. Mali, MD, PhD, Frans L. Moll, MD, PhD, Guy E.H.M. Rutten, MD, PhD, and Frank L. J. Visseren, MD, PhD.
Dr Selvarajah is supported by a grant from the AsiaLink program; an international teaching and exchange collaboration program funded by a European Commission grant. The abstract of this paper has been published in the AsiaLink Closing Conference booklet. The SMART study is supported by a grant of the University Medical Center Utrecht. The authors also gratefully acknowledge the long term help of the SMART study nurses and participants.
Authors' Affiliations
- Rydén L, Standl E, Bartnik M, Van den Berghe G, Betteridge J, de Boer M-J, Cosentino F, Jönsson B, Laakso M, Malmberg K, et al: Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary. European Heart Journal. 2007, 28: 88-136.View ArticlePubMedGoogle Scholar
- Authors/Task Force M, Mancia Ga, Co C, De Backer Gb, Dominiczak Ac, Cifkova Rd, Fagard Re, Germano Gf, Grassi Gg, Heagerty AMh, et al: 2007 ESH-ESC Practice Guidelines for the Management of Arterial Hypertension: ESH-ESC Task Force on the Management of Arterial Hypertension. Journal of Hypertension. 2007, 25: 1751-1762. 10.1097/HJH.0b013e3282f0580f.View ArticleGoogle Scholar
- Smulders Y, Burgers J, Scheltens T, van Hout B, Wiersma T, Simoons M: Clinical practice guideline for cardiovascular risk management in the Netherlands. The Netherlands Journal of Medicine. 2008, 66: 169-174.PubMedGoogle Scholar
- Safian RD, Textor SC: Renal-Artery Stenosis. New England Journal of Medicine. 2001, 344: 431-442. 10.1056/NEJM200102083440607.View ArticlePubMedGoogle Scholar
- El-Nahas AM, Tamimi N: The progression of chronic renal failure: a harmful quartet. QJM. 1999, 92: 421-424. 10.1093/qjmed/92.8.421.View ArticlePubMedGoogle Scholar
- Kanda T, Wakino S, Hayashi K, Plutzky J: Cardiovascular Disease, Chronic Kidney Disease, and Type 2 Diabetes Mellitus: Proceeding with Caution at a Dangerous Intersection. Journal of the American Society of Nephrology. 2008, 19: 4-7. 10.1681/ASN.2007111182.View ArticlePubMedGoogle Scholar
- Perneger TV, Brancati FL, Whelton PK, Klag MJ: End-Stage Renal Disease Attributable to Diabetes Mellitus. Annals of Internal Medicine. 1994, 121: 912-918.View ArticlePubMedGoogle Scholar
- Valderrabano F, Gomez-Campdera F, Jones EHP: Hypertension as cause of end-stage renal disease: Lessons from international registries. Kidney International. 1998, 54: S60-S66. 10.1046/j.1523-1755.1998.06815.x.View ArticleGoogle Scholar
- McClellan WM, Flanders WD: Risk Factors for Progressive Chronic Kidney Disease. Journal of the American Society of Nephrology. 2003, 14: S65-70. 10.1097/01.ASN.0000070147.10399.9E.View ArticlePubMedGoogle Scholar
- Group TEIS: Geographic, ethnic, age-related and temporal variation in the incidence of end-stage renal disease in Europe, Canada and the Asia-Pacific region, 1998-2002. Nephrology Dialysis Transplantation. 2006, 21: 2178-2183.View ArticleGoogle Scholar
- Fleming DM, Schellevis FG, Van Casteren V: The prevalence of known diabetes in eight European countries. The European Journal of Public Health. 2004, 14: 10-14.View ArticlePubMedGoogle Scholar
- Wolf-Maier K, Cooper RS, Banegas JR, Giampaoli S, Hense H-W, Joffres M, Kastarinen M, Poulter N, Primatesta P, Rodriguez-Artalejo F, et al: Hypertension Prevalence and Blood Pressure Levels in 6 European Countries, Canada, and the United States. The Journal of the American Medical Association. 2003, 289: 2363-2369. 10.1001/jama.289.18.2363.View ArticlePubMedGoogle Scholar
- Pugsley D: Racial and ethnic disparities in renal disease. Kidney International. 2005, 68: 1364-1365. 10.1111/j.1523-1755.2005.00545.x.View ArticlePubMedGoogle Scholar
- Missouris CG, Barley J, Jeffery S, Carter ND, Singer DRJ, MacGregor GA: Genetic risk for renal artery stenosis: Association with deletion polymorphism in angiotensin 1-converting enzyme gene. Kidney International. 1996, 49: 534-537. 10.1038/ki.1996.76.View ArticlePubMedGoogle Scholar
- Rimmer JM, Gennari FJ: Atherosclerotic Renovascular Disease and Progressive Renal Failure. Annals of Internal Medicine. 1993, 118: 712-719.View ArticlePubMedGoogle Scholar
- Brinkman JW, Bakker SJL, Gansevoort RT, Hillege HL, Kema IP, Gans ROB, de Jong PE, de Zeeuw D: Which method for quantifying urinary albumin excretion gives what outcome? A comparison of immunonephelometry with HPLC. Kidney International. 2004, 66: S69-S75. 10.1111/j.1523-1755.2004.09219.x.View ArticleGoogle Scholar
- Simons PCG, Algra A, van de Laak MF, Grobbee DE, van der Graaf Y: Second Manifestations of ARTerial disease (SMART) study: Rationale and design. European Journal of Epidemiology. 1999, 15: 773-781. 10.1023/A:1007621514757.View ArticlePubMedGoogle Scholar
- Graham I, Atar D, Borch-Johnsen K, Boysen G, Burell G, Cifkova R, Dallongeville J, De Backer G, Ebrahim S, Gjelsvik B, et al: European guidelines on cardiovascular disease prevention in clinical practice: executive summary. European Heart Journal. 2007, 28: 2375-2414.View ArticlePubMedGoogle Scholar
- Maione A, Navaneethan SD, Graziano G, Mitchell R, Johnson D, Mann JFE, Gao P, Craig JC, Tognoni G, Perkovic V, et al: Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and combined therapy in patients with micro- and macroalbuminuria and other cardiovascular risk factors: a systematic review of randomized controlled trials. Nephrology Dialysis Transplantation. 2011Google Scholar
- Ruilope L, Izzo J, Haller H, Waeber B, Oparil S, Weber M, Bakris G, Sowers J: Prevention of Microalbuminuria in Patients With Type 2 Diabetes: What Do We Know?. The Journal of Clinical Hypertension. 2010, 12: 422-430. 10.1111/j.1751-7176.2010.00289.x.View ArticlePubMedGoogle Scholar
- Eijkelkamp WBA, Zhang Z, Remuzzi G, Parving H-H, Cooper ME, Keane WF, Shahinfar S, Gleim GW, Weir MR, Brenner BM, et al: Albuminuria Is a Target for Renoprotective Therapy Independent from Blood Pressure in Patients with Type 2 Diabetic Nephropathy: Post Hoc Analysis from the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) Trial. Journal of the American Society of Nephrology. 2007, 18: 1540-1546. 10.1681/ASN.2006050445.View ArticlePubMedGoogle Scholar
- Haller H, Ito S, Izzo JL, Januszewicz A, Katayama S, Menne J, Mimran A, Rabelink TJ, Ritz E, Ruilope LM, et al: Olmesartan for the Delay or Prevention of Microalbuminuria in Type 2 Diabetes. New England Journal of Medicine. 2011, 364: 907-917. 10.1056/NEJMoa1007994.View ArticlePubMedGoogle Scholar
