Many studies demonstrated that surgical guides might reduce discrepancies compared with freehand implant placement. This randomized crossover study aimed to assess the effects of approaches, ...practitioners' experience and learning sequences on the accuracy of single tooth implantation via digital registration method. No similar study was found.
This in vitro randomized crossover study enrolled 60 novice students (Group S) and 10 experienced instructors (Group I). Sixty students were randomly and evenly assigned to two groups (Group SA and SB). In Group SA, 30 students first performed single molar implant on a simulation model freehand (Group SAFH), and then with a CAD/CAM surgical guide (Group SASG). In Group SB, another 30 students first performed guided (Group SBSG) and then freehand (Group SBFH). Ten instructors were also divided into Group IAFH/IASG (n = 5) and IBSG/IBFH (n = 5) following the same rules. The accuracy of implant placement was assessed by the coronal and apical distance (mm) and angular (°) deviations using the digital registration method. T tests and nonparametric tests were used to compare the results among different groups of approaches, experience and sequences.
For students, the coronal and apical distance and the angular deviations were significantly lower in surgical guide group than freehand group in total and in learning freehand first subgroup, but for learning surgical guide first subgroup the apical distance deviation showed no significant difference between two approaches. For students, the angular deviation of freehand group was significantly lower in learning surgical guide first group than learning freehand first group. For instructors, the coronal and apical distance and angular deviations showed no significant difference between two approaches and two sequences. For freehand approach, the coronal and apical distance and the angular deviations were significantly higher in student group than instructor group, while not significantly different between two groups for surgical guide approach.
For novices, using a surgical guide for the first implant placement may reduce the potential deviations compared with freehand surgery, and may reach a comparable accuracy with that of specialists. For simple single molar implantation, the surgical guide may not be significantly helpful for experienced specialists.
Arterial stiffness independently predicts cardiovascular disease. However, few studies have evaluated the associations of central and peripheral pulse wave velocity (PWV) with biomarkers of both ...myocardial stress (natriuretic peptide NT-proBNP) and damage (high-sensitivity cardiac troponin-T hs-cTnT) among persons without cardiac disease.
We examined 3,348 participants (67-90 years) without prevalent cardiac disease in the Atherosclerosis Risk in Communities (ARIC) Study (2011-13). The cross-sectional associations of PWV quartiles for central arterial segments (carotid-femoral, heart-carotid, heart-femoral) and peripheral artery (femoral-ankle) with NT-proBNP and hs-cTnT were evaluated accounting for potential confounders.
Most PWV measures demonstrated J- or U-shaped associations with the two cardiac biomarkers. The highest (Q4) vs. second lowest (Q2) quartile of central PWV measures (carotid-femoral, heart-carotid, heart-femoral PWV) were associated with higher levels of NT-proBNP independently of demographic characteristics. The associations were less evident for hs-cTnT. These associations were attenuated after adjusting for traditional cardiovascular risk factors, but the heart-carotid PWV-NT-proBNP relationship remained borderline significant (difference in log-NT-proBNP = 0.08 -0.01, 0.17 in Q4 vs. Q2, p = 0.07). Peripheral PWV demonstrated inverse associations. Higher values of NT-proBNP were seen in the lowest vs. second lowest quartile of all PWV measures.
Central stiffness measures showed stronger associations with cardiac biomarkers (particularly NT-proBNP) than peripheral measures among older adults without cardiac disease. Our findings are consistent with the concept of ventricular-vascular coupling and suggest that central rather than peripheral arterial hemodynamics are more closely related to myocardial stress rather than damage.
Background
Evidence regarding the association of lower extremity peripheral arterial disease with quality of life (QOL) is mainly from selected clinical populations or relatively small clinical ...cohorts. Thus, we investigated this association in community‐derived populations.
