FMO3 gene, and may be associated with hypertension. We investigated whether common polymorphisms of the FMO3 gene confer an increased risk for elevated blood pressure and/or essential hypertension.The recessive disorder trimethylaminuria is caused by defects in the FMO3 genotypes  were determined in 387 healthy subjects with ambulatory systolic and diastolic blood pressure measurements, and in a cardiovascular disease population of 1649 individuals, 691(41.9%) of whom had a history of hypertension requiring drug treatment. Haplotypes were determined and their distribution noted.There was no statistically significant association found between any of the 4 common haplotypes and daytime systolic blood pressure in the healthy population (p = 0.65). Neither was a statistically significant association found between the 4 common haplotypes and hypertension status among the cardiovascular disease patients (p = 0.80).FMO3 gene do not predispose to essential hypertension in this population.These results suggest that the variants in the  Essential hypertension is the most common reason for adult visits to office-based physicians and for the use of medication -3. It isFMO3, a phase 1 drug metabolising gene, is the main liver dependent human isoform[FMO3 cause TMAuria [Trimethylaminuria (TMAuria) is an inborn error of metabolism (MIM # 275700) resulting from diminished oxidation of the tertiary amine trimethylamine to trimethylamine N-oxide resulting in a severe body odour in affected individuals. The microsomal NADPH-dependent flavin-containing monooxygenases (FMOs) (E.C. 1.14.12.8) are a family of chemical and drug metabolising enzymes that catalyze the phase 1 oxygenation of a wide variety of nucleophilic heteroatom containing compounds including catecholamines,21. FMO3n isoform. We and  TMAuria -24.FMO3 gene [FMO3 gene. Endogenous substrates for FMO3 include tyramine and phenylethylamine [FMO3 gene could contribute to impaired catecholamine metabolism and hypertension.We have previously noted that a number of patients with TMAuria have idiopathic hypertension ,22. In aMO3 gene suggestinhylamine ,27 and tFMO3 gene  in a North American population[in vitro[FMO3 activity in the presence of the E158K polymorphism causing mild TMAuria[We have previously described the population frequencies of a number of common polymorphisms of the  E158K, V7M, E308Gopulation. Express E158K, V7M, E308Gd TMAuria,29. WhilFMO3 polymorphisms might predispose to essential hypertension. While null alleles in the FMO3 gene may be too rare to cause any appreciable effect on the population burden of hypertension, prevalent polymorphisms with documented in vitro evidence of variation in catecholamine metabolism may however potentially associate with and predispose to this condition.We hypothesised that common FMO3 gene with the phenotype of blood pressure in an occupational Irish adult population and with presence of essential hypertension in an Irish cardiovascular disease (CVD) population.Herein we report our investigations into a possible association of haplotypes of three polymorphic variants of the There were 2 population groups in this study. The first population was recruited from the Allied Irish Bank Phase II (AIB Phase II) study that commenced in 1989 and consists of 387 bank employees (Table The second were a group of 1649 patients with coronary disease (CHD), 1313 of whom were ascertained on the basis of having acute coronary syndromes (ACS)  or unstable angina) and 336 as having stable angina Table . MI was Informed consent and ethics approval from the Beaumont Hospital Ethics  Committee was obtained for all samples collected.FMO3 gene were genotyped in the above populations. These were E158K (G472A), V257M (G769A) and E308G (A923G). The E158K polymorphism was genotyped using the primer GAAGGTGACCAAGTTCATGCTTGGCCTTACCTGGAAAGGACTT for the G allele and GAAGGTCGGAGTCAACGGATTTTTGGCCTTACCTGGAAAGGACT for the A allele. The V257M polymorphism was genotyped using the primer GAAGGTGACCAAGTTCATGCTCAGCCATCTCTGACTGGTTGTACA for the G allele and GAAGGTCGGAGTCAACGGATTAGCCATCTCTGACTGGTTGTACG for the A allele. The E308G polymorphism was genotyped using the primer GAAGGTGACCAAGTTCATGCTGCCTAACGTGAAGGAATTCACAGA for the A allele and GAAGGTCGGAGTCAACGGATTGCCTAACGTGAAGGAATTCACA for the G allele.Three single nucleotide polymorphisms in the . Genomic DNA was isolated from blood. Genotyping was performed in 384-well microplates using a fluorescence resonance energy transfer (FRET)-based genotyping method. Amplification was initiated using allele-specific primers and a common downstream primer. The allele-specific primers were tailed with unique sequences that create corresponding complementary sequences in the two amplicons. In the second round of amplification, quenched Universal Amplifluor™ primers (in a hairpin formation) were used. These primers contain 3' tails that specifically bind to the unique tailed sequences in the amplicons and continue amplification. In the final round of amplification, the action of the DNA polymerase opened up the hairpin structure and the quencher and reporter moieties are spatially separated. The excited reporter moiety emitted either red or green fluorescence, the colour of which depends on which nucleotide is at the polymorphism site. The fluorescence was quantified by a microplate reader and then analysed via an Excel macro to provide genotypes for each SNP. Confirmation of the validation of the mutation detection method was based on the use of known positive DNA controls (which had been sequenced) for the three polymorphisms provided by McGill University .Genotyping was carried out using the Amplifluor™ method by K Biosciences Haplotypes for the 3 SNPs were inferred using a maximum likelihood approach and their association with the rank of the various mean blood pressure measurements in the AIB Phase II study group and their association with hypertension in the CVD group was determined using "haplo.score", a function written for the statistical package SPLUS 6.0. This meThe 2 primary analyses were (1) the association between haplotypes of the 3 SNPs and mean daytime systolic blood pressure in the AIB Phase II study population and (2) the association between haplotypes and the hypertension status in the CVD patients.The secondary analyses included (1) the association between genotypes and daytime systolic blood pressure in the AIB Phase II study, (2) the association between genotypes and hypertensive status in the CVD group, (3) the comparison of genotypic frequencies between the AIB Phase II study group, the hypertensives of the CVD group and the non-hypertensives of the CVD group, (4) the effect of haplotypes on mean daytime diastolic blood pressure, on mean night time systolic blood pressure and on mean night time diastolic blood pressure in the AIB Phase II study group, (5) the association between polymorphisms in the FMO3 gene and cardiovascular disease.Haplo.score was used to look for any associations between haplotypes and daytime systolic blood pressure/hypertensive status. We only tested for relatively common haplotypes, and defined as those at an inferred frequency of greater than 5% in the populations. For all of the above analyses, statistical significance was determined when p < 0.05.ANOVA was used to look for an association between the genotypes and mean daytime systolic blood pressure in the AIB Phase II study group. Both haplo.score and ANOVA were adjusted for age, sex and the number of alcohol units consumed per week.Chi-squared analysis was used to look for the difference in genotype frequencies between the hypertensive and non-hypertensive patients in the CVD group. Linear regression was then used to adjust for age and sex. Chi-squared analysis was also used to compare genotypic frequencies between the AIB Phase II study group, the hypertensives from the CVD group and the non-hypertensives of the CVD group. Logistic regression analysis was used to predict if any of the SNPs influence the risk of cardiovascular disease, including diabetes, BMI, hypercholesterolemia, smoking status, age and gender in the model. All of the above analyses were repeated stratifying according to gender.The AIB Phase II population consisted of 387 subjects, 224 (57.8%) of which were male. In comparison to the females, the males had on average higher blood pressure measurements, triglycerides and total cholesterol. Slightly more males in this group were smokers Table .The CVD group consisted of 1649 subjects, 691 (41.9%) of which were classified as having a history of hypertension requiring drug treatment. A greater percentage of those classified as hypertensive also had hypercholesterolemia and diabetes mellitus in comparison to those who were classified as non-hypertensive. As might be expected from a CVD group, most of the subjects were taking medication, with almost the same frequency of hypertensives and non-hypertensives taking each group of medications Table . Blood pThe most notable difference between the AIB Phase II study group and the CVD group is that there were a much greater proportion of current or ex smokers in the CVD group than in the AIB Phase II study group (73% vs. 30.1%).nd most frequent haplotype in the AIB Phase II study group, was the 3rd most frequent haplotype in the CVD group. However the difference in frequency was only 4%, which is most likely due to chance.The 3 SNPs were found to be in Hardy-Weinberg Equilibrium. 4 common haplotypes were inferred in the two populations  . When this analysis was stratified by gender, still no statistically significant differences are noted .Testing for any associations between haplotype and daytime diastolic blood pressure, night time systolic blood pressure and night time diastolic blood pressure in the AIB Phase II study yielded no statistically significant associations Table . LikewisFMO3 gene and hypertension. The FMO3 enzyme has a broad substrate specificity, which includes catecholamines as a minor pathway[FMO3 gene resulting in decreased enzymatic activity could result in decreased catabolism of catecholamines, which impact on blood pressure homeostasis. As catecholamines are at peak levels during the day, we elected to study the association between daytime SBP and variants in the FMO3 gene as a primary endpoint. In our analysis, we adjusted for alcohol use as tyramine is a substrate for FMO3 oxidation[The observation that a number of patients with TMAuria are hypertensive was the basis to the hypothesis that there may be an association between variants in the r pathway,26. Cateoxidation. Femalesoxidation. For thiIn this study, by constructing haplotypes based on the 3 SNPs, we discovered that none of the haplotypes were statistically significantly associated with either daytime systolic blood pressure in the AIB Phase II study group or with hypertensive status in the CVD group. There was also a lack of association between any of the genotypes of the SNPs with daytime SBP or with hypertension status. Neither did the stratified analyses show any statitically significant associations.While the definition of hypertension in the CVD population provides a rather arbitrary estimation of hypertension, the 24-hour blood pressure measurements in the AIB Phase II study were carefully controlled. Even so, the results from both groups showed that the variants had no association with blood pressure or hypertension status.FMO3 variants maintained in population, and in particular the E158K variant? It is proposed that genes such as FMO3, a drug and toxin detoxicating gene, may have survived as balanced polymorphisms in an ancient human or primate population to neutralise the effect of harmful exposures[FMO3 may have evolved in different geographic locations to buffer changes in the highly polymorphic drug metabolising genes, which show substantial geographic and ethnic variation. It is possible that 'low penetrance' polymorphisms of FMO3 alone may not independently affect blood pressure homeostasis but severe loss of function causing mutations may unmask pressor effects of variation in other drug metabolising enzymes previously buffered by FMO3[Why are exposures,33. Evold by FMO3. This hyFMO3 gene inherited singly or in specific haplotype combinations do not represent an independent susceptibility risk for hypertension as an absolute trait or continuous variable in a representative Irish population.In conclusion, these data indicate that these three polymorphisms of the CD carried out the statistical analysis and drafted the manuscript. DCS assisted in the statistical analysis and participated in the study design. AS contributed to the interpretation of the hypertension data and participated in the study design. EOB designed the data collection for the AIB Phase II study and participated in the study design. DML helped draft the manuscript. JKOB led the genotypic analysis component. EPT conceived the study and helped to draft the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


Interstitial photodynamic therapy has a number of potential advantages over superficial treatment. We have treated 50 subcutaneous and cutaneous tumours interstitially, in nine patients. An additional 22 tumours in the same patients, were treated by superficial PDT. Patients received 1.5-2.0 mg kg-1 of polyhaematoporphyrin and 72 h later underwent treatment using a copper vapour dye laser producing red light at 630 nm. All interstitial treatments were delivered using cylindrical diffusing fibres and a wide range of light doses (5-1500 J cm-3). The complete response rate for all tumours treated interstitially was 52%, rising to 81% in those patients who received 2.0 mg kg-1 PHP and light doses in excess of 500 J cm-3. The overall incidence of skin necrosis was 32% and was 79% in those treated with light doses of greater than 500 J cm-3. The incidence of skin necrosis with interstitial PDT is lower than that seen with superficial photodynamic therapy but higher volumetric light doses are required to produce tumour complete responses. All treatments were well tolerated and volumes of tumour up to 60 cm3 were successfully treated. The penetration depth of 630 nm light in human breast cancer tissue was determined as 4 mm. Little true tumour tissue selectivity was detected by analysis of porphyrin levels in biopsy material.


