Correction: Supported Telemonitoring and Glycemic Control in People with Type 2 Diabetes: The Telescot Diabetes Pragmatic Multicenter Randomized Controlled Trial.

[This corrects the article DOI: 10.1371/journal.pmed.1002098.].

Supported Telemonitoring and Glycemic Control in People with Type 2 Diabetes: The Telescot Diabetes Pragmatic Multicenter Randomized Controlled Trial.

BACKGROUND: Self-monitoring of blood glucose among people with type 2 diabetes not treated with insulin does not appear to be effective in improving glycemic control. We investigated whether health professional review of telemetrically transmitted self-monitored glucose results in improved glycemic control in people with poorly controlled type 2 diabetes. METHODS AND FINDINGS: We performed a randomized, parallel, investigator-blind controlled trial with centralized randomization in family practices in four regions of the United Kingdom among 321 people with type 2 diabetes and glycated hemoglobin (HbA1c) >58 mmol/mol. The supported telemonitoring intervention involved self-measurement and transmission to a secure website of twice-weekly morning and evening glucose for review by family practice clinicians who were not blinded to allocation group. The control group received usual care, with at least annual review and more frequent reviews for people with poor glycemic or blood pressure control. HbA1c assessed at 9 mo was the primary outcome. Intention-to-treat analyses were performed. 160 people were randomized to the intervention group and 161 to the usual care group between June 6, 2011, and July 19, 2013. HbA1c data at follow-up were available for 146 people in the intervention group and 139 people in the control group. The mean (SD) HbA1c at follow-up was 63.0 (15.5) mmol/mol in the intervention group and 67.8 (14.7) mmol/mol in the usual care group. For primary analysis, adjusted mean HbA1c was 5.60 mmol/mol / 0.51% lower (95% CI 2.38 to 8.81 mmol/mol/ 95% CI 0.22% to 0.81%, p = 0·0007). For secondary analyses, adjusted mean ambulatory systolic blood pressure was 3.06 mmHg lower (95% CI 0.56-5.56 mmHg, p = 0.017) and mean ambulatory diastolic blood pressure was 2.17 mmHg lower (95% CI 0.62-3.72, p = 0.006) among people in the intervention group when compared with usual care after adjustment for baseline differences and minimization strata. No significant differences were identified between groups in weight, treatment pattern, adherence to medication, or quality of life in secondary analyses. There were few adverse events and these were equally distributed between the intervention and control groups. In secondary analysis, there was a greater number of telephone calls between practice nurses and patients in the intervention compared with control group (rate ratio 7.50 (95% CI 4.45-12.65, p < 0.0001) but no other significant differences between groups in use of health services were identified between groups. Key limitations include potential lack of representativeness of trial participants, inability to blind participants and health professionals, and uncertainty about the mechanism, the duration of the effect, and the optimal length of the intervention. CONCLUSIONS: Supported telemonitoring resulted in clinically important improvements in control of glycaemia in patients with type 2 diabetes in family practice. Current Controlled Trials, registration number ISRCTN71674628. TRIAL REGISTRATION: Current Controlled Trials ISRCTN 71674628.

The case for home monitoring in hypertension.

Although the assessment of cardiovascular risk in individual patients takes into account a range of risk factors, the diagnosis and management of hypertension (high blood pressure) is largely determined by a single numerical value, albeit that often several readings are taken over time. Given the critical impact of a decision to embark on lifelong drug therapy, the importance of ensuring that a blood pressure (BP) record is both accurate and representative is clear. However, there is good evidence that the variability of BP is such that even if measurement is of the highest quality, it can be difficult to say with confidence whether a patient is above or below a treatment threshold. This commentary argues that current BP measurement is inadequate to make the clinical decisions that are necessary and that multiple readings are required to deliver an acceptable degree of accuracy for safe decision-making. This is impractical in a doctor's surgery, and the only realistic long-term strategy is to involve the patient in measuring his or her own BP in their own environment. Evidence is presented that such a strategy is better able to predict risk, is cost-effective for diagnosing hypertension, can improve BP control and is thus better able to protect individuals in the future. In this commentary, I explain why doctors and other healthcare professionals should increase their familiarity with the technology, be aware of its strengths and limitations and work with patients as they become more empowered in the management of their chronic condition, hypertension.

Phosphodiesterase type 5 inhibition reverses impaired forearm exercise-induced vasodilatation in hypertensive patients.

