Specific Subsets Of Population Research Articles

Association between telomere length and erectile dysfunction: a cross-sectional study.

Leukocyte telomere length (LTL) serves as a significant biomarker of aging. Erectile dysfunction (ED) is a commonly observed condition among middle-aged and older men. The objective of this study is to explore the potential association between LTL and ED. We utilized data from the National Health and Nutrition Examination Survey (NHANES) to examine the association between LTL and ED. Weighted multivariate regression analyses were performed as the primary statistical method. Subgroup analyses were conducted to investigate specific population subsets, and restricted cubic spline (RCS) analyses were employed to assess the non-linear relationship between LTL and ED. The results of weighted multivariate regression analyses revealed a negative correlation between LTL and the risk of ED. Individuals with ED exhibited shorter LTL compared to those without ED. For each unit increase in LTL, there was a 54% reduction in the risk of ED (odds ratios[OR] 0.46, 95% confidence intervals[CI] 0.25-0.85). When LTL was considered as a categorical variable, the group with the longest LTL (Q5) had a 44% lower risk of ED compared to the group with the shortest LTL(Q1) (OR 0.56, 95% CI 0.39-0.81). A non-linear relationship was observed between TL and ED. Various sensitivity analyses were conducted to validate the stability of the results, and consistent findings were obtained. The negative association between leukocyte LTL and ED suggests that delaying the shortening of LTL may decrease the risk of ED.

Emerging and Re-Emerging Parasitic Infections of the Central Nervous System (CNS) in Europe.

In a rapidly evolving global landscape characterized by increased international travel, migration, and ecological shifts, this study sheds light on the emergence of protozoal and helminthic infections targeting the central nervous system (CNS) within Europe. Despite being traditionally associated with tropical regions, these infections are progressively becoming more prevalent in non-endemic areas. By scrutinizing the inherent risks, potential outcomes, and attendant challenges, this study underscores the intricate interplay between diagnostic limitations, susceptibility of specific population subsets, and the profound influence of climate fluctuations. The contemporary interconnectedness of societies serves as a conduit for introducing and establishing these infections, warranting comprehensive assessment. This study emphasizes the pivotal role of heightened clinician vigilance, judicious public health interventions, and synergistic research collaborations to mitigate the potential consequences of these infections. Though rare, their profound impact on morbidity and mortality underscores the collective urgency required to safeguard the neurological well-being of the European populace. Through this multifaceted approach, Europe can effectively navigate the complex terrain posed with these emergent infections.

Impact of Moderate Aortic Stenosis on Long-Term Clinical Outcomes: A Systematic Review and Meta-Analysis.

The clinical course of patients with moderate aortic stenosis (AS) remains incompletely defined. This study sought to analyze the clinical course of moderate AS and compare it with other stages of the disease. Multiple electronic databases were searched to identify studies on adult moderate AS. Random-effects models were used to derive pooled estimates. The primary endpoint was all-cause death. The secondary endpoints were cardiac death, heart failure, sudden death, and aortic valve replacement. Among a total of 25 studies (12,143 moderate AS patients, 3.7 years of follow-up), pooled rates per 100 person-years were 9.0 (95%CI: 6.9 to 11.7) for all-cause death, 4.9 (95%CI: 3.1 to 7.5) for cardiac death, 3.9 (95%CI: 1.9 to 8.2) for heart failure, 1.1 (95%CI: 0.8 to 1.5) for sudden death, and 7.2 (95%CI: 4.3 to 12.2) for aortic valve replacement. Meta-regression analyses detected that diabetes (P = 0.019), coronary artery disease (P = 0.017), presence of symptoms (P< 0.001), and left ventricle (LV) dysfunction (P = 0.009) were associated with a significant impact on the overall estimate of all-cause death. All-cause mortality was higher in patients with reduced LV ejection fraction (<50%) than with normal LV ejection fraction: 16.5 (95%CI: 5.2 to 52.3) and 4.2 (95%CI: 1.4 to 12.8) per 100 person-years, respectively. Compared with moderate AS, the incidence rate difference of all-cause mortality was -3.9 (95%CI: -6.7 to -1.1) for no or mild AS and+2.2 (95%CI:+0.8 to +3.5) for severe AS patients. Moderate AS appears to be associated with a mortality risk higher than no or mild AS but lower than severe AS, which increases in specific population subsets. The impact of early intervention in moderate AS patients having high-risk features deserves further investigation.

