Current Treatment Goals Research Articles

Survival following CyberKnife Radiosurgery and Hypofractionated Radiotherapy for Newly Diagnosed Glioblastoma Multiforme

Current therapeutic goals for treatment of Glioblastoma Multiforme (GBM) involve gross total resection followed by multifractionated focal external beam radiation therapy (EBRT). Patients treated with optimal therapy have a median survival of approximately 12-15 months. In the present study, we sought to determine whether a hypofractionated dosing schedule using CyberKnife is at least as effective as multifractionated focal EBRT. A retrospective analysis was conducted on 20 histopathologically confirmed GBM patients treated with CyberKnife at Okayama Kyokuto Hospital in Japan after gross total resection (n=11), subtotal resection (n=8), or biopsy (n=1). Eight patients also received adjuvant ACNU and Vincrisitine chemotherapy according to local protocol; however, no patient received any other form of radiation besides post surgical/biopsy CyberKnife treatment. The treated tumor volumes ranged from 9.62 cm(3)-185.81 cm(3) (mean: 86.08 cm(3)). The marginal dose (D90) ranged from 19.99 Gy-41.47 Gy (mean: 34.58 Gy) with a maximum mean dose of 43.99 Gy (range: 23.33 Gy-56.89 Gy). The prescribed isodose line ranged from 50.38%-85.68% with a mean of 79.25%. Treatment was delivered in 1-8 fractions (mean: 5.65). Patients were followed from 2-36 months (mean: 16.45 months). Overall median survival was 16 months with 55% of patients alive at 12 months and 34% of patients alive at 24 months. Median survival of patients in Recursive Partitioning Analysis (RPA) classes III or IV was 32 months versus 12 months for those in RPA class V. Median survival for patients who received gross total resection was 36 months versus 8 months for those who underwent subtotal resection or biopsy. The results of this study using CyberKnife stereotactic radiosurgery (SRS) and hypofractionated radiotherapy compared favorably to historic data using focal EBRT in newly diagnosed post surgical GBM patients. A larger prospective analysis that compares CyberKnife SRS and hypofractionated radiotherapy to focal EBRT is warranted.

Type 2 diabetes mellitus: prevention of macrovascular complications

Type 2 diabetes mellitus is a disease that affects a rapidly increasing number of patients. Most patients with Type 2 diabetes will develop vascular complications. This may be microvascular disease, such as nephropathy, retinopathy or polyneuropathy, and also macrovascular disease, such as coronary heart disease, stroke or peripheral artery disease. Optimal control of elevated blood glucose levels will reduce the symptoms of hyperglycemia and help to prevent the development of complications. In addition, treatment of hypertension and lipid disturbances has been shown to reduce the incidence and severity of vascular complications significantly. The current treatment goals focus on adequate and aggressive treatment of these three risk factors. The central dogma for treatment of blood glucose, blood pressure and cholesterol levels is ‘the lower the better’. Ongoing trials evaluate the effect of further lowering these treatment goals and of specific types of medication on cardiovascular events.

Effects of fluvastatin extended-release (80 mg) alone and in combination with ezetimibe (10 mg) on low-density lipoprotein cholesterol and inflammatory parameters in patients with primary hypercholesterolemia: A 12-week, multicenter, randomized, open-label, parallel-group study

