Cost-effectiveness analysis of olanzapine-containing antiemetic therapy for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV) in highly emetogenic chemotherapy (HEC) patients.

PURPOSE: Olanzapine-containing regimens have been reported to be effective in preventing CINV following highly emetogenic chemotherapy (HEC), but it is unsure whether it is cost-effective. There has been no cost-effectiveness analysis conducted for olanzapine using costs from the USA. The aim of this study is to determine whether olanzapine-containing antiemetic regimens are cost-effective in patients receiving HEC. METHODS: A decision tree model was constructed to evaluate the cost and health outcomes associated with olanzapine-containing antiemetic regimens and otherwise-identical regimens. One-way sensitivity analyses were conducted to individually investigate the effect of (i) lower complete response (CR) rates of olanzapine, closer to non-olanzapine-containing regimens; (ii) higher FLIE scores for patients who achieved no/incomplete response, closer to FLIE scores of patients achieving a complete response; (iii) differing costs of olanzapine to reflect different costs per hospitals, globally, due to different insurance systems and drug costs; and (iv) varying costs for uncontrolled CINV, to account for varying durations of chemotherapy and accompanying uncontrolled CINV. RESULTS: Olanzapine regimens have an expected cost of $325.24, compared with $551.23 for non-olanzapine regimens. Meanwhile, olanzapine regimens have an expected utility/index of 0.89, relative to 0.87 for non-olanzapine regimens. Olanzapine-containing regimens dominate non-olanzapine-containing regimens even if CR of olanzapine-containing regimens fall to 0.63. Only when CR is between 0.60 and 0.62 is olanzapine both more effective and more costly. CONCLUSION: Olanzapine-containing regimens are both cheaper and more effective in the prophylaxis of CINV in HEC patients, compared with non-olanzapine-containing regimens. Future CINV trial resources should be allocated to understand newer antiemetics and compare them to olanzapine-containing regimens as the control arm. Further analysis should use nationally representative data to examine medication costs by payer type.

Olanzapine for the prophylaxis and rescue of chemotherapy-induced nausea and vomiting: a systematic review, meta-analysis, cumulative meta-analysis and fragility assessment of the literature.

INTRODUCTION: The aim of this study is to rigorously review the efficacy and safety of olanzapine in defined hematology oncology settings including (1) the setting of highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC) settings (2) at 5 mg and 10 mg doses, and (3) for response rates for use in the acute, delayed, and overall settings post-MEC and HEC. METHODS: Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched through April 23, 2020. The primary efficacy endpoints were the rate of complete response, in the acute (0-24 h post-chemotherapy), delayed (24-120 h post-chemotherapy), and overall (0-120 h post-chemotherapy) phases. The secondary efficacy endpoints were the rates of no nausea and no emesis, for each phase. Safety endpoints were the rate of no serious adverse events (i.e., no grade 3 or 4 toxicities), as assessed by Common Terminology Criteria for Adverse Events (CTCAE) criteria. The Mantel-Haenszel, random-effects analysis model was used to compute risk ratios and accompanying 95% confidence intervals for each endpoint. For endpoints that statistically favored one arm, absolute risk differences were computed to assess whether there is a 10% or greater difference, used as the threshold for clinical significance by MASCC/ESMO. Fragility indices were also calculated for each statistically significant endpoint, to quantitatively assess the robustness of the summary estimate. A cumulative meta-analysis was conducted for each efficacy meta-analysis with more than 5 studies, also using the Mantel-Haenszel random-effects analysis model. RESULTS: Three studies reported on olanzapine for the rescue of breakthrough chemotherapy-induced nausea and vomiting (CINV); 22 studies reported on olanzapine in the prophylactic setting. For studies reporting on HEC patients, olanzapine-containing regimens were statistically and clinically superior in seven of nine efficacy endpoints in the prophylaxis setting. When olanzapine is administered at a 10-mg dose, it is statistically and clinically superior to control patients in eight of nine endpoints among adults. Olanzapine may be effective in the MEC setting and when administered at 5-mg doses, but the paucity of data leads to notable uncertainty. CONCLUSION: Further RCTs are needed in the setting of MEC patients and administration of olanzapine at a lower 5-mg dose, which may be given to reduce the sedative effect of olanzapine at 10 mg.

