Measured and not estimated glomerular filtration rate should be used to assess renal function in heart transplant recipients.

BACKGROUND: In organ transplanted patients, impaired renal function is of major prognostic importance and influences therapeutic decisions. Therefore, monitoring of renal function with glomerular filtration rate (GFR) is of importance, both before and after heart transplantation (HTx). The GFR can be measured directly (mGFR) or estimated (eGFR) with equations based on circulating creatinine or cystatin C levels. However, these equations have not been thoroughly validated in the HTx population. METHODS: We investigated the correlation, agreement and accuracy between mGFR (using (51)Cr-ethylenediaminetetraacetic acid or iohexol clearance) and three commonly used eGFR equations (Modification of Diet in Renal Disease, Cockcroft-Gault and Chronic Kidney Disease Epidemiology Collaboration) in a retrospective analysis of 416 HTx recipients followed between 1988 and 2012. Comparisons were performed prior to transplantation and at 1, 5 and 10 years of follow-up. RESULTS: The correlations between eGFR and mGFR were only moderate, with r-values ranging from 0.55 preoperatively to 0.82 during follow-up. Most importantly, the level of agreement between eGFR and mGFR was very low for all three estimates, with percentage errors ranging from 93.3 to 157.3%. Also, the percentage of patients with eGFR within 30% of mGFR (P30) rarely reached the National Kidney Foundation recommended minimum level of 75%. CONCLUSION: We argue that the accuracy and the precision of the most commonly used estimation equations for assessment of kidney function are unacceptably low and we believe that mGFR should be used liberally as the basis for clinical decision-making both before and after HTx when eGFR is subnormal.

Medication reviews for nursing home residents to reduce mortality and hospitalization: systematic review and meta-analysis.

AIMS: Medication reviews by a third party have been introduced as a method to improve drug treatment in older people. We assessed whether this intervention reduces mortality and hospitalization for nursing home residents. METHODS: Systematic literature searches were performed (from January 1990 to June 2012) in Medline, EMBASE, Cochrane Library, ProQuest Nursing & Allied Health Sources and Health Technology Assessment databases. We included randomized and nonrandomized controlled trials (RCTs and non-RCTs) of medication reviews compared with standard care or other types of medication reviews in nursing home residents. The outcome variables were mortality and hospitalization. Study quality was assessed systematically. We performed meta-analyses using random-effects models. RESULTS: Seven RCTs and five non-RCTs fulfilled the inclusion criteria. The mean age of included patients varied between 78 and 86 years. They were treated with a mean of 4-12 drugs. The study quality was assessed as high (n = 1), moderate (n = 4) or low (n = 7). Eight studies compared medication reviews with standard care. In six of them, pharmacists were involved in the intervention. Meta-analyses of RCTs revealed a risk ratio (RR) for mortality of 1.03 [medication reviews vs. standard care; five trials; 95% confidence interval (CI) 0.85-1.23]. The corresponding RR for hospitalization was 1.07 (two trials; 95% CI 0.61-1.87). CONCLUSIONS: Our findings indicate that medication reviews for nursing home residents do not reduce mortality or hospitalization. More research in the setting of controlled trials remains to be done in order to clarify how drug treatment can be optimized for these patients.

Rosuvastatin and cardiovascular events in patients undergoing hemodialysis.