Prior literature has shown that racial/ethnic minorities with hypertension may receive less aggressive treatment for their high blood pressure. However, to date there are few data available regarding the confounders of racial/ethnic disparities in the intensity of hypertension treatment.We reviewed the medical records of 1,205 patients who had a minimum of two hypertension-related outpatient visits to 12 general internal medicine clinics during 7/1/01-6/30/02. Using logistic regression, we determined the odds of having therapy intensified by patient race/ethnicity after adjustment for clinical characteristics.Blacks (81.9%) and Whites (80.3%) were more likely than Latinos (71.5%) to have therapy intensified (P = 0.03). After adjustment for racial differences in the number of outpatient visits and presence of diabetes, there were no racial differences in rates of intensification.We found that racial/ethnic differences in therapy intensification were largely accounted for by differences in frequency of clinic visits and in the prevalence of diabetes. Given the higher rates of diabetes and hypertension related mortality among Hispanics in the U.S., future interventions to reduce disparities in cardiovascular outcomes should increase physician awareness of the need to intensify drug therapy more agressively in patients without waiting for multiple clinic visits, and should remind providers to treat hypertension more aggressively among diabetic patients. Hypertension is among the most prevalent chronic diseases in the United States . DespiteHypertension is particularly burdensome among racial/ethnic minority groups and hypertension-related cardiovascular disease has been shown to be the greatest contributor to previously documented racial differences in mortality -12. AlthWe previously examined the association of patients' race/ethnicity with processes of hypertension care . We founTo determine which patient-centered characteristics are associated with providers intensifying drug therapy for hypertension and whether provider experience is related to differences in intensification of therapy, we studied a random subset of 1,205 patients who had a minimum of two hypertension-related outpatient visits to one of twelve general medicine clinics in community health centers and community practices affiliated with a large urban academic medical center from July 1, 2001 through June 30, 2002 . To determine hypertension-related visits, we reviewed the electronic medical record (EMR) for all clinic visits with a primary or secondary diagnostic code of hypertension (HTN) . The study protocol was approved by the Human Studies Committee at the Brigham and Women's Hospital.We hired three abstractors who were trained by the primary investigator to review the EMR of each patient in our study sample, each abstractor reviewed records for approximately 400 individual patients. From each hypertension-related visit note in the EMR they collected the following data: patient race/ethnicity, name of the patient's primary provider, patient age at time of initial study period visit, sex, primary insurer at time of initial study period visit, presence of comorbid disease , coronary artery disease (CAD), or renal failure) listed on the patient problem list, BP control , and any changes made to antihypertensive drug therapy during visit .The EMR of each patient contains racial/ethnic data obtained via self-report the first time each patient registers in his/her clinic that then is classified by the data entry clerk as Hispanic ethnicity or not and race is then classified as Black, White, other, or unknown. Hence, it is impossible to know the country of origin of our Hispanic participants and we could not determine the exact racial/ethnic mix of patients classified as "other" or "unknown." For these reasons, we excluded patients who's EMR listed their racial/ethnic classification as "other" (N = 25) or "unknown" (N = 67) and we limited our analyses to White patients (who identify themselves as non-Hispanic), Black patients (who identify themselves as non-Hispanic), and self-identified Hispanic patients.From the medical center's administrative database, we abstracted each provider's level of experience . Patient zip code was also obtained and linked to 2000 U.S. Census data to obtain the median annual household income in each patient's zip code.Our methods for identifying intensified cases among our cohort have been previously described . BecauseOur intensification algorithm is potentially limited because it does not account for differences in the number of times medication is increased in comparison to the number of uncontrolled BP visits for each patient. To address this issue, we created a secondary measure of intensification by calculating the proportion of times each patient had their therapy increased when their BP was uncontrolled (0 representing no increases and 1 representing an increase in therapy with every uncontrolled visit). We then determined whether the two intensification measures were correlated in order to further validate our algorithm and found that the two measures were highly correlated . Because our algorithm-derived method has the additional advantage of using more than a single visit's BP in determining whether therapy intensification is indicated, we used this measure of intensification for all subsequent analyses.We compared patients' demographic, clinical, and provider's characteristics by patient race/ethnicity Table  using chUsing logistic regression, we assessed whether race/ethnicity was associated with intensification of therapy after adjusting for all measured confounders. Data were available on every variable for 685 of the 757 patients (90.5%) for multivariable analyses. We report adjusted odds ratios with 95% confidence intervals for the intensified cases. In secondary analyses, we included interaction terms for patient race/ethnicity and provider experience level to determine whether racial/ethnic differences in intensification differed by provider experience level. All non-significant interaction terms were removed from the final model. All models were estimated using SUDAAN statistical software to adjust for within clinic correlation of visits .Of the 757 patients, 304 (40%) were White, 309 41%) were Black, and 144 (19%) were Hispanic  who had their medications intensified. Hispanic patients were significantly less likely to have their medications intensified than White and Black patients Table . DiabetiAfter adjustment for age, insurance status, number of hypertension-related visits, diabetes, and physician experience, there were no remaining racial/ethnic differences in rates of intensification Table . CompareIn our prior work, we found that Hispanic patients were more likely to receive the JNC recommended antihypertensive drug class then Whites, however, Hispanics were also significantly less likely than Whites to have their therapy appropriately intensified in response to an uncontrolled BP . FurtherThere is substantial literature, that suggests that racial/ethnic minority groups are less likely to have their antihypertensive therapy appropriately intensified -19. HoweAn important national priority in health care is the elimination of racial/ethnic disparities in healthcare; however, a better understanding of the determinants of disparities is needed to address this issue ,21. Our Our study has several limitations. We were unable to collect measures of patient adherence to prescribed therapy from the EMR. Providers may not want to intensify therapy at the same rate for patients they know are less compliant with therapy, although it is hard to identify these patients. We were also unable to determine English proficiency of each patient from the medical records. When a language barrier exists providers may be less likely to intensify therapy.We examined disparities in quality of hypertension care, as measured by intensification of therapy, among a cohort of patients and physicians during 2001–2002 using the established guidelines available during that time period, the JNC VI, as the reference for our analyses. In comparison to JNC VI, the JNC VII guidelines recommend much more aggressive management of hypertension both in terms of the accepted level of BP control  and the recommendations to providers to intensify antihypertensive therapy more rapidly when BP is uncontrolled [Lastly, we examined patients who received their care at primary care practices affiliated with a single large urban teaching hospital, and although there was substantial socioeconomic diversity in our sample our results may not be generalizable to smaller, rural, or non-teaching hospitals.We found significant racial/ethnic differences in intensification of drug therapy, and that these differences were largely accounted for by differences in frequency of clinic visits and in the prevalence of diabetes. Future interventions should focus on increasing physician awareness of the need to intensify drug therapy more, particulary among Hispanic patients, and on encouraging providers to treat hypertension more intensively in diabetic patients.The author(s) declare that they have no competing interests.LH conceived of the study, and participated in its design and coordination and helped to draft the manuscript. SS participated in the design of the study, performed the statistical analysis, and helped to draft the manuscript. DWB and JZA participated in the design of the study, and helped to draft the manuscript.The pre-publication history for this paper can be accessed here:


A tremendous amount of scientific evidence regarding the physiology and physiopathology of high blood pressure combined with a sophisticated therapeutic arsenal is at the disposal of the medical community to counteract the overall public health burden of hypertension. Ample evidence has also been gathered from a multitude of large-scale randomized trials indicating the beneficial effects of current treatment strategies in terms of reduced hypertension-related morbidity and mortality.hypertension management is overshadowed by widespread diagnostic inaccuracies  as well as by treatment failures generated by undertreatment, overtreatment, and misuse of medications.In spite of these impressive advances and, deeply disappointingly from a public health perspective, the real picture of The scientific, medical and patient communities as well as decision-makers worldwide are striving for greatest possible health gains from available resources.A seemingly well-crystallised reasoning is that comprehensive strategic approaches must not only target hypertension as a pathological entity, but rather, take into account the wider environment in which hypertension is a major risk factor for cardiovascular disease carrying a great deal of our inheritance, and its interplay in the constellation of other, well-known, modifiable risk factors, i.e., attention is to be switched from one's "blood pressure level" to one's absolute cardiovascular risk and its determinants. Likewise, a risk/benefit assessment in each individual case is required in order to achieve best possible results.Nevertheless, it is of paramount importance to insure generalizability of ABPM use in clinical practice with the aim of improving the accuracy of a first diagnosis for both individual treatment and clinical research purposes. Widespread adoption of the method requires quick adjustment of current guidelines, development of appropriate technology infrastructure and training of staff . Progress can be achieved in a few years, or in the next 25 years. The majority of the medical community as well as renowned medical textbooks have considered it a pathological entity requiring diagnostic and appropriate treatment in most individuals having it.During the past decades, mild hypertension and two higher cut-off values to define moderate and severe hypertension. This classification, still maintained as such by the ESH . Su. Su34]. A