- Tong S, Lu Y: Identification of Confounders in the Assessment of the Relationship between Lead Exposure and Child Development. Annals of Epidemiology. 2001, 11: 38-45. 10.1016/S1047-2797(00)00176-9.View ArticlePubMedGoogle Scholar
- Benetos A, Thomas F, Bean K, Gautier S, Smulyan H, Guize L: Prognostic Value of Systolic and Diastolic Blood Pressure in Treated Hypertensive Men. Archives of Internal Medicine. 2002, 162: 577-581. 10.1001/archinte.162.5.577.View ArticlePubMedGoogle Scholar
- Sirtori CR, Fumagalli R: LDL-cholesterol lowering or HDL-cholesterol raising for cardiovascular prevention: A lesson from cholesterol turnover studies and others. Atherosclerosis. 2006, 186: 1-11. 10.1016/j.atherosclerosis.2005.10.024.View ArticlePubMedGoogle Scholar
- Chan JC, So W-Y, Yeung C-Y, Ko GT, Lau I-T, Tsang M-W, Lau K-P, Siu S-C, Li JK, Yeung VT, et al: Effects of Structured Versus Usual Care on Renal Endpoint in Type 2 Diabetes: The SURE Study. Diabetes Care. 2009, 32: 977-982. 10.2337/dc08-1908.View ArticlePubMedPubMed CentralGoogle Scholar
- Vlahakos DV, Marathias KP, Madias NE: The Role of the Renin-Angiotensin System in the Regulation of Erythropoiesis. American Journal of Kidney Diseases. 2010, 56: 558-565. 10.1053/j.ajkd.2009.12.042.View ArticlePubMedGoogle Scholar
- Kong APS, Yang X, Ko GTC, So W-Y, Chan W-B, Ma RCW, Ng VWS, Chow C-C, Cockram CS, Tong PCY, et al: Effects of Treatment Targets on Subsequent Cardiovascular Events in Chinese Patients With Type 2 Diabetes. Diabetes Care. 2007, 30: 953-959. 10.2337/dc06-2443.View ArticlePubMedGoogle Scholar
- Cederholm J, Nilsson PM, Anderberg C-P, Fröberg L, Petersson U: Blood pressure and other cardiovascular risk factors among treated hypertensives in Swedish primary health care. Scandinavian Journal of Primary Health Care. 2002, 20: 224-229. 10.1080/028134302321004881.View ArticlePubMedGoogle Scholar
- Kristianson K, Fyhrquist F, Devereux RB, Kjeldsen SE, Lindholm LH, Lyle PA, Nieminen MS, Snapinn SM: An analysis of cholesterol control and statin use in the losartan intervention for endpoint reduction in hypertension study. Clinical Therapeutics. 2003, 25: 1186-1199. 10.1016/S0149-2918(03)80075-9.View ArticlePubMedGoogle Scholar
- MacDonald TM, Morant SV, Mozaffari E: Drug treatment discontinuation and achievement of target blood pressure and cholesterol in United Kingdom primary care. Current Medical Research and Opinion. 2007, 23: 2765-2774. 10.1185/030079907X233124.View ArticlePubMedGoogle Scholar
- Vlek ALM, van der Graaf Y, Braam B, Moll FL, Nathoe HM, Visseren FLJ: Blood Pressure and Decline in Kidney Function in Patients With Atherosclerotic Vascular Disease: A Cohort Study. American Journal of Kidney Diseases. 2009, 54: 820-829. 10.1053/j.ajkd.2009.07.007.View ArticlePubMedGoogle Scholar
- Laverman GD, Andersen S, Rossing P, Navis G, de Zeeuw D, Parving H-H: Renoprotection with and without blood pressure reduction. Kidney International. 2005, 67: S54-S59. 10.1111/j.1523-1755.2005.09414.x.View ArticleGoogle Scholar
- Adler AI, Stevens RJ, Manley SE, Bilous RW, Cull CA, Holman RR: Development and progression of nephropathy in type 2 diabetes: The United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney International. 2003, 63: 225-232. 10.1046/j.1523-1755.2003.00712.x.View ArticlePubMedGoogle Scholar
- Radbill B, Murphy B, LeRoith D: Rationale and Strategies for Early Detection and Management of Diabetic Kidney Disease. Mayo Clinic Proceedings. 2008, 83: 1373-1381. 10.4065/83.12.1373.View ArticlePubMedGoogle Scholar
- Broekroelofs J, Stegeman CA, Navis GJ, de Haan J, van der Bij W, de Boer WJ, de Zeeuw D, de Jong PE: Creatinine-based estimation of rate of long term renal function loss in lung transplant recipients. Which method is preferable?. The Journal of Heart and Lung Transplantation. 2000, 19: 256-262. 10.1016/S1053-2498(99)00133-3.View ArticlePubMedGoogle Scholar
- Gera M, Slezak JM, Rule AD, Larson TS, Stegall MD, Cosio FG: Assessment of Changes in Kidney Allograft Function Using Creatinine-Based Estimates of Glomerular Filtration Rate. American Journal of Transplantation. 2007, 7: 880-887. 10.1111/j.1600-6143.2006.01690.x.View ArticlePubMedGoogle Scholar
- Connolly JO, Woolfson RG: A Critique of Clinical Guidelines for Detection of Individuals with Chronic Kidney Disease. Nephron Clinical Practice. 2009, 111: c69-c73.View ArticlePubMedGoogle Scholar
- Remuzzi G, Benigni A, Remuzzi A: Mechanisms of progression and regression of renal lesions of chronic nephropathies and diabetes. The Journal of Clinical Investigation. 2006, 116: 288-296. 10.1172/JCI27699.View ArticlePubMedPubMed CentralGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2261/11/40/prepub
Pre-publication history
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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by a $500 million judgment, drugmaker Schering-Plough is racing to comply with government regulations. Will technology slow it down?
Schering-Plough, a $9.8 billion drugmaker best known for its Claritin allergy pills, is a chronic violator of Food and Drug Administration rules on making medicines.
The company just paid $250 million to cover half of a $500 million settlement with the FDA. But it still has a lot of work to do. While Schering-Plough tries to improve its use of technology, the company's initiatives may well be hampered by the regulatory thicket in which it's already stuck.
The pharmaceutical industry has always faced close government scrutiny. Schering-Plough, however, is a special case. Since 1998, the FDA has inspected four primary Schering-Plough factories in New Jersey and Puerto Rico 13 times, and found the same problems again and again. Among them: failure to reject drugs that didn't meet established specifications; missing data from laboratory tests; incomplete records related to various quality assurance routines; and workers performing tasks that aren't part of written procedures.
After at least 21 FDA "warning letters"—notices of what the agency says are serious violations—Schering-Plough still didn't move fast or well enough to correct defects at its plants. The FDA took legal action last year. A year's worth of negotiations resulted in a 25-page consent decree in May and the $500 million assessment—the biggest ever by the FDA.
