Benefits Of Intensive Treatment Research Articles

Comparison of Standard vs. Relative Risk Models to Define Candidates for Deintensification in Locoregionally Advanced P16+ Oropharyngeal Cancer

Various methods to identify candidates for treatment deintensification with p16+ oropharyngeal squamous cell carcinoma (OPSCC) have been used, but the optimal approach is unknown. Multi-institutional cohort study of 385 patients with previously untreated p16+ OPSCC undergoing definitive radiotherapy (RT) with or without systemic therapy between 2009-2020. Chemotherapy intensity was categorized as high (bolus cisplatin and/or induction chemotherapy), medium (weekly cisplatin), or low (non-cisplatin or RT alone). Standard favorable vs. unfavorable risk was defined using NRG HN005 eligibility criteria. High vs. low relative risk (RR) group was defined using the HNCIG omega score (≥ 0.80 vs. < 0.80), which quantifies the proportion of a patient's overall event risk due to cancer. We used multivariable ordinal logistic regression to estimate effects of age (yrs), sex, performance status (PS), Charlson comorbidity index (CCI), T/N (AJCC 8th), current smoking, and pack-years (> 10 vs. ≤ 10) on treatment allocation. Effects on relative event hazards were estimated using generalized competing event regression. Median follow-up time was 44.2 months. Chemotherapy intensity was high in 206 (54%), medium in 108 (28%), and low in 71 (18%). 280 patients (73%) were unfavorable risk and 197 (51%) were high RR. 178 patients (46%) had discordant risk classification. On univariable analysis, significant predictors of higher intensity chemotherapy (normalized odds ratio (OR)) were CCI 0-1 (OR 1.49, 95% CI: 1.23-1.79), high omega score (OR 1.46; 1.20-1.77), decreased age (OR 1.43; 1.18-1.74), and PS 0 (OR 1.22; 1.01-1.48). Controlling for CCI, higher omega score was associated with significantly higher odds of intensive chemotherapy (OR 1.35; 1.10-1.65, but unfavorable risk (HN005 ineligibility) was not (OR 1.19; 0.98-1.44). Higher omega score was also associated with significantly higher RR for cancer recurrence (Rec) vs. competing mortality (CM) events (relative HR (rHR) 1.76; 1.12-2.75), but unfavorable risk was not (rHR 1.05; 0.63-1.75). Among patients receiving cisplatin, 50 favorable risk patients (58%) had high RR; all of their event risk was due to cancer recurrence (Table). The 110 unfavorable risk patients (48%) with low omega score had significantly lower RR for cancer events compared to the high omega score group (rHR 0.49; 0.29-0.84). Many patients with favorable risk p16+ OPSCC have high relative risk for cancer events, which correlates with a benefit of intensive treatment. The HNCIG omega score is a strong predictor of allocation to intensive chemotherapy and may help identify candidates for deintensification.

An audit of perioperative end-of-life care practices and documentation relating to patients who died in a surgical unit in three Victorian hospitals.

The number of older, frail patients undergoing surgery is increasing, prompting consideration of the benefits of intensive treatment. Despite collaborative decision-making processes such as advance care planning being supported by recent Australian legislation, their role in perioperative care is yet to be defined. Furthermore, there has been little evaluation of the quality of end-of-life care in the surgical population. We investigated documentation of the premorbid functional status, severity of illness, intensity of treatment, operative management and quality of end-of-life care in patients who died in a surgical unit, with a retrospective study of surgical mortality which was performed across three hospitals over a 23-month period in Victoria, Australia. Among 99 deceased patients in the study cohort, 68 had a surgical operation. Preoperative functional risk assessment by medical staff was infrequently documented in the medical notes (5%) compared with activities of daily living (69%) documented by nursing staff. Documented preoperative discussions regarding the risk of death were rarely and inconsistently done, but when done were extensive. Documented end-of-life care discussions were identified in 71%, but were frequently brief, inconsistent, and in 60% did not occur until 48 hours from death. In 35.4% of instances, documented discussions involved junior staff (registrars or residents), and 43.4% involved intensive care unit staff. Palliative or terminal care referrals also occurred late (1-2 days prior to death). Not-for-resuscitation orders were frequently changed when approaching the end of life. Overall, 57% of deceased patients had a documented opportunity for farewell with family. We conclude that discussions and documentation of end-of-life care practices could be improved and recommend that all surgical units undertake similar audits to ensure that end-of-life care discussions occur for high-risk and palliative care surgical patients and are documented appropriately.