OBJECTIVE: Established hypertension is characterized by increased peripheral vascular resistance and endothelial dysfunction, features that may underlie the reduced exercise-induced vasodilatation seen in hypertensive patients. Sildenafil citrate is a phosphodiesterase type 5 (PDE5) inhibitor used clinically for the treatment of male erectile dysfunction. Its vasodilating properties are due to the inhibition of cyclic guanosine monophosphate (cGMP) breakdown and prolongation of the signalling actions of the nitric oxide (NO)-cGMP pathway in vascular smooth muscle cells. Sildenafil has beneficial effects on endothelial function and exercise tolerance in congestive heart failure and pulmonary hypertension, and we hypothesized that it would improve exercise-induced vasodilatation in hypertensive patients. METHODS AND RESULTS: Ten hypertensive patients and ten matched normotensive subjects were studied in a three-way, randomized, single-blind and placebo-controlled study. On each study day, forearm blood flow (FBF) responses to handgrip exercise were assessed before and after intra-arterial (brachial) infusion of sildenafil, verapamil (a control, cGMP-independent vasodilator), and saline (placebo). Preinfusion exercise-induced vasodilatation was significantly reduced in hypertensive patients compared to normotensive controls. Sildenafil and verapamil infusions both caused a similar increase in baseline FBF. However, while verapamil did not affect the vasodilator response to handgrip exercise in either group, sildenafil substantially enhanced this response in hypertensive patients, but not in normotensive subjects. CONCLUSIONS: Our data suggest that sildenafil, through an increase in cGMP levels in the vasculature, substantially and selectively improves the vasodilator response to handgrip exercise in hypertensive patients. These findings represent an essential first step in support of further studies exploring the potentially beneficial effects of PDE5 inhibition on impaired exercise capacity in hypertension.

How do we use ambulatory measurement of blood pressure in the management of hypertension?

We have explored the use and interpretation of ambulatory blood pressure monitoring (ABPM) among clinicians at an Edinburgh Cardiovascular Risk Clinic and among a group of international experts in blood pressure monitoring. Locally, we were able to demonstrate major discrepancies in management advice between doctors and nurses. Although all of the international experts used ABPM regularly, they did not agree on thresholds levels for treatment or target BP. This gives food for thought as we consider how to advise internists and primary care physicians on the use and interpretation of ABPM.

Do SpaceLabs ambulatory non-invasive blood pressure recorders measure blood pressure consistently over several years use?

OBJECTIVE: To assess the measurement consistency of SpaceLabs ambulatory recorders (Spacelabs, Washington, USA) that are in regular use. METHODS: A total of 14 SpaceLabs 90207 and one 90217 ambulatory recorders were tested for measurement consistency using the Dynatech CuffLink (Dynatech, Nevada, USA), a commercially available non-invasive blood pressure (NIBP) simulator. The NIBP recorders were tested at a range of pressures with 20 repeated determinations at a simulated 120/80 mmHg and five repeated determinations at simulated pressures of 80/50, 100/80, 150/100, 200/165 and 250/195 mmHg. Tests were carried out in 1998, 2002 and late 2003 or early 2004. CONCLUSIONS: All 15 SpaceLabs recorders measured consistently over the 6 years with 89.5% of the differences in average pressures, recorded by any particular device at each recorded pressure, less than 2 mmHg between successive test episodes. The maximum difference was 4.5 mmHg and 60.1% of the differences were less than 1 mmHg. The measurements for all devices were within the tolerances specified by the supplier for the device when tested with the simulator. Maintenance records also show that most devices required breakdown maintenance less than once every 3 years. The results show that the SpaceLabs devices maintain measurement consistency in the demanding conditions of ambulatory pressure recording over several years.

Ten years on: Safety of short synacthen tests in assessing adrenocorticotropin deficiency in clinical practice.

Since 1988, when a retrospective study of patients attending this unit was published, we have advocated the use of the short synacthen test (SST) as the primary screening investigation to detect ACTH deficiency. However, others have published comparisons of SST and insulin tolerance tests that suggest a significant false negative rate with SST, leading to concern that some patients who pass the SST are in danger from the clinical consequences of ACTH deficiency. To address this, we audited biochemical results and clinical outcome in 63 patients who did not have ACTH deficiency detected (i.e. who passed the test) by SST after pituitary surgery. Twelve of the 63 patients who passed a SST after pituitary surgery became ACTH-deficient later as diagnosed by SST: 4 within the first year, 2 of whom had received postoperative radiotherapy (3 had symptoms of tiredness and 1 was admitted to the hospital with a viral infection); 8 in yr 3-5, 7 of whom had received postoperative radiotherapy (all had either no symptoms or symptoms of tiredness alone). Thus, the predictive value of the SST in excluding ACTH deficiency is approximately 97% (2 of 63 patients who initially passed the SST were found to be ACTH-deficient within 12 months without having received postoperative radiotherapy). Only 1 patient was ill enough to require hospital admission. Setting the risk of false negatives with SST against the morbidity and manpower implications associated with insulin tolerance tests, SST remains the primary screening test for ACTH deficiency in our practice. However, a high index of clinical suspicion to detect false negative results must be maintained.