The FDA oversees all aspects of the pharmaceutical industry, from research to manufacturing to marketing. Its "Current Good Manufacturing Practices (CGMP) are the commandments of drugmaking—non-negotiable rules that every company must follow. The FDA inspects pharmaceutical plants at least once every two years to make sure they comply with these practices. Infractions are written up in what's called a 483 Form—widely viewed as the equivalent of a traffic ticket—and given to the plant's operations manager to address. If the problems go on, correspondence escalates to a "warning letter." Legal action, such as in Schering-Plough's case, is the last step.
Schering-Plough's noncompliance "was an ongoing situation," an FDA spokeswoman says. "They weren't fixing their problems."
The consent decree stops Schering-Plough from making 73 human and veterinary products and mandates recalls of two older asthma medications that it had already stopped making last summer. The FDA didn't say the company's drugs were dangerous. The issue was that Schering-Plough had repeatedly breached so many regulations that nobody could say with certainty that the products from the four factories involved were made 100% right. A criminal investigation is also under way by the FDA and state of New Jersey into whether Schering-Plough used unapproved ingredients in some of its products.
The Long List of Tasks Schering-Plough Now Has to Perform Under the Consent Decree Will, in Part, Force Improvements in the Information Technology and Business Processes at the Company. by the End of Last Month, Schering-Plough Was to Have Taught All Supervisors and Managers What the Consent Decree Means. for the Next Three Years, All New Supervisors and Managers Must Be Given a Copy of the Decree and An Explanation of It Within 10 Days of Being Hired. the Company Must Also Hire Four Decree Administrators—One for Each Factory in Question—To Oversee Compliance With the Decree and to Report Findings Every Month to the Chief Executive. An Outside Expert Must Be Hired to Help Formulate a Plan and a Timetable for Correcting Problems at Each Facility.
Schering-Plough Must Also Reimburse the Fda $471,500 for Inspection Expenses Already Incurred and for What the Fda Will Spend to Make Sure the Company Complies With the Decree. the Billing Rate Is $65 to $78 Per Hour, Plus Mileage and Expenses.
"What the FDA is trying to drive home to pharmaceutical firms is the need to start looking at things systemically," says Terryn Barill, who runs a consulting firm that specializes in drug-company compliance issues. "And that's going to take technology," she adds.
Announcing the decree two months ago, the company insisted it has cooperated with the FDA throughout the audits and consent decree talks. A Schering-Plough spokesman refused to comment further and declined to make executives available for interviews with Baseline.
However, in other public statements, Schering-Plough has said that it will spend $60 million to clean up problems at its manufacturing facilities. According to a company executive close to the project, part of that sum will go toward a technology revamp at those locations.
Schering-Plough is rearranging its technology groups, the executive says. The head of information systems at the company's health care products division will now oversee key systems—servers and applications—at the pharmaceutical factories as well.
Schering-Plough Health Care Products, which makes Dr. Scholl's footpads, Coppertone sunscreen and other over-the-counter items, is known for clean manufacturing facilities. The hope is that at least some processes can be duplicated in the pharmaceuticals group. Also part of the impetus for combining technology supervision in the two divisions is that Schering-Plough is moving production of Claritin from the pharmaceuticals division to Health Care Products. That's because the patent on its blockbuster Claritin allergy medication will expire in December and Schering-Plough hopes to start selling it as an over-the-counter medication. (The FDA hasn't ruled yet on whether it will allow that.)
Claritin is still in wide use, though. Clarinex, the patented follow-on, has replaced just about 33% of Claritin prescriptions so far. So Health Care Products plans to upgrade server hardware to ensure that its distribution and supply chain systems can handle the high-volume manufacturing that goes with Claritin.
On top of dealing with oversight of technology in the pharmaceuticals manufacturing group, Health Care Products must also contend with a critical server migration. The division largely runs Tru64 AlphaServer hardware from Compaq. When Hewlett-Packard bought Compaq two months ago, the vendor said it planned to phase out the Tru64 operating system in favor of HP's Unix. Meanwhile, the hardware running at the pharmaceuticals unit is mainly IBM, with some older, proprietary HP 3000s and HP 9000s. Both Health Care Products and pharmaceuticals will likely migrate to servers running HP/UX starting this year. It will be "a handful" of servers expected to cost up to $300,000 in all, the executive says. But a plan and budget haven't been finalized yet.
One project will be to integrate and streamline the 70 separate supply chain and manufacturing applications the corporation runs. Health Care Products uses two warehouse management packages: DigitaLogistix from RedPrairie in Waukesha, Wis., and PC/AIM from Ann Arbor Computer in Ann Arbor, Mich. For supply chain, the division uses SAP software.
Pharmaceuticals, meanwhile, runs virtually no packaged software. It's all custom-coded. But SAP will soon be installed, the company executive says, adding, "I call it catching up, but 'modernization' is a nicer word for it."
Schering-Plough Is Like Most Drugmakers. It Has Spent the Last Several Years Investing Heavily in Technology for Upfront Research and Development and Clinical Trials, Ignoring Production of the Drugs. That Happens for Two Big Reasons. One Is That Pharmaceutical R&d Is One of the Most Complex and Competitive Arenas in 21st Century Business. Along With Brilliant Scientists, a Company Needs Technology to Get Any Edge at All.
The other reason is that the FDA makes it painful to bring new technology to factories, says Janit Buccella, a consultant at Omnival in Newton, N.J. Omnival guides drug and biotechnology companies through the process of validating their equipment against government regulations.
The FDA must sign off on every aspect of drug production. A company must submit a thick package of documents detailing the minutia of how it plans to manufacture a product—down to how the software inside a tablet press, for example, interacts with quality control data stored in a proprietary application running on a different computer. Once a company wins approval, it is reluctant to change the setup one bit. If it did, Buccella says, it would have to prove to the FDA that the change wouldn't affect the outcome—the drug.
"It's a lot easier to develop and install and test new technologies in R&D [because] you're still playing with your process and product," she says. "The rigors of having to validate become much more strenuous as you get closer to production."
Plus, validation is the responsibility of the user company, not the supplier selling the software, notes Denise McDade, a quality assurance manager at Genentech, a $2.1 billion biotechnology company in South San Francisco. Vendors do ensure that their products comply in principle with FDA regulations. But because all customer implementations are different—the pharmaceutical industry is full of quirks in how people work and how products are made—vendors can't validate their software across the board, says McDade, who focuses on validation. "It's a growing area of concern for pharmaceutical companies," she says. "In my world, you spend a lot of time and money."
Thus, drug companies tend to be conservative with technology in the manufacturing process. They don't dabble. Not when a simple upgrade from version 3.0 to 3.1 of a given application would set off a revalidation routine that might cost more than the value of upgrading and could slow production.
At Schering-Plough factories, new document-management software and other upgrades have interrupted production of some drugs, the company says. Extra managers, consultants and scientists also have been hired to help with revalidation.
Drug Companies' Reluctance to Change Technol- Ogy in Their Plants Is Diminishing. Drug Manufacturing Now Is Where the Auto Industry Was 15 or 20 Years Ago, When Carmakers Started to Use Massive Doses of Technology in Their Factories to Improve Car Quality and Compete With Japanese Imports, Says Barill, the Compliance Consultant.
