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Tanaya Bharatan,1 Ratna Devi,2,3 Pai-Hui Huang,4 Afzal Javed,5 Barrett Jeffers,6 Peter Lansberg,7 Kaveri Sidhu,1 Kannan Subramaniam8 1Research Development & Medical, Upjohn Division, Pfizer Ltd, Mumbai, India; 2Executive Office, Daksham A Health and Education, Gurgaon, India; 3International Alliance of Patient Organizations, London, UK; 4Medical Affairs, Viatris, Taipei, Taiwan; 5Warwick Medical School, University of Warwick, Warwick, UK; 6Medical Affairs, Viatris Inc, New York, NY, USA; 7Department of Pediatrics, University Medical Center, Groningen, the Netherlands; 8Medical Affairs, Viatris | Mylan New Zealand Ltd, Auckland, New ZealandCorrespondence: Kannan SubramaniamViatris | Mylan New Zealand Ltd, PO Box 11183, Ellerslie, Auckland 1542, New ZealandTel +64 21 592 064Fax +61 2 8080 8181Email kannan.subramaniam@viatris.comAbstract: Noncommunicable diseases (NCDs) are responsible for 71% of all worldwide mortality each year, and have an exceptionally large impact in low- and middle-income countries (LMICs). However, there is often a lack of local data from these countries to inform practice and policy improvements. Generating locally contextualized evidence base for NCDs that can help identify gaps, aid decision-making and improve patient care in LMICs needs an innovative approach. The approach used in Mapping the Patient Journey Towards Actionable Beyond the Pill Solutions (MAPS) is designed to quantitatively map different stages of the patient journey in four critical NCDs, ie, hypertension, dyslipidemia, depression, and pain (chronic and neuropathic) across selected LMICs in Africa, the Middle East, South East Asia, and Latin America. The key touchpoints along the patient journey include awareness, screening, diagnosis, treatment, adherence, and control or remission. MAPS employs an evidence mapping methodology that follows a three-step semi-systematic review: 1) systematic peer-reviewed database search; 2) unstructured searches of local or real-world data; and 3) expert opinion. Evidence generation and visualization is based on locally validated and deduplicated data published over the last 10 years. This approach will be the first to provide quantitative mapping of the different stages of the patient journey for selected NCDs in LMICs. By focusing on local, patient-centric data, the goal of the MAPS initiative is to address and prioritize local research and knowledge gaps, then contribute to evidence-based, high-quality, and affordable advances in the management of NCDs in LMICs. This will ultimately improve patient outcomes and contribute towards the achievement of global NCD targets.Keywords: noncommunicable diseases, low- and middle-income countries, decision-making, patient journey, evidence mapping

Aakash Ganju,1 Alessandra C Goulart,2 Amrit Ray,3 Anurita Majumdar,4 Barrett W Jeffers,3 Gloria Llamosa,5 Henry Cañizares,6 Ianne Jireh Ramos-Cañizares,6 Ibtihal Fadhil,7 Kannan Subramaniam,8 Lee-Ling Lim,9 Luna El Bizri,10 M Ramesh,11 Mathew Guilford,12 Raghib Ali,13 Ratna Duddi Devi,14,15 Rayaz A Malik,16 Shekhar Potkar,17 Yuan-Pang Wang18 1Executive Office, Saathealth, Mumbai, India; 2Center for Clinical and Epidemiological Research, University Hospital, University of São Paulo, São Paulo, Brazil; 3Research, Development and Medical, Upjohn – a Pfizer Division, New York, NY, USA; 4Research, Development and Medical, Emerging Markets, Upjohn – a Pfizer Division, Singapore; 5Mexican Neurology and Psychiatry Society, Mexico City, Mexico; 6Vicente Sotto Memorial Medical Center, Cebu City, Philippines; 7Eastern Mediterranean NCD Alliance, Kuwait City, Kuwait; 8Research, Development and Medical, Upjohn – a Pfizer Division, Sydney, Australia; 9Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 10School of Pharmacy, Lebanese University, Hadath, Lebanon; 11Lee Kuan Yew School of Public Policy, National University of Singapore, Singapore; 12Executive Office, Common Health, Kuala Lumpur, Malaysia; 13Public Health Research Center, New York University, Abu Dhabi, United Arab Emirates; 14Executive Office, DakshamA Health and Education, Gurgaon, India; 15Board of Directors, International Alliance of Patient Organizations, London, England; 16Weill Cornell Medicine, Doha, Qatar; 17Research, Development and Medical, Upjohn – a Pfizer Division, Dubai, United Arab Emirates; 18Instituto de Psiquiatria (LIM-23), Hospital das Clinicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, BrazilCorrespondence: Kannan SubramaniamResearch, Development and Medical, Upjohn – a Pfizer Division, Sydney, NSW 2000, AustraliaTel +61 413 569 077Email Kannan.Subramaniam@pfizer.comAbstract: Non-communicable diseases (NCDs) have been on the rise in low- and middle-income countries (LMICs) over the last few decades and represent a significant healthcare concern. Over 85% of “premature” deaths worldwide due to NCDs occur in the LMICs. NCDs are an economic burden on these countries, increasing their healthcare expenditure. However, targeting NCDs in LMICs is challenging due to evolving health systems and an emphasis on acute illness. The major issues include limitations with universal health coverage, regulations, funding, distribution and availability of the healthcare workforce, and availability of health data. Experts from across the health sector in LMICs formed a Think Tank to understand and examine the issues, and to offer potential opportunities that may address the rising burden of NCDs in these countries. This review presents the evidence and posits pragmatic solutions to combat NCDs.Keywords: low- and middle-income countries, multisectoral, non-communicable diseases, public–private partnership, universal health coverage