cut-off point set at 0 would mean a "test"  with 100% sensitivity and ability to detect all patients with genuine hypertension . However, all normal individuals  would screen positive, as reflected by a 100% false-positive error rate (overdiagnosis). The corresponding point would be placed in the right upper corner of the graph.In the other extreme, a hypothetical cut-off point of 350 mmHg, for example, would imply that virtually all hypertensive patients were missed (underdiagnosis), reflected by 0% sensitivity. This point would be placed in the lower left corner of the graph.Using a similar reasoning, the sensitivity and the false-positive error rate can be computed for increasing threshold values. Connecting the points plotted on the graph would generate a ROC curve.As the left upper corner represents a sensitivity of 100% and 0% false-positive rate, the real best cut-off point is the one lying closest to it.Fig. In fact, despite the drawbacks mentioned above, of an arbitrarily selected office blood pressure cut-off point for practical purposes, the office BP measurement as a method as such, need not be entirely discarded.compelling indication :On the contrary, there are three different instances in which it may be used with certainty to decide whether to treat or not to treat patients. The first two instances are discernable from Fig. sustained essential hypertension (or a secondary form of hypertension) [1). The great majority of individuals with office BP > 160/95 mmHg are genuine hypertensives. They may have tension) . Approxitension) .high-normal prehypertension category (130/85-139/89 mmHg).2). Likewise, the great majority of individuals with office BP < 130/80 mmHg are likely to be free of hypertension and/or the need for pharmacologic blood pressure lowering treatment . RegularIn this context, it is worth re-emphasizing that blood pressure values below the 140/90 mmHg cut-off point do not confer total protection against a cardiovascular events. Data from Framingham Study have shown that more than one half (57%) of all heart attacks and almost one half of all strokes in some population studies occur in persons with normal office blood pressure -41.3). The third instance pertains to patients with known diabetes mellitus and renal dysfunction. For these patients, the office blood pressure measurement functions merely as a quasi-"gold standard" test.Fig. A justifiable question that may arise is why a somewhat lower cut-off point, i.e., 130/80 mmHg, can be considered as more reliable than the 140/90 mmHg, given that office BP measurement is likely to carry the same sort of problems in both cases.The answer is pretty simple. An assumed overlap of the two distributions Fig. , leadingFurthermore, Fig. uncertainty range (≥ 130/85 to <160/95 mmHg) • Subjects with prehypertension .Fig. A recent analysis of the worldwide global burden of hypertension  indicateA multinational sample surveys carried out in six European countries, Canada and US, in the 1990s indicated the age-adjusted prevalence of hypertension was 28% in the North American countries and 44% in the European countries .About 59 million American adults (29%) fall into prehypertension category (SBP 120-139 mmHg or DBP 80-89 mmHg) .Extrapolating roughly from the above figures, the prevalence of hypertension in economically developed countries (37.3%) and the estimation of prehypertension in US (29%) would add up to a 66.3% of the entire population having a form of hypertension or prehypertension. This average figure might be somewhat lower in America and Canada but may reach 75% in the European countries.uncertainty range. Given that the lower bound of the uncertainty range extends to 130/85 mmHg , it might encompass as much as 80% of the total community burden of BP-related CVD risk.Furthermore, epidemiological data  indicateThe new JNC-7-hypertension category  was subjThis is, certainly, not a strong argument even if it may contain a grail of truth. Obviously, the sudden and unexpected awareness that one, despite knowing him/herself to be in good health, belong to a group of people "at risk for heart disease", might trigger a more or less uncomfortable feeling.high normal blood pressure and labelled as being prehypertensives, are also known to run a considerable higher risk for cardiovascular disease than people with optimal (<120/80 mmHg) and with normal BP (120-129/80-84 mmHg) [However, people with BP values in the range of 130-139/85-89 mmHg, known to have 84 mmHg) ,51,52.high-normal blood pressure at the initial screening have developed hypertension [optimal blood pressure and 20% of those with normal blood pressure have developed hypertension [high-normal BP who were 35-64 years old and 50% among subjects aged 65 or older, likewise, with high-normal blood pressure at screening. Worthwhile emphasizing, about 15% of the subjects with high-normal blood pressure have progressed to stage II or greater degree of hypertension over 4 years of follow-up.In a survey of 9845 Framingham Heart Study participants over a 4-year period, 43% of the total of 1907 individuals  who had rtension . In contrtension . Hyperteoptimal blood pressure, high-normal blood pressure was associated with a 5- (age 35-64 years) to 12-fold (age 65 years or over) elevated odds of hypertension on follow-up [Overall, compared with ollow-up , justifyfalse negative area of the uncertainty range, suggesting that the condition per se is perceived as normotension as assessed by office blood pressure measurement. However, MH is genuine hypertension, as assessed by daytime ABP of >135/85 mmHg [As depicted by Fig. /85 mmHg -58.The reported prevalence rates of MH are 9% , 14% 6060, 23%  and 31% Missed diagnosis of MH in these patients leaves them untreated and at risk for long-term consequences of hypertension.Selenta et al.  have demThe high prevalence rates of MH and the high level of misdiagnosis rate by office BP measurement of the condition calls for generalization of ABPM use in clinical practice, for diagnosis and management purposes of this large patient population.Subjects with white coat hypertension have a normal average daytime blood pressure outside a medical setting ,65 but pThe prevalence rate of the WCH is reported to be in the area of 15 to 35% of patients in whom hypertension is diagnosed ,71 and iwhite coat effect, the latter being a quantitative measure of the blood pressure rise in the presence of a physician. This transient blood pressure rise has been quantified by Mancia et al. [The use of a distinct cut-off point is important for diagnostic and management purposes. It also distinguishes WCH from the a et al.  who demoa et al. . Such a a et al. ,76.false positive area of the uncertainty range, i.e., beyond the 140/90 mmHg cut-off point as assessed by office BP measurement, and count thereby as overdiagnosis.As illustrated by Fig. Indeed, the consequences of failing to identify white coat hypertension are considerable. People may be penalized for insurance and pension policies, and for employment .Long-term treatment may be prescribed unnecessarily with all the risks derived from potential treatment-emergent adverse reactions -80.Given the seriousness as well as the high risk for such consequences in the clinical practice, several hypertension guidelines recommend use of ABPM for diagnosis of WCH -83.In 2001, the CMS in USA has selected "patients with suspected WCH" as having indication for ABPM, with the use of method itself being reimbursed .uncertainty range (≥ 130/85 to <160/95 mmHg).Speculations on what clinical characteristics might suggest the presence of WCH and thereby the need for ABPM, in an attempt to preclude indiscriminate use of the method, is certainly not justified anymore . On the Once WCH has been diagnosed, ABPM should be repeated at annual or biannual intervals  with theuncertainty range. Indeed, combining office blood pressure (OBP) measurement values with ABPM recording results  allows for discrimination among the following diagnostic entities  – (ABPM > 140/90 and OBP ≥ 140/90)• Masked Hypertension (MH) – (ABPM > 135/85 and OBP < 140/90)• White Coat Hypertension (WCH) – (ABPM < 135/85 and OBP ≥ 140/90)high-normal BP) (PH) – (ABPM < 135/85 and OBP 130/85-139/89)• Prehypertension .The well-known, multifactorial inaccuracies imbedded in the office blood pressure measurement and, in contrast to that, the widespread agreement as to the superiority and multi-purpose use of ABPM -102, as More recent studies provide evidence that the ABP testing is generally well-accepted and tolerated by patients. A survey of 177 patients, who underwent ABPM in primary care office setting in US over a 2.5 years period , showed uncertainty range (≥ 130/85 to < 160/95 mmHg). The top part of the figure suggests that two different units are involved in the management/investigation of such patients, a usual GP or specialist office and a laboratory specialised in ABPM recordings and results interpretation.Fig. An initial assessment is commonly performed in the GP's office where blood pressure is recorded, according to current guidelines, by the physician or a trained nurse. Patients whose average BP, derived from two measurements per visit, in two or several visits, lies in the uncertainty range should be referred for 24-hour ABP monitoring.high-normal level).The result of the daytime ABPM assessed together with the OBP generates a diagnostic conclusion matching one of the following alternatives: SH/MH/WCH or PH . Instead, using a range, i.e., the interval between two cut-off points (≥ 130/85 to <160/95 mmHg) for further decision making, avoids the well-known diagnostic uncertainties.high-normal prehypertension.The 140/90 cut-off point retains, however, its (arbitrary) value in the next stage of ABPM investigation. The value of the OBP, whether below or above the 140/90 mmHg threshold is corroborated with the ABPM result for selection of one out of four different diagnostic alternatives: sustained hypertension, masked hypertension, white coat effect or Once diagnosed, the patient returns to his/her physician who remains in charge with the further management decision whatever the diagnosis might be .secondary prevention. Likewise, patients with target organ damage such as LVH, heart failure, proteinuria or renal impairment need treatment of even very mild hypertension.Obviously, diagnosis and management of patients who have any form of symptomatic atherosclerotic vascular disease including previous myocardial infarction, by pass graft surgery, angina, stroke or transient ischaemic attack, peripheral vascular disease or atherosclerotic renovascular disease, need treatment of even mild hypertension (≥ 140/90 mmHg) for Patients with type I and II diabetes mellitus and associated mild hypertension (≥ 130/80 mmHg) generally have diabetic nephropathy and should be treated.compelling indications require drug treatment for any level of raised blood pressure.All the aforementioned uncertainty range ≥ 130/85 to <160/95 mmHg).This translates in the need to apply the algorithm in Fig. Accurate diagnosis and management of high blood pressure is of paramount importance for the prevention of long-term, cardiovascular, cerebrovascular and renal complications. Aggressive attempts to identify and treat "high blood pressure values" must be balanced carefully with the risks of overdiagnosis and overtreatment in these patients.uncertainty range.ABPM has a proven value not only as a research tool but also as a valuable investigative method for a large segment of the hypertensive population belonging to the Practical management of these patients, once accurate diagnosis has been established, should be based on absolute cardiovascular disease risk and on a risk-communication dialog between the physician and patient as well as on their mutual agreement regarding the specific treatment to be initiated and the appropriate long-term follow-up.The author(s) declare that they have no competing interests.