BACKGROUND: Statins reduce the incidence of cardiovascular events in patients at high cardiovascular risk. However, a benefit of statins in such patients who are undergoing hemodialysis has not been proved. METHODS: We conducted an international, multicenter, randomized, double-blind, prospective trial involving 2776 patients, 50 to 80 years of age, who were undergoing maintenance hemodialysis. We randomly assigned patients to receive rosuvastatin, 10 mg daily, or placebo. The combined primary end point was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Secondary end points included death from all causes and individual cardiac and vascular events. RESULTS: After 3 months, the mean reduction in low-density lipoprotein (LDL) cholesterol levels was 43% in patients receiving rosuvastatin, from a mean baseline level of 100 mg per deciliter (2.6 mmol per liter). During a median follow-up period of 3.8 years, 396 patients in the rosuvastatin group and 408 patients in the placebo group reached the primary end point (9.2 and 9.5 events per 100 patient-years, respectively; hazard ratio for the combined end point in the rosuvastatin group vs. the placebo group, 0.96; 95% confidence interval [CI], 0.84 to 1.11; P=0.59). Rosuvastatin had no effect on individual components of the primary end point. There was also no significant effect on all-cause mortality (13.5 vs. 14.0 events per 100 patient-years; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P=0.51). CONCLUSIONS: In patients undergoing hemodialysis, the initiation of treatment with rosuvastatin lowered the LDL cholesterol level but had no significant effect on the composite primary end point of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. (ClinicalTrials.gov number, NCT00240331.)

Best supportive care and therapeutic plasma exchange with or without eculizumab in Shiga-toxin-producing E. coli O104:H4 induced haemolytic-uraemic syndrome: an analysis of the German STEC-HUS registry.

BACKGROUND: May 22nd marks the beginning of a Shiga-toxin-producing Escherichia coli (STEC) O104:H4 outbreak in Northern Germany. By its end on 27 July, it had claimed 53 deaths among 2987 STEC and 855 confirmed haemolytic-uraemic syndrome (HUS) cases. METHODS: To describe short-term effectiveness of best supportive care (BSC), therapeutic plasma exchange (TPE) and TPE with eculizumab (TPE-Ecu) in 631 patients with suspected HUS treated in 84 hospitals in Germany, Sweden and the Netherlands using the web-based registry of the DGfN (online since 27 May). RESULTS: Of 631 entries, 491 fulfilled the definition of HUS (median age 46 years; 71% females). The median (inter-quartile range) hospital stay was 22 (14-31) days. Two hundred and eighty-one (57%) patients underwent dialysis and 114 (23%) mechanical ventilation. Fifty-seven patients received BSC, 241 TPE and 193 TPE-Ecu. Treatment strategy was dependent on disease severity (laboratory signs of haemolysis, thrombocytopenia, peak creatinine level, need for dialysis, neurological symptoms, frequency of seizures) which was lower in BSC than in TPE and TPE-Ecu patients. At study endpoint (hospital discharge or death), the median creatinine was lower in BSC [1.1 mg/dL (0.9-1.3)] than in TPE [1.2 mg/dL (1.0-1.5), P < 0.05] and TPE-Ecu [1.4 mg/dL (1.0-2.2), P < 0.001], while need for dialysis was not different between BSC (0.0%, n = 0), TPE (3.7%; n = 9) and TPE-Ecu (4.7%, n = 9). Seizures were absent in BSC and rare in TPE (0.4%; n = 1) and TPE-Ecu (2.6%; n = 5) patients. Total hospital mortality in HUS patients was 4.1% (n = 20) and did not differ significantly between the TPE and TPE-Ecu groups. CONCLUSIONS: Despite frequent renal impairment, advanced neurological disorders and severe respiratory failure, short-term outcome was better than expected when compared with previous reports. Within the limitations of a retrospective registry analysis, our data do not support the notion of a short-term benefit of Ecu in comparison to TPE alone in the treatment of STEC-HUS. A randomized trial comparing BSC, TPE and Ecu seems to be prudent and necessary prior to establishing new treatment guidelines for STEC-HUS.

The effect of decreasing renal function on lipoprotein profiles.