Background: Combining lipid-lowering agents with complementary mechanisms of action can provide greater cholesterol reductions than using either agent alone, improving achievement of target low-density lipoprotein cholesterol (LDL-C) levels. Objectives: The aim of this study was to assess the effects of fluvastatin extended-release (XL) 80 mg/d administered alone or combined with ezetimibe 10 mg/d on plasma lipid levels and inflammatory parameters in patients with primary hypercholesterolemia. The tol-erability of both regimens was also evaluated. Methods: In this multicenter, randomized, open-label, parallel-group study, patients with hypercholesterolemia were randomized in a 1:1 ratio to receive fluvastatin XL 80 mg/d alone or in combination with ezetimibe 10 mg/d for 12 weeks. The primary end point was the percentage change from baseline to week 12 in LDL-C level with fluvastatin XL + ezetimibe combination therapy compared with fluvastatin XL alone. Plasma concentrations of inflammatory biomarkers were measured at baseline and week 12. Proportions of patients who achieved National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) LDL-C goals were calculated. Tolerability was assessed by the monitoring and recording of all adverse events (AEs) and laboratory values. Results: A total of 82 patients were enrolled (mean [SD] age, 50.0 [12.0] years; 44% male; 100% white; mean [SD] weight, 73.5 [14.9] kg; combination group, 38 patients; monotherapy group, 44). Fluvastatin XL + ezetimibe and fluvastatin XL monotherapy were associated with significant decreases from baseline in mean LDL-C level (by 49.9% and 35.2%, respectively; between-group difference, P < 0.001). Fluvastatin XL + ezetimibe was associated with significantly greater reductions from baseline than fluvastatin XL monotherapy in total cholesterol (38.2% vs 27.5% P < 0.001), triglycerides (21% vs 3.8% P = 0.02) and apolipoprotein B (34.8% vs 22.5% P < 0.001). NCEP ATP III LDL-C goals were achieved by 87% of patients receiving fluvastatin XL + ezetimibe and 67% of patients receiving fluvastatin XL monotherapy (between-group difference, P = 0.042). The combination was associated with significantly lowered high-sensitivity C-reactive protein (hs-CRP) levels in patients with high baseline hs-CRP (>2 mg/L; P < 0.02), >1 cardiovascular risk factor (P < 0.05), or hypertension ( P = 0.015); both regimens were associated with significantly reduced plasma levels of interleukin-1B. No significant between-group differences in the incidences of AEs were found. Most AEs were mild or moderate in intensity. Headache was the most common AE, occurring in 5/44 (11.4%) patients in the fluvastatin XL group and 2/38 (5.3%) patients in the fluvastatin XL + ezetimibe group. One serious AE (convulsive crisis) occurred in a patient receiving fluvastatin XL + ezetimibe, but was not suspected to be related to study medication. Conclusion: Fluvastatin XL in combination with ezetimibe was found to be well-tolerated and effective, allowing the majority (87%) of these patients with primary hypercholesterolemia to achieve current treatment goals, and reduced hs-CRP levels in patients at higher cardiovascular risk.

Current and emerging trends in the treatment of metastatic colorectal cancer

Despite current screening recommendations, colorectal cancer remains the second leading cause of death from cancer in both men and women combined and will result in an estimated 52,180 deaths in the year 20(t7 [11. Metastases are the mNor cause of death in patients with colorectal c~mcer, with 20% to 70% of patients developing liver metastases and 10% to 20% of patients developing lung metastases [2]. After several years of limited progress, many new treatment options for patients with metastatic colorectal c~mcer have been approved over the last few years with the median survival time having doubled in the last decade. Continued development and refinement of treatment options continue to be evaluated as exemplified by the consideration of neoadjuvant chemotherapy in potential resectable liver metastases. Current advances in chemotherapy regimens have also allowed resection of previously unresectable metastases in some patients [3,4]. First-line chemotherapy options for patients with metastatic colorectal cancer include 1 of 3 standard regimens: irinotecan combined with infusional 5-fluorouracil (5-FU) and leucovorin (LV), oxaliplatin combined with infusional 5-FU and I ~V, ~md for patients that may be poor candidates for irinotecan or oxaliplatin-based therapy, 5-FU and IN alone [51. ~Ihe oral fluoropyrimidine, capecitabine, has also been introduced mad has been evaluated as a potential substitute fl~r intravenous 5-FU. Capecitabine is metabolized to 5-FU with prior studies in both local and advanced colorectal cancer showing similar efficacy but improved safety profiles when compared with bolus 5-FU [6,7]. ~[t~e addition of newer targeted molecular therapies, such as bevacizumab and cetuximab, may significantly enh~mce the efficacy of conventional chemotherapy at the cost of mild increases in toxicity [8,91. Panitumumab is the most recent molecular therapeutic to receive US Food and Drug Administration (Fl)A) approval as a single agent in previously treated metastatic colorectal cancer patients [10]. Current goals for treatment of metastatic colorectal cancer are to indMdualize selection and sequencing of treatment options to achieve maximum antitumor activity while limiting toxicity. ~Ihe development and refinement of chemotherapy approaches to achieve these goals are areas of significmlt research interest. Several clinical trials have recently been conducted to evaluate the eflicacy ~md safety of new chemotherapy regimens for patients with advanced colorectal cancer. ~II~is paper reviews recent studies that have evaluated the treatment of metastatic colorectal cancer, including options available for patients with unresectable disease, with an emphasis on treatment regimens.