Methods and Results
Using data of 5115 participants aged 66 to 90 years from visit 5 (2011‐2013) of the Atherosclerosis Risk in Communities Study, we quantified the associations of ankle‐brachial index (ABI) with several QOL parameters, including 12‐item Short‐Form Health Survey (SF‐12), after accounting for potential confounders using linear and logistic regression models. Peripheral arterial disease defined by an ABI <0.90 (n=402), was independently associated with a low SF‐12 Physical Component Summary score (−3.26 95% CI −5.60 to −0.92), compared to the ABI reference 1.10 to 1.19 (n=1900) but not with the Mental Component Summary score (−0.07 −2.21 to 2.06). A low ABI was significantly associated with poorer status of all SF‐12 physical domains (physical functioning, role‐physical, bodily pain, and general health) but only vitality out of 4 mental domains. Similarly, low ABI values were more consistently associated with other physically related QOL parameters (leisure‐time exercise/activity/walking) than mentally related parameters (significant depressive symptoms and hopeless feeling). Lower physical QOL was observed even in individuals with borderline low ABI (0.90 to 0.99; n=426).
Conclusions
Low ABI (even borderline) was independently associated with poor QOL, especially for physical components, in community‐dwelling older adults. QOL is a critical element for older adults, and thus, further studies are warranted to assess whether peripheral arterial disease‐specific management can improve QOL in older populations.
Background Antiplatelets, anticoagulants, and statins are commonly prescribed for various indications. The associations between these medications and the risk of intracerebral hemorrhage (ICH) and ...cerebral microbleeds (CMBs) are unclear. Methods and Results We performed a retrospective study of the ARIC (Atherosclerosis Risk in Communities) study cohort, recruited from 4 US communities in 1987 to 1989 with follow-up. In 2011 to 2013, a subset (N=1942) underwent brain magnetic resonance imaging with CMB evaluation. Time-varying and any antiplatelet, anticoagulant, or statin use was evaluated at subsequent study visits in participants not on each medication at baseline. To determine the hazard of ICH and odds of CMB by medication use, logistic and Cox proportional hazard models were built, respectively, adjusting for the propensity to take the medication, concomitant use of other medications, and cognitive, genetic, and radiographic data. Of 15 719 individuals during up to 20 years of follow-up, 130 participants experienced an ICH. The adjusted hazard of ICH was significantly lower among participants taking an antiplatelet at the most recent study visit before ICH versus nonusers (hazard ratio HR, 0.53; 95% CI, 0.30-0.92). Statin users had a significantly lower hazard of an ICH compared with nonusers (adjusted HR, 0.13; 95% CI, 0.05-0.34). There was no association of CMB and antiplatelet, anticoagulant, or statin use in adjusted models. Conclusions In this US community-based study, antiplatelet and statin use were associated with lower ICH hazard, whereas no association was noted between CMBs and antiplatelets, anticoagulants, and statins. Further study is needed to understand the differential roles of these medications in cerebral microhemorrhages and macrohemorrhages.
OBJECTIVES/SPECIFIC AIMS: Our study seeks to answer the following questions: (1) To determine whether higher numbers of gravidity and parity are associated with a decreased risk of mild cognitive ...impairment or dementia; (2) To determine whether higher numbers of gravidity and parity are associated with a decreased risk of amyloid deposition by PET MRI. METHODS/STUDY POPULATION: Our study population includes all female study participants in the Atherosclerosis Risk in Communities (ARIC) study who did not have a diagnosis of dementia before enrollment. Participants were also required to have been evaluated for cognitive impairment in the ARIC-NCS ancillary study, or to have received an MRI PET scan of their brain as part of the ARIC-PET ancillary study. Baseline information on the gravidity and parity of all the women was recorded at initial enrollment. We use statistical analyses and epidemiological measures to explore our study questions. For our first question, we use logistic regression to evaluate the association of gravidity and parity as two separate ordinal variables using adjudicated mild cognitive impairment (MCI) and dementia. For our second question, we use logistic regression to evaluate the association of gravidity and parity (again as ordinal variables) with amyloid positivity. We use STATA for our statistical analyses. RESULTS/ANTICIPATED RESULTS: We hypothesize that increased gravidity and parity will have either no effect or a protective effect against MCI, dementia, and amyloid deposition. Our preliminary analyses show that older age of a woman at first pregnancy and at first live birth are both positively correlated with increased incidence of cognitive impairment. No relationship was found between these surrogates of lifetime estrogen exposure and cerebral amyloid deposition. DISCUSSION/SIGNIFICANCE OF IMPACT: Multiple basic science and clinical research studies have shown that estrogen exposure has an effect on cognitive function, likely through a complex interplay of multiple physiologic systems. Our study expands the research in this area by using a large, established epidemiologic cohort to examine gravidity and parity as important factors in lifetime estrogen exposure as they relate to cognitive impairment and amyloid plaque deposition.