BACKGROUND: Progressive chronic kidney disease (CKD) is accompanied by dyslipidemia that is characterized by increased concentrations of intact and partially metabolized ApoB and ApoC-III-containing triglyceride-rich lipoproteins in very low-density lipoprotein, intermediate density lipoprotein (IDL) and low-density lipoprotein. The purpose of the present study was to characterize the distribution of individual discrete lipoprotein subclasses in relation to the glomerular filtration rate (GFR) in nondiabetic CKD subjects. METHODS: Fifty-one subjects (33 patients with CKD and 18 asymptomatic subjects) with GFR ranging from 12 to 120 mL/min were studied. Individual ApoA- and ApoB-containing lipoprotein subclasses (Lp) were determined in plasma by sequential immunoaffinity chromatography and subsequent determination of apolipoprotein composition by electroimmunoassays. GFR was measured as plasma clearance of iohexol or (51)Cr-ethylenediaminetetraacetic acid. RESULTS: There were no changes in concentrations of ApoA-containing lipoproteins with decreasing GFR. The levels of ApoB-containing lipoproteins increased significantly with decreasing GFR. There was a moderate increase of cholesterol-rich LpB and a 3-fold increase of ApoB- and ApoC-III-containing lipoproteins in subjects in the two lowest quintiles of GFR. This was accompanied by a significant increase of plasma ApoC-III. CONCLUSIONS: Reduced renal function is associated with a complex alteration of the lipoprotein profile that is predominantly characterized by increased concentrations of triglyceride-rich lipoprotein subclasses containing both ApoB and ApoC-III.

Repetitive transcranial magnetic stimulation of the primary motor cortex in management of chronic neuropathic pain: a systematic review.

OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) with frequencies 5-20 Hz is an expanding non-invasive treatment for chronic neuropathic pain (NP). Outcome data, however, show considerable inhomogeneity with concern to the levels of effect due to the great diversity of treated conditions. The aim of this review was to survey the literature regarding the efficacy and safety of M1 rTMS, and the accuracy to predict a positive response to epidural motor cortex stimulation (MCS) which is supposed to give a more longstanding pain relief. METHODS: A systematic literature search was conducted up to June 2019 in accordance with the PRISMA guidelines. We used the PICO Model to define two specific clinical questions: (1) Does rTMS of M1 relieve NP better than sham treatment? (2) Can the response to rTMS be used to predict the effect of epidural MCS? After article selection, data extraction, and study quality assessment, the certainty of evidence of treatment effect was defined using the GRADE system. RESULTS: Data on 5-20 Hz (high-frequency) rTMS vs. sham was extracted from 24 blinded randomised controlled trials which were of varying quality, investigated highly heterogeneous pain conditions, and used excessively variable stimulation parameters. The difference in pain relief between active and sham stimulation was statistically significant in 9 of 11 studies using single-session rTMS, and in 9 of 13 studies using multiple sessions. Baseline data could be extracted from 6 single and 12 multiple session trials with a weighted mean pain reduction induced by active rTMS, compared to baseline, of -19% for single sessions, -32% for multiple sessions with follow-up <30 days, and -24% for multiple sessions with follow-up ≥30 days after the last stimulation session. For single sessions the weighted mean difference in pain reduction between active rTMS and sham was 15 percentage points, for multiple sessions the difference was 22 percentage points for follow-ups <30 days, and 15 percentage points for follow-ups ≥30 days. Four studies reported data that could be used to evaluate the accuracy of rTMS to predict response to MCS, showing a specificity of 60-100%, and a positive predictive value of 75-100%. No serious adverse events were reported. CONCLUSIONS: rTMS targeting M1 can result in significant reduction of chronic NP which, however, is transient and shows a great heterogeneity between studies; very low certainty of evidence for single sessions and low for multiple sessions. Multiple sessions of rTMS can maintain a more longstanding effect. rTMS seems to be a fairly good predictor of a positive response to epidural MCS and may be used to select patients for implantation of permanent epidural electrodes. More studies are needed to manifest the use of rTMS for this purpose. Pain relief outcomes in a longer perspective, and outcome variables other than pain reduction need to be addressed more consistently in future studies to consolidate the applicability of rTMS in routine clinical practice.

Dyslipidemia of kidney disease.