The metabolic syndrome is a cluster of cardiovascular risk factors leading to an increased risk for the subsequent development of diabetes and cardiovascular morbidity and mortality. Blocking the renin-angiotensin system has been shown to prevent cardiovascular disease and delay the onset of diabetes. Irbesartan is an angiotensin receptor blocker (ARB) which has been shown to possess peroxisome proliferator-activated receptor gamma (PPARγ) activating properties, and to have a favorable metabolic profile. Current discussion is whether the addition of small doses of hydrochlorothiazide changes this profile. Therefore the efficacy, safety and metabolic profile of Irbesartan either as monotherapy or in combination therapy was assessed in patients with the metabolic syndrome in a large observational cohort in primary care.Multicenter, prospective, two-armed, post authorization study over 9 months in 14,200 patients with uncontrolled hypertension with and without the metabolic syndrome (doctors' diagnosis based on the Adult Treatment Panel III criteria 2001). Blood pressure was measured sphygmomanometrically and cardiovascular risk factors making up the criteria for the metabolic syndrome were assessed.Systolic (SBP) and diastolic (DBP) blood pressure reduction, – response, and – normalization (systolic and diastolic), changes in fasting glucose, waist circumference , serum triglycerides and HDL cholesterol as well as the proportion of patients fulfilling the criteria for the metabolic syndrome. Number and nature of adverse events (AEs).Irbesartan in monotherapy resulted in a significant reduction of blood pressure  in patients with the metabolic syndrome. This was accompanied by a reduction in cardiovascular risk factors: HDL cholesterol , serum triglycerides , fasting blood glucose  and waist circumference  were significantly improved. Irbesartan combination therapy (12.5 mg HCTZ) in patients with the metabolic syndrome: blood pressure reduction , improvement in HDL cholesterol , triglycerides , fasting blood glucose  and waist circumference . Tolerability was excellent: only 0.6% of patients experienced an AE.After 9 month the use of There was a significant improvement in blood pressure and metabolic risk factors as a result of Irbesartan treatment. There was no evidence of a difference between monotherapy and combination therapy with regard to the cardiovascular risk profile. The pThe lack of a universally agreed definition has complicated the epidemiologic research on the prevalence of this syndrome . NeverthIn general, risk factors of the metabolic syndrome are treated separately and there is currently no available treatment that targets all components. Some classes of antihypertensive drugs, notably calcium channel blockers, angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), have been shown to reduce or at least not to increase the incidence of new-onset diabetes, particularly as compared to diuretics and betablockers . This suTreat to Target to investigate in more detail the influence of the PPARγ activating ARB Irbesartan with or without HCTZ on metabolic parameters. It was conducted as an observational study in primary care in order to acquire a broad spectrum of patients in clinical practice. The intention was to investigate three core questions: 1) Characteristics and comorbidity pattern of patients with the metabolic syndrome, 2) Blood pressure response to Irbesartan alone and in combination with hydrochlorothiazide , and 3) accompanying changes in cardiovascular risk factors (components of the metabolic syndrome) in monotherapy vs. combination therapy.It was therefore the aim of the present analysis of the post authorization study This was a 9-month, multicenter, open-label, two-armed, prospective, observational post-authorization survey (PAS), which was conducted by 3,609 general physicians, practitioners and internists (GPs) throughout Germany. This specific study type is regulated by the German Drug Law (AMG) §67(6) and is primarily intended to gather knowledge about the safety and efficacy of marketed drugs in daily practice. The federal panel doctors' associations as well as the higher authorities were duly notified about this investigation. The participating GPs received a small remuneration for the documentation of each patient, which is common practice for this type of PAS. Importantly, as in any PAS, the protocol stipulated no interventions different from routine treatment. In a PAS the drug can only be prescribed in the labeled indication according to the Summary of Product Characteristics (SmPC). The procedures and decisions of the physicians were not influenced and the physicians were completely free to select which patients to treat with the licensed drug being studied, which diagnostic measurements they used, and the way in which they monitored the course of treatment or which concurrent or additional medication they prescribed. Due to the non-interventional type of the study, no ethics committee approval or patient informed consent has to be obtained in accordance with the German local laws and regulations. The participating physicians collected data on the background characteristics of the patients and on key efficacy variables and adverse events (AEs) and documented them in case report forms (CRFs). If any serious adverse events (SAEs) occurred, the GPs were obliged to report them by completing a form within 24 hours and transmitting it to the manufacturer, who then forwarded the report in a standardized format to the relevant authority . The collected data, SAE forms and CRFs were not consistently verified in comparison with the source data in the patient files, but the forms were systematically screened for plausibility and completeness.Patients with an indication for treatment with Irbesartan with or without HCTZ were selected by the GPs, using a cohort approach. Only adult patients could be included (18 years), and there were no additional exclusion criteria regarding concomitant medication or concomitant diseases except those specified in the SmPC. Patients were stratified into the metabolic syndrome cohort if they fulfilled the criteria set forth by the National Cholesterol Education Program Expert Panel (NCEP) in 2001 .The parameters documented in the study included demographic characteristics , medical diagnoses . Blood pressure was to be taken as a mean of three sphygmomanometric measurements, and pulse rate  and the respective target blood pressure for each patient were also to be recorded. If available from the charts, the following laboratory parameters were collected: fasting blood glucose, HbA1c, triglycerides, HDL and LDL cholesterol, creatinine and urinary albumin. In addition, concomitant disease was documented: stroke/transient ischemic attack (TIA), neuropathy, coronary heart disease (CHD), heart failure, previous myocardial infarction (MI), aorto-coronary venous bypass operation (ACVB), retinopathy, previous PTCA/stent, left ventricular hypertrophy (LVH), lipid disorders and peripheral arterial disease (PAD). Antihypertensive therapy within the previous 12 months was documented as well as the modifications after switching medications at the baseline visit.After 3 and 9 months blood pressure measurements were repeated and the following parameters obtained if available: weight, hip and waist circumference, pulse, triglycerides, HDL and LDL cholesterol, fasting blood glucose, HbA1c, creatinine and urinary albumin. Modifications of antihypertensive therapy were documented and whether patients reached blood pressure targets was determined.The following features of AEs were recorded if these occurred: description, first occurrence, grade of severity, outcome of events , likelihood of causal relationship .According to the predefined statistical analysis plan, the statistical analysis was performed descriptively and was interpreted in an explorative way. Comparisons were made for blood pressure and proportions of patients with components of the metabolic syndrome positive between baseline and the two post-baseline visits. The absolute and relative frequencies of AEs and the efficacy and tolerability ratings were reported. Post-hoc analyses for subgroups defined by gender, BMI, waist circumference, duration of hypertension, strength of antihypertensive response, and previous and concomitant antihypertensive treatment, respectively, were carried out. The analysis of data was performed with the statistical software package SAS, version 8.2. Test applied are indicated in the legend of tables and figures . Regardi2 without and 31.2 ± 5.0 kg/m2 with the MS. Accordingly, both male and female patients with the MS had a higher waist circumference: men 111.3 ± 12.8 vs. 96.9 ± 10.2 cm and women 100.7 ± 14.6 vs. 85.9 ± 11.9 cm.In the observational period between January 2005 and July 2006, a total of 14,200 patients were documented, of which 9281 were diagnosed as having the metabolic syndrome (MS); 4919 patients served as controls. Men and women were balanced  and 62.4 ± 10.2 years (with MS). Mean BMI was 26.8 ± 3.7 kg/mFigure In line with the documentation of cardiovascular risk factors is the observation that patients that have been assigned the diagnosis metabolic syndrome by their treating physicians have many more comorbid conditions than their controls  on metabolic risk factors in patients with vs. in patients without the metabolic syndrome, remarkable differences can be found. While there is no effect of treatment on HDL cholesterol in women without the metabolic syndrome , in men there is an increase of 0.8 ± 6.2 mg/dL (p < 0.0001). In patients with the metabolic syndrome there is a significant increase in both genders . Likewise there is no clinical benefit on fasting plasma glucose in normal patients  as compared to metabolic syndrome patients . All other comparisons are significant and show an improvement in the parameters documented, but still, patients with the metabolic syndrome seem to benefit more from Irbesartan treatment than patients without (see table To assess the suitability of Irbesartan combination therapy with HCTZ for use in patients with the metabolic syndrome the same parameters as above were assessed and patients on monotherapy were compared with those on the combination. There were consistent and highly significant (p < 0.0001) reductions of blood pressure, fasting plasma glucose, abdominal obesity, triglycerides and an increase in HDL cholesterol after 9 months of treatment with Irbesartan monotherapy as well as with the combination therapy  irrespective of whether hypertension was considered or not. Figure The rate of AEs was very low. Only 141 AEs were noted in 88 patients . 65 SAEs were noted in 34 patients (0.24%). There were 17 deaths in 14,200 patients during a study period of 9 months. For details see Table In the present study 14,200 unselected primary care patients with or without the metabolic syndrome were treated with Irbesartan alone or in combination with 12.5 mg HCTZ. The observation of the 9-month treatment period and the comparison of monotherapy and combination therapy in terms of blood pressure reduction and interference with cardiovascular risk factors yielded the following results: 1) There was a significant improvement in metabolic risk factors as a result of Irbesartan treatment. 2) There was no evidence of a difference between monotherapy and combination therapy with regard to the cardiovascular risk profile. 3) There was a pronounced blood pressure lowering effect with both monotherapy and combination therapy, with a slightly better blood pressure response in patients without the metabolic syndrome. 4) There was a favorable reduction in the number of tablets to be taken.During the 9-month study period an improvement in metabolic parameters was noted that was substantial for fasting plasma glucose, triglycerides and HDL cholesterol (patients with the metabolic syndrome > patients without). Interestingly, even a reduction in abdominal obesity was noted; this was small, but resulted in a reduction in waist circumference of up to 3.2 cm (in patients on Irbesartan/HCTZ combination therapy after 9 months).It cannot be ruled out that the observed effects are due to the study conduct that may have improved patient compliance, but several lines of reasoning point toward a metabolic profile of Irbesartan that may be in part responsible for these results. 