United network for organ sharing outcomes after heart transplantation for al compared to ATTR cardiac amyloidosis.

Light-chain (AL) cardiac amyloidosis (CA) has a worse prognosis than transthyretin (ATTR) CA. In this single-center study, we compared post-heart transplant (OHT, orthotopic heart transplantation) survival for AL and ATTR amyloidosis, hypothesizing that these differences would persist post-OHT. Thirty-nine patients with CA (AL, n = 18; ATTR, n = 21) and 1023 non-amyloidosis subjects undergoing OHT were included. Cox proportional hazards modeling was used to evaluate the impact of amyloid subtype and era (early era: from 2001 to 2007; late era: from 2008 to 2018) on survival post-OHT. Survival for non-amyloid patients was greater than ATTR (P = .034) and AL (P < .001) patients in the early era. One, 3-, and 5-year survival rates were higher for ATTR patients than AL patients in the early era (100% vs 75%, 67% vs 50%, and 67% vs 33%, respectively, for ATTR and AL patients). Survival in the non-amyloid cohort was 87% at 1 year, 81% at 3 years, and 76% at 5 years post-OHT. In the late era, AL and ATTR patients had unadjusted 1-year, 3-year, and 5-year survival rates of 100%, which was comparable to non-amyloid patients (90% vs 84% vs 81%). Overall, these findings demonstrate that in the current era, differences in post-OHT survival for AL compared to ATTR are diminishing; OHT outcomes for selected patients with CA do not differ from non-amyloidosis patients.

Enteral and parenteral nutrition in cancer patients, a comparison of complication rates: an updated systematic review and (cumulative) meta-analysis.

INTRODUCTION: Weight loss in cancer patients is a worrisome constitutional change predicting disease progression and shortened survival time. A logical approach to counter some of the weight loss is to provide nutritional support, administered through enteral nutrition (EN) or parenteral nutrition (PN). The aim of this paper was to update the original systematic review and meta-analysis previously published by Chow et al., while also assessing publication quality and effect of randomized controlled trials (RCTs) on the meta-conclusion over time. METHODS: A literature search was carried out; screening was conducted for RCTs published in January 2015 up until December 2018. The primary endpoints were the percentage of patients achieving no infection and no nutrition support complications. Secondary endpoints included proportion of patients achieving no major complications and no mortality. Review Manager (RevMan 5.3) by Cochrane IMS and Comprehensive Meta-Analysis (version 3) by Biostat were used for meta-analyses of endpoints and assessment of publication quality. RESULTS: An additional seven studies were identified since our prior publication, leading to 43 papers included in our review. The results echo those previously published; EN and PN are equivalent in all endpoints except for infection. Subgroup analyses of studies only containing adults indicate identical risks across all endpoints. Cumulative meta-analysis suggests that meta-conclusions have remained the same since the beginning of publication time for all endpoints except for the endpoint of infection, which changed from not favoring to favoring EN after studies published in 1997. There was low risk of bias, as determined by assessment tool and visual inspection of funnel plots. CONCLUSIONS: The results support the current European Society of Clinical Nutrition and Metabolism guidelines recommending enteral over parenteral nutrition, when oral nutrition is inadequate, in adult patients. Further studies comparing EN and PN for these critical endpoints appear unnecessary, given the lack of change in meta-conclusion and low publication bias over the past decades.

Correction to: Enteral and parenteral nutrition in cancer patients, a comparison of complication rates: an updated systematic review and (cumulative) meta-analysis.

The appendices were incorrectly numbered in the original article. Please see below correcct appendices.