Objective: Differences in the perspectives of severely and persistently ill patients, their family members, and clinical care providers on key aspects of community-based care were examined to help inform community service planning and development. Methods: A sample of 183 patients being considered for relocation from psychiatric facilities in Alberta, Canada, to community-based care, were interviewed, as were their primary clinical care providers. Family members of 130 patients were also interviewed. Results: Among the 130 patient-family pairs, 41 percent disagreed about the desirability of relocation, with fewer patients favoring relocation than families. Forty-nine percent of the pairs disagreed about the desired proximity to the family of the relocated patient, with the patient desiring closer proximity than the family member in about half of these cases. Fifty-three percent of the pairs disagreed about the amount of financial and emotional support that the family would provide after relocation. In half of these cases, patients believed the family would provide a higher level of support than the family indicated it could. Among the patients, 49 percent preferred independent living, whereas only 10 percent of family members and 17 percent of clinical care providers preferred it. Fifty-five percent of patients expressed a clear desire to work, whereas care providers believed that only 12 percent of patients were employable. Conclusions: Persistently mentally ill residents of psychiatric facilities express clear preferences about key aspects of community-based care when they are asked, and these preferences often reflect different views from those expressed by either family members or clinical care providers. [ABSTRACT FROM AUTHOR]

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This study examines whether there was an association between smoking and nephropathy in patients with non-insulin-dependent diabetes mellitus enrolled in the Appropriate Blood Pressure Control in Diabetes Trial. Sixty-one percent of the patients were smokers; 26% had microalbuminuria, and 14% had overt nephropathy. There was a univariate association between diabetic nephropathy and gender, smoking status, duration of diabetes, hypertension, glycosylated hemoglobin level, creatinine level, body mass index, and cholesterol level. Stepwise logistic regression demonstrated an independent association between smoking and diabetic nephropathy (odds ratio 1. 61; 95% confidence interval 1.01, 2.58). These findings may have important implications for patients with non-insulin-dependent diabetes mellitus who smoke. [ABSTRACT FROM AUTHOR]

Barrett W Jeffers, Rahul Bhambri, Jeffery Robbins Pfizer Inc., New York, NY, USA Abstract: Diabetic patients with hypertension are approximately twice as likely to develop cardiovascular disease as non-diabetic patients with hypertension. Given that hypertension affects ~60% of patients with diabetes, effective blood pressure (BP) management is important in this high-risk population. This post-hoc analysis pooled data from six clinical studies to quantify additional BP efficacy achieved when titrating hypertensive diabetic patients from amlodipine 5 mg to 10 mg. Approximately half of the diabetic patients were male (44/98; 44.9%) with a mean (standard deviation [SD]) age of 60.6 (9.6) years and a baseline mean (standard error [SE]) systolic blood pressure/diastolic blood pressure (SBP/DBP) of 150.8 (1.30)/87.5 (0.94) mmHg while on amlodipine 5 mg (159.1 [1.40]/92.6 [0.94] mmHg prior to treatment). In comparison, 350/610 (57.4%) non-diabetic patients were male with a mean (SD) age of 58.7 (11.1) years and baseline mean (SE) SBP/DBP of 150.3 (0.62)/90.9 (0.41) mmHg while on amlodipine 5 mg (160.0 [0.67]/96.2 [0.45] mmHg prior to treatment). Increasing amlodipine from 5 mg to 10 mg lowered sitting SBP by -12.5 mmHg (95% confidence interval (CI): -15.5, -9.5; P

Kazuomi Kario,1 Jeffery Robbins,2 Barrett W Jeffers21Division of Cardiovascular Medicine, Jichi Medical University, Shimotsuke, Japan; 2Pfizer, New York, NY, USAAbstract: In this retrospective analysis, data pooled from two Phase III/IV open-label Asian studies were used to quantify the additional blood pressure efficacy achieved when titrating amlodipine from 5 mg to 10 mg in mild/moderate hypertensive patients, and compared to data pooled from three Western studies. The primary efficacy end point was the change from baseline in sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP) to the specified time point (4–8 weeks, depending on the trial). For the Asian analysis (n=174), both mean SBP and DBP were significantly decreased at the final visit (SBP -13.3 mmHg, 95% confidence interval [CI] -15.5 to -11.0; DBP -9.2 mmHg, 95% CI -10.6 to -7.8; both P