PURPOSE OF REVIEW: Chronic kidney disease is associated with specific alterations of lipoprotein metabolism that may be linked to accelerated atherosclerosis and cardiovascular disease. This review summarizes current knowledge of the pathophysiology of renal dyslipidemia and the therapeutic options. RECENT FINDINGS: The renal dyslipidemia is characterized by accumulation of intact and partially metabolized triglyceride-rich apoB-containing and apoC-containing lipoproteins. Increased concentrations of atherogenic apoC-III rich lipoproteins, the hallmark of renal dyslipidemia, may result from disturbances of insulin metabolism and action in chronic kidney disease. Novel findings strongly suggest that apoC-III triggers a cascade of pro-inflammatory events, which ultimately can result in endothelial dysfunction and vascular damage. Disappointingly, recently reported intervention trials with statins have failed to show any benefit on cardiovascular disease in patients with advanced renal failure. SUMMARY: During recent years, our understanding of the character and biological significance of the dyslipidemia of chronic kidney disease, and its link to cardiovascular disease, has increased. However, our knowledge about its proper management is still very limited.

The influence of renal function on clinical outcome and response to beta-blockade in systolic heart failure: insights from Metoprolol CR/XL Randomized Intervention Trial in Chronic HF (MERIT-HF).

BACKGROUND: Limited information is available on the risk and impact of renal dysfunction on the response to beta-blockade and mode of death in systolic heart failure (HF). METHODS AND RESULTS: Renal function was estimated with glomerular filtration rate (eGFR) using the simplified Modification of Diet in Renal Disease (MDRD) equation. Patients from the Metoprolol CR/XL Controlled Randomized Intervention Trial in Chronic HF (MERIT-HF) were divided into 3 renal function subgroups (MDRD formula): eGFR(MDRD) > 60 (n = 2496), eGFR(MDRD) 45 to 60 (n = 976), and eGFR(MDRD) < 45 mL/min per 1.73 m(2) body surface area (n = 493). Hazard ratio (HR) was estimated with Cox proportional hazards models adjusted for prespecified risk factors. Placebo patients with eGFR < 45 had significantly higher risk than those with eGFR > 60: HR for all-cause mortality, 1.90 (95% confidence interval [CI], 1.28 to 2.81) comparing placebo patients with eGFR < 45 and eGFR > 60, and for the combined end point of all-cause mortality/hospitalization for worsening HF (time to first event): HR, 1.91 (95% CI, 1.44 to 2.53). No significant increase in risk with deceased renal function was observed for those randomized to metoprolol controlled release (CR)/extended release (XL) due to a highly significant decrease in risk on metoprolol CR/XL in those with eGFR < 45. For total mortality, metoprolol CR/XL vs placebo: HR, 0.41 (95% CI. 0.25 to 0.68; P < .001) in those with eGFR < 45 compared with HR, 0.71 (95% CI, 0.54 to 0.95; P < .021) for those with eGFR > 60; corresponding data for the combined end point was HR, 0.44 (95% CI, 0.31 to 0.63; P < .0001) and HR, 0.75 (0.62 to 0.92; P = .005, respectively; P = .095 for interaction by treatment for total mortality; P = .011 for combined end point). Metoprolol CR/XL was well tolerated in all 3 renal function subgroups. CONCLUSIONS: Renal function as estimated by eGFR was a powerful predictor of death and hospitalizations from worsening HF. Metoprolol CR/XL was at least as effective in reducing death and hospitalizations for worsening HF in patients with eGFR < 45 as in those with eGFR > 60.

[Severe COPD can benefit from endobronchial valves]. / Svår KOL är en indikation för endobronkiella ventiler - Ger bättre livskvalitet, lungfunktion och prestationsförmåga enligt ny HTA-analys.