Should palonosetron be a preferred 5-HT3 receptor antagonist for chemotherapy-induced nausea and vomiting? An updated systematic review and meta-analysis.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) continues to be a common side effect of systemic anticancer therapy, decreasing quality of life and increasing resource utilization. The aim of this meta-analysis was to investigate the comparative efficacy and safety of palonosetron relative to other 5-HT3RAs. METHODS: A literature search was carried out in Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. Full-text references were then screened and included in this meta-analysis if they were an RCT and had adequate data regarding one of the five primary endpoints-complete response (CR), complete control (CC), no emesis, no nausea, or no rescue medications. RESULTS: A total of 24 RCTs were included in this review. Palonosetron was statistically superior to other 5-HT3RAs for 10 of the 19 assessed endpoints. Only one endpoint-emesis in the overall phase-had noticeable more favorable data for palonosetron to the point that it approached the 10% risk difference (RD) threshold as specified by the MASCC/ESMO antiemetic panel; another two endpoints (CR in the overall phase and nausea in the delayed phase) approached the 10% threshold. CONCLUSIONS: Palonosetron seems to be more efficacious and safe than other 5-HT3RAs-statistically superior in 10 of 19 endpoints. It is, however, only clinically significant in one endpoint and approached clinically significant difference in another two endpoints. Within the limits of this meta-analysis, our results indicate that palonosetron may not be as superior in efficacy and safety as reported in a previous meta-analysis, and supports the recent MASCC/ESMO, ASCO, and NCCN guidelines in not generally indicating palonosetron as the 5-HT3RA of choice.

A prospective study of docetaxel-associated pain syndrome.

PURPOSE: To investigate the natural history of taxane-associated acute pain syndrome (TAPS) in a docetaxel patient cohort and to examine the long-term manifestation of TAPS. PATIENTS AND METHODS: For three consecutive treatment cycles, taxane-naive breast cancer patients completed diaries on days 1-7, 14, and 21 and telephone questionnaires 1, 3, 6, 9, and 12 months following treatment. Questionnaires to assess pain and interference were adapted from the Brief Pain Inventory. To examine the experience of arthralgia and myalgia as one syndrome, information on patient experiences with arthralgia or myalgia was elicited separately in order to determine how closely experiences of each toxicity correlated with each other. A ≥2 point increase from baseline was defined as an arthralgia or myalgia "pain flare," and only those with "flare" were included in calculations of incidence. RESULTS: A total of 278 patients were accrued. Thirty-eight patients were omitted due to missing information, and 24 patients were omitted due to metastatic disease, for a total of 216 patients overall and 188 in the docetaxel cohort. A total of 74.5% of docetaxel patients experienced joint pain flare, and 78.2% experienced muscle pain flare at some point in the overall course of three treatment cycles. Joint and muscle pain peaked on days 4-5 for each cycle, and median pain severity for both joint and muscle pain was 4/10 during the 21-day period. Median onset of joint pain flare was 3 days for cycle 1 and 4 days for cycles 2 and 3, with an average median duration of 4 days. Median onset of muscle pain flare was 4 days for all three cycles, with a median duration of 4 days for cycles 1 and 2, and 5 days for cycle 3. Both joint and muscle pain persisted 1 year after treatment in approximately half of responding patients. CONCLUSION: This study documents the significant incidence of TAPS in patients treated with docetaxel chemotherapy and shows a long-term persistence of the syndrome.

Taxane-induced arthralgia and myalgia: A literature review.

