A series of pyrrolyl and dipyrrinyl isoporphyrins carrying different phenyl and thienyl groups is reported. The compounds are obtained by a one‐pot approach in the presence of a template reagent. ...Thienyl derivatives gave better yields, and were the only subclass to form with steric hindrance. The structural analyses carried out on compounds 1 and 14 revealed distinct conformational differences which are likely to result from an intramolecular NH…Cl hydrogen bridge of the pyrrolyl subclass. In addition, this hydrogen bridge strongly favors one of the two possible atropisomers. Hindered rotation of the meso‐aryl groups is observed only in the cases of methylbenzothienyl derivatives 10 and 15 and leads to the observation of several diastereomers. NIR absorptions up to 923 nm are found throughout. Electrochemical investigations into the 1e− and 2e− reduced species unravel axial ligand exchange dynamics for the zinc isoporphyrin radical, and the probable formation of a zinc phlorinate.
A new sign has risen in the porphyrin sky! Stable isoporphyrins can be produced as non‐aromatic NIR dyes in yields up to 36 % by a one‐pot process. Non‐planar distortion modes are the key to control the optical spectra and the occurrence of isomers by means of synthesis. For the first time, the redox chemistry of isoporphyrins was studied by electrochemical methods, which is significant with regard to potential applications in photovoltaics.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Tramadol is commonly prescribed for pain control because it presents a lower risk for addiction and respiratory depression compared to other opioids. However, tramadol's serotonin and norepinephrine ...reuptake inhibitory effects result in a unique adverse effect profile. Two such adverse events are serotonin syndrome and seizures. The prevalence of tramadol-induced serotonin syndrome and seizures is modest in the general population, but if left untreated, the morbidity and mortality can be high; therefore, prompt recognition and management is essential. Various risk factors such as medical comorbidities, use or abuse of supratherapeutic doses of tramadol, and concomitant administration of proconvulsant serotonergic cytochrome P-450 inhibitors will help clinicians identify individuals at an elevated risk for serotonin toxicity and seizures. Serotonin syndrome and seizures can be effectively treated by administering benzodiazepines, providing supportive care, and discontinuing tramadol and other contributing agents. Cyproheptadine should be administered in moderate to severe cases of serotonin syndrome. Our objective is to summarize the literature on the pharmacology, epidemiology, risk factors, clinical presentations, and evidence-based management of tramadol-related seizures and serotonin syndrome.
Purpose To provide guidance regarding the practical assessment and management of vulnerabilities in older patients undergoing chemotherapy. Methods An Expert Panel was convened to develop clinical ...practice guideline recommendations based on a systematic review of the medical literature. Results A total of 68 studies met eligibility criteria and form the evidentiary basis for the recommendations. Recommendations In patients ≥ 65 years receiving chemotherapy, geriatric assessment (GA) should be used to identify vulnerabilities that are not routinely captured in oncology assessments. Evidence supports, at a minimum, assessment of function, comorbidity, falls, depression, cognition, and nutrition. The Panel recommends instrumental activities of daily living to assess for function, a thorough history or validated tool to assess comorbidity, a single question for falls, the Geriatric Depression Scale to screen for depression, the Mini-Cog or the Blessed Orientation-Memory-Concentration test to screen for cognitive impairment, and an assessment of unintentional weight loss to evaluate nutrition. Either the CARG (Cancer and Aging Research Group) or CRASH (Chemotherapy Risk Assessment Scale for High-Age Patients) tools are recommended to obtain estimates of chemotherapy toxicity risk; the Geriatric-8 or Vulnerable Elders Survey-13 can help to predict mortality. Clinicians should use a validated tool listed at ePrognosis to estimate noncancer-based life expectancy ≥ 4 years. GA results should be applied to develop an integrated and individualized plan that informs cancer management and to identify nononcologic problems amenable to intervention. Collaborating with caregivers is essential to implementing GA-guided interventions. The Panel suggests that clinicians take into account GA results when recommending chemotherapy and that the information be provided to patients and caregivers to guide treatment decision making. Clinicians should implement targeted, GA-guided interventions to manage nononcologic problems. Additional information is available at www.asco.org/supportive-care-guidelines .