Intenzivno lečenje pacijenata sa kraniocerebralnom traumom - kako nam akronimi mogu pomoći?

Traumatic brain injury (TBI) is considered to be a "silent global epidemic" and is the leading cause of death in young males in developed countries, major cause of disability, morbidity, and mortality worldwide. The classification of TBI severity was performed using the Glasgow coma scale (GCS) into mild (GCS = 15-13), moderate (GCS = 12-9), and severe (GCS = 8-3). Despite developments in modern intensive care, improvements in resuscitation and vital organ support, the management of critically ill patients with traumatic brain injury presents a challenge to all members of the critical care team. Since severe head injury is often associated with poor functional outcomes due to secondary brain insults, the benefits of intensive treatment and care may not become apparent until months or years later during rehabilitation after injury. Due to the complexity and specificity of TBI, implementation of an easy-to-remember mnemonic can significantly help anesthesiologists and clinicians in conducting intensive therapy. Mnemonic GOST CAP was implementing to help with treatment of patients with primary craniocerebral trauma and prevention of secondary brain injury. GOST CAP acronym emphasizes the significance of glycemic control in neurotrauma, maintaining haemoglobin levels, oxygen support, sodium concentration, temperature maintenance, pain and agitation control, arterial blood pressure control in maintaining cerebral perfusion pressure, and partial pressure of CO2 control. The aim of this paper is to display acronyms that address the most important steps in treating patients with TBI.

Baseline predictors of remission, pain and fatigue in rheumatoid arthritis: the TITRATE trial

BackgroundClinical trials show intensive treatment to induce remission is effective in patients with highly active rheumatoid arthritis (RA). The TITRATE trial showed that the benefits of intensive treatment also extend to moderately active RA. However, many patients failed to achieve remission or show improvements in pain and fatigue. We investigated whether baseline predictors could identify treatment non-responders.MethodsThe impact of obesity, depression, anxiety and illness perception on RA outcomes, including disease activity, remission, pain and fatigue were determined using a pre-planned secondary analysis of the TITRATE trial data.ResultsBody mass index was associated with disease activity levels and remission: obese patients had a higher overall disease activity and fewer obese patients achieved remission. Intensive management was not associated with increased remission in these patients. Obesity was also associated with increased overall pain and fatigue. Anxiety, depression and health perceptions had no discernible impact on disease activity but were associated with high levels of pain and fatigue. There was a strong association between anxiety and high pain scores; and between depression and high fatigue scores; and health perception was strongly related to both. None of the predictors had an important impact on pain and fatigue reduction in cross-sectional analysis.ConclusionsDisease activity is higher in obese patients and they have fewer remissions over 12 months. Anxiety, depression and health perceptions were associated with higher pain and fatigue scores. Intensive management strategies need to account for these baseline features as they impact significantly on clinical and psychological outcomes.Trial registrationISRCTN 70160382; date registered 16 January 2014

Restricted Mean Survival Time in Action to Control Cardiovascular Risk in Diabetes (ACCORD) Blood Pressure

Background: Restricted mean survival time (RMST) provides mean time lost or gained by an intervention. This may be a more intuitive way to understand treatment effect. Objective: To determine overall and subgroup treatment effects from blood pressure targets in older adults with diabetes. Methods: We analyzed the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial data. Our outcome was cardiovascular disease free survival. We measured 5-year RMST (days) between standard and intensive blood pressure control, and compared the difference by age (≥70 or <70 years old) and glycemic control (standard vs. intensive). Results: Over 5 years, those with intensive treatment lived, on average, 1716 days compared to 1714 days with standard treatment, with a RMST difference of 1.3 days (95% confidence interval, -22.1, 12.4). Among adults ≥70 years old, compared to standard treatment, intensive treatment resulted in an additional 13.6 (95% CI, -43.2, 70.3) days, where the difference was -0.5 (-20.8, 19.7) days for those aged <70 years old (p-for-interaction=0.673). Compared to standard treatment, intensive treatment resulted in 28.1 (0.4, 55.9) more days for those assigned to standard glycemic control, but it appeared to result in 25.2 fewer days (-52.3, 1.9) for those assigned to intensive glycemic control (p-for-interaction=0.007). Discussion: The benefit of intensive treatment over standard treatment varies by age and glycemic control. RMST difference may allow for more intuitive and personalized weighing of benefits and risks of intensive blood pressure control.