Purpose Arthralgia and myalgia following taxane chemotherapy has been documented in the literature. However, these two toxicities associated with taxane treatment have not been closely examined in the literature, and data remain inconsistent in terms of the reported incidences of these toxicities. The purpose of this literature review was to provide a more comprehensive understanding of the incidence of taxane-induced arthralgia and myalgia, as well as to document the risk factors and preventative and therapeutic treatments that have been investigated. Methods A literature search was conducted in Ovid Medline, OldMedline, Embase, Embase Classic, and Cochrane Central Register of Controlled Trials using relevant subject headings and keywords such as: "arthralgia," "myalgia," "muscle pain," "joint pain," "taxane," "chemotherapy," "docetaxel," "paclitaxel." Results The reported incidences of arthralgia and myalgia were variable. Taxane chemotherapy was found to be associated with greater incidences of arthralgia and myalgia than non-taxane forms of chemotherapy. Moreover, docetaxel and nab-paclitaxel seem to be associated with lower incidences of arthralgia and myalgia than paclitaxel. Finally, the literature on prevention and therapeutic treatment of taxane-induced arthralgia and myalgia is scarce. Conclusion More studies should be done in order to more conclusively identify optimal therapeutic and preventative treatments as well as different risk factors. We recommend that a prospective study be done in order to better understand the true incidence of arthralgia and myalgia in patients being treated with the paclitaxel, docetaxel, and nab-paclitaxel.

Symptoms and quality of life in patients with brain metastases receiving whole-brain radiation therapy.

PURPOSE: Patients with multiple brain metastases may be treated with whole-brain radiation therapy (WBRT). For these patients, symptom palliation and improvement of quality of life (QOL) and performance status is of the upmost importance. The objective of the present study was to determine the symptom experience and overall QOL in patients with brain metastases before and after WBRT. METHODS: A total of 14 symptom scores and overall QOL were collected prospectively in 217 patients for up to 3 months. Wilcoxon signed rank test was applied to determine significant symptoms and QOL changes. Spearman's correlations were applied to determine the relationship between symptom scores and QOL. RESULTS: Appetite loss, weakness, and nausea significantly increased from baseline, while balance, headache, and anxiety significantly decreased from baseline. At baseline, all symptoms other than coordination were significantly correlated with QOL. At 1-month follow-up (FU), changes in concentration, weakness, coordination, and balance were significantly associated with QOL changes. At 2-month FU, changes in pain, insomnia, concentration, balance, and depression were significantly associated with QOL changes. At 3-month FU, only change in nausea was significantly associated with QOL changes. CONCLUSIONS: Following WBRT, certain symptoms may influence overall QOL to a greater extent than others, which may fluctuate with time.

Efficacy and safety of olanzapine for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV) as reported in phase I and II studies: a systematic review.

INTRODUCTION: Olanzapine is an atypical antipsychotic drug that inhibits serotonergic, dopaminergic, alpha-1 adrenergic, histaminic, and muscarinic receptors. Several phase I and II trials have been published documenting the use of olanzapine in controlling chemotherapy-induced nausea and vomiting (CINV). This review aims to summarize all phase I and II trials that reported on olanzapine for the prophylaxis of CINV. METHODS: A literature search was conducted in Ovid MEDLINE from 1946 to July week 1 2015, Embase Classic and Embase from 1947 to 2015 week 28, and the Cochrane Central Register of Controlled Trials up until June 2015. Phase I and II trials reporting on olanzapine for the prophylaxis for CINV were included if they reported on at least one of four primary endpoints: complete response (CR), complete control (CC), no nausea, and no emesis. Other endpoints of interest included the safety of olanzapine as measured by the M.D. Anderson Symptom Inventory. RESULTS: Across the seven included studies, there were a total of 201 patients. The CR across four studies was 97.2, 83.1, and 82.8 % for the acute, delayed, and overall phases, respectively. The CC for acute, delayed, and overall phases was 92.5, 87.5, and 82.5 %, respectively. The overall no nausea rate was 92.7, 71.8, and 70.6 % for the acute, delayed, and overall phases, respectively. The overall no emesis rates for the acute, delayed, and overall phases were 100, 94.5, and 90.4 %, respectively. Fatigue, drowsiness, and disturbed sleep were common side effects. CONCLUSION: Olanzapine is efficacious and safe when used as a prophylaxis for CINV.

Efficacy of olanzapine for the prophylaxis and rescue of chemotherapy-induced nausea and vomiting (CINV): a systematic review and meta-analysis.