Lung volume reduction using endobronchial one-way valves (EBV) have been introduced as a new treatment for end-stage COPD and emphysema. They cause the lung parenchyma distal to the valve to collapse by causing an atelectasis. Nine randomized controlled trials (RCTs) studying the effects of insertion of EBVs in patients with severe emphysema were identified. In two of the RCTs both lungs were treated whereas in seven a unilateral approach was used. In comparison with optimal medical therapy, unilateral placement of EBVs resulted in clinically and statistically significant improvements in lung function, quality of life, and physical capacity in patients with heterogeneous or homogeneous emphysema. There were no significant differences in mortality. The frequency of serious complications and adverse events, especially pneumothorax, was higher. Bilateral EBV treatment did not show corresponding improvements in the outcome variables.

Mechanistic modelling of tesaglitazar pharmacokinetic data in subjects with various degrees of renal function--evidence of interconversion.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Tesaglitazar, is predominantly metabolized (to an acyl glucuronide of the parent compound) and 20% of given dose is found unchanged in the urine. Acyl glucuronides are know to be unstable and can become hydrolysed back to parent compound, a phenomena called interconversion. WHAT THIS STUDY ADDS: A likely mechanism (interconversion) for the cause of the increased exposure of tesaglitazar in subjects with impaired renal function. A possible modelling framework to evaluate interconversion without dosing of the metabolite based on the simultaneous analysis of plasma and urine data from a group of subjects with varying renal function. A mechanistic understanding of the pharmacokinetic properties of tesaglitazar and its metabolite. AIMS To develop a mechanistic pharmacokinetic (PK) model for tesaglitazar and its metabolite (an acyl glucuronide) following oral administration of tesaglitazar to subjects with varying renal function, and derive an explanation for the increased plasma exposure of tesaglitazar in subjects with impaired renal function. METHODS: Data were from a 6-week study in subjects with renal insufficiency and matched controls undergoing repeated oral dosing with tesaglitazar (n = 41). Compartmental population PK modelling was employed to describe the PK of tesaglitazar and its metabolite, in plasma and urine, simultaneously. Two hypotheses were tested to investigate the increased exposure of tesaglitazar in subjects with renal functional impairment: tesaglitazar metabolism is correlated with renal function, or metabolite elimination is reduced in renal insufficiency, leading to increased hydrolysis (interconversion) to the parent compound via biliary circulation. RESULTS: The hypothesis for interconversion was best supported by the data. The population PK model included first-order absorption, two-compartment disposition and separate renal (0.027 l h(-1)) and metabolic (1.9 l h(-1)) clearances for tesaglitazar. The model for the metabolite; one-compartment disposition with renal (saturable, V(max) = 0.19 micromol l(-1) and K(m) = 0.04 micromol l(-1)) and nonrenal clearances (1.2 l h(-1)), biliary secretion (12 h(-1)) to the gut, where interconversion and reabsorption (0.8 h(-1)) of tesaglitazar occurred. CONCLUSION: A mechanistic population PK model for tesaglitazar and its metabolite was developed in subjects with varying degrees of renal insufficiency. The model and data give insight into the likely mechanism (interconversion) of the increased tesaglitazar exposure in renally impaired subjects, and separate elimination and interconversion processes without dosing of the metabolite.

Renal function and outcome after heart transplantation.