Cancer is a disease of aging and, as the world's population ages, the number of older persons with cancer is increasing and will make up a growing share of the oncology population in virtually every ...country. Despite this, older patients remain vastly underrepresented in research that sets the standards for cancer treatments. Consequently, most of what we know about cancer therapeutics is based on clinical trials conducted in younger, healthier patients, and effective strategies to improve clinical trial participation of older adults with cancer remain sparse. For this systematic review, the authors evaluated published studies regarding barriers to participation and interventions to improve participation of older adults in cancer trials. The quality of the available evidence was low and, despite a literature describing multifaceted barriers, only one intervention study aimed to increase enrollment of older adults in trials. The findings starkly amplify the paucity of evidence‐based, effective strategies to improve participation of this underrepresented population in cancer trials. Within these limitations, the authors provide their opinion on how the current cancer research infrastructure must be modified to accommodate the needs of older patients. Several underused solutions are offered to expand clinical trials to include older adults with cancer. However, as currently constructed, these recommendations alone will not solve the evidence gap in geriatric oncology, and efforts are needed to meet older and frail adults where they are by expanding clinical trials designed specifically for this population and leveraging real‐world data.
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Adults aged 85 years and older, the “oldest old,” are the fastest‐growing age group in the United States, yet relatively little is known about their cancer burden. Combining data from the National ...Cancer Institute, the North American Association of Central Cancer Registries, and the National Center for Health Statistics, the authors provide comprehensive information on cancer occurrence in adults aged 85 years and older. In 2019, there will be approximately 140,690 cancer cases diagnosed and 103,250 cancer deaths among the oldest old in the United States. The most common cancers in these individuals (lung, breast, prostate, and colorectum) are the same as those in the general population. Overall cancer incidence rates peaked in the oldest men and women around 1990 and have subsequently declined, with the pace accelerating during the past decade. These trends largely reflect declines in cancers of the prostate and colorectum and, more recently, cancers of the lung among men and the breast among women. We note differences in trends for some cancers in the oldest age group (eg, lung cancer and melanoma) compared with adults aged 65 to 84 years, which reflect elevated risks in the oldest generations. In addition, cancers in the oldest old are often more advanced at diagnosis. For example, breast and colorectal cancers diagnosed in patients aged 85 years and older are about 10% less likely to be diagnosed at a local stage compared with those diagnosed in patients aged 65 to 84 years. Patients with cancer who are aged 85 years and older have the lowest relative survival of any age group, with the largest disparities noted when cancer is diagnosed at advanced stages. They are also less likely to receive surgical treatment for their cancers; only 65% of breast cancer patients aged 85 years and older received surgery compared with 89% of those aged 65 to 84 years. This difference may reflect the complexities of treating older patients, including the presence of multiple comorbidities, functional declines, and cognitive impairment, as well as competing mortality risks and undertreatment. More research on cancer in the oldest Americans is needed to improve outcomes and anticipate the complex health care needs of this rapidly growing population.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK, VSZLJ
Objective This study used a large national administrative in-hospital database to compare utilization and age-specific outcomes between open repair (OAR) and endovascular (EVAR) repair for the ...treatment of abdominal aortic aneurysm (AAA). Methods Discharges with the principal International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) procedure codes for EVAR and OAR and principal diagnosis code of intact AAAs were selected from the 2001 to 2006 Nationwide Inpatient Sample (NIS). Weighted least-square regression was used to test the trend of utilization by age. Multiple linear and logistic regression analyses were used to assess the risk-adjusted outcomes. Results Nationally, the estimated number of elective AAAs treated with EVAR increased from 11,171 in 2001 to 21,725 in 2006 ( P = .003). The number of elective AAAs treated with OAR declined from 17,784 to 8451 during the same period ( P < .001). By 2006, EVAR was more frequently used than OAR for patients of all ages. Compared with the younger age groups, patients aged ≥85 years had a significant increase in the total number of asymptomatic AAA repairs, driven almost entirely by an increase in the use of EVAR. Compared with open patients, EVAR patients had a significantly shorter length of hospitalization (adjusted mean, 2.99 days 95% confidence interval (CI), 2.97-3.01 vs 8.78 days 95% CI, 8.53-8.57), less in-hospital mortality (odds ratio OR, 0.23; 95% CI, 0.19-0.28), fewer in-hospital complications (OR, 0.27; 95% CI, 0.25-0.28), and a higher likelihood of being discharged to home (OR, 3.95; 95% CI, 3.62-4.31). The reduction of complications from the use of EVAR versus OAR was most dramatic for the oldest patients. Conclusions As short-term surgical outcomes are consistently improving for patients undergoing AAA repair, elective EVAR has replaced OAR as the more common method of repair in the United States. The introduction of this technology has been rapidly adopted, particularly for the oldest-old surgical patients, aged ≥85 years, who previously may not have been offered surgical intervention for asymptomatic AAA. Further investigation is necessary to examine whether this trend improves the long-term survival and quality of life for this elderly population.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
ABSTRACT
BACKGROUND
An early sign of cognitive decline in older adults is often a disruption in social function, but our understanding of this association is limited.