Ford, Chrysler and GM wanted to reduce defects, raise quality, create an audit trail and cut costs. "What they did in their manufacturing plants is [build] a system that depends more on technology and less on people," Barill says, adding that she sees pharmaceutical plants starting to do the same.
The pharmaceutical industry will step up spending on information technology during the next few years, says Anne Lu, an analyst at International Data Corp. Drug companies are expected to spend $5.5 billion on information technology this year, a 4% rise over last year. But in 2005, Lu predicts, they will spend a whopping 11% more than they do in 2004.
The movement to mirror car companies will start in smaller pharmaceutical firms that make generic versions of medications once protected by patents. Those companies generally have a smaller product line with, consequently, fewer validation worries, Barill says. They can move faster.
Even so, the glimmer is there at Schering-Plough. More efficient manufacturing processes save money. At the same time, the FDA has recently put out new, more stringent rules for some electronic aspects of manufacturing. It wants, for example, more complete quality control records and audit trails tracking who accessed which data when.
"Now everybody's saying, if we can trim costs, let's do it. If we can plan the production cycle better, let's do it," says the insider at Schering-Plough. When it comes time to seek funding for SAP software for the pharmaceuticals division, "we'll justify it by saying the FDA has these demands," the executive says. "It's becoming a cost of doing business."
Schering-Plough Base Case
Headquarters: 2000 Galloping Hill Rd., Kenilworth, NJ 07033
Phone: (908) 298-4000
Business: Pharmaceutical and health care products
Chief Information Officer: Donald Lemma
Financials in 2001: $9.8 billion in sales, $2.9 billion operating income, $1.9 billion net income
Challenge: To fix chronic manufacturing problems that led to a $500 million fine by the Food and Drug Administration
Baseline Goals:
- Increase return on equity, from 3% in 2001. It had been 43% in 2000.
- Submit plans for fixing manufacturing problems by Sept. 17 to Food and Drug Administration
- Stop receiving FDA warning letters by 2005, down from 34 from 1997 through 2001


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Mercedes-Benz is a top rated car in the world. It has an inbuilt class C night vision technology with it. There are many special features in this night vision technology; this technology has high quality original Japanese chip that contains all the programs of night vision. The images are captured with the help of the night vision rear view camera and with this camera, it detects the pedestrians within the road.
Added to this, the camera is made up of high-quality plastic that is durable and water resistant. The class C technology has a wide coverage area and detects the obstacle easily and avoids the obstacle completely. It also gives the warning signal to the driver about an obstacle and urges them to apply break. This device also has a high-quality auto-breaking system with it.


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Rome as any other european city can be extremely overwhelming especially with kids – it is a relief / the answer for any parent that Katja & her team exist!
Rome is one of the most fascinating sights in the world – though to see Rome through the eyes of a guide who loves and is passionate about the city, you will experience a different Rome !
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Know more about this business than we do? Cool! Please submit any corrections or missing details you may have.Help us make it right
Be the first AL.com user to add photos or videos of Nassef Engineering & Equipment
Enviromential Engineering And Consulting Service & Design Of Pollution Control Equipment Environmental Services, Business and corporate management consultation services, New business start up consultation services, Corporate mergers consultation services
Nassef Engineering & Equipment Company Inc can be found at W Nine Mile Rd 301. The following is offered: Waste Consulting. The entry is present with us since Sep 9, 2010 and was last updated on Nov 14, 2013. In Pensacola there are 16 other Waste Consulting. An overview can be found here.


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About us
What we do
StreetGames is a sports charity that changes lives and communities. We do it by supporting a network of projects which give sports and volunteering opportunities to young people in disadvantaged communities across the UK. Doorstep sport is StreetGames' delivery method, whereby we bring sport close to the home in disadvantaged communities at the right time, for the right price, to the right place and in the right style.
The aim of each StreetGames project, accredited by StreetMark, is to be sustainable and become part of the fabric of the community. This leads to stronger and safer communities, a championing of social action and volunteering, as well as improved health and wellbeing.
StreetGames is proud that it gives young people exactly what they're seeking – the chance to enjoy sport, give back to their communities and aspire to greater things. The enthusiasm that this breeds leads to an increase in sports participation and a recognition of the enjoyment that can be gained from taking part in sport.
At StreetGames we offer our projects Us Girls, The Co-operative StreetGames Young Volunteers, StreetGames – Legacy Leaders and Training Academy programmes to maximise their chances of creating positive change.
Who we are
StreetGames was launched in 2007 to change lives and change communities for the better. We were inspired by the success of joint work by The FA, The Football Foundation and agencies working in deprived areas. Since then, projects across the UK have benefitted from the StreetGames doorstep sport method.
StreetGames is registered as a charity with the Charity Commission (registered charity number 1113542) and as a company limited by guarantee with the Registrar of Companies (registered company number 5384487).
Read the StreetGames Strategic Plan 2013 - 2017 here »
our values
StreetGames is the national charity which develops doorstep sport in disadvantaged communities.
Social inclusion
StreetGames advocates that sport is a catalyst for social change in disadvantaged communities.
StreetGames helps people to become the best they can be through taking part in and leading sport initiatives.
StreetGames values partnerships which draw on each others' strengths and expertise and believes in sharing good ideas and resources.
Doorstep sport is an emerging style of community engagement and sports delivery – there is still much to learn and techniques to be tested. We bring a creative and flexible eye to new situations and challenges.
StreetGames challenges the barriers which prevent so many women and girls, black and minority ethnic communities and disabled people who live in disadvantaged areas from taking part in sport.
View StreetGames' Equality Policy here »


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The project is going to prepare a framework of knowledge and skills, that the "sharing economy service providers" will have to possess and demonstrate to the users of these services (e.g. tourist vehicle driver, rental accommodation, translator – guide etc.).
Hence the objectives of the project, include:
|Four Intellectual Outputs:
Two Multiplier Events,
A Short Term Training session:
|More info?
This project has been funded with support from the European Commission.
This publication [communication] reflects the views only of the author, and the Commission cannot be held responsible for any use which may be made of the information contained therein.


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Friend's Email:
Subject: I have found a CD that I think you would enjoy
Genres: Folk, World Music, New Age, Pop, Rock
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CD Reviews
Runaway-The Corrs
lowernatalie | Forrest Beach, QLD4840, Australia | 07/15/2000
(5 out of 5 stars)
"This is a song that would make a singe person want to be in love again, to be with someone. It makes one who is aready in love feel like a fairy tale, to run into the sunset with the love of her life. It is such a great song to make love to, the whole song is like my thoughts come to life. You could sit back and visualise everything in such a beautiful way. I can sit and listen to this song for hours and still every time feel new and incredibale emotions come to life. For someone to be able to come up with a song that can touch anyone so deep is incredible and that is what the corrs have done with this song. I also believe it is their particular voice and the way they play with the tunes, pitches, at the best parts of the song so soft and not very noticable, this song does the group so much credit. It has always and will remain my most favourite song."