Heart failure events in a clinical trial of arterial hypertension. The acquittal of the SPRINT trial

Abstract Introduction The Systolic Blood Pressure Intervention Trial (SPRINT) was a randomized trial showing that intensive lowering of systolic blood pressure (BP), as compared to standard treatment (i.e. &amp;lt;120 vs &amp;lt;140 mm Hg) was associated with a reduced risk (HR 0.75 [95% CI 0.64–0.79], p&amp;lt;0.001) for the primary composite outcome (CE), defined as myocardial infarction, an acute coronary syndrome other than myocardial infarction, stroke, acute exacerbation of heart failure and cardiovascular death. primary outcome event in subjects at high cardiovascular risk. However, the primary endpoint events in the intensive treatment arm were only 76 fewer than in the standard treatment arm (243 vs 319 events), and he reduction in heart failure events was responsible for half of the effect (62 vs 100 events, i.e. 38 events fewer). Thus, several experts in hypertension argued that these results were mainly driven by a reduction of heart failure events, and questioned the main conclusion of the study. Aim To assess the effect of SPRINT intervention on a redefined CE: the primary SPRINT endpoint with HF events excluded. Material and methods We used limited SPRINT data, available from the NHLBI Biologic Specimen and Data Repository to assess the impact of BP intervention in SPRINT on a redefined CE excluding HF events. The Chi-square test, Cox proportional model and survival analysis were applied. Results Among 9361 SPRINT participants (mean age 67.9±9.5 years, 35.6% female, 20% with previous cardiovascular disease), there was 461 CE events. There were fewer CE events in the intensive treatment arm than in the standard treatment arm (204 [4.4%] vs 257 [5.5%], p=0.0117, respectively). Intensive systolic BP lowering was associated with lower risk for CE than standard treatment (HR 0.79 [95% CI 0.66–0.95], p=0.0115). Kaplan-Meier curves show that intensive treatment was associated with better outcome (Figure 1). Analyses in subgroups (age &amp;gt;75 vs &amp;lt;75 years, female vs male, black vs non-black, prior cardiovascular disease vs no cardiovascular disease, prior chronic kidney disease vs no chronic kidney disease) showed no difference in benefit of intensive treatment (p for interaction &amp;gt;0.05 in all subgroup). Conclusion The reduction in cardiovascular events by intensive BP lowering in SPRINT was not explained by a difference in heart failure events. This supports the concept that more intensive BP reduction may provide benefit in reducing cardiovascular event risk. Figure 1. Kaplan-Meier curves Funding Acknowledgement Type of funding source: None

Should Patients With Cardiovascular Risk Factors Receive Intensive Treatment of Hypertension to

Opposing Viewpoint, see p 1311 On the basis of the main results of the SPRINT (Systolic Blood Pressure Intervention Trial), we strongly believe that older hypertensive patients at high cardiovascular risk should receive intensive treatment to a target systolic blood pressure (SBP) of <120 mm Hg.1,2 SPRINT tested the hypothesis that intensive treatment of SBP to a target of <120 mm Hg would reduce clinical events more than standard treatment to a target of <140 mm Hg. SPRINT enrolled persons ≥50 years of age with an SBP from 130 to 180 mm Hg (treated or untreated) and at high cardiovascular risk. In particular, SPRINT overenrolled high-risk subgroups, including those ≥75 years of age (SPRINT-Senior), blacks, and those with chronic kidney disease or cardiovascular disease. The mean 10-year Framingham cardiovascular disease risk score for all participants was 20%. SBP fell rapidly in the intensive-treatment group (target SBP <120 mm Hg), reaching a level ≈15 mm Hg lower than in the standard group at 1 year (121.4 vs 136.7 mm Hg) with administration of an average of 1 more antihypertensive medication. The SPRINT intervention was stopped early (median 3.26 years of follow-up) because of a 25% reduction in the primary composite end point (myocardial infarction, non–myocardial infarction acute coronary syndrome, stroke, acute decompensated heart failure, and cardiovascular death) and a 27% reduction in all-cause mortality in the intensive-treatment group. The effects of the intensive intervention on the primary outcome and all-cause mortality were consistent across all prespecified subgroups (presence or absence of previous cardiovascular disease or chronic kidney disease, male or female sex, black or nonblack race, ≥75 or <75 years of age, and baseline SBP tertile). The benefits of intensive treatment were numerically greater (34% reduction in the primary outcome and 33% reduction in all-cause …

Celebrating 30 years of research accomplishments of the diabetes control and complications trial/epidemiology of diabetes interventions and complications study.