The enigma of quality of life in patients with heart failure

Current treatment goals in heart failure (HF) aim to improve both survival and quality of life (QoL) of patients. In this brief communication, we reviewed randomized controlled trials that assessed the impact of pharmacological treatment on QoL, and we discussed some methodological limitations of QoL assessment in HF. Studies that assessed QoL with a disease-specific questionnaire were included. We found that at present there is a paradox in HF treatment. Life prolonging therapies, such as angiotensin-converting-enzyme-inhibitors, and angiotensin receptor blockers improve modestly or only delay the progressive worsening of QoL in HF. Treatment with beta blockers does not affect QoL in any way. However, this neutral effect of beta blockers may also be due to some methodological limitations, such as the small number of patients included in beta blocker trials or the short duration of follow-up. Disease-specific questionnaires may also have some limitations, e.g. are not sensitive enough to detect small changes in QoL. On the other hand, therapies that significantly improve QoL in HF (e.g. inotropic agents) do not seem beneficial in relation to survival. We conclude that QoL in HF remains an open field, in which new therapies but also clarification of methodology is required. In the mean time, the use of life prolonging therapies appears as a safe measure to modestly improve or maintain QoL.

Glycemic and Risk Factor Control in Type 1 Diabetes

This study was designed to investigate the clinical characteristics of a large type 1 diabetic population and to evaluate the degree of fulfillment of recently updated treatment goals. The Swedish National Diabetes Register was initiated in 1996 as a tool for quality assurance in diabetes care. A1C levels, treatment, and risk factors were analyzed in two cross-sectional samples of 9,424 patients in 1997 and 13,612 patients in 2004 and in a smaller longitudinal sample from 1997 to 2004. Mean A1C decreased from 8.2 +/- 1.3% in 1997 to 8.0 +/- 1.2% in 2004 (P < 0.001). The proportion of patients reaching A1C <7.0% increased from 17.4 to 21.2% in 2004. A slow but significant improvement in blood pressure levels was seen, but only 61.3% reached the blood pressure goal of <130/80 mmHg in 2004. Lipid control improved, and the use of lipid-lowering drugs increased. Among patients treated with lipid-lowering agents, 38% reached the goal of total cholesterol <4.5 mmol/l, and 48% reached the goal of LDL cholesterol <2.5 mmol/l. Successful long-term glycemic and blood pressure control were both independently predicted by low BMI and the absence of microalbuminuria in 1997. In this large cohort of type 1 diabetic patients, there was a slow improvement in glycemic and risk factor control from 1997 to 2004, although the gap between the clinical results and current Swedish and American treatment goals is still unsatisfactory. It is crucial that additional measures be taken to improve risk factor control in type 1 diabetic patients.

Awareness, treatment and control of hypertension in Denmark. The Inter99 study

Objective. We describe the current status of awareness, treatment and control of hypertension in Denmark and identify predictors for not being optimally treated. Methods. A population‐based sample, the Inter99 study, of 6784 individuals aged 30–60 years completed a questionnaire about lifestyle and risk factors for cardiovascular disease and had a physical examination including at least two blood pressure (BP) measurements. Hypertension was defined as BP⩾140/90 mmHg or receiving medical treatment for hypertension. Predictors for awareness, treatment and control were analysed in logistic regression models. Results. Nearly 40% were diagnosed with hypertension and more than 60% were not aware of the diagnosis. Half of those aware of the diagnosis did not receive medical treatment and among those who did, only 21% had their hypertension controlled. Only 10% of all persons aware of their hypertension had a BP below 140/90 mmHg. A higher degree of awareness and treatment of hypertension was positively associated with female sex, diabetes, cardiovascular disease, age, contact to general practitioner, healthy diet and increasing body mass index and age. We did not identify predictors for control of hypertension. Conclusion. There is a major gap between how hypertensive patients are managed in Denmark and the current treatment goals and recommendations of hypertension.