Approximately 1 million patients in the United States with type 2 diabetes mellitus and mild-to-moderate kidney disease do not receive guideline-directed therapy with metformin. This may reflect ...uncertainty regarding the risk of acidosis in patients with chronic kidney disease.
To quantify the association between metformin use and hospitalization with acidosis across the range of estimated glomerular filtration rate (eGFR), accounting for change in eGFR stage over time.
Community-based cohort of 75 413 patients with diabetes in Geisinger Health System, with time-dependent assessment of eGFR stage from January 2004 until January 2017. Results were replicated in 67 578 new metformin users and 14 439 new sulfonylurea users from 2010 to 2015, sourced from 350 private US health systems.
Metformin use.
Hospitalization with acidosis (International Classification of Diseases, Ninth Revision, Clinical Modification code of 276.2).
In the primary cohort (n = 75 413), mean (SD) patient age was 60.4 (15.5) years, and 51% (n = 38 480) of the participants were female. There were 2335 hospitalizations with acidosis over a median follow-up of 5.7 years (interquartile range, 2.5-9.9 years). Compared with alternative diabetes management, time-dependent metformin use was not associated with incident acidosis overall (adjusted hazard ratio HR, 0.98; 95% CI, 0.89-1.08) or in patients with eGFR 45 to 59 mL/min/1.73 m2 (adjusted HR, 1.16; 95% CI, 0.95-1.41) and eGFR 30 to 44 mL/min/1.73 m2 (adjusted HR, 1.09; 95% CI, 0.83-1.44). On the other hand, metformin use was associated with an increased risk of acidosis at eGFR less than 30 mL/min/1.73 m2 (adjusted HR, 2.07; 95% CI, 1.33-3.22). Results were consistent when new metformin users were compared with new sulfonylurea users (adjusted HR for eGFR 30-44 mL/min/1.73 m2, 0.77; 95% CI, 0.29-2.05), in a propensity-matched cohort (adjusted HR for eGFR 30-44 mL/min/1.73 m2, 0.71; 95% CI, 0.45-1.12), when baseline insulin users were excluded (adjusted HR for eGFR 30-44 mL/min/1.73 m2, 1.16; 95% CI, 0.87-1.57), and in the replication cohort (adjusted HR for eGFR 30-44 mL/min/1.73 m2, 0.86; 95% CI, 0.37-2.01).
In 2 real-world clinical settings, metformin use was associated with acidosis only at eGFR less than 30 mL/min/1.73 m2. Our results support cautious use of metformin in patients with type 2 diabetes and eGFR of at least 30 mL/min/1.73 m2.
To examine the association between systemic inflammation measured during midlife and 20-year cognitive decline.
Within the Atherosclerosis Risk in Communities cohort study, inflammatory biomarkers ...were measured during middle adulthood. We created an inflammation composite score using 4 blood biomarkers measured at visit 1 (fibrinogen, white blood cell count, von Willebrand factor, and factor VIII); we measured C-reactive protein (CRP) at visit 2. Cognition was assessed over 3 visits spanning 20 years using measures of memory, executive function, and language.
A total of 12,336 participants (baseline age 56.8 5.7, 21% black, 56% women) were included. After adjusting for demographic variables, vascular risk factors, and comorbidities, each standard deviation (SD) increase in midlife inflammation composite score was associated with an additional 20-year decline of -0.035 SD (95% confidence interval: -0.062 to -0.007) on the cognitive composite score. We found a similar association between each SD increase in midlife CRP level and additional 20-year cognitive decline (-0.038 SD, 95% confidence interval: -0.057 to -0.019). Participants with a midlife inflammation composite score in the top quartile had a 7.8% steeper cognitive decline, compared to participants in the lowest quartile; CRP in the top quartile was associated with an 11.6% steeper cognitive decline. In cognitive domain-specific analyses, elevated midlife inflammatory markers were most consistently associated with declines in memory. Results were similar after adjusting for attrition using inverse probability weighting.
Our findings highlight what may be an early pathogenic role for systemic inflammation as a driver of cognitive decline in the decades leading up to older adulthood.