Self-monitored blood pressure: a role in clinical practice?

Electronic self-monitoring of blood pressure is increasing in popularity and most international guidelines on the management of hypertension approve cautious use of the technique in the assessment of potentially hypertensive individuals. A recent editorial in the Archives of Internal Medicine suggested that it was "appropriate to encourage the widespread use of self recorded BP as an important adjunct to the clinical care of the patient with hypertension". Such a statement is based on increasing evidence that self-monitoring of blood pressure gives similar information to daytime ambulatory blood pressure -- a now well-established technology in the management of hypertension. Suggested strategies for the use of self-monitoring of blood pressure include monitoring in individuals whose clinical risk status is low enough that they need not necessarily be given medical therapy simply on the basis of a clinic pressure (i.e. at a 10 year risk of cardiovascular disease below 20%). The threshold for defining 'normotension/hypertension' is now regarded as being broadly similar for ABPM and SBPM and is set at 135/85 mmHg. In a recent meta-analysis of all available studies the average difference between these techniques, using the same patients, is -1.7/1.2 mmHg. There is some evidence that careful use of self-monitoring may improve blood pressure control in patients who are otherwise resistant to care. Self-monitoring of blood pressure has now been shown in at least one major prospective study to predict outcome better than clinic pressures and in that setting it now has equivalence to the use of ABPM. There remain issues regarding the availability of validated devices, the quality of training of patients in their use and the possibility that inaccurate recording might occur, either deliberately or by accident. Self-monitoring of blood pressure may well not give the same readings as carefully measured blood pressure by research nurses but its use is clearly superior to routine clinical practice. The technique is ripe for widespread application.

Variability of office, 24-hour ambulatory, and self-monitored blood pressure measurements.

BACKGROUND: The diagnosis of hypertension is difficult when faced with several different blood pressure measurements in an individual. Using the average of several office measurements is recommended, although considerable uncertainty remains. Twenty-four-hour ambulatory monitoring is often considered the gold standard, but self-monitoring of blood pressure has been proposed as a superior method. AIM: Determination of within-individual variability of blood pressure measured in the office, by ambulatory monitoring, and by a week of self-monitoring. DESIGN OF STUDY: Retrospective analysis of a clinical trial of 163 subjects. METHOD: Within-patient variability of office and ambulatory blood pressure was determined from measurements at 0 and 6 weeks. Subjects had performed self-monitoring of blood pressure twice each morning and evening, for at least 6 weeks; variability was determined from the means of week 1 and week 6. RESULTS: The within-individual coefficients of variation (CVs) for systolic blood pressure were: office, 8.6%; ambulatory, 5.5%; self, 4.2%. Equivalent values for diastolic blood pressure were 8.6%, 4.9%, and 3.9%. CVs tended to be lower with longer self-monitoring duration, and higher with longer intervals between self-monitoring. CONCLUSION: Office blood pressure is impractical for precise assessment, as 10-13 measurements are required to give the accuracy required for rational titration of antihypertensive drugs. Twenty-four-hour ambulatory monitoring is better than a single office measurement, but considerable uncertainty remains around the estimate. A week of self-monitoring appears to be the most accurate method of measuring blood pressure, but remains imperfect. Further research may identify superior self-monitoring schedules. Given the inherent accuracy in blood pressure measurement, the importance of considering overall cardiovascular risk is emphasised.

Nocturnal dipping is reproducible in the long term.

OBJECTIVE: To examine the long-term reproducibility of nocturnal dipping as a dichotomous and continuous variable. METHODS: Retrospective review of an ambulatory blood pressure monitor (ABPM) database of approximately 15 000 patients. Reproducibility of ABPM was assessed by repeatability coefficient. Kappa (kappa) statistic and intraclass correlation coefficient were used to quantify dipping as a dichotomous and continuous variable, respectively. RESULTS: There were 512 never-treated patients with two ABPM assessments, a mean of 29 (+/-19) months apart. Blood pressure was 2/0 mmHg (awake) and 2/1 mmHg (asleep) higher on the second ABPM. The repeatability coefficient for awake systolic and awake diastolic pressure was 5.9 and 6.2%, respectively. When the dipper/non-dipper (dichotomous) classification was applied to both ABPMs, dipping status was unchanged in 76% of patients, kappa = 0.29. When nocturnal dip was expressed as a continuous variable, the mean nocturnal dip was 14% and the median absolute change between assessments was 3.8%, intraclass correlation coefficient = 0.60. The time interval between assessments was subdivided into (i) within 6 months, (ii) 6 months to 1 year, (iii) 1-2 years, (iv) 2-3 years and (v) more than 3 years. There was remarkable consistency independent of time interval for dipping expressed as a continuous variable but not as dipper/non-dipper. CONCLUSION: These findings show that in the long term, nocturnal dip is more stable when expressed as a continuous variable. As recent evidence show cardiovascular risk to be inversely related to nocturnal blood pressure in a continuous manner, surely it makes more sense to express nocturnal dip in a similar way to aid stratification of overall cardiovascular risk.