Gender Affirmative Care Clinic: An Overview.

Transgender healthcare is an evolving multispecialty field including medical and social domains catering to the needs of a specific subset of population presenting with gender incongruence, differences in sexual development/orientation, requiring care rather than cure. Delivery of transgender healthcare is done through gender friendly healthcare facilities, which are designated as “gender affirmative care clinics (GACC).” The primary purpose of the gender affirmative care clinic is to be the “one stop solution” for a person seeking affirmative care. The main objective is to facilitate care with compassion and prevent/mitigate dysphoria. The components of the GACC should include reception cum front office; affirmative mental healthcare department; affirmative medical, surgical, and sexual healthcare department; diagnostics, legal, and ethics department, as well as inpatient care. The GACC should be preferably located in a place that is easily accessible to the community members and has an “open plan.”

Food groups that exacerbate Sinusitis among Saudi Patients

Objectives: Chronic rhinosinusitis is an extremely common health complaint which decreases productivity and quality of life. The objective of this study was to identify associations between specific food categories and aggravation of symptoms of chronic rhinosinusitis. Methods: This was a prospective, cross-sectional questionnaire study. Patients provided details about the categories of food that they consumed, as well as symptoms related to sinusitis. The data was extracted onto a spreadsheet and analysed using chi-square testing. Results: A small percentage of patients (4%) associated food categories with exacerbations of sinus symptoms. Chocolate was the most common trigger, followed by white flour foods. Several patients (33%) were not aware of the association between food and sinus symptoms. Conclusion: Some food categories can exacerbate sinusitis in a specific population subset. Patients should be encouraged to maintain a food diary so that they can identify relevant triggers and these can be avoided in the future.

P–375 Intralipid supplementation in women with unexplained recurrent implantation failure and elevated uterine natural killer cell levels - A randomized placebo controlled trial