PURPOSE: Olanzapine is a potent antipsychotic medication that inhibits a wide variety of receptors. It has been used in trials for the prophylaxis and rescue of chemotherapy-induced nausea and vomiting (CINV). This study systematically investigates the efficacy of olanzapine in relation to other antiemetics in the prophylaxis and rescue of CINV. METHODS: A literature search of Ovid MEDLINE, EMBASE, and CENTRAL was conducted to identify randomized controlled trials (RCTs) comparing olanzapine to other standard antiemetics for either prevention or rescue. The primary endpoints were the percentage of patients achieving no emesis or no nausea, in the acute, delayed, and overall phases. RESULTS: Ten RCTs in the preventative setting and three RCTs in the breakthrough setting were identified. Subgroup analysis demonstrated a similar degree of benefit from a 5- and 10-mg dose of olanzapine for the no emesis endpoint in the overall phase. In the prophylaxis setting, olanzapine was statistically superior in five of six endpoints and clinically superior in four of six endpoints. In the breakthrough setting, olanzapine was statistically and clinically superior in the only endpoint analyzed: no emesis. CONCLUSION: Olanzapine is more efficacious than other standard antiemetics for the rescue of CINV and its inclusion improves control in the prevention setting. Given the possible reduction in side effects, the use of a 5-mg dose of olanzapine should be considered. Future RCTs should compare the 5-mg versus the 10-mg dosages further and report on the efficacy and percentage of patients developing side effects. Further analyses should be done without the influence of corticosteroids.

Which pain intensity scale from the Brief Pain Inventory correlates most highly with functional interference scores in patients experiencing taxane-induced arthralgia and myalgia?

PURPOSE: The purpose of this study was to assess which pain intensity dimension scale (worst, least, average, or current pain) from the Brief Pain Inventory (BPI) correlates most highly with functional interference scores in patients experiencing taxane-induced arthralgia and myalgia. METHODS: Breast cancer patients scheduled to receive docetaxel, paclitaxel, or albumin-bound paclitaxel (nab-paclitaxel) were enrolled in the study. Patients completed an initial baseline questionnaire and subsequently filled out a diary based on the BPI on days 1-7, 14, and 21 for three consecutive treatment cycles. Pain scores for worst, least, average, and current pain intensity dimensions as well as pain interference scores were recorded in the diaries and questionnaires using the BPI. Worst, least, average, and current pain scores were correlated with functional pain interference scores using Spearman's rank correlation coefficients. A general linear mixed model of each functional interference measure was performed over time for cycles 1-3 with each pain intensity dimension scale. RESULTS: Among worst, average, least, and current joint pain dimensions, average joint pain scores correlated best with all BPI interference responses while average muscle pain scores correlated best with all BPI interference responses except for sleeping probability and normal work. CONCLUSION: We recommend the BPI scale measuring average pain for future studies evaluating pain scores in patients experiencing taxane-induced arthralgia and myalgia.

Inadequacy of Palliative Training in the Medical School Curriculum.

This report examines the literature on palliative training in the current medical school curriculum. A literature search was conducted to identify relevant articles. Physicians and medical students both report feeling that their training in end-of-life care and in palliative issues is lacking. The literature expresses concerns about the varied and non-uniform approach to palliative care training across medical schools. The authors recommend the development of more palliative training assessment tools in order to aid in the standardization of curriculum involving end-of-life care. In addition, increased exposure to dying patients will aid students in building comfort with palliative care issues. Such a goal may be accomplished through required clerkships or other similar programs.

Correlates of Plasma NT-proBNP/Cyclic GMP Ratio in Heart Failure With Preserved Ejection Fraction: An Analysis of the RELAX Trial.