OBJECTIVE
We aimed to determine ...whether those screening positive for early stages of cognitive impairment have differences across multiple dimensions of social function and whether associations differ by gender.
DESIGN
United States nationally representative cohort (2010), the National Social life, Health, and Aging Project (NSHAP).
PARTICIPANTS
Community-dwelling adults aged 62–90 years (
N
= 3,310) with a response rate of 76.9 %.
MAIN MEASURES
Cognition was measured using a survey adaptation of the Montreal Cognitive Assessment categorized into three groups: normal, mild cognitive impairment (MCI), and dementia. We measured three domains of social relationships, each comprised of two scales: network structure (size and density), social resources (social support and social strain), and social engagement (community involvement and socializing). We used multiple linear regression to characterize the relationship of each social relationship measure to cognition.
KEY RESULTS
Individuals screened as at risk for MCI and early dementia had smaller network sizes by 0.3 and 0.6 individuals (
p
< 0.001), and a 10 % and 25 % increase in network density (
p
< 0.001), respectively. For social resources, individuals at risk for MCI and dementia had 4 % and 14 % less social strain (
p
= 0.01), but only women had 3 % and 6 % less perceived social support (
p
= 0.013), respectively. For social engagement, individuals screened positive for MCI and dementia had 8 % and 19 % less community involvement (
p
= 0.01), but only men had 8 % and 13 % increased social involvement with neighbors and family members (
p
< 0.001), respectively.
CONCLUSION
Changes in social functioning provide an early indication to screen for cognitive loss. Recognition that early cognitive loss is associated with differences in social function can guide counseling efforts and help identify social vulnerabilities to ease the transition to overt dementia for both patients and caregivers.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Limited tools exist to predict the risk of chemotherapy toxicity in older adults with early-stage breast cancer.
Patients of age ≥ 65 years with stage I-III breast cancer from 16 institutions treated ...with neoadjuvant or adjuvant chemotherapy were prospectively evaluated for geriatric and clinical features predictive of grade 3-5 chemotherapy toxicity. Logistic regression with best-subsets selection was used to identify and incorporate independent predictors of toxicity into a model with weighted variable scoring. Model performance was evaluated using area under the ROC curve (AUC) and goodness-of-fit statistics. The model was internally and externally validated.
In 473 patients (283 in development and 190 in validation cohort), 46% developed grade 3-5 chemotherapy toxicities. Eight independent predictors were identified (each assigned weighted points): anthracycline use (1 point), stage II or III (3 points), planned treatment duration > 3 months (4 points), abnormal liver function (3 points), low hemoglobin (3 points), falls (4 points), limited walking (3 points), and lack of social support (3 points). We calculated risk scores for each patient and defined three risk groups: low (0-5 points), intermediate (6-11 points), or high (≥ 12 points). In the development cohort, the rates of grade 3-5 chemotherapy toxicity for these three groups were 19%, 54%, and 87%, respectively (
< .01). In the validation cohort, the corresponding toxicity rates were 27%, 45%, and 76%. The AUC was 0.75 (95% CI, 0.70 to 0.81) in the development cohort and 0.69 (95% CI, 0.62 to 0.77) in the validation cohort. Risk groups were also associated with hospitalizations and reduced dose intensity (
< .01).
The Cancer and Aging Research Group-Breast Cancer (CARG-BC) score was developed and validated to predict grade 3-5 chemotherapy toxicity in older adults with early-stage breast cancer.
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