The landmark Diabetes Control and Complications Trial (DCCT) and its follow-up study, the Epidemiology of Diabetes Interventions and Complications (EDIC), have changed the way that type 1 diabetes is treated, and have led to improvements in the health and quality of life of people with the disease. In this Perspective, we look back at the 30 years since the start of DCCT to celebrate the scientific achievements of the DCCT/EDIC study group and patient volunteers—achievements that have had far-reaching benefits for type 1 diabetes and beyond. The insights that continue to emerge from DCCT/EDIC underscore the importance of supporting long-term research on chronic diseases such as type 1 diabetes. We also describe factors that contributed to the success of DCCT/EDIC, its public health implications, and how results continue to inform current-day research directions supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH). A complementary Perspective from the DCCT/EDIC investigators summarizes the methods, and results, and clinical implications of these seminal studies (1). In the late 1970s to the early 1980s, there was considerable debate about whether the potential benefits of intensive glycemic control in reducing the development of diabetes complications outweighed the risks of hypoglycemia (2–4). The studies done before the DCCT were small and short in duration and had enrolled subjects with preexisting retinopathy, thus failing to resolve the controversy about the risks and benefits of intensive treatment or to address primary prevention. Moreover, some studies in individuals with established eye disease showed an early worsening of retinopathy with intensive blood glucose control (5–7). Delineation of the natural history of the preproliferative phases of diabetic retinopathy in conventionally treated type 1 diabetes and validation of retinal photography as an outcome measure provided the …

Metabolic Memory and Individual Treatment Aims in Type 2 Diabetes – Outcome-Lessons Learned from Large Clinical Trials

Reducing the burden of long-term complications in type 2 diabetic patients remains a major task, and represents a huge challenge. Whilst tight glycemic control has been shown to reduce the risk of microvascular complications, controversy remains regarding the benefit of intensive treatment in relation to the prevention of cardiovascular events. Recent large trials (including ACCORD, ADVANCE, and VADT) were unable to show a significant impact of glycemic control on cardiovascular events. Also, it has been argued that these trials included patients with a long duration of the disease, and with previous unsatisfactory glycemic control. Chronic exposure to hyperglycemia may cause a kind of negative metabolic memory, and thereby reduce the potential impact of good glycemic control. This concept has been corroborated by the UKPDS which recruited only subjects with newly diagnosed diabetes and without prior cardiovascular events. In these patients, early achievement of glycemic control translated into a long-term reduction of the risk of micro- and macrovascular complications. This observation prompted the UKPDS investigators to propose a positive "glycemic legacy", supporting the need for early and appropriate treatment of hyperglycemia and associated metabolic disturbances. This should be feasible now through the selection of individual targets and personalized pharmacologic treatments. In doing so, the potential risks of intensive treatment might then be avoided.

Multidisciplinary Approach for the Treatment of Diabetes in the Elderly

Elderly patients living with diabetes are a highly heterogeneous population with unique care needs. Unlike younger patients, elderly patients may experience an atypical presentation and nontraditional complications of diabetes. Diabetes management and education require greater individualization in elderly adults because of differences in goals of care, risks and benefits of intensive treatment and abilities to practically carry out care regimens. A multidisciplinary approach to diabetes care requires an in-depth knowledge of diabetes, an awareness of geriatric issues and access to decision and educational support. This approach may be the most successful way of delivering individualized diabetes care. Future trials of diabetes care innovations in the elderly will be required to confirm the clinical benefits of this approach.

Acute myeloid leukaemia in childhood: the costs and benefits of intensive treatment

Response to treatment and resource implications were compared in two groups of children with acute myeloid leukaemia (AML) treated during consecutive periods. Event-free survival at 5 years improved from 12% (SE 3.4) during 1972-82 (group A) to 45% (SE 6.9) during 1983-87 (group B). The median time spent in hospital increased from 35 to 170 d. Allogeneic marrow transplantation was offered to all eligible children in group B. Eleven of the 53 children had a suitable donor and 10 proceeded to bone marrow transplantation (BMT). The relapse rate was lower after BMT than after chemotherapy, although not significantly so. We conclude that there has been a real improvement in prognosis for children with AML; that modern treatment requires intensive hospital resources and that these results should encourage further efforts to improve outlook and to explore treatments not involving radiation.