Aldosterone and refractory hypertension.

PURPOSE OF REVIEW: Evidence from clinical trials suggests that refractory hypertension is increasingly common. The underlying mechanisms are largely unknown but recent data have implicated increased aldosterone activity as an important mediator of resistance to routinely used antihypertensive agents. RECENT FINDINGS: Epidemiological studies have suggested a significant rise in the prevalence of primary aldosteronism among patients with hypertension. This reflects the increasing use of an aldosterone-to-renin ratio as a screening tool. Recent reports have demonstrated that relative aldosterone excess is common in individuals with refractory hypertension, and that the use of aldosterone antagonists leads to better blood pressure control in such patients. SUMMARY: These data highlight the potential role of aldosterone in the pathogenesis of hypertension. The syndrome of primary aldosteronism, however, encompasses a wide spectrum of disorders that will require better definition. Similarly, although aldosterone blockade is apparently beneficial in individuals with refractory hypertension, this evidence is not currently based on robust randomized, double-blind trial.

Assessing the HPA axis in patients with pituitary disease: a UK survey.

OBJECTIVE: Assessing the integrity of the hypothalamic-pituitary-adrenal (HPA) axis following pituitary surgery is necessary to determine the requirement for glucocorticoid replacement therapy, but there remains controversy about the optimum way to measure this. DESIGN AND MEASUREMENTS: Postal questionnaire survey among UK endocrinologists to evaluate the current methods used. RESULTS: The response rate was low (81 out of 598 questionnaires mailed), although 85% were consultants. Fifty-five percent measured 9:00 h plasma cortisol in the immediate postoperative phase. Most carried out definitive testing between 4 and 12 weeks: 36% routinely used the insulin tolerance test (ITT), 59% used the short synacthen test (SST). The 30-min cortisol value was used by 67% as a 'pass' when interpreting the results. Others included cortisol measurement at 60 min (17%) or incremental value (7%). For long-term follow-up of patients not rendered ACTH-deficient by surgery, 64% used the SST for patients who had received radiotherapy. If patients had not had radiotherapy, 42% used the SST, whereas 33% did no routine testing unless the patient was symptomatic or there was evidence of tumour recurrence on imaging. If patients were symptomless but 'failed' the chosen test, 28% still treated the patient with glucocorticoid replacement, 38% retested before treatment and 24% recommended glucocorticoid cover for when unwell or 'stressed'. Fifty-six percent used hydrocortisone at doses of 20 mg/day as replacement therapy. CONCLUSION: Thus, assessment of the HPA axis remains controversial. Although the SST is becoming more popular, there is still considerable variation in the interpretation of results and, in particular, the decision of whether or not to treat with lifelong glucocorticoid replacement therapy.

[Three simple steps for improving diagnostic accuracy in hypertension.].

OBJECTIVE: Most patients have only had three measurements of blood pressure before being labelled as hypertensive. This abbreviated assessment may lead to inaccurate classification, unnecessary treatment and dilution in treatment benefit for the population. We aimed to explore how accurate current methods are in diagnosing mild hypertension, and to explore practical methods of improving targeting of antihypertensive treatment using clinic visits but without lengthy observation. MATERIAL AND METHODS: We applied current diagnostic methods to 3965 individuals with mild hypertension who were followed for a year in the placebo arm of the MRC Mild Hypertension Trial (Medical Research Council). We thus calculated the proportion selected for treatment by current methods and the diagnostic accuracy, using average blood pressure beyond six months as representing "true" long-term blood pressure. We looked at the benefit of averaging blood pressures, prolonging observation modestly and estimating within-person blood pressure variability. RESULTS: Prolonging observation to three months selects a smaller (by about 12%) proportion of the sample for treatment. At three months the proportion of the sample selected is similar to the proportion defined as "truly" hypertensive. The diagnostic accuracy of current methods is poor with up to 69% discrepancy in classification. This discrepancy was improved in absolute terms by up to 18% by prolonging observation to three months and using average blood pressures. Identifying those individuals with low within-person variability allows marked improvement in the prediction of "true" hypertension. CONCLUSION: Although some inaccuracy in the diagnosis of hypertension is inevitable, observation for three months, averaging blood pressures and estimating within-person blood pressure variability can markedly improve upon current methods used for targeting antihypertensive treatment.