Introduction: Multi-etiology dementia necessitates in-vivo markers of copathologies including misfolded α -synuclein (syn). We measured misfolded syn aggregates (syn-seeds) via qualitative seed amplifcation assays (synSAA) and examined relationships with markers of Alzheimer's disease (AD)., Methods: Cerebrospinal fluid (CSF) was obtained from 420 participants in two Wisconsin AD risk cohorts (35% male; 91% cognitively unimpaired; mean (SD) age, 65.42 (7.78) years; education, 16.17 (2.23) years). synSAA results were compared to phosphorylated tau (T), beta amyloid (A), and clinical outcomes. Longitudinal cognition was modeled with mixed effects., Results: Syn positivity (synSAA+) co-occurred with T (in synSAA+ vs synSAA-, 36% vs 20% T+; p=0.011) and with cognitive impairment (10% vs 7% MCI; 10% vs 0% dementia; p=0.00050). synSAA+ participants' cognitive performance declined ∼40% faster than synSAA-for Digit Symbol, but not other tests., Discussion: Findings support prevalent syn copathology in a mostly-unimpaired AD risk cohort. Future work will explore relationships with disease progression.

Purpose: Previous comparative effectiveness studies have not demonstrated a benefit of proton beam therapy (PBT) compared with intensity-modulated radiation therapy (IMRT) for prostate cancer. An updated comparison of GI and genitourinary (GU) toxicity is needed., Methods: We investigated the SEER-Medicare linked database, identifying patients with localized prostate cancer diagnosed from 2010 to 2017. Procedure and diagnosis codes indicative of treatment-related toxicity were identified. As a sensitivity analysis, we also identified toxicity based only on procedure codes. Patients who underwent IMRT and PBT were matched 2:1 on the basis of clinical and sociodemographic characteristics. We then compared GI and GU toxicity at 6, 12, and 24 months after treatment., Results: The final sample included 772 PBT patients matched to 1,544 IMRT patients. The frequency of GI toxicity for IMRT versus PBT was 3.5% versus 2.5% at 6 months ( P = .18), 9.5% versus 10.2% at 12 months ( P = .18), and 20.5% versus 23.4% at 24 months ( P = .11). The frequency of only procedure codes indicative of GI toxicity for IMRT versus PBT was too low to be reported and not significantly different. The frequency of GU toxicity for IMRT versus PBT was 6.8% versus 5.7% ( P = .30), 14.3% versus 12.2% ( P = .13), and 28.2% versus 25.8% ( P = .21) at 6, 12, and 24 months, respectively. When looking only at procedure codes, the frequency of GU toxicity for IMRT was 1.0% at 6 months, whereas it was too infrequent to report for PBT ( P = .64). GU toxicity for IMRT versus PBT was 3.3% versus 2.1% ( P = .10), and 8.7% versus 6.7% ( P = .10) at 12 and 24 months, respectively., Conclusion: In this observational study, there were no statistically significant differences between PBT and IMRT in terms of GI or GU toxicity.

Background: The sensitivity of amyloid to pre-analytic factors complicates cerebrospinal fluid (CSF) diagnostics for Alzheimer disease. We report reliability and validity evidence for automated immunoassays from frozen and fresh CSF samples in an ongoing, single-site research program., Methods: CSF samples were obtained from 2 Wisconsin cohorts (1256 measurements; 727 participants). Levels of amyloid beta 1-42 (Aβ42), phosphorylated tau 181 (pTau181), and total tau (tTau) were obtained using an Elecsys cobas e 601 platform. Repeatability and fixed effects of storage tube type, extraction method, and freezing were assessed via mixed models. Concordance with amyloid positron emission tomography (PET) was investigated with 238 participants having a temporally proximal PET scan., Results: Repeatability was high with intraclass correlation (ICC) ≥0.9, but tube type strongly affected measurements. Discriminative accuracy for PET amyloid positivity was strong across tube types (area under the curve [AUC]: Aβ42, 0.87; pTau181Aβ42 , 0.96), although optimal thresholds differed., Conclusions: Under real-world conditions, the Elecsys platform had high repeatability. However, strong effects of pre-analytic factors suggest caution in drawing longitudinal inferences., (© Association for Diagnostics & Laboratory Medicine 2024.)