OBJECTIVES: To investigate whether measured glomerular filtration rate (mGFR) is a risk factor for death and/or end-stage renal disease (ESRD) after heart transplantation (HTx). METHODS: All adult patients (n = 416) who underwent HTx between 1988 and 2010 were included. mGFR was performed both preoperatively and postoperatively as annual follow-up. Eight patients received a concomitant kidney transplant (KTx), and 15 underwent late KTx due to chronic renal failure after HTx. RESULTS: The mean drop in mGFR compared with the preoperative value was 12% during the first year after HTx. Preoperative mGFR was not predictive of mortality or ESRD. Older or the use of a ventricular assist device (VAD) were preoperative predictors of death. Long-term survival was significantly worse in the patients who experienced a >25% decrease in mGFR during the first year after transplantation. The need for acute postoperative renal replacement therapy (RRT) was associated with impaired survival but did not predict ESRD among survivors. On multivariable analyses, previous heart surgery, preoperative VAD, and a lower mGFR were all predictors of RRT. In the most recent period, death without previous ESRD was lower, and the only preoperative factors associated with ESRD by multivariable analyses were mechanical ventilation and diabetes mellitus. CONCLUSIONS: Pretransplantation mGFR was not predictive of mortality or ESRD after HTx, but necessitated simultaneous or late-stage KTx in this selected population of patients. However, patients with a decrease in >25% mGFR during the first year post-transplantation, as well as early postoperative dialysis-dependent acute renal dysfunction, had a poor prognosis. We suggest that patients with severely impaired kidney function, irrespective of pretransplantation renal function, still should be considered for HTx, but also encourage careful interpretation of our results given the selection bias involved in this population.

Positron emission tomography and computed tomographic (PET/CT) imaging for radiation therapy planning in anal cancer: A systematic review and meta-analysis.

To improve the accuracy of chemoradiation therapy in anal cancer patients PET/CT is frequently used in the planning of radiation therapy. A systematic review was performed to assess impact on survival, quality of life, symptom score, change in target definition and treatment intention. Systematic literature searches were conducted in Medline, EMBASE, the Cochrane Library, and Centre for Reviews and Dissemination. Ten cross-sectional studies were identified. No data were available on survival or quality of life. The summary estimate of the proportion of patients in which PET/CT had an impact on the target definition, was 23% (95% CI 16;33). The corresponding summary estimate of a change in treatment intent from curative to palliative was 3% (95% CI 2;6). Almost one in four patients had a change in target definition, which supports the use of PET/CT in radiation therapy planning, but the consequence regarding survival and quality of life is still uncertain.

Benefits and risks with acellular dermal matrix (ADM) and mesh support in immediate breast reconstruction: a systematic review and meta-analysis.

In modern implant-based immediate breast reconstruction, it has become common to use biological acellular dermal and synthetic matrices in combination with a tissue expander or an implant. The aim of this systematic review was to examine differences in recurrence of cancer, impact on oncological treatment, health related quality of life, complications and aesthetic outcome between matrix and no matrix in immediate breast reconstruction. Systematic searches, data extraction and assessment of methodological quality were performed according to predetermined criteria. Fifty-one studies were eligible and included in the review. The certainty of evidence for overall complication rate and implant loss is low (GRADE ⊕⊕□ □). The certainty of evidence for delay of adjuvant treatment, implant loss, infection, capsular contraction and aesthetic outcome is very low (GRADE ⊕□ □ □). No study reported data on recurrence of cancer or health related quality of life. In conclusion, there is a lack of high quality studies that compare the use of matrix with no matrix in immediate breast reconstruction. Specifically, there are no data on risk of recurrence of cancer, delay of adjuvant treatment and Health related quality of life (HRQoL). In addition, there is a risk of bias in many studies. It is often unclear what complications have been included and how they have been diagnosed, and how and when capsular contracture and aesthetic outcome have been evaluated. Controlled trials that further analyse the impact of radiotherapy, type of matrix and type of procedure (one or two stages) are necessary.

Diabetes in treated hypertension is common and carries a high cardiovascular risk: results from a 28-year follow-up.