1) Both Telmisartan and Irbesartan activate the PPARγ receptor ,14 and tAnother interesting observation is that the thiazide component when given in low dose together with Irbesartan did not lead to unfavorable consequences in terms of metabolic control. Whereas thiazide diuretics have proved to be highly effective blood pressure agents , HCTZ isIn conclusion, there seems to be a quantitative difference in the beneficial metabolic profile of Irbesartan between patients with and without the metabolic syndrome. Particularly patients with the metabolic syndrome benefit from the addition of Irbesartan to their antihypertensive regimen, an effect that is seen less so in normal patients but may even be less pronounced in diabetic patients, but this topic still awaits further studies.The observed blood pressure lowering effect with Irbesartan . In previous open-label observational studies with ARBs in the primary-care setting, the respective rates had been considerably higher ,37. InteThe present results have to be considered against the background of potential limitations. The study was not controlled and therefore the contribution of placebo effects or the withdrawal of other antihypertensive agents is unknown. Second, in the absence of randomization procedures the influence of unknown biases, e.g. through patient selection, cannot be assessed. Third, concomitant medication influencing the metabolic profile  have not been documented in the present study, but since patients were mostly non-diabetic the latter two treatments are not likely to be prescribed in greater numbers. Among the strengths of the study was the choice of the setting. Observational studies in primary care, which include typical patient groups and reflect current treatment approaches, are useful for complementing the findings of randomized controlled trials .The present study demonstrates in a large patient cohort with or without the metabolic syndrome that treatment with an Irbesartan-based regimen for 9 months not only results in a pronounced blood pressure reduction, but also might have a favorable impact on important metabolic parameters such as HDL cholesterol, triglycerides and blood glucose. An Irbesartan-based regimen therefore seems to be a rational treatment for patients with the metabolic syndrome.


Neglected renal stones remain a major cause of morbidity in developing countries. They not only result in functional impairment of affected kidney, but also act as an important predisposing factor for development of urothelial neoplasms. It is not uncommon to miss an associated urothelial tumor in a patient of nephrolithiasis preoperatively.In last 3 years, we came across two patients with giant staghorn calculus and poorly functioning kidneys who underwent laparoscopic nephrectomy. In view of significant perirenal adhesions & loss of normal tissue planes both these patients were electively converted to open surgery. The pathological examination of specimen revealed an unsuspected urothelial carcinoma in both these patients. The summary of our cases and review of literature is presented.It is important to keep a differential diagnosis of associated urothelial malignancy in mind in patient presenting with long standing renal calculi. The exact role of a computerized tomography and cytology in preoperative workup for detection of possible associated malignancy in such condition is yet to be defined. Similarly if laparoscopic dissection appears difficult during nephrectomy for a renal calculus with non-functional kidney, keeping a possibility of associated urothelial malignancy in mind it is advisable to dissect in a plane outside gerotas fascia as for radical nephrectomy. Since the first clinical report in 1991, laparoscopic nephrectomy has been embraced by urologists worldwide . From JaA 52 year old man presented for evaluation of left flank pain of 1 year duration. He was nonsmoker with a history of left nephrolithotomy for staghorn calculus 20 years back. He had hypertension and ischemic heart disease as co-morbid conditions. He also had history of pulmonary kochs in childhood. On clinical examination patient had a scar of left flank incision with a palpable hard kidney. His urine analysis showed microscopic hematuria and culture was sterile. His renal biochemistry was normal. On renal ultrasound a staghorn calculus was detected without associated hydronephrosis. The kidney was nonvisualised on intravenous urogram  declare that they have no competing interests.The pre-publication history for this paper can be accessed here:


Patients with a history of a fracture have an increased risk for future fractures, even in short term. The aim of this study was to assess the number of patients with falls and to identify fall risk factors that predict the risk of falling in the first three months after a clinical fracture.Prospective observational study with 3 months of follow-up in a large European academic and regional hospital. In 277 consenting women and men aged ≥ 50 years and with no dementia and not receiving treatment for osteoporosis who presented to hospital with a clinical fracture, fall risk factors were assessed according to the guidelines on fall prevention in the Netherlands. Follow-up information on falls and fractures was collected by monthly telephone interview. Incidence of falls and odds ratio's  were calculated.512 consecutive patients with a fracture were regarded for analysis, 87 were not eligible for inclusion and 137 patients were excluded. No follow-up data were available for 11 patients. Therefore full analysis was possible in 277 patients.A new fall incident was reported by 42 patients (15%), of whom five had a fracture. Of the 42 fallers, 32 had one new fall and 10 had two or more.Multivariate analysis in the total group with sex, age, ADL difficulties, urine incontinence and polypharmacy showed that sex and ADL were significant fall risk factors. Women had an OR of 3.02 (95% CI 1.13–8.06) and patients with ADL-difficulties had an OR of 2.50 (95% CI 1.27–4.93).Multivariate analysis in the female group with age, ADL difficulties, polypharmacy and presence of orthostatic hypotension indicated that polypharmacy was the predominant risk factor . The incidence of falls was 35% in women with low ADL score and polypharmacy compared to 15% in women without these risk factors (OR 3.56: CI 1.47 – 8.67).15% of patients reported a new fall and 5 patients suffered a new fracture within 3 months. Female sex and low ADL score were the major risk factors and, in addition, polypharmacy in women. A history of fracture indicates a risk for future fractures. The absolute risk for fractures is highest in the first year after a clinical fracture  . TherefoOne third of the people aged 65 years and above fall every year and in one to five percent the fall results in a fracture -8. The pPrevious research identified the following fall risk factors: age of 65 years and above, female sex, mobility problems, previous falls, muscle weakness, visual impairment, disturbances of the equilibrium, low bone mineral density, multi-medication use such as sedatives, previous fractures, low grip strength, low physical activity, impaired activities of daily living, depression, cognitive impairment, use of assistive devices, urinary incontinence, Parkinson's disease, fear of falling, living in a nursing home, diabetes mellitus, high blood pressure, orthostatic hypotension and others ,10-23. CThe aim of this study was to assess the number of patients with falls within 3 months after a recent clinical fracture, and to identify fall risk factors that predict the risk of falling within 3 months after a recent clinical fracture.In September 2004, based on the guideline of the Dutch Institute for Health Care Improvement (CBO) on osteoporosis and the guideline on fall prevention, a large European hospital initiated a fracture and osteoporosis outpatient clinic in which fracture patients aged 50 years and above are investigated for osteoporosis ,10. The For the present study, all patients with a clinical fracture that visited the hospital for fracture treatment between April and September 2005 were invited to participate. During the first consultation, the nurse specialized in osteoporosis and fall risk assessment informed and invited every patient individually. If the patient agreed to participate in the study, an informed consent form was signed and handed over to the osteoporosis nurse. The second consultation was combined with a dual-energy x-ray absorptiometry (DXA) measurement. During the second visit, patients were informed about the results of the DXA scan and anamnesis for fracture and fall risk assessment were performed. Patients were included if they were willing to undergo 1) a fall risk assessment and 2) a bone mineral density (BMD) measurement by DXA. Patients were excluded for the following reasons: not completing one of both assessments , deceased, established dementia written down in medical history, living in another region, having a pathological (non – osteoporotic) fracture, no informed consent or no show on DXA appointment. Patients already receiving adequate treatment for osteoporosis were not invited to attend the fracture and osteoporosis clinic where the recruitment for the study occurred. The study was approved by the medical ethical committee of the hospital.Follow-up information on falls and fractures was collected by telephone interview, performed monthly for 3 months after the fracture. This three-month period was chosen to evaluate fall risk in the recovery period of the fracture. The osteoporosis nurse asked whether the patient had a fall, and if so, the number and timing of falls and whether the fall resulted in a fracture.The primary outcome of this study is the incidence of patients who had a fall within the three months of follow-up. Falls were defined as unintentional events which result in a person coming to rest on the floor or a lower level ,9,22,24.Fall risk was assessed by measuring balance, mobility, lower limb muscle strength, handgrip strength, cognitive status, activities of daily living, visual impairment and general measurement such as blood pressure. These risk factors were chosen based on their description in the Dutch guideline for prevention of falls in the elderly .Balance was evaluated by the Four-Test Balance Scale, in which the patient was asked to perform feet together stand, semi-tandem stand, tandem stand and one leg stand . If the Mobility was assessed by the Timed Get Up and Go Test, in which the patient is asked to rise from a chair, walk 3 meters, turn, walk back and sit down in the chair. If the patient was not able to perform the test within 12 seconds this was regarded as a reduced mobility and increased fall risk ,27.Lower limb muscle strength was measured by the Chair Stand Test. In this test, the patient was asked to rise up and sit down from a chair as quickly as possible five times, while not using their arms if possible. If the patient was not able to complete the test within two minutes this was regarded as a fall risk .Handgrip strength was measured by the Jamar dynamometer . The patient was asked to squeeze two times on a handgrip strength indicator with both hands separately. For each hand the maximum score (in kg) was added up. If people squeezed with only one hand, the score of the other hand was replaced by the mean of the group that squeezed with both hands taking sex and dominant hand into account. For women, the cut-off point was < 30 kg, for men the cut-off point was < 50 kg .The Abbreviated Mental Test, a questionnaire to test the cognitive status, was used to assess if patients were cognitive impaired. The cut-off point of this test is 8 (range: 0–10), with a score less than 8 suggesting abnormal cognitive functioning ,31.The Groningen Activity Restriction Scale (GARS) was used to test disability in activities of daily living (ADL) . PatientBlood