Abstract Study question Does intralipid supplementation in women with unexplained recurrent implantation failure (RIF) with elevated uterine natural killer cell (uNK) levels improve pregnancy outcomes during IVF? Summary answer Intralipid supplementation appears to improve clinical pregnancy rate in women with unexplained RIF with elevated uNK cell levels. What is known already The increased numbers of uNK cells in peri-implantation endometrium have been reported in women with recurrent miscarriage (RM) and RIF after IVF. However, reports are contradictory when it comes to correlation of increased numbers of uNK cells with pregnancy outcome. Current opinion suggests there is a potential for intralipid therapy in improving reproductive outcome, although data on live birth rate is very limited. No studies have assessed the effect of intralipid on IVF outcomes in RIF women based on elevated uNK cells. Identified studies have all used pNK cell testing as preferred diagnostic tool for analysis of NK cell levels. Study design, size, duration A randomized placebo controlled trial was conducted at Division of Reproductive Medicine at tertiary care institute. Thirty women with RIF and fifty fertile controls with age &amp;lt;35 years having regular menstrual cycles and no hormonal treatment in last 3 months were enrolled in the study from January 2019 to December 2020 for uNK cell testing. Randomization was done using random numbers and sealed envelopes. Only the subjects were masked and allocation concealment was done. Participants/materials, setting, methods Subjects included RIF 20–35 years, normal ovarian reserve, unexplained and tubal factors, normal karyotype and normal uterine cavity. Cut off for uNK cells was derived from fertile controls by immunohistochemical staining of CD56+ cells from midluteal endometrial biopsy sample. Subjects with elevated uNK cell levels were randomized during IVF to group A (Intralipid) or group B ( saline ). The infusion was repeated within one week of positive pregnancy test and then every 2 weeks. Main results and the role of chance The mean age and BMI were comparable between fertile control and study group(29.45±3.3 vs 31.17±3.3 years, 22.97±1.89 vs 23.21±2.2 kg/m2 ;p&amp;gt;0.05). The median uNK cell levels was 7%(used as cut off) in fertile controls and 13.5% in RIF. 18 women (60%, 18/30) with RIF who had elevated uNK cell level (&amp;gt;7%) were randomized. Four women were lost to follow up. The median age, BMI, number of previous failed cycles and duration of infertility were comparable between Group A(n = 7) and Group B(n = 7){30(IQR:27–31) vs 33(IQR:30–34)years, 22.7(IQR:21.08–24.4) vs 22.6(IQR:21.37–24.2)kg/m2, 2(IQR:2–3) vs 2(IQR:2–3), 8(IQR:7–8) vs 8(IQR:7–10)years}. The median FSH, AMH and AFC were 5.86(IQR:5.13–7.67)mIU/l, 2.4(IQR:2.16–6.12)ng/ml, 10(IQR:8–12) in Group A which were comparable with Group B {6.2(IQR:4.78–6.5)mIU/l, 4.8(IQR:2.67–6.25)ng/ml, 12(IQR:12–16) }. All patients underwent antagonist protocol. The clinical pregnancy rate was 57.14%(4/7) in group A which was significantly higher as compared to 28.6%(2/7) in group B(p &amp;lt; 0.05). None of the patients reported any side effects due to intralipid. Limitations, reasons for caution The limitation of present study is its small sample size. However, the study is currently recruiting more RIF patients, and these are the interim results of the same. More RCTs with larger sample size are required to assess the efficacy of intralipid in this specific subset of population. Wider implications of the findings: The present study suggests the beneficial effect of intralipid in women with unexplained RIF with elevated uNK cell levels in increasing the chemical and clinical pregnancy rate. However, ongoing pregnancy rate and live birth rate should be investigated further in this subset of population. Trial registration number CTRI/2019/01/017213

FOOD GROUPS THAT EXACERBATE SINUSITIS - A CROSS-SECTIONAL QUESTIONNAIRE STUDY

Objectives: Chronic rhinosinusitis is an extremely common health complaint which decreases productivity and quality of life. The objective of this study was to identify associations between specific food categories and aggravation of symptoms of chronic rhinosinusitis Methods: This was a prospective, cross-sectional questionnaire study. Patients provided details about the categories of food that they consumed, as well as symptoms related to sinusitis. The data was extracted onto a spreadsheet and analysed using chi-square testing. Results:A small percentage of patients (4%) associated food categories with exacerbations of sinus symptoms. Chocolate was the most common trigger, followed by white flour foods. Several patients (33%) were not aware of the association between food and sinus symptoms. Conclusion:Some food categories can exacerbate sinusitis in a specific population subset. Patients should be encouraged to maintain a food diary so that they can identify relevant triggers and these can be avoided in the futureThis was a prospective, cross-sectional questionnaire study. Patients provided details about the categories of food that they consumed, as well as symptoms related to sinusitis. The data was extracted onto a spreadsheet and analysed using chi-square testing.

Managing Transition of Care in Adolescent Females with Epilepsy

AbstractTransition of care from pediatric epilepsy clinics to adult health care is often a challenging process, especially due to limited availability of relevant guidelines. It carries even more significant implications in specific population subsets such as adolescent females, given a myriad of physiological as well as psychosocial changes seen in this age group. Women with epilepsy face distinct challenges because of hormonal variations on seizures (catamenial epilepsy). Furthermore, seizures and antiepileptic drugs impact menstruation, pregnancy, and lactation. These patients are at a higher risk for developing mental health problems, and a close follow-up with appropriate screening for psychiatric disorders is prudent.Several factors contributing to poor transition of care include limited availability of a multidisciplinary set-up and social-support services, delayed referral to specialist(s), and tendency for treatment nonadherence. In this review, we discuss the current scenario of transition of care in adolescent females with epilepsy and explore avenues for improvement based on our subspecialty clinic experiences. We illustrate the value of interdisciplinary care proactively involving neurologists/epileptologists, primary care physicians, obstetricians–gynecologists, and relevant social services and emphasize shared decision-making, effective contraceptive methods, preconceptual counseling, maintenance of bone-health, and enhanced quality of life.