Purpose: To maximize the therapeutic ratio, it is important to identify adverse prognostic features in men with prostate cancer, especially among those with intermediate risk disease, which represents a heterogeneous group. These men may benefit from treatment intensification. Prior studies have shown pretreatment mpMRI may predict biochemical failure in patients with intermediate and/or high-risk prostate cancer undergoing conventionally fractionated external beam radiation therapy and/or brachytherapy. This study aims to evaluate pretreatment mpMRI findings as a marker for outcome in patients undergoing stereotactic body radiation therapy (SBRT)., Methods and Materials: We identified all patients treated at our institution with linear accelerator based SBRT to 3625 cGy in 5 fractions, with or without androgen deprivation therapy (ADT) from November 2015 to March 2021. All patients underwent pretreatment Magnetic Resonance Imaging (MRI). Posttreatment Prostate Specific Imaging (PSA) measurements were typically obtained 4 months after SBRT, followed by every 3 to 6 months thereafter. A 2 sample t test was used to compare preoperative mpMRI features with clinical outcomes., Results: One hundred twenty-three men were included in the study. Pretreatment MRI variables including median diameter of the largest intraprostatic lesion, median number of prostate lesions, and median maximal PI-RADS score, were each predictive of PSA nadir and time to PSA nadir ( P < .0001). When separated by ADT treatment, this association remained for patients who were not treated with ADT ( P < .001). In patients who received ADT, the pretreatment MRI variables were each significantly associated with time to PSA nadir ( P < .01) but not with PSA nadir ( P > 0.30). With a median follow-up time of 15.9 months (IQR: 8.5-23.3), only 3 patients (2.4%) experienced biochemical recurrence as defined by the Phoenix criteria., Conclusions: Our experience shows the significant ability of mpMRI for predicting PSA outcome in prostate cancer patients treated with SBRT with or without ADT. Since PSA nadir has been shown to correlate with biochemical failure, this information may help radiation oncologists better counsel their patients regarding outcome after SBRT and can help inform future studies regarding who may benefit from treatment intensification with, for example, ADT and/or boosts to dominant intraprostatic lesions., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Purpose: The autosegmentation algorithm of Siemens Healthineers version VA 30 (AASH) (Siemens Healthineers, Erlangen, Germany) was trained and developed in the male pelvis, with no published data on its usability in the female pelvis. This is the first multi-institutional study to describe and evaluate an artificial intelligence algorithm for autosegmentation of the pelvic nodal region by gender., Methods and Materials: We retrospectively evaluated AASH pelvic nodal autosegmentation in both male and female patients treated at our network of institutions. The automated pelvic nodal contours generated by AASH were evaluated by 1 board-certified radiation oncologist. A 4-point scale was used for each nodal region contour: a score of 4 is clinically usable with minimal edits; a score of 3 requires minor edits (missing nodal contour region, cutting through vessels, or including bowel loops) in 3 or fewer computed tomography slices; a score of 2 requires major edits, as previously defined but in 4 or more computed tomography slices; and a score of 1 requires complete recontouring of the region. Pelvic nodal regions included the right and left side of the common iliac, external iliac, internal iliac, obturator, and midline presacral nodes. In addition, patients were graded based on their lowest nodal contour score. Statistical analysis was performed using Fisher exact tests and Yates-corrected χ 2 tests., Results: Fifty-two female and 51 male patients were included in the study, representing a total of 468 and 447 pelvic nodal regions, respectively. Ninety-six percent and 99% of contours required minor edits at most (score of 3 or 4) for female and male patients, respectively ( P = .004 using Fisher exact test; P = .007 using Yates correction). No nodal regions had a statistically significant difference in scores between female and male patients. The percentage of patients requiring no more than minor edits was 87% (45 patients) and 92% (47 patients) for female and male patients, respectively ( P = .53 using Fisher exact test; P = .55 using Yates correction)., Conclusions: AASH pelvic nodal autosegmentation performed very well in both male and female pelvic nodal regions, although with better male pelvic nodal autosegmentation. As autosegmentation becomes more widespread, it may be important to have equal representation from all sexes in training and validation of autosegmentation algorithms., Competing Interests: Kareem Rayn reports an ASTRO-Varian funded fellowship. Garima Gokhroo, Vibhor Gupta, and Suresh Chaudhari report being employed by a Varian-funded entity. Ryan Clark, Anthony Magliari, and Sushil Beriwal report being employed by Varian., (© 2023 The Author(s).)

Purpose: A scoring mechanism called the scorecard that objectively quantifies the dosimetric plan quality of pancreas stereotactic body radiation therapy treatment plans is introduced., Methods and Materials: A retrospective analysis of patients with pancreatic ductal adenocarcinoma receiving stereotactic body radiation therapy at our institution between November 2019 and November 2020 was performed. Ten patients were identified. All patients were treated to 36 Gy in 5 fractions, and organs at risk (OARs) were constrained based on Alliance A021501. The scorecard awarded points for OAR doses lower than those cited in Alliance A021501. A team of 3 treatment planners and 2 radiation oncologists, including a physician resident without plan optimization experience, discussed the relative importance of the goals of the treatment plan and added additional metrics for OARs and plan quality indexes to create a more rigorous scoring mechanism. The scorecard for this study consisted of 42 metrics, each with a unique piecewise linear scoring function which is summed to calculate the total score (maximum possible score of 365). The scorecard-guided plan, the planning and optimization for which were done exclusively by the physician resident with no prior plan optimization experience, was compared with the clinical plan, the planning and optimization for which were done by expert dosimetrists, using the Sign test., Results: Scorecard-guided plans had, on average, higher total scores than those clinically delivered for each patient, averaging 280.1 for plans clinically delivered and 311.7 for plans made using the scorecard ( P  = .003). Additionally, for most metrics, the average score of each metric across all 10 patients was higher for scorecard-guided plans than for clinically delivered plans. The scorecard guided the planner toward higher coverage, conformality, and OAR sparing., Conclusions: A scorecard tool can help clarify the goals of a treatment plan and provide an objective method for comparing the results of different plans. Our study suggests that a completely novice treatment planner can use a scorecard to create treatment plans with enhanced coverage, conformality, and improved OAR sparing, which may have significant effects on both tumor control and toxicity. These tools, including the scorecard used in this study, have been made freely available., Competing Interests: Ryan Clark, Anthony Magliari, and Lesley Rosa are employed by Varian., (© 2023 The Author(s).)