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(5 out of 5 stars)
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Rad Song: Runaway by The Corrs
iceeblue | 09/20/2000
(5 out of 5 stars)
"i think this song is about two best friends who are so in love with each other but they don't know what to do about it. sounds crazy? this song is so beautiful and real touching. although the action is something is so impulsive. i like the idea of running away with someone you're so crazy in love with. the song's lyrics are simple but they hit you best where it should. andrea's voice and singing is so haunting that you'll really fall in love with the song. simple yet profound...that's the song. one of my fve songs by the corrs and any other artists."


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I did go see the delightful movie - Julie and Julia, and I thoroughly enjoyed it. There wasn't very much dancing - just a bit in the wedding scene - but Paris looked stunning, and even Queens in the "Julie" part seemed exciting and fun.
One interesting note about the subject of learning to cook by cooking every recipe in Julia Child's book classic "Mastering The Art of Trench Cooking." There once was a marvelous dancer named - Earle Sieveling; He had trained with E. V. Williams, danced for her when she had The New England Civic Ballet which was the precurser of BB, The Boston Ballet, and was a member of the New York City Ballet back in the 60s and 70s. He often Guest Starred with us in Boston during that time. He was part of the dance family.
After his dance career ended in the late 70s rather suddenly - that is another story - he needed a new career. He decided to learn to cook by using Julia Child's book; he made every recipe from the book in his apartment, and it took him a year. He became a fantastic chef who worked in a restaurant in Saratoga Springs owned by dance fan and hotelier, Sheila P., who shared this wonderful story with me a few years ago. Earle did it first!


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Bay Gourmet Editorial and Design
Cathy is a native San Franciscan who balances her professional passion for helping clients navigate their financial lives with her longstanding love for good food and good times. Cathy chairs the Bay Gourmet forum of the Commonwealth Club and organizes creative, informative events inspired by our local food culture. She prides herself on being "in the know" about the people and places that drive our vibrant Bay Area food community. Cathy is also a Board Member of CUESA (Center for Urban Education About Sustainable Agriculture) and a member of the Advisory Council for CAFF (Community Alliance for Family Farmers).
Chad's career in public education spans more than twenty years and includes roles as teacher, legislative assistant, curriculum developer, and attorney. He recently left his law firm to offer school districts better rates and personalized service and to allow time for new creative projects. Originally from Nebraska and a part-time Paris resident, he loves high-quality, honest ingredients brought to the plate with integrity and intelligence. Chad serves on the Advisory Board to the School of Education at UC Berkeley and is a passionate supporter of the Growth Art Creative Center, Telluride Film Festival, and the Bay Gourmet Forum of the Commonwealth Club.
Richard is a professional writer who lives to get to the heart of the matter. He has clients in four verticals: Technology, Education, Health Care and the Arts. As a writer, he helps marketing professionals and business owners communicate their value proposition clearly and with passion. Speaking of passion: Richard's passion for good food began in the Bay Area when he and a future well known chef shared a roof and a kitchen in the Sunset district. Richard makes claims to making the juiciest, best tasting roast chicken you've ever eaten.
Joann's creative eye and appreciative palette are born of a childhood on a cattle ranch in northwestern Nebraska. Open terrain and passionate food production excite her senses. A leading Bay Area physician for nearly 15 years, Joann loves to help her patients eat intelligently and enjoy what our local farms and ranches offer. Also a part-time resident of Paris with her husband Chad, Joann is moved by light, energy, and an honest moment.


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EAT THIS CITY is your weekly tour of the best restaurants in one of our favorite cities, as chosen by top chefs. This week, we head to the city of lights, Las Vegas!
They say that what happens here, stays here. Vegas may be decked out in bright lights, but it promises a cover for your secret fantasies and wildest deeds. Whether it's attending a burlesque show, hitting the slots, or yes, watching Carrot Top live, the city doesn't judge. Known as the Entertainment Capital of the World, it might be hard to imagine Sin City as a burgeoning center for ocean conservation and seafood sustainability. But it won't be hard to imagine that for long, thanks to the passion and drive of Chef Rick Moonen.
Says Chef Moonen of sustainability:
It's pretty much the core value of my company. It's everything I live, breathe, and get creative for. Sustainability, connection with our environment, eating clean, good food, and leaving a healthier planet are all things that are extremely important to me.
Chef Moonen, who graduated first in his class from the Culinary Institute of America in Hyde Park, New York in 1978, went on to develop his talents at some of New York's most iconic restaurants: Le Relais, Century Cafe, Chelsea Central, and The Water Club. From there, it was on to a position as partner and executive chef at Oceana, which earned three stars from The New York Times, and then on to his restaurants Molyvos and New York City's rm. Both garnered three star reviews in turn.
Not one to rest on his laurels, in 2005 he was offered a challenge: move to Las Vegas, a city he'd never visited, and open a restaurant.
Technically, he opened two: rm seafood and Rx Boiler Room, and The Shoppes at Mandalay Place.
Occupying the top level, Rx Boiler Room offers a playful shared dining experience in an equally playful steampunk-inspired atmosphere. Guests enjoy comfort food inspired and reimagined, and handcrafted cocktails using the finest of spirits.
On the lower level, rm seafood continues to reflect Chef Moonen's commitment to the environment. All of the seafood served is sustainably sourced, in accordance with Monterey Bay Aquarium's Seafood Watch Program, which the chef has long championed (along with being a founding member of Seafood Choices Alliance).
If the desert town of Las Vegas still seems like an unusual place for this epicenter of ocean sustainability, don't worry. Chef Moonen has thought about it a lot, too:
Actually, I think it's a great place to do it, because it's the most unlikely of things to happen. I don't like things that are easy. I love challenges. So, I took the challenge…Here I am. Sustainability. In the middle of the desert. Love it. Love this city. I've embedded myself deeply into the community. Into the inner fiber of it, the growth of it. Watching a city before your eyes bubble like yeast budding out?…We get recognition for who we are, what we grow ourselves into being, and I get to be embedded in the nucleus of that? I am the happiest man alive because I get to cook for a living, I get to connect to people through food.


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How to solve Microsoft Visual Basic Automation Unspecified error
Asked By 50 points N/A Posted on - 05/26/2014
After the running, the update for Microsoft Visual Basic I ended up with an error message while working in a project. The error message does not specific any information about the error and why it happened. The error says there is an 'automation error or unspecified error'. How do I correct this error? Please help. Thanks.
Microsoft Visual Basic
Automation error
Unspecified error


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Whether you attend one of our free classes, schedule an installation appointment at YOUR home or at one of our locations, you will leave with confidence!
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- Description
Product Description
TP Crazywavy Slide Body Green with Handles
- Made from injection moulded polyethylene, with ultra violet stabilisers so strong there's no need for steel supports, which makes the Crazywavy slide easier to assemble.
- Chunky wave design makes for a roller coaster ride from start to finish. Built-in galvanised handrails and high side walls make the Crazywavy an extra safe ride.
- Extra wide body means the Crazywavy is suitable for older children too.
The new TP Apple Green Crazywavy slide is the new replacement for this model, however it does not feature that extra safe handles that this model does, at the top. Once these ones are gone we can not get any more.