Contemporary Management of Alopecia: A Systematic Review and Meta-analysis for Surgeons.

The decision of surgical approach for hair restoration often involves evaluation of the type of alopecia; however, the impact of surgical hair restoration from existing techniques in specific population subsets has not been comprehensively investigated. The authors sought to systematically review the literature on micrografts, minigrafts, mini-micrografts, tissue grafts, tissue flaps and expanders, as well as evaluate graft survival and satisfaction within specific populations in a meta-analysis. PubMed and Scopus literature searches between 1980 and 2018 yielded 57 articles for systematic review and 34 articles for meta-analysis. Study design, mean patient age and gender, patient alopecia type, surgical hair restoration technique, number of treatment areas, mean follow-up, graft survival rate and satisfaction rate were extracted from each study, and a meta-analysis was performed. The pooled rates of graft survival were 84.98% (95% CI 78.90-91.06) using micrografts and 93.11% (95% CI 91.93-94.29) using micrografts and minigrafts in nonscarring alopecia patients, as well as 88.66% (95% CI 80.12-97.20) using micrografts and 86.25% (95% CI 74.00-98.50) using micrografts and minigrafts in scarring alopecia patients. The pooled rates of satisfaction were 89.70% (95% CI 82.64-96.76) using micrografts and 97.00% (95% CI 92.48-100.0) using micrografts and minigrafts in nonscarring alopecia patients, as well as 97.80% (95% CI 94.59-100.0) using micrografts and 88.70% (95% CI 66.49-100.0) using micrografts and minigrafts in scarring alopecia patients. Dot plots depict rates of graft survival rate from micrografts and satisfaction from micrografts and minigrafts. Surgical hair restoration for nonscarring and scarring alopecia yields high graft survival and satisfaction rates. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

879 Post-ERCP Pancreatitis in Solid Organ Transplant Recipients

INTRODUCTION: Post-ERCP pancreatitis (PEP) is the most common post-procedure complication of ERCP with an incidence of 3.5-15%. The prevalence of PEP and the role of immunosuppression in PEP among solid organ transplant (SOT) recipients is not well established. We aimed to study the prevalence of PEP and the effect of immunosuppressants in SOT recipients. METHODS: A retrospective analysis of 55 million individuals was performed using a cloud-based database, IBM Explorys. Explorys aggregates de-identified electronic health record data from 26 health care systems across the US and rounds to the closest 10 for statistical de-identification. PEP was defined as the elevation of lipase level &gt; 500 U/L along with SNOMED CT (Systematized Nomenclature of Medicine Clinical Terms) diagnosis code of acute pancreatitis within 72 hours of ERCP procedure. The prevalence of PEP and the all-cause 30-day re-admission rate after an episode of PEP were calculated for SOT recipients (lung/kidney/heart/liver). Characteristics were compared using univariate chi-square test between SOT and non-transplant patients as well as liver transplant (LT) recipients and non-transplant patients. P &lt; 0.05 was determined as statistically significant. RESULTS: There was no significant difference in the prevalence of PEP (8.03% vs 8.4%, P = 0.676) and re-admission rate (22.2% vs 20.3%, P = 0.645) between SOT recipients and non-transplant patients. Subgroup analysis of liver transplant (LT) recipients revealed a significantly lower rates of PEP (5.66% vs 8.4%, P = 0.002). Compared to the general population, transplant recipients were less likely to be women [Odds ratio OR 0.567, 95% confidence interval CI (0.375 – 0.866), P = 0.008] (Table 1). Among the transplant recipients, individuals with PEP were more likely to be under 50 years [OR 3.179, CI (1.980 - 5.102), P &lt; 0.001]. PEP rates were lower with SOT recipients on steroids [OR 0.240 CI (0.113 - 0.509), P &lt; 0.001] and calcineurin inhibitors [OR 0.078 CI (0.0317 - 0.194), P &lt; 0.001] (Table 2). CONCLUSION: In this population-based study, the prevalence of PEP was not elevated in SOT recipients. Steroids and calcineurin inhibitors were associated with a protective effect against PEP. To our knowledge, this is the largest cohort to report on PEP in SOT recipients. Since population level database limits access to patients’ charts, studies with details on anatomical and peri-operative risk factors of PEP will further enhance our understanding in this specific subset of population.