The association between late-life blood pressure (BP) and cognition may depend on the presence and chronicity of past hypertension. Late-life declines in blood pressure following prolonged ...hypertension may be associated with poor cognitive outcomes.
To examine the association of midlife to late-life BP patterns with subsequent dementia, mild cognitive impairment, and cognitive decline.
The Atherosclerosis Risk in Communities prospective population-based cohort study enrolled 4761 participants during midlife (visit 1, 1987-1989) and followed-up over 6 visits through 2016-2017 (visit 6). BP was examined over 24 years at 5 in-person visits between visits 1 and 5 (2011-2013). During visits 5 and 6, participants underwent detailed neurocognitive evaluation. The setting was 4 US communities: Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and Minneapolis, Minnesota. Follow-up ended on December 31, 2017.
Five groups based on longitudinal patterns of normotension, hypertension (>140/90 mm Hg), and hypotension (<90/60 mm Hg) at visits 1 to 5.
Primary outcome was dementia onset after visit 5, based on Ascertain Dementia-8 informant questionnaires, Six-Item Screener telephone assessments, hospital discharge and death certificate codes, and the visit 6 neurocognitive evaluation. Secondary outcome was mild cognitive impairment at visit 6, based on the neurocognitive evaluation.
Among 4761 participants (2821 59% women; 979 21% black race; visit 5 mean SD age, 75 5 years; visit 1 mean age range, 44-66 years; visit 5 mean age range, 66-90 years), there were 516 (11%) incident dementia cases between visits 5 and 6. The dementia incidence rate for participants with normotension in midlife (n = 833) and late life was 1.31 (95% CI, 1.00-1.72 per 100 person-years); for midlife normotension and late-life hypertension (n = 1559), 1.99 (95% CI, 1.69-2.32 per 100 person-years); for midlife and late-life hypertension (n = 1030), 2.83 (95% CI, 2.40-3.35 per 100 person-years); for midlife normotension and late-life hypotension (n = 927), 2.07 (95% CI, 1.68-2.54 per 100 person-years); and for midlife hypertension and late-life hypotension (n = 389), 4.26 (95% CI, 3.40-5.32 per 100 person-years). Participants in the midlife and late-life hypertension group (hazard ratio HR, 1.49 95% CI, 1.06-2.08) and in the midlife hypertension and late-life hypotension group (HR, 1.62 95% CI, 1.11-2.37) had significantly increased risk of subsequent dementia compared with those who remained normotensive. Irrespective of late-life BP, sustained hypertension in midlife was associated with dementia risk (HR, 1.41 95% CI, 1.17-1.71). Compared with those who were normotensive in midlife and late life, only participants with midlife hypertension and late-life hypotension had higher risk of mild cognitive impairment (37 affected individuals (odds ratio, 1.65 95% CI, 1.01-2.69). There was no significant association of BP patterns with late-life cognitive change.
In this community-based cohort with long-term follow-up, sustained hypertension in midlife to late life and a pattern of midlife hypertension and late-life hypotension, compared with midlife and late-life normal BP, were associated with increased risk for subsequent dementia.
Purpose
Choosing four or six implants to support immediate full‐arch fixed prostheses (FAFPs) is still controversial worldwide. This study aims to analyze and compare the long‐term results of ...All‐on‐4 and All‐on‐6.
Materials and Methods
This retrospective cohort study enrolled 217 patients rehabilitated with 1222 implants supporting 271 FAFPs, including 202 prostheses supported by 4 implants (All‐on‐4 group) and 69 prostheses supported by 6 implants (All‐on‐6 group), and followed up for 3–13 years. Implant survival, prosthesis survival, complications, and implant marginal bone loss (MBL) were evaluated and compared between two groups. Patient characteristics including age, gender, jaw, opposite dentition condition, smoking habit, bruxism, bone quantity and quality, cantilever length (CL), prosthesis material, and oral hygiene were analyzed to assess their influence on the clinical results of the two groups. Six surgeons and three prosthodontists who performed FAFPs more than 5 years were invited for questionnaires, to assess patient‐ and clinician‐related influences on implant number.