Purpose: To create a three-dimensional endoscopic model of the biliary tract from magnetic-resonance cholangiopancreatography imaging and to evaluate its effectiveness as a tool for training in endoscopic biliary interventions., Materials and Methods: A magnetic-resonance cholangiopancreatography study was performed on a patient with biliary obstruction secondary to a distal bile duct cholangiocarcinoma. Using Vitrea, a three-dimensional volume-rendered image was created, and exported as a standard tessellated language file. The standard tessellated language model was then edited with MeshMixer. Three cylindrical entry ports were created. The ports were aligned and overlapped with the dominant ducts in three separate areas of the model and fused to the model. A 0.2 cm shell was created around the model and the model was hollowed. The ends of the ports were cut off, allowing access to the hollowed-out model. The model was printed at 125% scale to allow easy access with a 9.5-French (≤3.23 mm) endoscope. The model was printed using a Stratasys Dimension Elite Plus printer. After printing, the model was post-processed to remove support materials. A 10-question survey was administered to all trainees before and after use of the printed phantom to practice endoscopy skills., Results: 11 trainees participated in the three-dimensional endoscopy simulation with most of the trainees (73%) having no prior formal endoscopy training. Using a 10-point Likert scale, the mean comfort-level of the trainees to use endoscopy alone for cholecystostomy, percutaneous biliary drainage, percutaneous nephrostomy, and percutaneous gastrostomy increased by 38.9%, 32.8%, 32.8%, and 34.3%, respectively, following the training experience., Conclusion: The use of a three-dimensionally printed endoscopic model as a simulation tool has the potential to improve trainee comfort using endoscopy during interventional radiology procedures., (Copyright © 2018. Published by Elsevier Inc.)

Purpose: To characterize the interventional radiology Twitter network by analyzing tweets bearing the #IRad hashtag., Materials and Methods: A total of 61,055 consecutive tweets bearing the hashtag #IRad composed by 5,704 Twitter users from January 8, 2015 to October 13, 2017 were analyzed. Twitter analytics, including activity metrics, content analysis, user characteristics, engagement, and network analysis, were obtained with the use of Symplur Signals, a health care social media analytics platform., Results: The number of tweets bearing the #IRad hashtag, the number of users, and the number of impressions increased by 124%, 76%, and 102%, respectively, over the past year. Regarding tweet content, 4,571 tweets (7.5%) reported new or innovative topics and 4,040 tweets (6.6%) pertained to patients; 19,409 (31.8%) tweets contained at least 1 image and 15,245 tweets (25.0%) included links to websites or journals. Embolization, ablation, and stent placement were commonly discussed topics. Endoscopy, transarterial chemoembolization, uterine artery embolization, and prostate artery embolization discussions were trending more commonly. As for engagement, there were 39,953 retweets (65.4%), 50,452 mentions (82.6%), and 1,704 replies (2.8%). Physicians and patients authored 29,182 (47.8%) and 127 (0.8%) tweets, respectively. Network analysis demonstrated advocate, provider, and media organizations, and physicians as the most active participants using the #IRad hashtag on Twitter., Conclusions: The use of the #IRad hashtag by interventional radiologists is growing rapidly, with the majority of discussions involving medical professionals and medical-related organizations., (Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.)

Background: Fractional lasers were introduced to provide increased safety, while maintaining high efficacy and patient satisfaction. Patients with virtually all Fitzpatrick skin types could be safely treated using a wide spectrum of wavelengths and a broad array of skin conditions, and aging could be addressed. Although safety studies have been reported for ablative CO 2 and erbium lasers, surprisingly few data are available on adverse events and complications associated with fractional lasers., Objective: We report the frequency of adverse events, skin improvement and complications in a broad range of skin types using a standardized protocol that can be safely tailored to the patient's presenting complaints by varying the laser wavelength and number of treatments., Materials and Methods: The medical records of 730 patients (>90% females, age ranged from 50.5. to 59.9 years.) who had been treated at FACES+ Aesthetic Facility were reviewed. Patients were followed from 1 to 10 months and were reviewed to determine the frequency of complications, as well as their frequency, type, cause, treatment and resolution thereof. Patients were categorized by Fitzpatrick skin type (I-IV) to determine whether skin type was related to the frequency of complications. Improvement in skin condition (wrinkles, nasolabial folds and pigment) was rated by a technician before and after treatment using a Likert scale, 0-5, with 0 being no change and 5 being the most improvement., Results: Seven hundred thirty patients underwent procedures using fractional lasers in our center. Procedures were carried out with 3 different laser wavelengths, depending on the condition(s) treated (wrinkling vs. pigmentation issues, etc.) and the patients' desired length of downtime. The fractional Fraxel 1927-nm laser was used in 224 patients [Fitzpatrick skin type I (2.2%), II (38.4%), III (46.0%), IV (12.5%)]; the fractional Fraxel 1550-nm laser was used in 334 [type I (4.5%), II (31.9%), III (50.0%), IV (13.3%)], and the fractional Fraxel CO 2 laser was used in 172 [type 1 (4.7%), II (49.7%), III (41.5%), IV (4.1%)]. The Fraxel CO 2 laser showed greater improvement in wrinkles and naso-labial fold (p < 0.001). The greatest improvement in pigmentation was seen with the Fraxel 1927-nm laser (p < 0.001). Adverse events and complications occurred in 31 of 730 patients (4.2%). There was no significant difference in the rate of complications among the three treatments (p = 0.26). Complications were generally minor, and all resolved completely with treatment. Complications occurred in 4.0% of patients having the fractional Fraxel 1927-nm laser, 3.3% of patients having the fractional Fraxel 1550 nm and 6.4% of patients having the fractional Fraxel CO 2 laser. Complications included 5 herpes simplex virus breakouts, 13 acne eruptions, 1 abrasion, 1 bacterial infection, 9 dermatitis, 1 drug eruption, 4 prolonged erythema, 1 hyperpigmentation, 1 increased swelling and 1 telangiectasia. There was no significant relationship between Fitzpatrick skin type and incidence of complications (p = 0.37)., Conclusions: Fractional lasers in general have reduced complication rates, while maintaining high degrees of patient satisfaction. Since their inception in early 2004, our clinic has utilized fractional lasers to treat patients from a variety of ethnic backgrounds and diverse skin types with an overall complication rate of 4.2%, all of which resolved. Comprehensive care of patients with facial aging is not limited to surgery alone and should include these types of strategies to appropriately and safely address photo-damage and photo-aging., Level of Evidence Iv: 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 .