Obesity and cardiovascular risk factors in type 2 diabetes: results from the Swedish National Diabetes Register

To compare obese with normal and overweight type 2 diabetic patients regarding body mass index (BMI) and cardiovascular risk factors, and to analyse changes in weight versus risk factors. A cross-sectional study of 44 042 type 2 patients, and a 6-year prospective study of 4468 type 2 patients. Obese patients (BMI > or = 30 kg m(-2)), 37% of all patients, had high frequencies of hypertension (88%), hyperlipidaemia (81%) and microalbuminuria (29%). Only 11% had blood pressure <130/80 mmHg. Their ratio of triglycerides to HDL cholesterol was considerably elevated, whilst the mean total and LDL cholesterol were similar as in normal weight subjects. Obese patients had elevated odds ratios for hypertension, hyperlipidaemia and microalbuminuria: 2.1, 1.8 and 1.4 in the cross-sectional study, similarly confirmed in the prospective 6-year study. BMI was an independent predictor of these risk factors (P < 0.001), although only slightly associated with HbA1c and not with total or LDL cholesterol. A change in BMI during the prospective study was related to a change in HbA1c in patients treated with diet and oral hypoglycaemic agents (OHAs) but not with insulin. In all patients, an increase in BMI was related to the development of hypertension, and a change in BMI to change in blood pressure, also mostly confirmed when treated with diet, OHAs or insulin. The high frequencies of risk factors in obese type 2 patients implies an increased risk of cardiovascular disease and the need for therapeutic measures. The paradox that hypoglycaemic treatment accompanied by weight gain may increase cardiovascular risk factors seems to be verified here concerning hypertension but not concerning microalbuminuria.

Unlocking the opportunity of tight glycaemic control

The long‐term benefits of providing intensive insulin therapy to control blood glucose levels have been demonstrated in people with type 1 or type 2 diabetes mellitus. However, achieving good glycaemic control in clinical practice continues to be a major challenge with only a small proportion of people with diabetes achieving current treatment goals. Some of the reasons for this include ineffectual diet and weight control initiatives, limited efficacy of therapeutic agents or association with excessive adverse events, delayed initiation of insulin therapy and poor patient acceptance and compliance with a regimen of multiple daily insulin injections. New ways of delivering insulin without the need for subcutaneous injections may overcome many of these limitations and thus help in the early adoption of insulin treatment by patients, assist in achieving and maintaining long‐term optimal glycaemic control and improve patients' quality of life.

Efficacy Comparison between preprandial and postprandial insulin aspart administration with dose adjustment for unpredictable meal size

Background: Patients with type 1 diabetes mellitus (DM) may encounter situations in which meal size and content is unpredictable. In theory, postprandial injection of rapid-acting insulin analogues could prove more effective in achieving glucose control at such times because this treatment strategy could allow adjustment of insulin dose for the actual size of the meal consumed rather than being based on an estimate of what will be consumed. Objective: This study compared the postprandial glycemic control achieved with meal-related insulin aspart injected immediately before a meal with that injected immediately after a meal. Methods: This randomized, crossover study was conducted at Sansum Diabetes Research Institute, Santa Barbara, California. Adult patients with type 1 DM were enrolled. At study visit 1, patients were randomly assigned to inject insulin aspart 0 to 5 minutes before the start of the meal or immediately after the meal. The timing of injection relative to the meal was reversed at study visit 2. The meal-related dose was calculated based on the anticipated caloric and carbohydrate intake (preprandial injection) or actual calories and carbohydrates ingested (postprandial injection). Postprandial blood glucose concentrations were evaluated as markers of efficacy of postprandial aspart administration. Results: Twenty patients were enrolled in the study (mean [SE] duration of DM, 22.5 [3.2] years; mean [SE] body mass index, 26.2 [1.0] kg/M 2; age range, 22–82 years); 19 completed it. Total glucose AUC during the meal test was 22% less when insulin aspart was injected immediately before the study meal (mean [SE], 23,014 [1832] mg/dL.min) than when injected immediately after the meal (mean [SE], 29,535 [2243] mg/dL·min) ( P < 0.001), but baseline-adjusted AUC was similar. Maximum mean (SD) glucose concentrations in the postprandial period were <180 mg/dL, the current DM treatment goals specified by the American Diabetes Association (149.0 [9.9] mg/dL and 102.0 [9.2] mg/dL, following postprandial insulin aspart injection and preprandial injection, respectively; P < 0.001). There was variation in the number of calories consumed, but patients consumed a similar number of calories in the 2 treatment regimens. The frequency of postprandial hypoglycemia was comparable. Adjustment of postprandial insulin aspart dose for the actual meal size consumed maintained postprandial glucose concentrations within currently recommended treatment guidelines. Conclusions: Preprandial insulin aspart injection produced a better glucose profile and is preferred when conditions permit. However, both preprandial and postprandial insulin aspart administration achieved postprandial glucose concentrations within currently recommended treatment guidelines.