DUI recidivism by intervention adherence: a multiple risk factor approach

ABSTRACTBackground: Multi-component impaired driving interventions can reduce driving under the influence (DUI) recidivism rates; however, outcomes are better for those who complete the interventions and are adherent with program expectations. Research is needed to examine the differences between DUI offenders who are adherent vs. non-adherent to intervention efforts. Objective: The current study utilized a multi-risk factor model to predict recidivism among first-time DUI offenders enrolled in an intervention program. Differences between offenders who were adherent (including program completion) vs. non-adherent with the intervention were examined. Method: Using data from the Mississippi Alcohol Safety Education Program (MASEP) and state administrative records, the current study examined both recidivism rates and rates of intervention completion for all individuals enrolled in the program. The sample was predominantly White (58.8%) and male (80.2%). Results: Individuals who were adherent with the intervention were significantly less likely to recidivate within 3 years. Prior traffic or other criminal violations positively predicted recidivism rates. The likelihood of recidivism varied, with males, African Americans, and younger individuals with less education at greater risk of recidivism. Adherence with the intervention was more common for African American and older participants. Conclusion: The MASEP participants who were adherent with the intervention were significantly less likely to recidivate than those who were non-adherent. However, variance in the multi-component intervention completion rates suggests that the program resonates better with specific population subsets. We argue for researchers and policymakers to further explore how specific population subsets react to varying intervention programs to maximize efforts to reduce impaired driving.

Clinical impacts of inhibition of renin–angiotensin system in patients with acute ST-segment elevation myocardial infarction who underwent successful late percutaneous coronary intervention

BackgroundSuccessful percutaneous coronary intervention (PCI) of the occluded infarct-related artery (IRA) in latecomers may improve long-term survival mainly by reducing left ventricular remodeling. It is not clear whether inhibition of renin–angiotensin system (RAS) brings additional better clinical outcomes in this specific population subset. MethodsBetween January 2008 and June 2013, 669 latecomer patients with acute ST-segment elevation myocardial infarction (STEMI) (66.2±12.1 years, 71.0% males) in Korea Acute Myocardial Infarction Registry (KAMIR) who underwent a successful PCI were enrolled. The study population underwent a successful PCI for a totally occluded IRA. They were divided into two groups according to whether they were prescribed RAS inhibitors at the time of discharge: group I (RAS inhibition, n=556), and group II (no RAS inhibition, n=113). ResultsDuring the one-year follow-up, major adverse cardiac events (MACE), which consist of cardiac death and myocardial infarction, occurred in 71 patients (10.6%). There were significantly reduced incidences of MACE in the group I (hazard ratio=0.34, 95% confidence interval 0.199–0.588, p=0.001). In subgroup analyses, RAS inhibition was beneficial in patients with male gender, history of hypertension or diabetes mellitus, and even in patients with left ventricular ejection fraction (LVEF) ≥40%. In the baseline and follow-up echocardiographic data, benefit in changes of LVEF and left ventricular end-systolic volume was noted in group I. ConclusionsIn latecomers with STEMI, RAS inhibition improved long-term clinical outcomes after a successful PCI, even in patients with low risk who had relatively preserved LVEF.

Constipation incidence and impact in medical critical care patients: importance of the definition criterion.