Objectives: This study was designed to determine the predictive value of lipid hydroperoxide (LOOH) levels for adverse cardiovascular outcomes in patients with stable coronary artery disease (CAD)., Background: Oxidative modification of circulating lipids contributes to inflammation and endothelial dysfunction, which are hallmark features of atherosclerosis. A serum biomarker of oxidation is LOOH, which is a primary product of fatty acid peroxidation., Methods: Serum LOOH levels were measured and correlated with clinical events over a 3-year period in 634 patients with angiographic evidence of CAD., Results: Baseline LOOH levels in the highest quartile were associated with hazard ratios of 3.24 (95% confidence interval [CI] 1.86 to 5.65; p = 0.0001) for nonfatal vascular events (n = 149), 1.80 (95% CI 1.13 to 2.88; p = 0.014) for major vascular procedures (n = 139), and 2.23 (95% CI 1.44 to 3.44; p = 0.0003) for all vascular events and procedures. Baseline LOOH levels correlated with serum levels of soluble intercellular adhesion molecule-1 (p = 0.001) and thiobarbituric acid reactive substances (p = 0.001) as well as the mean percent change in stenosis for large segments >50% stenosed (p = 0.048). A multivariate proportional hazards model, adjusted for traditional risk factors and inflammatory markers, showed an independent effect of LOOH on nonfatal vascular events, vascular procedures, and all events or procedures. Amlodipine treatment was associated with reduced cardiovascular events and changes in LOOH levels compared with placebo., Conclusions: Elevated LOOH levels were predictive of nonfatal vascular events and procedures in patients with stable CAD, independent of traditional risk factors and inflammatory markers.

Objectives: The objective of this study was to test the predictive value of an oxidative stress biomarker in 634 patients from the Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT)., Background: Oxidative stress contributes to mechanisms of atherosclerosis and plaque instability. Biomarkers of oxidation, such as malondialdehyde (MDA), may represent independent indicators of risk for patients with stable coronary artery disease (CAD)., Methods: Serum MDA levels were measured as thiobarbituric acid reactive substances (TBARS) in 634 patients with documented CAD using reverse-phase high-performance liquid chromatography and spectrophotometric approaches., Results: During the three-year study, there were 51 major vascular events such as fatal/nonfatal myocardial infarction, 149 hospitalizations for nonfatal vascular events, and 139 patients underwent a major vascular procedure. At baseline, patients with TBARS levels in the highest quartile had a relative risk (RR) of 3.30 (95% confidence interval [CI] 1.47 to 7.42; p = 0.038) for major vascular events, RR of 4.10 (95% CI 2.55 to 6.60; p < 0.0001) for nonfatal vascular events, and RR of 3.84 (95% CI 2.56 to 5.76; p < 0.0001) for major vascular procedures. The effect of TBARS on events and procedures was also seen in a multivariate model adjusted for inflammatory markers (C-reactive protein, soluble intercellular adhesion molecule-1, interleukin-6), and other risk factors (age, low-density lipoprotein, high-density lipoprotein, total cholesterol, triglycerides, body mass index, and blood pressure). This analysis showed an independent effect of TBARS on major vascular events (p = 0.0149), nonfatal vascular events (p < 0.0001), major vascular procedures (p < 0.001), and all vascular events and procedures (p < 0.0001)., Conclusions: Serum levels of TBARS were strongly predictive of cardiovascular events in patients with stable CAD, independently of traditional risk factors and inflammatory markers.