pressure was measured to determine if orthostatic hypotension was present . It was Statistical analyses were performed using SPSS for Windows version 12.0.1. Individuals without falls were compared with those with falls. First, univariate logistic regression models were fitted with all individual fall risk factors for the total group and women. If a risk factor had an Odds Ratio (OR) ≥ 2.0 it was retained for subsequent multivariate analysis.The logistic regression analysis was fitted by the "Forward Likelihood Ratio" method. To identify the relationship between the fall risk factors and falling, OR's and 95% confidence intervals were calculated. Interaction was tested for all significant variables resulting from the univariate analysis.During an inclusion period of 6 months, 512 patients over the age of 50 with a clinical fracture visited the emergency department or the outpatient clinic .In this study the majority of patients were women (72.2%).A fall within 3 months after a recent clinical fracture was reported by 42 of the patients 15.2%); the number of women with a fall was higher than the number of men . Of the 42 fallers, 10 were recurrent fallers. The fall rate was 1.5 falls/patient year. In 5 patients a fall resulted in a fracture. Mean age of female fallers was 69.9 years (range: 51–86), and 66.6 years in male fallers (range: 51–78) (p = 0.069). All fallers reported that their baseline clinical fracture was the result of a fall from maximum standing height , ADL-problems vs. no ADL problems , and polypharmacy vs. no polypharmacy (use of ≥ 5 pills per day) . In women, ADL difficulties  and polypharmacy  were significant fall risk factors.Univariate analysis was carried out for 15 fall risk factors Table . SignifiMultivariate analysis in the total group with sex, age, ADL difficulties, urine incontinence and polypharmacy showed that sex and ADL were significant fall risk factors. Women had an OR of 3.02 (95% CI 1.13–8.06) and patients with ADL-difficulties had an OR of 2.50 (95% CI 1.27–4.93).Multivariate analysis in the female group with age, ADL difficulties, polypharmacy and presence of orthostatic hypotension indicated that polypharmacy was the predominant risk factor . The incidence of falls was 35% in women with polypharmacy and low ADL score. This risk of falls was three times higher than in women without polypharmacy and with normal ADL score. .In this study of people over 50 presenting with a fracture, who were not already on osteoporosis treatment, who are not demented and who were able to give informed consent, the incidence of patients with a fall within three months after a clinical fracture was 18.5% in women and 6.5% in men. In 11.9% the fall resulted in a new fracture.The predominant fall risk factors that predicted a new fall were sex and difficulties in ADL in the total group. In line with other studies, women more often experienced a new fall compared to men -8. NearlThis study has several limitations. The male group was to small for separate analysis.The information of the main outcome variable, i.e. falls during follow-up, relied on patients recall of falls, so the possibility of incomplete or biased reports of falls cannot be excluded.The sample may not be completely typical in view of the various exclusion criteria. Only significant risk factors chosen to measure were described, which by definition can not be exhaustive and some of these assessments were not of the kind that could be carried out within routine clinical practice, but only in a research context.The follow-up period of three months was short but chosen to evaluate fall risk in the time patients were recovering from their fracture.Based on the results of our study, a health care provider can identify patients with the highest risk of falls after a fracture examining ADL in all patients, and polypharmacy in women.Future studies should be large enough to include sufficient numbers of men and perform subgroup analysis on different ages. Eventually a very large cohort analysis with fracture risk as endpoint would be most interesting.Patients with a recent clinical fracture have a high risk for new falls. In a group of 277 patients, 15% reported a new fall and 5 patients suffered a new fracture within 3 months. Female sex and low ADL score were the major risk factors and, in addition, polypharmacy in women.SH is member of an advisory board of Merck Sharp Dohme. SH and PG received an unrestricted grant for research by MSD (not current study).All other auhors have no conflict of interestSH coordinated study concept and design, performed acquisition of data together with analysis and interpretation and prepared the final manuscript. CW performed analysis and interpretation of data and took part in manuscript preparation. PD took part in analysis and interpretation of data and preparation of the manuscript. MD performed analysis and interpretation of data together with preparation of the manuscript. GW did acquisition of subjects and data. PB took part in preparation of the final manuscript. PG was involved in study concept and design, analysis and interpretation of data and preparation of the final manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


The objective of this study was to determine the rate of blood pressure control according to 4 sets of Canadian guidelines published over a decade in patients with diabetes mellitus attending Diabetes Centres in the province of Nova Scotia.One hundred randomly selected charts from each of 13 Diabetes Centres audited between 1997 and 2001 were extracted from the Diabetes Care Program of Nova Scotia Registry. Multivariate logistic regression analyses examined the relationship between individual characteristics and self-reported antihypertensive use. Included were 1132 adults, mean age 63 years , with 9 years mean time since diagnosis of diabetes.According to the 1992 guidelines, 63% of the patients and according to the 2003 guidelines, 84% of patients were above target blood pressure or receiving antihypertensive medications. Forty-seven percent of patients are considered to be hypertensive and not on treatment according to 2003 guidelines. The results of the multivariate analyses showed that the only factors independently associated with anti-hypertensive use was oral anti-hyperglycemic use.Hypertension is an additional risk factor in those with diabetes mellitus for macrovascular and microvascular complications. The health and budgetary impacts of addressing the treatment gap need to be further explored. Achievement of target blood pressures in hypertensive patients is often difficult. In Halifax County, Nova Scotia, 57% of men and 42% of women with hypertension were not well controlled. AdequatA Canadian study reported 43% of people age 18–74 years) had an optimal blood pressure (<120/80 mmHg), and of those with a diagnosis of hypertension, only 13% were below target (defined as 140/90 mm Hg). In this study, about 50% of patients with diabetes were hypertensive, and of these only 9% were under control[4 years hThe United Kingdom Prospective Diabetes Study (UKPDS) emphasized the need for adequate blood pressure control in type 2 diabetes. The evidence suggested that good blood pressure control may be as important if not more important than blood glucose control in reduction of the cardiovascular complications,9,10. FuThe treatment of hypertension in patients with diabetes has changed over the last decade. Studies and Clinical Practice Guidelines for the management of hypertension in patients with diabetes suggest lower blood pressure targets for diagnosis and control than for the general population,15-17.This study determined the degree of blood pressure control in patients with diabetes according to four sets of Canadian Clinical Practice Guidelines published between 1992 and 2003-20 and dThe cohort was selected as part of a DCPNS (Diabetes Care Program of Nova Scotia) internal audit of approximately 100 records from each of 13 Diabetes Centres between 1997 and 2001. All patients were referred to the Diabetes Centre following a diagnosis of diabetes by a physician. Information gathered included: age, gender, weight, blood pressure, duration of diabetes, serum creatinine, urinary protein and specific antihypertensive treatment regimens. The mercury sphygmomanometer was used for blood pressure measurement and recorded by nurses and averaged over all visits for all individuals. The nurses were aware of the correct procedure for obtaining a blood pressure measurement, and performed the procedure regularly. Eligibility criteria for the cohort included being a non-pregnant adult over the age of 19; a diagnosis of type 1 or 2 diabetes; a visit to the centre within 12 months of the audit date; and at least 15 months of followup.The final cohort included 1132 subjects. The population consists of both genders , with an average age of 63 (SD 12). Over 95% of patients had type 2 diabetes, and the average length of time since diagnosis was 9.3 (SD 8) years previous. Average scores were obtained for most tests and attributes. Kidney function was estimated using both Couchoud cutpoints and the Cockroft-Gault formula ,22 Drug Guidelines used for analysis included the following: 1992 Clinical Practice Guidelines for Treatment of Diabetes Mellitus – hypertension subcategory ; 1998 ClHypertension was defined using anti-hypertensive drug use and blood pressure records. Patients with any antihypertensive drug use and/or average blood pressure above the guideline cutpoints  were designated to be hypertensive. Rates and risk factors for hypertension were calculated for each specific guideline. Logistic regression was performed to determine predictors of antihypertensive treatment.SAS version 8.2  was used for analysis.The use of the 2003 guidelines  increased the percentage of patients not meeting target to 84% from 63% using 1992 guidelines . Those considered to be hypertensive and not on treatment increased to 47% using the 2003 guidelines from 26% with the 1992 guidelines.  declare that they have no competing interests.Cory Russell was involved with the design of the study, analysis and interpretation of the data, drafting and editing the manuscript, and gave final approval of the manuscript. All other authors were involved with the design of the study, interpretation of the data, editing and revising the manuscript, and gave final approval of the manuscript to be published.Cory Russell was funded by the Drug Use Management and Policy Residency, a summer studentship that aims to build student and faculty understanding about how the creation of knowledge and dissemination of evidence is used by decision makers for drug used management and policy analysis. The Canadian Health Services Research Foundation, Canadian Institutes of Health Research and the Nova Scotia Health Research Foundation support this residency.Dr. Ingrid Sketris holds a Chair funded by the Canadian Health Services Research Foundation(CHSRF)/Canadian Institutes for Health Research (CIHR) Chair in Health Services Research, co-sponsored by the Nova Scotia Health Research Foundation (NSHRF).The data used in this research was made available by the Diabetes Care Program of Nova Scotia. Any opinions expressed by the authors do not necessarily reflect the opinion of DCPNS.Presented in part at the 2004 Canadian Association for Population Therapeutics conference, June 6–8 2004 in Winnipeg, MbThe Effect of Clinical Practice Guidelines Changes on the Percentage of Nova Scotia Patients with Diabetes Classified as Hypertensive