Constipation incidence and impact remain controversial in the ICU. This may depend on the definition criterion used in the previous studies on the field. We aimed to determine the frequency and significance of constipation according to its definition criterion. This is a prospective observational study. Adult patients without a cause of transit time modification and laxative intake within the first 3 days were screened. Constipation was defined by a first stool passage occurring after 3 days of ICU stay. Thereafter, we identified two subgroups of patients: absence of stool passage more than 3 days but less than 6 days (3-day subgroup), and no stool passage for 6 days or more (6-day subgroup). Survival, length of stay and time spent under mechanical ventilation (MV) were compared according to constipation status. Among 189 included patients [age 60.8 (49.5-74.2) years, SAPS II 44 (34-53)], 98 (51.9%) exhibited constipation (3-day subgroup n=53, 6-day subgroup n=45). Constipated patients were more likely to receive MV, sedation, vasopressors, enteral nutrition and neuromuscular blocking agents. ICU length of stay and time spent under MV was longer in the 6-day subgroup but not in the 3-day subgroup of patients. With regard to outcomes, defining constipation by the absence of stool passage less than 6 days after ICU admission does not identify a specific subset of population. Further studies on the management of this condition should focus on these 'long-term' constipated patients.

An introduction to the partial least squares approach to structural equation modelling: a method for exploratory psychiatric research.

In psychiatry and psychology, relationship patterns connecting disorders and risk factors are always complex and intricate. Advanced statistical methods have been developed to overcome this issue, the most common being structural equation modelling (SEM). The main approach to SEM (CB-SEM for covariance-based SEM) has been widely used by psychiatry and psychology researchers to test whether a comprehensive theoretical model is compatible with observed data. While the validity of this approach method has been demonstrated, its application is limited in some situations, such as early-stage exploratory studies using small sample sizes. The partial least squares approach to SEM (PLS-SEM) has risen in many scientific fields as an alternative method that is especially useful when sample size restricts the use of CB-SEM. In this article, we aim to provide a comprehensive introduction to PLS-SEM intended to CB-SEM users in psychiatric and psychological fields, with an illustration using data on suicidality among prisoners. Researchers in these fields could benefit from PLS-SEM, a promising exploratory technique well adapted to studies on infrequent diseases or specific population subsets. Copyright © 2015 John Wiley & Sons, Ltd.

Reduction of ST-elevation myocardial infarction in Canton Ticino (Switzerland) after smoking bans in enclosed public places--No Smoke Pub Study.

Second-hand smoke increases the risk of acute myocardial infarction. Canton Ticino (CT) first introduced a smoking ban in public places in 2007. This offered the opportunity to assess the long-term impact of a smoking ban on the incidence of ST-elevation myocardial infarctions (STEMI) compared with a population where the law was not yet implemented. We assessed the incidence of STEMI hospitalizations per 100 000 inhabitants both during 3 years before and after the ban application in CT and in Canton Basel City (CBC), where this law was not yet applied. Data were obtained from the codified hospital registry (ICD-10 codes). In CT, the mean incidence of STEMI admissions during the 3 pre-ban years (123.7) was significantly higher than the incidence of admissions in each of the 3 post-ban years (92.9, 101.6 and 89.6 respectively; P <.024). Analysing population subsets, a post-ban reduction was observed among ≥65-year-old people of both sexes in each of the 3 post-ban years and in the <65-year age group during the first post-ban year (P = 0.02). Conversely, the mean incidence of STEMI hospitalizations in CBC (92.4) didn't change significantly in each of the 3 post-ban years (83.9, 83.3 and 79.5, P = NS) during the same period. However, a significant long-term reduction in STEMI admissions was observed in CBC among the male group with ≥65 years (P < 0.01). Our work suggests a significant impact of the smoke-free policy on the number of annual STEMI. Specific population subsets (i.e. ≥65-year-old females) were particularly affected by the smoking ban, showing a significant reduction in STEMI hospitalizations.