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On Display at Wicken Toys Yes Product code tp969 Manufacturer TP Toys Weight (kg) 14.0000 Age Range 3 - 14 yrs Max Load (kg) No Platform Height No Platform Height (cm) No Platform Size (cm) No Second Platform Height cm No Second Platform Size No Slide Length (cm) No Depth (cm) 2.5 Width (cm) 48 Height (cm) No diameter No Safety Standard Domestic Family Use Only - Use in a commercial setting will void all warranties. Warranty 5 years against rust causing failure / 1 yr all other parts
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I was Asked How Is it You believe That You Know the difference Between a good Homeless services Agency and A Bad One Joseph?
I was Hesitant at first to reply, and I replied In Kind, Facing A question with a Question, Why Would You Ask Me That? you refuse To speak To Me In Public You have Me Blocked On Twitter And You removed yourself from My Facebook account!
I also Explained That answering That was almost Like giving Ammo To someone who keeps Shooting at you. However I feel That Everyone Is entitled To answers To their Questions.
It was almost Comical To Me because I had a conversation just a few days Back with someone as To why I felt Like Faith Based Homeless services Should Like any other Organization Be able to Exclude People who Do Not Meet their requirements. And If those Requirements Be That You Attend A Short Service Before Dinner and A bed Or observe A moment of silence While they Pray than It is as A privately Funded Service Organization Their Choice. That Flies In the Face Of Many But It is Or Has Been A fact For some Number Of Years That Faith Based Programs That Have A requirement Of Attending Any Service Based On that Faith Are Excluded From Federal Funding and Cannot within Any of their Services Requiring It, Partake Of community Development Block Grants. So why Should They Not Have That freedom Of Choice?
I do However Believe That There are Organizations That Are Out there That Are Good And Bad Both Secular And Faith Based. The Way To Tell The difference Is To Me relatively Simple, One Could Either Live On the streets For decades and Try to Get Them To Help You Or You could Look at what They Say about themselves.
Answer This Question? Do Homeless Service Organizations House People? In Short NO! There are many that will tell you they Do, Fact is It Is the Dept of Housing and Urban Development, and The section 8 Vouchering system that Houses the Overwhelming Majority Of Homeless In this Country. The Ones Claiming, We Housed I housed, I house, We House, Are in essence Deceiving People. Most Homeless services Agencies If you Look at their Charters and Guidelines Are simply Referral Agencies. They Refer Homeless To State and federal Agencies That Are already available For the Homeless. The Referral Agencies have received Funding In most cases To Help Homeless Individuals Through The Painstaking Application Process. In doing so They are as deceptive as The Counter man at McDonalds if Asking Him What He does For a Living He replies I feed The Hungry! These Are Bad Agencies and Cost ineffective.
Then There are Good agencies and They Do Not Claim We do This Or that They tell you right Up front I am Sorry we are simply a referral Agency. and They do Not Look for Praise. They more often than Not Share with People How they Were blessed To have assisted someone In meeting the right People to Get into Housing, and The generally Talk about How It was a Humbling experience, And They Were Grateful To have Helped.
But the True separation Is the former feel the Homeless Are Lucky To have them to Help, while the Latter feel as If they Were Lucky to have Been able to Help. Look the Only Point I am Trying to Make is that, Bad Homeless services Agencies Are sucking the Life out of the Homeless and The good ones are struggling to survive Just like the Homeless themselves. Only the Good Ones Aren't Begging For funding, And The Bad ones will tell you Your better off to Give to Us Than too the Homeless themselves!
What I find Even More Comical Is this After writing About This For Well over a year Now, People Still Just Blindly Follow And Praise These Organizations That Have Failed Us For so Long Believing That They Must be doing Good They say So in their Pamphlets, and their News Letter. Why I even seen Them Tweet How Much Good They Do So It Must Be True. And People never Bother Too actually Find Out what they do and where their Funding Goes.
The Only Up side Is, That I have also Watched Over the Last year as Some people Have woke Up and Began To question Organizational Failure.
However Knowing It will Never effect Change If in than Knowing You remain Silent!


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This week has been a big week for our house. With Angel starting kindergarten, I discovered a difficult truth. I no longer have the sole influence on any of my children. It's certainly not a bad thing, consider the line "It takes a village to raise a child." I have carefully chosen my 'team' to help raise my kids. Now, I have to put my faith into our collective efforts for yet another life.
There are no longer any morning snuggles with Angel after the boys go to school. My mornings are now rushed and busy. Three different schools to get to (on time) every morning. Waking up four of us and making sure we are all ready for the day is not always going to go smoothly.
The transition has been hardest on my Angel. Grandma has always been home in the mornings, so Angel generally woke up just after I took the boys to school. Now, she is up at the same time and leaves when the boys do. She has been the only child of mine who had the luxury of having Mommy home all day, everyday, since she was born. With my work from home job, I was rarely away from her except for occasional meetings.
Now, not only is Mommy leaving, but I am leaving her in an unfamiliar place. The first day of Kindergarten was terribly hard. She cried the WHOLE morning. The second day, she had a few moments without tears. I stayed in close contact with the teacher and we worked together to smooth her transition as much as possible. Monday was hard. Tuesday she said she didn't want to go to school anymore. Wednesday, I left her crying in the classroom again, but this time she was full of smiles when I picked her up.
Wednesday night was Meet The Teacher night. I knew that the importance of this night was not really about meeting the teacher, but giving Angel an opportunity to share her classroom with the rest of the family. Particularly Daddy. After she had shown everyone the things she likes about kindergarten and had the reassurance from all of us, she felt more comfortable in the classroom. (The Trucker often underestimates his influence on the children.)
Thursday she said she had a good morning, but she didn't want to talk about it. I didn't push. I do not want to overwhelm her with questions or make her think that I am worried about what she is doing while I am away. Friday was even better, though she still doesn't want to talk about it much. She now says she likes school and is looking forward to seeing her friends again next week.
My first full week of University was challenging. Yes, I had homework. Textbooks to read, terms and definitions to memorize. I knew this was going to be difficult. I was prepared for a week of figuring out my schedule, my adjusted daily routines. I've made a few steps in the right direction this week. But I ended up with a bigger priority.
I felt like I was drowning at a few points. The Trucker has injured his shoulder and is suffering low back pain again, so he's not really much more help than just another body in the house. I've scrambled to get dinners cooked and lunches made. I've stayed up past midnight to do homework because I just didn't have time in the daylight. I've left dishes on the counter and fell behind on laundry. I am grateful for my mother right now, she is picking up my slack with housework. She's not even complaining. In fact, she has mentioned how it's almost boring having no one in the house with her in the mornings! (Yay for me)
I'm exhausted and mentally drained.
But, I know with every ounce of my soul that I got things right this week. My number one priority was helping the kids adjust. School transition may be easier for the boys than for Angel, but it is still Transition. Art has new orthotics and also a new expectation to carry his Epi-pen on his body this year. He's had a lot of changes to remember and he is doing well. Macboy moved to grade eight and we had several issues with his class schedule this week. It is still not completely sorted out.
Angel had it the hardest by far. She has rarely been away from me at all. And when she has been away, it's almost always been that she stays home and I go out. I spent my week focused on her more than anything else. I played cars and built ramps. I made crafts and colored pictures. I played with Playdough for hours. It's paying off. It's showing her that even though we all have to change our mornings now, that is all that is changing. Home is still home. Mommy is still Mommy. We can and will always have time to play. I won't stop reading her stories even if the teacher is reading stories at school. I won't even stop when she learns how to read by herself.