Tools and Techniques for Working With Young People With Diabetes

Diabetes is one of the most common chronic conditions in school-age children, affecting 151,000 children and adolescents in the United States, or approximately one in every 400–500 youth under 20 years of age. Every year, more than 13,000 youth are diagnosed with type 1 diabetes. In addition, more and more children and teens are being diagnosed with type 2 diabetes, a condition usually diagnosed in adults over the age of 40. It is now estimated that type 2 diabetes accounts for 8–45% of pediatric patients with newly diagnosed diabetes in large U.S. pediatric centers.1 Consensus statements and treatment guidelines for the medical management of type 1 and type 2 diabetes in children have been published by the American Diabetes Association (ADA).2,3 These publications outline the current recommendations and treatment goals for this special population with diabetes. Medical nutrition therapy (MNT) is an integral component of any treatment plan for a child with type 1 or type 2 diabetes, but often is the most difficult part of the treatment plan to successfully implement. The ADA’s position statement “Evidence-Based Nutrition Principles and Recommendations for the Treatment and Prevention of Diabetes and Related Complications”4 includes a section on nutritional recommendations for children and adolescents. The nutrient requirements for children and adolescents with type 1 or type 2 diabetes appear to be similar to other same-age children and adolescents without diabetes, with an important difference: the food plan must be balanced with optimal glycemic control, exercise, and possibly diabetes medications to promote normal linear growth. Growing children who do not receive adequate calories will not grow to their height potential. Table 1 summarizes the nutrition goals for children with either type 1 or type 2 diabetes.3,5,6 Many children and adolescents with type 1 or …

Pedophilia.

This article addresses the risk factors associated with the psychiatric disorder pedophilia, its treatment, and treatment outcomes. It addresses physician responsibilities associated with case identification of victims and possible roles in the medical management of pedophilia. The essential feature of pedophilia is that an individual is sexually attracted exclusively or in part to prepubescent children. While pedophilia may be limited to fantasies and impulses, pedophilic behaviors are the primary concern of both the mental health and criminal justice systems. Remote risk factors for development of pedophilia often include the individual having been sexually abused as a child. Proximate risk factors for its behavioral expression are prevalence of comorbid psychiatric disorders and substance abuse disorders. Current treatment goals focus on stopping the behavior and achieving long-term behavioral control in the community. Common treatment methods are cognitive-behavioral, group therapy, and, when appropriate, medications such as androgen-lowering agents that can act as sexual appetite suppressants. Meta-analyses have established that treatment is more effective than nontreatment in preventing recidivism of sexual offenders in general, a finding that has a high probability of application to individuals with pedophilia. Pedophilia is a chronic psychiatric disorder, but it is treatable in terms of developing strategies for preventing behavioral expression. Ultimately, reducing the prevalence of pedophilic behavior requires further collaboration between the criminal justice system and the health care communities.

Cholesterol absorption inhibitors for the treatment of hypercholesterolaemia.

The benefits of lipid lowering therapy on coronary heart disease have been clearly established in many clinical trials on primary and secondary prevention. Despite the availability of potent lipid lowering drugs, many patients do not reach the current treatment goals. This paper reviews new therapeutic approaches in lipid lowering drugs focusing on compounds which lower cholesterol absorption. The role of plant sterols and stanols, new acyl-CoA:cholesterol O-acyl transferase (ACAT) inhibitors, microsomal triglyceride transfer protein (MTP) inhibitors, and ezetimibe are summarised. Although the lipid lowering effect of plant sterols and plant stanols is only moderate, their use as functional foods is beneficial for patients with mild hypercholesterolaemia and is able to enhance the lipid lowering effect of HMG-CoA reductase inhibitors (statins). The role of ACAT inhibitors that might also inhibit cholesterol absorption remains unclear. Avasimibe, the first oral bioavailable ACAT inhibitor, has entered phase III trials. However, the presently available data in humans do not indicate a clear clinical benefit. The role of MTP inhibitors, which exhibit remarkable effects on all plasma lipids, also remains unclear, as safety concerns must first be addressed. Ezetimibe, the first available 2-azetidinone, succeeded in phase III trials showing remarkable effects in inhibition of cholesterol absorption as well as cholesterol lowering. The synergistic effect of co-administration of ezetimibe with statins seemingly offers a new approach in reaching the therapeutic goals.