Recent scientific and technologic advances generated from the human genome project have increased the ability of researchers to study human biological materials. This has enhanced the ease with which highly personal information such as genetic makeup can be revealed about individuals, families, and communities. In addition, a change in the societal value of human biological tissue from waste to commercial resource has occurred. A new model of stewardship is developed that can be used as a guide for protecting human research participants who are involved in studies that include collecting and handling human biological samples. Nursing implications to ensure protection of human research participants are discussed.

Objective: The Appropriate Blood Pressure Control in Diabetes (ABCD) Trial is a prospective randomized blinded clinical trial that compares the effects of intensive versus moderate blood pressure control on the incidence and progression of type 2 diabetic complications. The current article discusses the results of 5.3 years of follow-up of 470 patients with hypertension and evaluates the effects of intensive and moderate blood pressure therapy using nisoldipine versus enalapril as the initial antihypertensive medication for nephropathy, retinopathy, and neuropathy., Research Design and Methods: The 470 hypertensive subjects, defined as having a baseline diastolic blood pressure of > or = 90 mmHg, were randomized to intensive blood pressure control (diastolic blood pressure goal of 75 mmHg) versus moderate blood pressure control (diastolic blood pressure goal of 80-89 mmHg)., Results: The mean blood pressure achieved was 132/78 mmHg in the intensive group and 138/86 mmHg in the moderate control group. During the 5-year follow-up period, no difference was observed between intensive versus moderate blood pressure control and those randomized to nisoldipine versus enalapril with regard to the change in creatinine clearance. After the first year of antihypertensive treatment, creatinine clearance stabilized in both the intensive and moderate blood pressure control groups in those patients with baseline normo- or microalbuminuria. In contrast, patients starting with overt albuminuria demonstrated a steady decline in creatinine clearance of 5-6 ml.min-1.1.73 m-2 per year throughout the follow-up period whether they were on intensive or moderate therapy. There was also no difference between the interventions with regard to individuals progressing from normoalbuminuria to microalbuminuria (25% intensive therapy vs. 18% moderate therapy, P = 0.20) or microalbuminuria to overt albuminuria (16% intensive therapy vs. 23% moderate therapy, P = 0.28). Intensive therapy demonstrated a lower overall incidence of deaths, 5.5 vs. 10.7%, P = 0.037. Over a 5-year follow-up period, there was no difference between the intensive and moderate groups with regard to the progression of diabetic retinopathy and neuropathy. In addition, the use of nisoldipine versus enalapril had no differential effect on diabetic retinopathy and neuropathy., Conclusions: Blood pressure control of 138/86 or 132/78 mmHg with either nisoldipine or enalapril as the initial antihypertensive medication appeared to stabilize renal function in hypertensive type 2 diabetic patients without overt albuminuria over a 5-year period. The more intensive blood pressure control decreased all-cause mortality.

Non-insulin-dependent diabetes mellitus (NIDDM) and hyperhomocysteinemia are both associated with premature vascular disease. We tested the hypothesis that homocysteine is associated with vascular disease and other diabetic complications in patients with NIDDM. The current investigation is a cross-sectional analysis of baseline variables for participants in the Appropriate Blood Pressure Control in Diabetes (ABCD) Trial. Men and women aged 40 to 74 years with NIDDM and a mean diastolic blood pressure (BP) of 80 mm Hg or higher were eligible. We measured serum levels of total homocysteine (tHcy), cystathionine, and methylmalonic acid (MMA) and correlated these values with clinical and other laboratory measures of the complications of diabetes mellitus in 452 subjects. tHcy was higher in males than in females and correlated with the duration of hypertension and systolic BP. tHcy was significantly correlated with MMA (r = .35, P < .0001) and cystathionine (r = .53, P < .0001) levels and inversely correlated with serum B12 (r = -.23, P < .0001) and folate (r = -.18, P < .0001). It was significantly correlated with serum creatinine (r = .28, P < .0001 for males and r = .39, P < .0001 for females) and inversely correlated with creatinine clearance (r = -.19, P < .005 for males and r = -.30, P < .0001 for females). tHcy was not increased in subjects with cardiovascular disease or retinopathy, but it was increased in those with neuropathy (10.3 v 9.3 micromol/L, P < .05) and macroalbuminuria (11.0 v 9.2 micromol/L, P < .005). Of these subjects, 2.2% met the criteria for vitamin B12 deficiency and 1% met the criteria for folate deficiency. We conclude that elevations of tHcy in this population appear to be the result of a combination of vitamin deficiency and decreased renal function and do not appear to be a predictor of cardiovascular disease.

Previous studies evaluating the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism have revealed that expression of the DD genotype is associated with an increase in myocardial infarction, cardiomyopathy, and left ventricular (LV) mass in nondiabetic patients. In the present study, a cross-sectional analysis was performed to evaluate the potential relationship between the ACE I/D genotypes and the LV mass index in 289 non-insulin-dependent diabetes mellitus (NIDDM) subjects without known coronary artery disease. Two dimensional directed M-mode echocardiograms along with selected patient characteristics were obtained from the study population. The distribution of the I/D polymorphism was as follows: 63 were II (22%), 137 were ID (47%), and 89 were DD (31%). Univariately, the DD genotype was associated with an increase in LV mass in men but not in women. When subjected to a multiple regression model that included age, systolic blood pressure, duration of diabetes, duration of hypertension, presence of the black race, and the presence of the DD genotype, the DD genotype was independently associated with an increase in the LV mass index with a parameter estimate of 10.5 g/m2 (95% CI = 3.9, 17.0; P < .002) in the male subjects. Thus, in this NIDDM study population, male patients with the DD genotype are independently associated with an increased LV mass.