I reinforced her sense of security. (I have had to do a lot of that with all three kids this summer.) I showed her that I will be waiting right outside her classroom door every day and that she can count on me. I will not leave her at school. I am not giving her away. I am COMING BACK. Every day.
I know that starting University is a big deal. I know that focusing on my homework and studying is important. I will not say that I avoided that in any way. It remained a priority, of course. But it was not the most important thing I did this week.
I've worked on my schedule and made a weekly planner for the fridge so I can keep track of four of us in school. Lots of things have needed to change and will continue to change. It's been a long challenging week. I expected it to be hard. Some days are actually easier than I expect while others are painful.
Being thirty five and starting University with three kids is complicated. I have to think creatively. I have to stay motivated. I have to constantly review and assess my priorities. They change every day. I have to sit through a lecture, while thinking constantly about leaving my poor little girl in hysterics at school. YOU try to focus in that situation!!
This is only the beginning, I have a lot of time to get the daily routine nailed down. I can find a babysitter when I need it. I can leave the Trucker with the kids and go study away from my house. I can make this work.
It will be so much easier to manage going forward because I spent the time to show my children that everything is going to be okay and our lives don't really have to change that much. Every minute that I spend showing my kids that I am STILL here for them, every extra hug and snuggle, every moment of one on one time to ease their minds will come back to me. Each second lays groundwork for easier studying time in the weeks to come. The kids know what to expect and what will be expected of them.
I had many moments this week where I thought I wasn't going to make it. I thought I'd made a horrible selfish mistake. I thought I could never do what I needed to do. But I can, I have and I will. I have chosen to go back to school for my own reasons. Yes, purely selfish. It's got nothing to do with money or because I want to support my children better. I've had pretty decent wages in my past. I just want to spend my time doing things that I love. And that is definitely the message I want to send my kids.
I am not doing this at their expense, even if I am doing this only for me. I am showing them that the only person in the world who really knows what each of them wants to do with their life is themselves. I want them to learn this early. So they don't have to start over at 35.
My work, focus, effort this week has not been without reward. We are all learning and growing. No degree in the world can ever change the fact that I am a Mom. I will fight to remain the Mommy I have been. We will not just survive this time in our lives, we will thrive. Because I have learned that being the Mommy they need, the Mommy I always wanted to be, is the most important thing I can do every single day.


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Archives of Michigan
The Archives of Michigan is responsible for preserving the records of Michigan government and other public institutions. The collections also include documents, maps, photographs and film from private individuals and organizations.
702 W. Kalamazoo St.
Lansing, MI 48915
Phone Hours
M-F: 8 a.m. - 5 p.m.
Research Hours
M-F: 1 - 5 p.m.
Sa: 10 a.m. - 4 p.m.


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Thank you to our Alban's Angels
The Alban's Angels appeal invited individuals, schools, groups, and churches to help support the Alban, Britain's First Saint project. By joining and donating £25 or more, their names were written on beautiful hand carved angels and displayed in five separated clouds in the Cathedral's Crossing. These clouds added to the incredible atmosphere of the Cathedral from June 2015 to February 2016.
The Alban's Angels appeal has now come to an end and we would like to thank everyone who helped make it so successful. With a total of 550 angels donated, together we have raised over £34,000 towards the Alban, Britain's First Saint project!
A Huge Thank You Goes to All Our Alban's Angels...
The Archbishop of Canterbury
The Countess of Verulam
Thank You Schools!
The Abbey CE VA Primary School
Hillborough Junior School, Luton
Abbot's Hill School, Hemel Hempstead
Aldenham School
Thank You Companies!
Austin Trueman Associates
Kingston Smith
G. D. Golding (Tailors) Ltd
St Albans Chamber of Commerce
Thank You Churches!
All Saints with St Peters, Luton
Christ Church, Waltham Cross
King Charles the Martyr, Potters Bar
Little Wymondley Parochial Church, Little Wymondley
St Francis of Assisi Church, Welwyn Garden City
Parish Church of St John the Baptist, Royston
All Saints' Church, Kempston
Parish Church of St James, Biddenham
St Mark's Church, Hitchin
All Saint's Church, Renhold
St Stephens and St Julians, St Albans
St John's Church, Boxmoor
St Clement's Church, Turnford
Christ Church and St John's, Radlett
St James, Goffs Oak
St Marks, Bedford
St Andrew's, Bedford
St Alban's Church, Warners End & Gadebridge
St Mary's Church, Apsley End
St Faith's Church, Hitchin
St Oswald's, Croxley Green
St Paul's Church, Langleybury
St Mary the Virgin, Rickmansworth
St Mary the Virgin, Maulden, Bedfordshire
St Andrew's, Woodside
St Andrew's Church, Langford
St Mary, Hertingfordbury
St James the Great, Silsoe
St Michael's Church, St Albans
St Michael with St Mary, Letchworth
Holy Trinity, Leverstock Green
The Parish of Abbots Langley
St Andrews, Hertford
The Parish of St Alban, Protomartyr, Romford
Ampthill/ Shefford Deanery
Clapham Parish Church, Bedford
St Mary the Virgin, Baldock
St Paul's Church, Luton
St Peter's Church, St Albans
St. Lawrence Church, Bovingdon
St Hugh & St John, Chells, Stevenage
St Augustine's Church, Dunstable
St Peter's Church, Tewin
St Alban's Anglican Episcopal Church, Tokyo Japan
St Luke's Church, Watford
All Saints Church, Datchworth
St Leonard's Church, Sandridge
Thank You Clubs and Groups!
Aldenham Womens Institute
St Albans Lions Club
St Albans Art Society
Harpenden Ladies Probus Luncheon Club
St Albans Civic Society
St Albans 41 Club
Thank You Everyone!
Abbi-Rose Prudence Abrahams Katharine Adlard Emma Adlard A.J.J.B.