BACKGROUND: Phosphodiesterases degrade cyclic GMP (cGMP), the second messenger that mediates the cardioprotective effects of natriuretic peptides. High natriuretic peptide/cGMP ratio may reflect, in part, phosphodiesterase activity. Correlates of natriuretic peptide/cGMP in patients with heart failure with preserved ejection fraction are not well understood. Among patients with heart failure with preserved ejection fraction in the RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure With Preserved Ejection Fraction) trial, we examined (1) cross-sectional correlates of circulating NT-proBNP (N-terminal pro-B-type natriuretic peptide)/cGMP ratio, (2) whether selective phosphodiesterase-5 inhibition by sildenafil changed the ratio, and (3) whether the effect of sildenafil on 24-week outcomes varied by baseline ratio. METHODS AND RESULTS: In 212 subjects, NT-proBNP/cGMP ratio was calculated at randomization and 24 weeks. Correlates of the ratio and its change were examined in multivariable proportional odds models. Whether baseline ratio modified the sildenafil effect on outcomes was examined by interaction terms. Higher NT-proBNP/cGMP ratio was associated with greater left ventricular mass and troponin, the presence of atrial fibrillation, and lower estimated glomerular filtration rate and peak oxygen consumption. Compared with placebo, sildenafil did not alter the ratio from baseline to 24 weeks (P=0.17). The effect of sildenafil on 24-week change in peak oxygen consumption, left ventricular mass, or clinical composite outcome was not modified by baseline NT-proBNP/cGMP ratio (P-interaction >0.30 for all). CONCLUSIONS: Among patients with heart failure with preserved ejection fraction, higher NT-proBNP/cGMP ratio associated with an adverse cardiorenal phenotype, which was not improved by selective phosphodiesterase-5 inhibition. Other phosphodiesterases may be greater contributors than phosphodiesterase-5 to the adverse phenotype associated with a high natriuretic peptide/cGMP ratio in HFpEF. REGISTRATION INFORMATION: clinicaltrials.gov. Identifier: NCT00763867.

The impact of clinical and sociodemographic features on quality of life in patients with early stage cancers using the Functional Assessment of Cancer Therapy-General assessment tool.

PURPOSE: This study aims to compare the Functional Assessment of Cancer Therapy-General (FACT-G) quality of life (QOL) scores of patient groups with varying clinical and sociodemographic features in the early stage cancer population. METHODS: A literature search was conducted on both the Embase and OvidSP platforms. Weighted analysis of variance (ANOVA) was performed for binary predictors and weighted linear regression analysis was conducted for continuous predictors. RESULTS: Six binary features predicted at least one domain of QOL: primary cancer site (homogeneous versus heterogeneous), total per capita healthcare expenditures, mean age, previous chemotherapy, radiotherapy, and previous hormonal therapy. Two continuous factors had predictive value with respect to QOL: completion of postsecondary education and marital status. CONCLUSION: Although there are limitations of the current study, similar correlations to our own have been previously described between QOL and healthcare expenditures, mean age and education. Currently, the literature conflicts in its analysis of previous radiotherapy and chemotherapy as predictors of QOL. No published evidence exists describing the presently found relationships in primary cancer site, marital status and hormonal therapy. Future work may focus on determining cause and effect relationships between these predictors and QOL.

Cancer-related fatigue-pharmacological interventions: systematic review and network meta-analysis.

INTRODUCTION: Cancer-related fatigue (CRF) is a very common symptom in patients with cancer, and one of the five areas of highest priority in cancer research. There is currently no consensus on pharmacologic interventions for treating CRF. The aim of this systematic review is to provide more clarity on which pharmacologic interventions may be most promising, for future clinical trials. The network meta-analysis provides the ability to compare multiple agents when no direct head-to-head trials of all agents have been performed. METHODS: Medline (PubMed), EMBASE and Cochrane Central Register of Controlled Trials were searched up until 5 March 2021. Studies were included if they reported on a pharmacologic intervention for CRF. Standardised mean differences and corresponding 95% CIs were computed using a random-effects maximum-likelihood model. RESULTS: This review reports on 18 studies and 2604 patients, the most comprehensive review of pharmacologic interventions for CRF at the time of this publication. Methylphenidate, modafinil and paroxetine were superior to placebo. Methylphenidate and modafinil were equivalent to one another. Paroxetine was superior to modafinil. CONCLUSION: Paroxetine should be further studied in future trials. As well, more safety data are needed on pharmacologic interventions.