Acute Myocardial Infarction in Young Adults: Study of Risk factors, Angiographic Features and Clinical Outcome

Background and aims: Acute myocardial infarction below 45 years of age constitutes a specific subset of population having different risk factors and clinical features as compared to older patients. Pattern of coronary artery involvement and clinical outcome also varies suggesting different underlying pathophysiology. Better understanding this specific problem will lead to further improvement in management. Methods: One hundred and fifteen consecutive patients diagnosed as acute myocardial infarction and were below 45 years over the period of one year were enrolled in the study. Clinical parameters, risk factors, angiographic patterns were analysed. Patients were assessed daily during hospital stay to study in-hospital outcome and complications. Results: Out of total patients studied, 64.3% were smokers, 27.8% were hypertensive, 15.65% were diabetic and 9.6% had history of dyslipidemia. There was history of recreational drug abuse in 4.3% of patients. Most patients present as ST elevation myocardial infarction (87%). Majority of patients were in Killip class I (69.5%) at presentation in emergency. Single vessel disease (58.3%) was the most common finding in coronary angiography and 7.6% patients have normal or non obstructive coronary lesions. Complications include arrhythmia (6%), cardiogenic shock (5.2%) and mortality (1.7%). Conclusions: In young acute myocardial infarction patients, smoking is the single most important modifiable risk factor. Other conventional risk factors are less strongly associated than older patients. Young patients tend to have less extensive coronary artery lesions. In few patients, presence of normal or non obstructive coronary lesions would suggest possibility of different mechanism of myocardial necrosis. Overall, these patients had favourable outcome and better prognosis. Nepalese Heart Journal | Volume 10 | No.1 | November 2013| Pages 12-16 DOI: http://dx.doi.org/10.3126/njh.v10i1.9740

Prone Position in Acute Respiratory Distress Syndrome. Rationale, Indications, and Limits

In the prone position, computed tomography scan densities redistribute from dorsal to ventral as the dorsal region tends to reexpand while the ventral zone tends to collapse. Although gravitational influence is similar in both positions, dorsal recruitment usually prevails over ventral derecruitment, because of the need for the lung and its confining chest wall to conform to the same volume. The final result of proning is that the overall lung inflation is more homogeneous from dorsal to ventral than in the supine position, with more homogeneously distributed stress and strain. As the distribution of perfusion remains nearly constant in both postures, proning usually improves oxygenation. Animal experiments clearly show that prone positioning delays or prevents ventilation-induced lung injury, likely due in large part to more homogeneously distributed stress and strain. Over the last 15 years, five major trials have been conducted to compare the prone and supine positions in acute respiratory distress syndrome, regarding survival advantage. The sequence of trials enrolled patients who were progressively more hypoxemic; exposure to the prone position was extended from 8 to 17 hours/day, and lung-protective ventilation was more rigorously applied. Single-patient and meta-analyses drawing from the four major trials showed significant survival benefit in patients with PaO2/FiO2 lower than 100. The latest PROSEVA (Proning Severe ARDS Patients) trial confirmed these benefits in a formal randomized study. The bulk of data indicates that in severe acute respiratory distress syndrome, carefully performed prone positioning offers an absolute survival advantage of 10-17%, making this intervention highly recommended in this specific population subset.

Abstract S3-5: Myelodysplatic syndrome and/or acute myelogenous leukemia (MDS and/or AML) after a breast cancer diagnosis: the National Comprehensive Cancer Network (NCCN) experience.