Family physicians can play an important role in encouraging patients to participate in community-based health promotion initiatives designed to supplement and enhance their in-office care. Our objectives were to determine effective approaches to invite older family practice patients to attend cardiovascular health awareness sessions in community pharmacies, and to assess the feasibility and acceptability of a program incorporating invitation by physicians and feedback to physicians.We conducted a prospective randomized trial with 1 family physician practice and 5 community pharmacies in Dundas, Ontario. Regular patients 65 years or older (n = 235) were randomly allocated to invitation by mail or telephone to attend pharmacy cardiovascular health awareness sessions led by volunteer peer health educators. A health record review captured blood pressure status, monitoring and control. At the sessions, volunteers helped patients to measure blood pressure using in-store machines and a validated portable device (BPM-100), and recorded blood pressure readings and self-reported cardiovascular risk factors. We compared attendance rates in the mail and telephone invitation groups and explored factors potentially associated with attendance.p < 0.001).The 119 patients invited by mail and 116 patients contacted by telephone had a mean age of 75.7  years and 46.8% were male. Overall, 58.3% (137/235) of invitees attended a pharmacy cardiovascular health awareness session. Patients invited by telephone were more likely to attend than those invited by mail (72.3% vs. 44.0%, OR 3.3; 95%CI 1.9–5.7; While the attendance in response to a telephone invitation was higher, response to a single letter was substantial. Attendance rates indicated considerable interest in community-based cardiovascular health promotion activities. A large-scale trial of a pharmacy cardiovascular health awareness program for older primary care patients is feasible. Hypertension is a major contributor to cardiovascular disease and associated morbidity and mortality among older adults in Canada. The prevalence of hypertension increases with age and more than half of men and women 65 to 74 years of age have a systolic or diastolic blood pressure above the target level of 140/90 mmHg (or 130/80 mmHg if diabetes or target organ damage is present) recommended by the Canadian guidelines . High blThe diagnosis of hypertension is primarily made in the offices of family physicians . AlthougEffective diagnosis and control of hypertension depends on physicians' awareness of a patient's blood pressure status and cardiovascular risk profile over time . DiagnosSince multiple, accurate blood pressure readings are needed to diagnose hypertension and regular monitoring is necessary for effective, on-going control of high blood pressure, accurate supplementary readings, a cardiovascular health profile, and more active involvement of patients in their care may help physicians to better manage hypertension in their practices. Blood pressure monitoring in a familiar, convenient community setting such as community pharmacies, with support from trained peer volunteers and delivery of patient-specific blood pressure readings and cardiovascular risk factor information to family physicians, pharmacists and the patients, could help overcome barriers to effective management .et al, a letter of invitation from the family physician was found to be an effective strategy to recruit women for routine mammography, with nearly 70% success [Family physicians can play an important role in encouraging patients to participate in health promotion initiatives designed to supplement and enhance their in-office care. In a study by McAuley  success . Given t success , patient success .The program described here seeks to: 1) maximize use of existing resources such as community pharmacies and volunteers in cardiovascular health promotion; 2) ensure that community-based cardiovascular risk assessment is linked to family physicians who can provide follow up. The program is unique because it incorporates collection of patient-reported risk factors in addition to blood pressure readings, and 'closes the loop' by delivering results to the physician. However, there are many community programs offering blood pressure monitoring, and the idea of inviting older adults via family practices to attend a new program for cardiovascular health assessment prompted some scepticism – would they come? A first step was to determine the effectiveness of different approaches for inviting older adults to participate in pharmacy cardiovascular health awareness sessions, and the appeal of a program incorporating invitation by physicians and feedback of patient-specific results to physicians.We conducted a randomized trial to determine the best method (mail or telephone) for family physicians' offices to invite patients to attend a session, and to identify factors that predicted attendance. In preparation for a larger scale randomized controlled trial, we also performed a cost analysis of invitation method and success rate, investigated the operational and methodological aspects of the proposed intervention, and queried patients' willingness to continue to attend community pharmacy blood pressure sessions and their preferences for the time and frequency of the sessions.The study design was a prospective randomized trial  was generated using billing data. Of these, 235 met the eligibility criteria and were included in the trial. The list was reviewed and eligibility verified by the physician. The targeting of regular patients reflects the increasing move to rostered practices in Ontario and the potential importance of an established relationship with the provider, where mail/telephone contact related to health promotion would not be unusual.Computer-generated random numbers were used to allocate eligible patients to invitation by mail (n = 119) or by telephone (n = 116) to attend one of five blood pressure monitoring sessions scheduled in five local pharmacies. To prevent potential contamination of the study arms, patients sharing the same address and/or surname were assigned identical identification numbers and thus randomly allocated to the same group. Mailed letters used an electronic signature from the physician. Patients assigned to the telephone group received a telephone call from a member of the physician's office staff who followed a protocol that limited repeat calls to three and included a structured script. Patients who were unreachable by either contact method  were included in the intention-to-treat analysis of attendance by invitation method in order to establish the feasibility of the program in real practice.Research nurses performed a baseline health record review to confirm patient eligibility, collect demographic and health status factors that might influence session attendance, and document blood pressure monitoring and control. Data collected included age, gender, formal diagnosis or suspicion of hypertension, related physician comments, cardiovascular risk factors , and all blood pressure readings recorded in the chart in the previous six months.VSM MedTech Ltd., Coquitlam, Canada) [The five pharmacy blood pressure sessions were held during a 10-day period in April of 2001. Attending patients were asked to provide signed informed consent to participate. Patients were able to 'opt-out' of the feedback to the physician, however no participants in this small trial objected to having their results forwarded to the physician. At the sessions, volunteer Peer Health Educators trained by a public health nurse helped participants to measure their blood pressure using both a portable, automated device   and the  Canada) ,14.The session recording form captured, in triplicate, blood pressure readings and a checklist of 14 cardiovascular risk factors for distribution to the patient, family physician and regular pharmacist. A patient questionnaire collected demographic and general health information, current blood pressure status and history, history of related health problems, and preferences for place, time and frequency of blood pressure monitoring.To achieve a power of 80% to detect a difference between groups of 20% or more, the significance level  was set at 0.05 and at least 103 patients were required for each study arm. The comparability of groups was established maintaining the denominator of all patients randomized (n = 235), regardless of whether or not telephone or mail contact was successful. The probability of a Type I error  was chosen to be 0.05 (two-tailed) in all analyses.Patients allocated to the mail or telephone contact group were compared on data collected in the health record review: median age, gender, mean blood pressure, level of blood pressure, previous diagnosis of hypertension, smoking status, family history of cardiovascular disease, high cholesterol, and diabetes. The mean of the blood pressure readings recorded in the last six months, collected in the health record review, were categorized in three levels, based on whether the systolic or diastolic pressure exceeded upper boundaries.To determine whether attending patients systematically responded differently to the invitation method, attenders and non-attenders were compared on median age, gender, mean blood pressure, and previous diagnosis of hypertension using t-tests or chi-square tests as appropriate. We examined the potential association of factors captured in the health record review  with attendance at the cardiovascular health promotion sessions, using chi-square tests.To determine what combination of variables best predicted the likelihood of patient attendance at community-based cardiovascular health promotion sessions, logistic regression was performed, controlling for allocation group. Variables entered into the stepwise model included contact method, age (65–74 yr or 75+), gender, diagnosis of hypertension, and the four cardiovascular risk factors  collected in the health record review.A retrospective cost-analysis compared the cost per one patient attending in each invitation arm.Patients allocated to each of the experimental groups (mail and telephone invitation) were found to be comparable on median age, gender, mean blood pressure, level of blood pressure, previous diagnosis of hypertension, and four additional cardiovascular risk factors , and patients with a family history of cardiovascular disease noted in their chart were also significantly more likely to attend . In multivariate logistic regression modelling (n = 226), factors remaining significantly associated with attendance were invitation method (telephone)  and family history of cardiovascular disease recorded in the health record   of invited patients attended a session. In the group invited by mail, 44.0% (51/116) patients attended, compared to 72.3% (86/119) among those invited by telephone. In univariate analyses, patients invited by telephone were significantly more likely to attend than were those invited by mail , 80.0% (95/119) indicated an interest in attending again and 70.2% (85/121) preferred a session in the morning. The preference expressed for different invitation methods was close to evenly divided (49.6% mail and 50.4% telephone) and there was a tendency for patients to state a preference for the type of invitation they had actually received, mail  or telephone , with more patients contacted by telephone attending.Mailing costs included postage ($0.47 × 116 patients = $54.52), stationary/printing ($8.50) and research assistant time to prepare the letters and correct addressing problems (4 hrs × $12/hr = $48.00). The telephone cost was for research assistant time to prepare a patient list and calling log (2 hrs × $12/hr = $24.00), and practice staff time (6 hrs at $25/hr = $150.00). Since 51 patients invited by mail attended, the cost per successful recruitment of one patient was $111.02 / 51 = $2.18. Of patients invited by telephone, 86 attended, for a per-patient cost of $174.00 / 86 = $2.02, indicating a minimal difference in efficiency.The pharmacy sessions were well attended, indicating that organized community-based blood pressure monitoring with feedback to the family physician is feasible, and could enhance the diagnosis and management of hypertension by increasing the number of accurate readings available to the physician, and raising awareness among older adults of cardiovascular risk factors. The pilot demonstrated the advantage of incorporating invitation by telephone rather than mail, however the attendance rates for both groups and preferences reported by attendees demonstrated the success and acceptance of either method. Although attendance was higher in the telephone group, results also support use of mailed invitations, which are