EPIDEMIOLOGIC DATA IN CLINICAL PRACTICE

Epidemiologic studies illustrate that PAD is a very common finding when screening is performed in older adults. The outcomes in those with PAD in population studies reflect and extend the findings from clinical studies of PAD, confirming that older adults with PAD are disabled and have a high risk for CVD and total mortality. With the aging of the population, the prevalence of PAD is increasing. It is common in both men and women and increases in prevalence with age, such that at least 12% of community-dwelling adults aged 65 and older will have significant disease on noninvasive testing, most without classic intermittent claudication. Furthermore, PAD is strongly related to other manifestations of CVD and its risk factors. Those with PAD identified in epidemiologic studies have a two- to three-fold risk in CVD morbidity and mortality. Current treatment goals for PAD patients include improving function, primarily using exercise and medical therapy, and reduction of systemic risk and can be extended to those identified by screening. In addition, PAD must be thought of as a marker of advanced systemic atherosclerosis. Inasmuch as the risk of CVD and mortality in those with PAD is similar to those with a history of MI or stroke, those with PAD can be approached with the same measures for secondary CVD prevention as recommended for MI and stroke survivors. A simple bedside measure of the AAI can be used to improve the detection of PAD in clinical practice. Although there is no study that shows directly that screening and preventive treatment will reduce complications of PAD, a preventive approach in PAD patients is likely to improve overall survival, reduce MI, and will, perhaps, also reduce the risk of disabling leg pain and amputation. Future descriptions of the natural history of PAD in ongoing cohort studies may indicate that this is already beginning to occur.

Commentary on “Interim Analysis of a Phase III Trial Comparing Cisplatin, Gemcitabine, and Vinorelbine vs. Either Cisplatin and Gemcitabine or Cisplatin and Vinorelbine in Advanced Non–Small-Cell Lung Cancer (NSCLC)”

The report in this issue by Comella et al1 of a randomized trial of cisplatin/gemcitabine/vinorelbine (PGV) versus cisplatin/ gemcitabine (PG) or cisplatin/vinorelbine (PV), showing a response and survival superiority for the three-drug combination, points out a number of successes we have achieved in the clinical management of advanced NSCLC in the last few years. Nevertheless, it also highlights some of our relative limitations in the treatment of this disease that warrant comment as well, and should not be interpreted as establishing a new of care just yet. Taken at face value, this study is an example of a relatively large, multicenter, randomized trial with survival as the primary endpoint. We need these phase III trials in this era of rapidly expanding therapeutic options in advanced NSCLC. In this clinical setting with such a poor prognosis, too often clinical decisions are made and new standards set based on preliminary phase I and II trials that may demonstrate encouraging early results. This trial takes as its control arms two well-studied regimens, PG and PV, based on large randomized phase III trials showing superiority over single-agent cisplatin, arguably the most important single agent in NSCLC identified to date.2,3 The PV regimen has also been proven superior to single agent vinorelbine or a European regimen of cisplatin-vindesine.4 Similarly, the regimen is worthy of comparison based on encouraging results from this same group in a prior phase II trial with a response rate of 57% and a 50-week median survival.5 Therefore, based on a well-designed trial with proper control arms and a promising investigational regimen, the preliminary response and survival data favoring PGV over PV (although not over PG, at least so far) does warrant close attention. Nonetheless, we also need to consider a few caveats in interpreting these results and how they can be applied clinically. The patient group in this study is highly selected with a better-than-average prognosis as patients over age 70 were excluded, as were those with an ECOG performance status > 1, or patients with prior surgery or radiation. Forty-two percent had stage IIIB disease, only 25% had weight loss, and only 15% had more than one site of metastasis. Only 3% of the population had CNS metastases. Therefore, these data cannot necessarily be applied to a wider, more diverse, and less healthy patient population characteristic of a typical United States oncology practice. It is unclear if the response and survival benefit, or the relatively favorable toxicity profile, would stand up in more general use. Despite these limitations, a 16-week improvement in survival of PGV over PV (51 weeks vs. 35) is impressive in a randomized trial. And in an environment with cisplatin as the preferred platinum analog, this threedrug regimen of PGV certainly would have to be considered as one new option. But current patient desires, treatment goals, and clinical practice in the United States preclude this regimen from becoming such a standard. If the proof of the pudding is in the eating, few US oncologists or patients are hungry for cisplatin and its associated toxicities and inconveniences. Whether driven by patient preferences, clinic time and space limitations, tighter external restrictions, or financial incentives, there has been widespread rejection of cisplatin with substitution of carboplatin. In fact, in the SWOG trial evaluating the experimental carboplatin-paclitaxel versus the standard cisplatin-vinorelbine regimen, response, survival, and quality of life were virtually identical.6 Yet SWOG chose to adopt a new based on the feasibility and convenience of the carboplatin regimen. The need to include any platinum compound at all remains largely untested with our new generation of chemotherapy agents. One randomized trial suggested the combination of docetaxel and gemcitabine was comparable to the cisplatin-docetaxel in that trial.7 Finally, the role of adding a third drug is not yet clear. Previous