OBJECTIVE: The objective of this study was to analyse predictive factors for development of type 2 diabetes during life-long therapy for hypertension and the alleged additional cardiovascular risk this constitutes. METHODS: The study group (n = 754) comprised the hypertensive subgroup of a randomized population sample of 7500 men, aged 47-54 years, screened for cardiovascular risk factors and followed for 25-28 years. The patients were treated with thiazide diuretics and beta-adrenergic blocking drugs with the addition of hydralazin during the first decade. Calcium antagonists were substituted for hydralazin and, if needed, angiotensin-converting enzyme inhibitors were added when these drugs became available. RESULTS: A total of 148 (20.4%) treated hypertensive patients developed diabetes during 25 years, and in multivariate Cox regression analysis body mass index, serum triglycerides and treatment with beta-blockers were positively related with this complication. New-onset diabetes implied a significantly increased risk for stroke [hazard ratio (HR): 1.67; 95% confidence interval (95% CI): 1.1-2.6; P < 0.05], myocardial infarction (OR: 1.66; 95% CI: 1.1-2.5; P < 0.05) and mortality (OR: 1.42; 95% CI: 1.1-1.9; P < 0.05). The greatest risk for stroke was new-onset diabetes, followed by smoking (OR: 1.46; 95% CI: 1-2.2; P = 0.07) and the greatest risk for myocardial infarction was new-onset diabetes, followed by smoking (HR: 1.64; 95% CI: 1.1-2.4; P < 0.01). The greatest risk for mortality was smoking (HR: 1.73; 95% CI: 1.3-2.2; P < 0.005). Achieved systolic and diastolic blood pressure were not predictive of cardiovascular complications or death. The mean observation time from onset of diabetes mellitus to a first stroke was 9.1 years and to a first myocardial infarction 9.3 years. CONCLUSION: Diabetes in treated hypertensive patients is alarmingly common and carries a high risk for cardiovascular complications and mortality.

Positron emission tomography and computed tomographic imaging (PET/CT) for dose planning purposes of thoracic radiation with curative intent in lung cancer patients: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: PET/CT is a proposed management to improve the accuracy of high dose radiochemotherapy in lung cancer patients. This systematic review was performed to investigate the possible impact on clinical outcome and to quantify the effect on patient selection and target definition. MATERIAL AND METHODS: Systematic literature searches were conducted, eligible full-text articles were assessed for quality and data were extracted. RESULTS: Thirty-five cross-sectional studies and one observational study fulfilled the inclusion criteria. No randomized trials or data with regard to clinical endpoints were found. The summary estimates of a change in target definition were 36% in patients with a former staging PET, and 43% and 26% in patients without a staging PET, for non small- and small cell lung cancer respectively. The corresponding summary estimates of a change in treatment intent from curative to palliative treatment were 20% and 22% and 9% respectively. CONCLUSION: PET/CT for dose planning improves target definition and patient selection. Approximately two in five patients had a significant change in target definition and one in five received palliative treatment instead. The proportions seem to be similar regardless of the availability of a previous staging-PET.

Should beta blockers remain first choice in the treatment of primary hypertension? A meta-analysis.

BACKGROUND: Beta blockers have been used widely in the treatment of hypertension and are recommended as first-line drugs in hypertension guidelines. However, a preliminary analysis has shown that atenolol is not very effective in hypertension. We aim to substantially enlarge the data on atenolol and analyse the effect of different beta blockers. METHODS: The Cochrane Library and PubMed were searched for beta blocker treatment in patients with primary hypertension. Data were then entered into the Cochrane Collaboration Review Manager package and were summarised in meta-analyses. 13 randomised controlled trials (n=105 951) were included in a meta-analysis comparing treatment with beta blockers with other antihypertensive drugs. Seven studies (n=27 433) were included in a comparison of beta blockers and placebo or no treatment. FINDINGS: The relative risk of stroke was 16% higher for beta blockers (95% CI 4-30%) than for other drugs. There was no difference for myocardial infarction. When the effect of beta blockers was compared with that of placebo or no treatment, the relative risk of stroke was reduced by 19% for all beta blockers (7-29%), about half that expected from previous hypertension trials. There was no difference for myocardial infarction or mortality. INTERPRETATION: In comparison with other antihypertensive drugs, the effect of beta blockers is less than optimum, with a raised risk of stroke. Hence, we believe that beta blockers should not remain first choice in the treatment of primary hypertension and should not be used as reference drugs in future randomised controlled trials of hypertension.