more easily implemented on a larger scale. The cost analysis demonstrated a minimal difference, and patient preference among attenders reflected the acceptability of either invitation method.These findings are in keeping with similar studies of reminder strategies for preventive services in family practice. One study found an equal procedure completion rate among patients 15 years of age or older (n = 5883) of five preventive procedures with use of letter and telephone reminders, which was higher than that achieved through computerized physician reminders [Attendance at the Dundas sessions was higher, at 58.3% of invited patients on average, than might be expected from a single contact, particularly since participation involved attending one of a limited number of sessions held on specific days at five community pharmacies. The excellent attendance in response to a single letter or telephone call from the physician's office demonstrates that engaging older adults to participate in community-based initiatives, in cooperation with family physicians, is an effective and low-cost approach to cardiovascular health promotion.Only two factors (invitation method and family history of cardiovascular disease) entered into the logistic regression model accounted for a significant portion of the variance in attendance, however these results are reassuring in the context of this population-health program. It was expected that male patients or very elderly patients might be less likely to attend community-based blood pressure monitoring, however, logistic regression analysis reveals that the program achieved good coverage of all patients, across the key variables of age, gender, hypertensive status, and cardiovascular risk factors.A number of limitations of this pilot could be remedied in a larger study. For instance, the results of this study in one family physician's practice may not be generalizable to other practices, the success of one nurse in inviting patients may not be representative, and the limited time period in which the sessions were offered may have precluded attendance by some patients.While the attendance in response to a telephone invitation was higher, response to a single letter was substantial. Contact by the family physicians office was effective in encouraging older patients to participate in community-based assessment of cardiovascular risk factors, with feedback of results to the family physician. The pilot provided important perspectives toward expanding the program to a larger number of family physician practices, pharmacies, and older adults.The author(s) declare that they have no competing interests.All authors reviewed the manuscript and contributed to its critical revision for important intellectual content. TK contributed to the study design and was responsible for the analysis and interpretation of data and preparation of the manuscript. JK contributed to the study design and supervised the analyses. LC contributed to the study design. CL was a co-investigator contributing to the study design. LD contributed to the study design and recruited pharmacists. BM contributed to the study design and was responsible for training volunteers, coordinating the sessions, and data collection. CP is a co-investigator contributing to the study design. JEW contributed to the study design and invited patients from his practice.The pre-publication history for this paper can be accessed here:


Invasive arterial blood pressure monitoring is a common practice in intensive care units (ICUs). Accuracy of invasive blood pressure monitoring is crucial in evaluating the cardiocirculatory system and adjusting drug therapy for hemodynamic support. However, the best site for catheter insertion is controversial. Lack of definitive information in critically ill patients makes it difficult to establish guidelines for daily practice in intensive care. We hypothesize that peripheral and central mean arterial blood pressures are interchangeable in critically ill patients.This is a prospective, observational study carried out in a surgical-medical ICU in a teaching hospital. Fifty-five critically ill patients with clinical indication of invasive arterial pressure monitoring were included in the study. No interventions were made. Simultaneous measurements were registered in central  and peripheral  arteries. Bias and precision between both measurements were calculated with Bland-Altman analysis for the whole group. Bias and precision were compared between patients receiving high doses of vasoactive drugs (norepinephrine or epinephrine >0.1 μg/kg/minute or dopamine >10 μg/kg/minute) and those receiving low doses (norepinephrine or epinephrine <0.1 μg/kg/minute or dopamine <10 μg/kg/minute).Central mean arterial pressure was 3 ± 4 mmHg higher than peripheral mean arterial pressure for the whole population and there were no differences between groups (3 ± 4 mmHg for both groups).Measurement of mean arterial blood pressure in radial or femoral arteries is clinically interchangeable. It is not mandatory to cannulate the femoral artery, even in critically ill patients receiving high doses of vasoactive drugs. Invasive arterial blood pressure monitoring is a common practice in intensive care units (ICUs). The most frequent indication for invasive arterial blood pressure monitoring is for continuous measurement in hemodynamically unstable patients . The radIn critically ill patients treated with vasoactive drugs, Dorman and colleagues  reportedLack of definitive information in critically ill patients makes it difficult to establish guidelines for daily practice in intensive care. We hypothesize that peripheral and central mean arterial blood pressures are interchangeable in critically ill patients. To test our hypothesis we compare simultaneous measurements of arterial blood pressure in peripheral and central arteries in a heterogeneous population of critically ill patients using formal Bland-Altman analysis .The study was approved by the Hospital Ethics Committee and the need for informed consent was waived because no additional procedures apart from usual intensive care practice were involved.Fifty-five critically ill patients admitted to our mixed  ICU from 16 December 1999 to 22 December 2000 were studied. Inclusion criteria were: clinical indication of invasive arterial pressure monitoring, such as cardiovascular instability, use of intravenous vasoactive agents, and need for frequent sampling of arterial blood . ExclusiThe clinical features of each patient's disease guided indications of invasive arterial blood pressure monitoring and all patients received standard treatments following the guidelines for the pathologies diagnosed or suspected.Patients were separated into two groups: those receiving high doses of vasoactive drugs (dopamine ≥10 μg/kg/minute or epinephrine or norepinephrine ≥0.10 μg/kg/minute); and those receiving low doses of vasoactive drugs (dopamine <10 μg/kg/minute or epinephrine or norepinephrine <0.10 μg/kg/minute) or no vasoactive. Demographic data (sex and age), APACHE II score  at enrolFor femoral arteries, 14- or 16-gauge catheters were used  and for radial arteries, a 20-gauge catheter was used . The catheters were inserted with their tips pointing towards the blood flow. Indwelling devices were connected to a continuous-flush transducer system through a rigid plastic tube measuring 120 cm in length in all cases, regardless of whether central or peripheral arteries were used . Both transducers were placed at the same level (right atrium) on a plastic support and zeroed to atmosphere. The arterial blood pressure signals were recorded and displayed on a bedside monitor  and the waveforms were simultaneously and permanently registered online. The whole tubing system was flushed with sterile normal saline to eliminate air bubbles and tested for system loss (for instance any kind of fluid leak from the circuit). The monitoring device was connected to a permanent pressurized washing system. Curve characteristics were constantly evaluated using a rapid flush test to rule out occlusion or catheter malposition [The readings over the first five minutes after the insertion of the second catheter were simultaneously recorded, and the mean values for systolic, diastolic, and mean arterial pressures were calculated for both catheters. The data from the entire population were analyzed to determine the global accuracy of the peripheral measurement of mean blood pressure. Next, the two groups were analyzed separately and differences between groups were evaluated to determine the interchangeability of peripheral and central mean arterial blood measurements. We focused the analysis of interchangeability on mean arterial pressure because the tissue perfusion pressure is mainly given by mean arterial pressure rather than by systolic or diastolic pressure.t tests. Descriptive data are expressed as mean ± standard deviation (SD). Statistical significance was defined as p < 0.05.Data were analyzed using the Bland and Altman method . Bias, pn = 12, doses ranging from 11 to 46 μg/kg/minute), norepinephrine , or epinephrine ; 5 patients in this group were also receiving dobutamine simultaneously. Five patients in the low-dose group were receiving dopamine in doses ranging from 3 to 7 μg/kg/minute, one patient was on norepinephrine 0.063 μg/kg/minute, and nine were not receiving any vasoactive drug.The characteristics of the 55 patients are shown in Table No differences were found in systolic, diastolic, or mean arterial blood pressure measured in the femoral artery versus the radial artery in the entire population or in either of the two groups Table .For the whole population, bias (mean difference between simultaneous measurements) ± precision  of simultaneous femoral and peripheral mean arterial blood pressure measurements was 3 ± 4 mmHg. With these values, the 95% limits of agreement (mean ± 2 SD of the difference between simultaneous measurements) are 16 mmHg  and a broader range of doses of different vasoactive drugs was used. Only 17 (16 in the high dose group and one in the low dose group) patients included in our study were receiving norepinephrine; however, bias and precision between peripheral and central arterial blood pressure was the same in the different groups.Another source of discrepancy might be the measurement technique used. We tried to minimize variability in the measurement system. For this reason, simultaneous recordings of both pressures were registered on the same monitor using transducers, plastic lines, and washing systems sharing similar features. Nevertheless, the size of the catheters inserted at different sites was different in our study. Although the intravascular portion of the catheter has minimal effect on the accuracy of measurement , we cannt tests to compare radial and femoral arterial blood pressure measurements; however, when the main issue to be addressed is agreement between different measurements of a variable, the best statistical approach is the Bland and Altman method [Finally, Dorman and colleagues used n method . There in method . The smaIn this study, peripheral and central measurements of arterial blood pressure showed good agreement regardless of vasoactive drug use. Our results suggest that these two measurements are interchangeable and it is, therefore, not mandatory to cannulate the femoral artery to measure arterial blood pressure, even in critically ill patients receiving high doses of vasoactive drugs.• 	Femoral and radial mean arterial blood pressures showed good agreement regardless of the use of vasoactive drugs.• 	Our results suggest that these two measurements are interchangeable.ICU = intensive care unit; SD = standard deviation.The authors declare that they have no competing interests.MAM and EAP participated in the conception and design of the study, in the acquisition analysis and interpretation of the data and drafted the manuscript. AD participated in the conception and design of the study, in the analysis and interpretation of the data, revised the manuscript critically for important intellectual content and gave final approval of the version to be published.