Result
In general, All‐on‐4 group indicated no significant difference with All‐on‐6 group in the implant survival (implant‐level: hazard ratio HR = 1.0 95% confidence interval (CI): 0.8–1.2, P = 0.96; prosthesis‐level: HR = 0.8 95% CI: 0.3–1.8, P = 0.54), prosthesis survival (odds ratio OR = 0.8 95% CI: 0.3–2.8, P = 0.56), biological complications (OR = 0.9 95% CI: 0.5–1.8, P = 0.78), technical complications of provisional prosthesis (OR = 1.3 95% CI: 0.7–2.3, P = 0.42), technical complications of definitive prosthesis (OR = 1.1 95% CI: 0.6–2.2, P = 0.33) and the 1st, 5th, and 10th year MBL (P = 0.65, P = 0.28, P = 0.14). However, for specific covariates, including elderly patients, opposing natural/fixed dentition, smoking, bruxism, long CL, low bone density, and all acrylic provisional prostheses, All‐on‐6 was more predictable in some clinical measurements than All‐on‐4. The implant prosthodontists and the medium‐experienced clinicians showed significant preference for All‐on‐6 (P < 0.05).
Conclusion
Based on this study, the long‐term clinical results showed no significant difference between All‐on‐4 and All‐on‐6 groups in general. However, for some specific characteristics, All‐on‐6 seemed to be more predictable in some clinical measurements than All‐on‐4. For the clinicians' decision‐making, medium‐experienced clinicians and the implant prosthodontists showed significant preference for All‐on‐6.
Hereditary transthyretin-mediated (ATTRv/hATTR) amyloidosis is a rare genetic disease that runs in families, affecting about 50,000 people worldwide. This condition results in abnormal protein ...deposits building up, causing damage to multiple nerves (polyneuropathy) and other organs, which can shorten lifespan and have other harmful effects. Polyneuropathy symptoms include weakness, numbness, pain, dizziness, and diarrhea. Over time, everyday activities become more difficult as patients become increasingly disabled and dependent on others. Several treatments have been approved for the polyneuropathy of ATTRv amyloidosis. Many of these work in different ways to impact the disease process. An indirect treatment comparison is a well-established statistical method used by healthcare decision-makers to compare treatments when head-to-head trials are unavailable. Indirect treatment comparisons using a common approach, the Bucher method, yield similar conclusions to head-to-head studies over 90% of the time. This method was used to compare clinical trial data for tafamidis and vutrisiran, two approved treatments for ATTRv amyloidosis with polyneuropathy. The findings show that vutrisiran is more effective than tafamidis at addressing the polyneuropathy of ATTRv amyloidosis as measured by changes to sensory or motor nervous system functioning and nutritional status. Also, vutrisiran showed greater maintenance of health-related quality of life compared to tafamidis. The expected benefits of vutrisiran over tafamidis are large enough to be noticeable and clinically meaningful to a patient or clinician. This highlights the potential advantages of vutrisiran compared to tafamidis with regard to preservation of physical function and quality of life when treating ATTRv amyloidosis with polyneuropathy.
Vutrisiran and tafamidis are approved therapies for treating hereditary transthyretin-mediated (ATTRv/hATTR) amyloidosis with polyneuropathy, a rapidly progressive and fatal disease. To assist healthcare decision-makers, an indirect treatment comparison (ITC) was undertaken to explore the comparative efficacy of vutrisiran and tafamidis.
Individual patient data (vutrisiran vs. placebo) and published results (tafamidis vs. placebo) from phase 3 randomized controlled trials were used in a Bucher analysis to assess differences in treatment effects between vutrisiran and tafamidis on: Neuropathy Impairment Score-Lower Limbs (NIS-LL), Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) score, NIS-LL Response, and modified Body Mass Index (mBMI).
Greater treatment effects were observed at 18 months with vutrisiran vs. tafamidis for all endpoints, with statistically significant improvements in polyneuropathy (relative mean change in NIS-LL: −5.3 95% confidence interval (CI): −9.4, −1.2; p = 0.011), health-related quality of life (HRQOL, relative mean change in Norfolk QOL-DN: −18.3 95% CI: −28.6, −8.0; p < 0.001), and nutritional status (relative mean change in mBMI: 63.9 95% CI: 10.1, 117.7; p = 0.020).
This analysis suggests vutrisiran has greater efficacy on multiple measures of polyneuropathy impairment and HRQOL compared to tafamidis in patients with ATTRv amyloidosis with polyneuropathy.
PDF