Trends in Blood Pressure Treatment Intensification in Older Adults With Hypertension in the United States, 2008 to 2018.

BACKGROUND: Hypertension control has worsened nationally, and treatment intensification is important for control. National trends for appropriate blood pressure intensification for older adults are unknown. We determine the proportion of ambulatory visits where older adults with hypertension were appropriately intensified on antihypertensives from 2008 to 2018. METHODS: Data from National Ambulatory Medical Care Survey were used. National Ambulatory Medical Care Survey is a nationally representative sample of ambulatory visits. Adults 60 years or older were included. Appropriate antihypertensive intensification was defined as addition of an antihypertensive for a blood pressure reading above target. We examined appropriate intensification by blood pressure targets set by the American College of Cardiology-American Heart Association, the European Society of Cardiology, and the American College of Physicians-American Academy of Family Physicians guidelines for older adults. Further, we defined an additional all-inclusive criterion meeting all 3 guidelines. RESULTS: From 2008 to 2018, appropriate intensification by American College of Cardiology/American Heart Association occurred at 11.1% (95% CI, 9.8%-12.5%) of visits, decreasing from 13.6% (95% CI, 15.6%-28.7%) of visits in 2008 to 2009 to 10.4% (95% CI, 10.9%-26.4%) in 2015 to 2018. Appropriate intensification by European Society of Cardiology occurred at 14.2% (12.1%-16.6%) of visits over 2008 to 2018, decreasing from 16.9% (95% CI, 13.5%-21.0%) in 2008 to 2009 to 12.5% (95% CI, 7.4%-20.3%) from 2015 to 2018. Appropriate intensification by American Academy of Family Physicians/American College of Physicians occurred at 18.9% (16.2%-22.0%) of visits over 2008 to 2018, decreasing from 24.7% (95% CI, 20.2%-29.0%) in 2008 to 2009 to 14.9% (95% CI, 9.0%-23.7%) from 2015 to 2018. By all-inclusive criteria, intensification trended toward worsening with time: odds ratio: 0.93 ([95% CI, 0.87-1.00]; P=0.07). CONCLUSIONS: Appropriate treatment intensification for older adults with hypertension in the United States was suboptimal over the past decade.

Meta-Analysis of Point-of-Care Lung Ultrasonography Versus Chest Radiography in Adults With Symptoms of Acute Decompensated Heart Failure.

Acute decompensated heart failure (ADHF) is a primary cause of older adults presenting to the emergency department with acute dyspnea. Point-of-care lung ultrasound (LUS) has shown comparable or superior diagnostic accuracy in comparison with a chest x-ray (CXR) in patients presenting with symptoms of ADHF. The systematic review and meta-analysis aimed to elucidate the sensitivity and specificity of LUS in comparison with CXR for diagnosing ADHF and summarize the rapidly growing body of evidence in this domain. A total of 5 databases were searched through February 18, 2021, to identify observational studies that reported on the use of LUS compared with CXR in diagnosing ADHF in patients presenting with shortness of breath. Meta-analysis was conducted on the sensitivities and specificities of each diagnostic method. A total of 8 studies reporting on 2,787 patients were included in this meta-analysis. For patients presenting with signs and symptoms of ADHF, LUS was found to be more sensitive than CXR (91.8% vs 76.5%) and more specific than CXR (92.3% vs 87.0%) for the detection of cardiogenic pulmonary edema. In conclusion, LUS is more sensitive and specific than CXR in detecting pulmonary edema. This highlights the importance of sonographic B-lines, along with the accurate interpretation of clinical data, in the diagnosis of ADHF. In addition to its convenience, reduced costs, and reduced radiation exposure, LUS should be considered an effective alternative to CXR for evaluating patients with dyspnea in the setting of ADHF.