Claire Alderson Gary Alderson Sharon Allen Francis Allum Marion Allum
BB Anderson Mary Anderson Jessica Ashton Ann Armstrong Jan Atkinson
Rt Revd Richard Atkinson Lauryn Awbrey Fadeke Ayoola Jane Ayres Christine & Roy Bain
Neil Baker Teresa Bannister Ann Banham Adrian Barker Louise Barker
Salli Barker Julia and Denys Barrett Christine Barron Alison Batemen-Jones
Ros Battersby Denys Barrett Ken Barrett Maree Barrett Horace Beman Dr. Tony Bentley
Brian Benson Jaqueline Berry Big Jon Richard Biggs Derek & Ann Bird
Kathleen Margaret Blake Peter and Rosemary Bladon Claudia Blair T and J Blinko
Julian & Rosalind Booth Shirley Bolton Elizabeth Bowles Michael Bowles Brigid Brennan
Sophie Brennan Isabella Brent James Brent Jason Brimson Robin and Vicky Brown
Beatrice Burgess Edward Burgess Canon Michael Burns James Burns
Linda Burton Mark Burton Sally Burton Johan Butler Pam & Tony Byfield
John Cadisch Madeleine Callaghan Nikki & Ben Callon Lizzy Canning Rosemary Carter
Jacqui Castiello Michele Castiello A Cecil Charles Cecil Jean Cecil
Joanna Chapman Jenny Charman Catherine Christian Eliana Christodoulou
Rose Chote Evalyu Clara Graham Clark Felicity Clarke Sylvia Cleary
Wendy Clements Hazel Clifton Sue Colman Ruth Coles Mark Comisky Elizabeth Conrad
Carol Cooke Sarah Cooper Anne Cosimini Hester Crabbutt Juliet Crisp Lesley Crews
Mick Crews Abbi-Rose Crook Irene & Jacques Crozier DDB Irene Davies
Robin Davies Sarah Dawkins Richard Dawson Carolyn Dealey Pat Defoe Roger Dennis
Mary Dobbie Richard Dockree Ersida Dogaj Beryl Dorrington Maggie Douglas
Lesley Duggan Nicholas Edmonds Susan East Liza Elliott Jean Embleton
Jacqueline England Bilge Erengul Clare Evans Susan Evans Fr Nevsky Everett
Jenny Faldon Brian & Bridget Fernandes Patricia Flanagan Elizabeth Fletcher
Martin Fletcher For Charlie For Daddy TRF CJF JCF CMF
Annabel Finley-Kensett Diane Finlayson Samantha Ford Richard and Jill Foulger
Jane Fowler Alison Gabriel Michelle Gardner Anne Gardiner Mary Gate Rita Gent
Nell Green Marilyn Gillin Sarah Gillin James Girdwood The Gordon Family
Emma Girdwood Tanya Gelsems David Charles Gould Martin William Gould Jennifer Graham
Father Grant The Gray Family Stacy Gray Sir Alexander and Mrs Graham
Martin Griffiths Mr & Mrs Grix Alban Guri Khaki-Gore Janet Goacher
Abigail Griffith Karin Groombridge Honor Guard Kitty Guard Rose Guard
Thirza Guard Lewis Family Pauline Hagerman Jessica Hall Margaret Hall Jessica Hallmark
Philip & Mary Halsey Jonathan Hamblin Lorraine Hammond David Hanns Catherine Hardwick
Derek and Jenny Harrison Martin Hawker Margaret Hebblethwaite Stuart Henderson
Virginia Herron Neill Hewitt Linda E Hill Will & Kate Hobhouse Amber & Arthur Hollebone
Sarah Hope Pauline & Richard Horsman John & Elizabeth Howard Jo Hudson Michael & Doris Hughes
Margaret Humphrey Richard & Elizabeth Hunt Peter & Pat Hurford Hazel Ireson
Sarah Jenkins Alex Johnson Thomas Johnson Rix Edward Johnson Rix Robert Johnson Rix
Rachel Jackson Judith James Teresa Janes Jeffrey John Elizabeth Jones Gemma Jones
Jennifer Jones Patricia Jones Rita Jones Terry & Louisa Jones Trevor Jones Robin Jopson
Anna Jordan Linda Jordan Christine Juett Quentin Keeling Sarah Keeling Sue Keeling Chris Keane
Pamela Kelly David Kemp Mary Kenward Stephanie Kyriacou Laura L
Tracy Lay Maureen Lacey Doug & Sandy Leedham Stuart Lewis Bridget Lewis
Emma Ling The Low Family Nikki Lewis Photography Emma Ling Xen Lu Janet Lynch
Carolyn Manley-Cooper Patricia Martin Will & Ina Martin Matilda Alison Matthews Gill Matthews
Ann McCormac V McKinnon Patricia McManus Marcus & Ikumi James Maxwell
Pat Maziane Sheila McGuire G C & A McMahon Mum & Sister Janet and Greville Megson
Christopher & Susie Melluish Naomi Message Robin Message
Scarlett and Matilda Miller Miriam James & Kathleen Mitchell Valerie & David Moor
Richard Morgan Julie Morrey Sue Morrison Berit Muller-Pebody The Muller-Pebody Family
Francid Needham Evelyn Needham Lena Nevers Joyce Newman Laura Newson
Christopher Nickolds Ben Noices Angela North Eleanor Nuttall David & Heather Nye
Rosalie O'Brien Lisa Ogarro Eamonn O'Malley Melanie O'Neill Judith Orrell Gill O'Sullivan
Barbara Ouston Andreas & Maritsa Papamichael Pamela & Trish Kate Charlotte
Glen Parsons Susanne Parsons Marie Parry (28/12/83 to 05/01/14) Pauline Audrey Palmer
Patellis Amanda Payne Dorothy Pears Sue Pegg Donald Pelmear
Gillian Peters John W Peters Jean Peyton The Pisharody Family Luy-Violet Pittam
Steve & Jean Potter Tony Prior Grace Protts Tessa Pyke The Rainey Family, Australia
Caroline Randall John Randall Karen Randall David Ratcliffe Stephanie Rebold Elaine Reed
Shania Reed Edit Rees Rodi Resch Jonathan Reynolds John & Pauline Ridgwell
Louisa Ringrose Valeria Riso Canon Bill Ritson Wilhelmina & Charles Rix
Wilma Rix John Rix Michael and Sophia Rock Jane Robson Claire Robinson Elizabeth Robinson
Roberts Family Helen Roberts Uli Robertson Pamela Roome Martin Rogers Liz Rose
The Rose Fellowship Rosewell Family Mags Ross Susan Rouse Maria Ryan-Datton S&K Olive Salt
Adele & Thomas Sammons Morao Saunders Robert Saunders Scarlett Geoffrey Seabrook
Pamela Seabrook Sandra Searle Janet Sexton Mary Shimell Heather Smith & Robert Raine
Janice Spalding Lucy Sidwell Julia Smith Janet Susan Stocks Margaret Stone
Clare & Ed Sutton Pauline Sweetingham The Tabraham-Johnson Family
Christopher Talbot-Ponsonby Hanna Tarnowski Alex Tarnowski Laura Tarnowski
Charlotte Tarnowski Isabella Taylor Sara Kate Taylor Carmen Thomas
Robert Thomson David Thompson Jo Throup Annemarie Timmers Teun Timmers
Ties Timmers Jane Tipler Sue Tomson Nicholas and Meriel Tufton Jackie and Hannah Turberville
Penny Turnbull Patricia Turner Antony Unwin Lawrence Verney Silvia Vitiello
Richard and Susie Walduck Carolyn Walker The Ward Family David Warner
June Warner Liz Warren John Wathen Nora Watson Howard Watts
John & Jacquie Webb Anthony Weber Dawn Wheeler John Wheeler James Wheeler
Margaret Wheeler Poppy Lily White Matthew Whitehead Roberts Leah Wildman
Alison Wilson Ray Wilson John Wood Antony Woodall Elizabeth Woolley Matthew Wratham
Amy Wren Angela York Ian & Alison Young


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Portable form of glockenspiel. It is mounted on a rod held perpendicularly in the left hand whilst the right hand holds the beater.
Subjects: Music.
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This is unlike any other winter holiday. You'll be riding lots, exploring whole mountain and starting to fully understand your own limits as a rider and how to overcome your fears and boost your skills.
One of Bootstrap 3's big points is responsiveness and Mobirise makes effective use of this by generating highly responsive website for you.
Our start (October) and end of season (May) social shred camps are an ideal opportunity to freshen up your skills in preparation for the winter and help maintain them through the summer.