The purpose of this study was to determine oxygen consumption (VO2), carbon dioxide production (VCO2), and energy expenditure (EE) in a group of preterm ventilated infants during the first 3 weeks of life, and to determine the major factors that influence EE. Thirty-eight indirect calorimetry studies were performed in 18 ventilated infants with mean gestational age of 27.9 +/- 0.6 (SEM) weeks. The relationship of demographic factors, nutrient intake, and severity of illness assessments of EE were determined by regression analysis. Repeated measure analysis was performed for the effect of multiple studies in the same patient. Although VO2, VCO2, and EE all tended to increase over the first 3 weeks of life, there was a wide range of values. EE was best predicted by nonprotein calorie intake and postnatal age, while there was no correlation with birthweight, weight at the time of study, gestational age, protein intake, or severity of illness. Multiple regression analyses demonstrated a strong interaction between PNA and EI. In this population EE is best predicted by PNA and EI. The interactive effect between PNA and EI on EE is probably explained by the clinical practice of daily increments in substrate intake in these patients.

Purpose: To explore the experiences, thoughts, and feelings of surrogates making decisions for older adults. To identify nursing practices perceived as helpful to surrogates., Sample: Eleven surrogate decision-makers., Method: Qualitative. Semi-structured interviews/descriptive data used to enrich a larger study., Findings: Four main themes were identified that described the surrogates' experiences: Contextualizing the decision Actualizing agency Reviewing and resolving Transcending, Clinical Implications: Three paradigm cases describe caregiving, protecting, and trusting response patterns of surrogates. Surrogates found decision-making an evolving and difficult process. Nurses can be more helpful to surrogates by giving them more opportunities to ask questions, solicit information, express emotions and obtain comfort and support.

In conditions associated with insulin resistance, insulin-like growth factor binding protein-I (IGFBP-I) levels have been shown to correlate inversely with insulin levels. Puberty is associated with insulin resistance and thus provides a model for comparing the relationship of IGFBP-I to both insulin levels and measures of insulin sensitivity. Our study population consisted of 104 healthy pubertal children, age 9.8-14.6 yr. Each subject had his/her insulin sensitivity (Si) assessed by the modified minimal model of Bergman, which employs a frequently sampled i.v. glucose tolerance test. Results showed that IGFBP-I levels were significantly higher in boys than in pubertally matched girls (P < 0.01). There was a strong positive correlation between IGFBP-I levels and Si (r = 0.65, P < 0.0001) and a weaker negative correlation with fasting insulin levels (r = -0.38, P < 0.0001). An inverse relationship was also found between IGFBP-I levels and body mass index (r = -0.46, P < 0.0001) and with IGF-I levels (girls only, r = -0.41, P < 0.003). Consequently, insulin sensitivity, obesity, and IGF-I are important predictors of IGFBP-I levels in pubertal children. It is possible that insulin-mediated suppression of IGFBP-I in obese children may increase free IGF-I levels and thus contribute to somatic growth. The same mechanism may operate in pubertal children, where insulin resistance and growth acceleration occur simultaneously.

Non-insulin-dependent diabetes mellitus (NIDDM) occurs with a higher frequency in Hispanic as compared with non-Hispanic whites. It also appears that there is a higher prevalence of diabetic nephropathy in the Hispanic population when compared with non-Hispanic whites. In the current study, 144 Hispanics and 671 non-Hispanic white NIDDM subjects were studied to determine the possible association of various risk factors and diabetic complications, including overt albuminuria, with diabetic retinopathy. Stereoscopic retinal fundus photographs were obtained and graded by the University of Wisconsin Fundus Photographic Reading Center. We also sought to determine whether risk factors for retinopathy vary between Hispanics and non-Hispanic whites. In the total group, duration of diabetes, glycosylated hemoglobin, neuropathy, diastolic hypertension, use of insulin, and Hispanic ethnicity correlated with the presence of retinopathy. Controlling for severity and duration of diabetes, Hispanics had a significantly increased risk of retinopathy relative to non-Hispanic whites (OR = 2.13, 95% CI = 1.34, 3.37, P = 0.0013). Duration of diabetes and presence of neuropathy were significantly correlated with the presence of diabetic retinopathy in Hispanics and non-Hispanic whites. The presence of overt albuminuria (>200 microg/min), although not related to diabetic retinopathy in non-Hispanic whites, conferred a high risk for diabetic retinopathy in Hispanics (OR = 11.14, CI = 1.20, 103.39, P = 0.0339) independent of other risk factors. In summary, Hispanics with NIDDM have an increased prevalence of diabetic retinopathy when compared with non-Hispanic whites. In addition, overt albuminuria in the Hispanic subjects appears to be a powerful predictor of the diabetic retinopathy.