Risk factor clustering in patients with hypertension and non-insulin-dependent diabetes mellitus. The Skaraborg Hypertension Project.

To assess the coexistence of hypertension and diabetes, associations with cardiovascular risk factors and the achievement of current treatment goals. A community-based, cross-sectional, observational study. Hypertension and diabetes outpatient clinics in primary health care, Skara, Sweden. All patients (n = 1116; 488 men, 628 women) who performed an annual follow-up from May 1992 to September 1993. Hypertension, non-insulin-dependent diabetes mellitus (NIDDM), blood pressure, fasting B-glucose, lipids, HbAlc, body mass index (BMI), waist hip ratio (WHR). Hypertension alone was found in 286 men and 430 women, hypertension and NIDDM combined in 102 men and 102 women, and NIDDM alone in 100 men and 96 women. Taking new cases into account, the proportion of hypertension among NIDDM patients was 57%, and the proportion of NIDDM among hypertensives was 26%. Men and women with both hypertension and NIDDM had a higher systolic blood pressure and women also had a higher diastolic blood pressure (men 168/88 mmHg, women 165/86 mmHg) than those with hypertension alone (men 152/87 mmHg, women 156/82 mmHg) (P < or = 0.001). Cardiovascular risk factors accumulated in patients with both hypertension and NIDDM (triglycerides, BMI and WHR). A diastolic blood pressure < or = 90 mmHg was achieved by 71% men and 84% women with hypertension. HbAlc < 7.5% was attained by 71% men and 70% women with NIDDM. A considerable coexistence of hypertension and NIDDM was demonstrated. Cardiovascular risk factors clustered in patients with both diseases and their blood pressure was less controlled. These patients thus comprised a clinically defined group at high risk. By current guidelines, control of hypertension and NIDDM seemed appropriate.

Quantitative Ultrasonographic Evaluation of the Carotid Arteries in Hypertension

Current treatment goals for hypertension include the prevention of end-organ injuries. Hypertension is certainly among the major contributors to atherogenesis, and many antihypertensive drugs seem to have wall-protecting properties. It is critical to identify, test, and implement non-invasive methods for the screening of the population in order to detect early wall abnormalities and to monitor the long-term effects of different antihypertensive treatments. Among these methods, B-mode ultrasound examination of carotid arteries has shown great potential in evaluating treatments that may prevent hypertension-related wall injuries.

The concept of cure in pediatric oncology. Altered realities.

Defining cure for a child with cancer is not simple. Such terms as "long-term disease-free survival" or "no evident disease" are expressions of our current clinical inadequacies. An equally important problem, however, is that the disease and its treatment are frequently associated with sequelae that prevent complete restoration of baseline health status or that alter subsequent growth and developmental patterns. This article describes the nature of cures that have been achieved for childhood cancer and reassesses current treatment goals, taking into consideration altered realities of survival. Tasks remaining include the construction of medical treatment regimens that minimize acute and late effects, the design of intervention strategies to reduce the psychological and social impact of the disease on children and families, and the modification of society's attitudes so that cancer survivors are more accepted in the community.