Improved outcome after acute coronary syndromes with an intensive versus standard lipid-lowering regimen: results from the Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22 (PROVE IT–TIMI 22) trial

The aim of the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial was to determine whether intensive low-density lipoprotein (LDL)-cholesterol lowering to a level of approximately 70 mg/dL (1.8 mmol/L) with atorvastatin 80 mg/day was more efficacious than standard LDL cholesterol lowering to 100 mg/dL (2.6 mmol/L) with pravastatin 40 mg/day in reducing the incidence of cardiovascular events in patients with acute coronary syndrome (ACS). In total, 4,162 men and women aged >18 years, who had been hospitalized for an ACS within the preceding 10 days, were randomized to receive either pravastatin 40 mg/day or atorvastatin 80 mg/day. The median LDL cholesterol levels achieved during follow-up were 95 mg/dL (2.5 mmol/L) in the pravastatin group and 62 mg/dL (1.6 mmol/L) in the atorvastatin group (P <0.001). Standard treatment (statin) with a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (pravastatin 40 mg/day) resulted in a 22% reduction in LDL cholesterol levels at 30 days compared with a 51% reduction with intensive therapy (atorvastatin 80 mg/day). At 2 years, a relative risk reduction of 16% (95% confidence interval, 5%-26%; P = 0.005) in the primary end point rate (death, myocardial infarction, documented unstable angina requiring hospitalization, coronary revascularization, or stroke) was seen in patients receiving intensive statin treatment compared with standard statin therapy. The benefit of intensive treatment was apparent as early as 30 days and was consistent over time. The PROVE IT-TIMI 22 data indicate that patients recently hospitalized for an ACS benefit from early and continued lowering of LDL cholesterol to levels substantially below current guideline recommendations.

Follow up Analysis for MRC Myeloma VII Trial.

The results of the MRC Myeloma VII trial and overview analysis of comparable trials have suggested that VAD-like induction chemotherapy followed by high dose therapy (HDT) with autologous transplantation may be regarded as a new standard treatment for multiple myeloma. However, there is a need for data from the extended follow up of patients in such trials to provide confirmatory evidence of the benefit of treatment incorporating HDT compared with conventional dose treatment, in particular to determine the long term difference in survival and the impact of attaining a complete response (CR) following intensive treatment. We present an updated analysis of Myeloma VII with median follow up of 5.5 years. Myeloma VII is the largest trial of its type in which patients with previously untreated multiple myeloma, age <65 years, were randomized to receive either standard conventional-dose combination chemotherapy (ABCM) or a sequence of treatment, C-VAMP followed by high dose therapy (HDT), typically melphalan 200g/m2 with autologous stem cell transplant. The planned maintenance in both arms was interferon α-2a. The trial, initiated in 1993 and closed to entry in 2000 and was conducted to MRC guidelines for good clinical practice in clinical trials. In the 401 evaluable patients the CR rate was 44% in the intensive therapy group, 8% in the standard therapy group (p<0.001). Intention to treat analysis showed a survival benefit of 14.1 months in the intensive arm (Figure 1); median 56.3 months (95% CI 46.0–74.6) vs. 42.2 months (95% CI 33.1–48.9), p=0.004 (log rank test). Progression free survival was also improved in the intensive group, median 31.2 months (95% CI 27.1–37.5) compared with 19.5 months (95% CI 16.2–21.6) in the standard group (p=<0.001). This analysis provides confirmatory evidence that treatment including high dose therapy is superior to conventional dose chemotherapy. Long term follow up of this study shows that the benefits of intensive treatment are maintained long term and that an important therapeutic aim is the achievement of CR. For the patients receiving the full protocol, the differences are accentuated, implying that maximising numbers of patients getting to transplant is an important therapeutic aim. These results would also support the continuing development of peri-HDT strategies to further improve outcomes. [Display omitted]

Review: Fifty years of diabetes management in primary care

The incidence of diabetes has increased exponentially over the last 50 years, meaning that the management of diabetes solely by specialist healthcare professionals is no longer feasible. Since the 1970s, primary and community healthcare professionals have increasingly treated patients with diabetes. Advances in diabetes equipment and new treatments have further enabled patients to be treated more conveniently and this has enhanced their quality of life. There has also been an evolution in health service strategies for diabetes — notably growing acknowledgement of the benefits of intensive treatment for patients with type 2, as well as type 1 diabetes, and the now well-recognised importance of effective shared care programmes between primary and secondary healthcare professionals. Thus, the organisation and delivery of care for patients with diabetes has improved dramatically since 1952.

Feasibility of Applying Recommendations from the Diabetes Control and Complications Trial to Saudi Adolescents with Insulin-Dependent Diabetes

Feasibility of Applying Recommendations from the Diabetes Control and Complications Trial to Saudi Adolescents with Insulin-Dependent Diabetes