Secondary and cumulative meta-analysis of olanzapine for antiemetic prophylaxis for chemotherapy-induced nausea and vomiting: do we still need to study its effectiveness?

BACKGROUND: Olanzapine has been found to have antiemetic properties due to its ability to inhibit multiple serotonergic, dopaminergic, alpha-1 adrenergic and histamine receptors. In 2016, a meta-analysis of 10 randomized controlled trials (RCTs) on olanzapine in the prophylactic setting found olanzapine to be more efficacious than other standard antiemetics in the prophylactic setting. However, since the review, many clinical trials using olanzapine for chemotherapy-induced nausea and vomiting (CINV) have been published-in many cases, contending that further trials would further help elucidate the efficacy of olanzapine for CINV given the continued paucity of literature. The primary aim of this study is to conduct a secondary, cumulative meta-analysis to assess the impact of the most recent trials on the published effect estimate of olanzapine and ultimately determine whether trials published since 2016 have significantly changed the summary estimate. METHODS: As reported previously, a literature search was conducted up until 2015, of Ovid Medline, Embase and the Cochrane Central Register of Controlled Trials; 10 RCTs with a total of over 1,000 patients were included, that compared olanzapine to other antiemetics in the prophylactic setting, which reported on at least one of two endpoints-no emesis and no nausea. The Mantel-Haenszel, random-effects analysis model was used to compute cumulative risk ratios (RR) and their accompanying 95% confidence intervals (CIs). RESULTS: For the endpoint of emetic control, the cumulative meta-analysis shows that the summary effect did not change noticeably with the inclusion of the most recent trials. In the acute phase, the RR shifted from 1.07 before 2011 to 1.10 after 2015, even after the inclusion of 7 trials. Similar small changes were noted in the delayed and overall phases. For the endpoint of nausea control, the cumulative meta-analysis does show a significant visual change in summary effect, except for nausea control in the acute phase. In the delayed phase, the RR shifts from 1.58 before 2011 to 1.50 after 2015. In the overall phase, the RR shifts from 1.642 before 2011 to 1.53 after 2015. CONCLUSIONS: Olanzapine's efficacy for the prophylaxis of CINV has been sufficiently documented, with respect to emetic control. There is, however, more limited data supporting its efficacy with respect to nausea control.

Weight changes of younger and older early breast cancer patients-a meta regression.

BACKGROUND: Weight gain during chemotherapy for breast cancer is quite common and has a major impact on the quality of life. Post-treatment weight gain can also impact on primary endpoints such as tumor recurrence and overall survival. Parameters thought to impact weight gain include menopausal status, age and chemotherapy regimen. Using meta-regression, we studied the effect of age on weight change by menopausal status and chemotherapy regimen. METHODS: Twenty-four studies were identified, and extracted for weight change, mean/median age, menopausal status and chemotherapy regimen. A meta-regression was performed using a random-effects model for high heterogeneity and fixed-effects inverse-variance model for low heterogeneity. Subgroup analyses by menopausal status and chemotherapy regimen were conducted. P values <0.05 were considered statistically significant. RESULTS: There exists no relationship between weight change and age (ß=0.00; P=0.987). Stratifying by menopausal status (ß=0.05 and P=0.150 for premenopausal patients; ß=0.09 and P=0.588 for postmenopausal patients) and chemotherapy regimens (ß=-0.07 and P=0.562 for patients receiving CMF alone; ß=0.08 and P=0.707 for patients receiving CMF in addition to others; ß=0.02 and P=0.807 for patients not receiving CMF), there likewise was no relationship between weight change and age. CONCLUSIONS: Management of weight gain due to chemotherapy has been focused on relatively young women who are generally at higher risk of mortality and tumor recurrence. However, our results suggest that age should not be used for differential care.