Abstract BACKGROUND: Cooperative group trials and institutional series reported the risk of MDS and/or AML after adjuvant chemotherapy for early stage breast cancer (eg, NSABP 0.21%, Smith JCO 2003; ECOG 2197 0.5%, Goldstein ASCO 2012). We examined the incidence of MDS and/or AML in breast cancer survivors that are part of the NCCN Breast Cancer Outcomes Database. METHODS: The NCCN Database prospectively identifies all incident breast cancers diagnosed at participating cancer centers, and patients that continue their care at an NCCN site are followed annually with information collected on subsequent treatment, recurrence, and new cancers. Mortality is also ascertained for all diagnosed patients every 2 years through the National Death Index. Women with stages 1–3 breast cancer (BC) diagnosed between 1997–2008 were included in this analysis. Univariate chi square analyses were used to compare characteristics between patients with BC and BC&amp;MDS and/or AML. Time from BC to MDS and/or AML and 5-/10-year cumulative incidence rates were analyzed using proportional subdistribution hazards regression models that account for death as a competing risk to MDS and/or AML. RESULTS: Among 21563 stage 1–3 BC patients from 8 NCCN sites, 39 (0.18%) subsequently developed MDS and/or AML. Median overall follow-up was 4.7 years and median time from BC to MDS and/or AML was 2.8 years (range, 0.6 to 8.3 years). Cumulative MDS and/or AML incidence was 0.19% at 5y and 0.27% at 10y. Overall, cancer characteristics at BC diagnosis within BC&amp;MDS and/or AML and within BC groups were similar (Caucasian 82%v82%, AA 8%v8%; ER+ 79%v75%, HER2+ 14%v21%, TNBC 15%v14%; contralateral BC 3%v2%; pancreas or ovarian cancer 0%v1%). 13191 had adjuvant chemo (75%v67%; anthracycline 89%v91%, AC-taxane 46%v35%, dose-dense 6%v5%). Trends observed included more patients in BC&amp;MDS and/or AML group with prior radiation (85%v70%, p = 0.06) and older age at BC diagnosis (median age 59v54 years, p = 0.09). Risk for developing MDS and/or AML after BC (adjusted for age at BC and race) was increased in those receiving any chemotherapy versus no chemotherapy (HR 2.16, 95% CI 0.98–4.77, p = 0.06), any RT versus no RT (HR 2.44, 95% CI 1.01–5.88, p = 0.04), and if chemo/RT given versus just chemo or just RT (HR 2.2, 95% CI 1.05–4.59, p = 0.04). No increased risk was observed if a taxane was added to an anthracycline regimen (HR 1.27, 95% CI 0.57–2.81, p = 0.56). CONCLUSIONS: In a large national prospective registry across NCCN sites, risk of MDS and/or AML is increased after adjuvant chemotherapy and/or adjuvant radiation therapy for stages 1–3 breast cancer, especially if both are used. Specific population subsets will be further examined. These rates are similar to those observed in clinical trials, but may underestimate actual numbers due to patients lost to follow-up. In addition, an MDS diagnosis was routinely under-reported in population databases until recently. Strategies to limit risk of subsequent cancers in patients likely to survive early stage breast cancer should be considered at the time of initial diagnosis. Predictors of MDS and/or AML in breast cancer survivors are needed. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr S3-5.

Targeted Therapy in Lung Cancer; Lessons Learned from Past Experiences

Targeted Therapy in Lung Cancer; Lessons Learned from Past Experiences

A regulator’s view of comparative effectiveness research

'Comparative effectiveness' is the current enthusiasm, and for good reason. After knowing a treatment works, the most critical question is how it compares with alternatives. Comparative studies are not commonly conducted by drug companies and they represent a significant methodological challenge. Comparative data could include evidence of overall superiority to an alternative or advantages in identifiable subsets, for example, people who do not respond to or tolerate alternatives, or members of a genetic subset and could also include convincing evidence that there is little difference between two treatments. To describe regulations, guidance, and Food and Drug Administration experience related to studies of comparative effectiveness, including approaches to showing superiority and problems encountered in showing similarity. Review of Food and Drug Administration regulations and guidance and experience with showing superiority and similarity, particularly related to randomized trials and epidemiologic studies. Methods exist, and they have been successful for showing overall superiority of one drug over another, advantages in specific population subsets. Efforts to show true equivalence face problems of definition and very large sample sizes needed to rule out small differences. There is need for further discussion of what is meant by similarity or equivalence of two treatments. Comparative studies are challenging because differences between effective therapies are likely to be small and can be detected reliably only in randomized trials, often large ones. Despite the difficulties, comparative trials have been successful and we clearly would like to see more of them.