Cost-effectiveness analysis of surgical proximal femur fracture prevention in elderly: a Markov cohort simulation model.

BACKGROUND: Hip fractures are a common and costly health problem, resulting in significant morbidity and mortality, as well as high costs for healthcare systems, especially for the elderly. Implementing surgical preventive strategies has the potential to improve the quality of life and reduce the burden on healthcare resources, particularly in the long term. However, there are currently limited guidelines for standardizing hip fracture prophylaxis practices. METHODS: This study used a cost-effectiveness analysis with a finite-state Markov model and cohort simulation to evaluate the primary and secondary surgical prevention of hip fractures in the elderly. Patients aged 60 to 90 years were simulated in two different models (A and B) to assess prevention at different levels. Model A assumed prophylaxis was performed during the fracture operation on the contralateral side, while Model B included individuals with high fracture risk factors. Costs were obtained from the Centers for Medicare & Medicaid Services, and transition probabilities and health state utilities were derived from available literature. The baseline assumption was a 10% reduction in fracture risk after prophylaxis. A sensitivity analysis was also conducted to assess the reliability and variability of the results. RESULTS: With a 10% fracture risk reduction, model A costs between $8,850 and $46,940 per quality-adjusted life-year ($/QALY). Additionally, it proved most cost-effective in the age range between 61 and 81 years. The sensitivity analysis established that a reduction of ≥ 2.8% is needed for prophylaxis to be definitely cost-effective. The cost-effectiveness at the secondary prevention level was most sensitive to the cost of the contralateral side's prophylaxis, the patient's age, and fracture treatment cost. For high-risk patients with no fracture history, the cost-effectiveness of a preventive strategy depends on their risk profile. In the baseline analysis, the incremental cost-effectiveness ratio at the primary prevention level varied between $11,000/QALY and $74,000/QALY, which is below the defined willingness to pay threshold. CONCLUSION: Due to the high cost of hip fracture treatment and its increased morbidity, surgical prophylaxis strategies have demonstrated that they can significantly relieve the healthcare system. Various key assumptions facilitated the modeling, allowing for adequate room for uncertainty. Further research is needed to evaluate health-state-associated risks.

Retinal vessel caliber and caliber responses in true normotensive black and white adults: The African-PREDICT study.

PURPOSE: Globally, a detrimental shift in cardiovascular disease risk factors and a higher mortality level are reported in some black populations. The retinal microvasculature provides early insight into the pathogenesis of systemic vascular diseases, but it is unclear whether retinal vessel calibers and acute retinal vessel functional responses differ between young healthy black and white adults. METHODS: We included 112 black and 143 white healthy normotensive adults (20-30 years). Retinal vessel calibers (central retinal artery and vein equivalent (CRAE and CRVE)) were calculated from retinal images and vessel caliber responses to flicker light induced provocation (FLIP) were determined. Additionally, ambulatory blood pressure (BP), anthropometry and blood samples were collected. RESULTS: The groups displayed similar 24 h BP profiles and anthropometry (all p > .24). Black participants demonstrated a smaller CRAE (158 ±â€¯11 vs. 164 ±â€¯11 MU, p < .001) compared to the white group, whereas CRVE was similar (p = .57). In response to FLIP, artery maximal dilation was greater in the black vs. white group (5.6 ±â€¯2.1 vs. 3.3 ±â€¯1.8%; p < .001). CONCLUSIONS: Already at a young age, healthy black adults showed narrower retinal arteries relative to the white population. Follow-up studies are underway to show if this will be related to increased risk for hypertension development. The reason for the larger vessel dilation responses to FLIP in the black population is unclear and warrants further investigation.

Dynamic retinal vessel response to flicker in obesity: A methodological approach.

Obesity and related metabolic disorders affect vascular endothelial function. The use of the Dynamic Vessel Analyzer (DVA) represents a modern methodological approach to analyze vascular function in the retinal microcirculation. Whether the dynamic reaction to flicker stimulation in retinal vessels is altered in obese subjects is investigated. Retinal vessel reactions to flicker stimulation were examined by DVA in 46 obese individuals (49.6±10.0years) and 46 age- and gender-matched healthy controls. The clinical examination included anthropometry, blood pressure measurements and blood sampling. Mean maximal arteriolar dilation in response to flicker was reduced in the obese group (3.2±1.8%) compared to controls (4.1±2.0%, p<0.05) and the time to maximal arteriolar dilation was prolonged (18.0±9.4s vs. 14.6±3.8s, p=0.03). In addition, mean maximal venular dilation was reduced in obese subjects (3.9±1.7% vs. 4.7±1.8%, p<0.05). Among the microvascular parameters, the most significant correlation with waist circumference was found for the "area under the reaction curve 50-80s after stimulation" in arterioles (r=-0.40; p<0.001). Functional retinal arteriolar reactivity to flicker stimulation differs between obese and healthy lean subjects. Time course analysis of retinal vessel response and its quantitative parameters can comprehensively characterize alterations of retinal vessel reactivity in metabolic disease.

Non-penetrating intracanalicular partial trabeculectomy via the ostia of Schlemm's canal.

BACKGROUND: In order to distinguish a more pronounced and sustained hypotensive effect of non-penetrating glaucoma surgery, a modified surgical procedure is proposed, which provides enlargement of the filtration membrane area with maximal maintenance of natural aqueous outflow pathways. METHODS: In 21 eyes of 17 patients with open-angle glaucoma (intraocular pressure: 32.4 ± 4.7 mmHg; age: 69.2 ± 4.4 years) the following non-penetrating surgery was performed. After the excision of the outer wall of Schlemm's canal, outer layers of the trabecular meshwork were removed with a trabecular spatula (Geuder AG, G-16240) at the site of the open area of Schlemm's canal. A cannula-harpoon (Geuder AG, G-S02199) was introduced through both Schlemm's canal ostia, between the less permeable and well-permeable trabecular layers and separating them. Due to the harpoon configuration of the cannula, the superficial less permeable trabecular layers were removed within Schlemm's canal adjacent to its ostia during the retracting movement of the cannula. Thus, the filtration zone became extended using the outflow pathways into Schlemm's canal. RESULTS: A postoperative intraocular pressure of 13.4 ± 2.3 mmHg after 2 years of follow-up was measured. In all 21 eyes the hypotensive effect was absolute (without medications). In seven cases (33%) a hyphema had occurred during surgery, which dissolved in all cases within 2-3 days postoperatively. CONCLUSIONS: The results of the study demonstrate a pronounced and sustained effect of the modified surgery technique, and show that this surgery can be applied successfully in patients with therapy-resistant open-angle glaucoma. Further randomized prospective studies with larger case numbers are needed for generalized conclusions for a large population.

Retinal microvasculature and masked hypertension in young adults: the African-PREDICT study.

Masked hypertension is known to induce microvascular complications. However, it is unclear whether early microvascular changes are already occurring in young, otherwise healthy adults. We therefore investigated whether retinal microvascular calibers and acute responses to a flicker stimulus are related to masked hypertension. We used the baseline data of 889 participants aged 20-30 years who were taking part in the African Prospective study on the Early Detection and Identification of Cardiovascular Disease and Hypertension. Clinic and 24-h ambulatory blood pressure were measured. The central retinal artery equivalent (CRAE) and central retinal vein equivalent were calculated from fundus images, and retinal vessel dilation was determined in response to flicker light-induced provocation. A smaller CRAE was observed in those with masked hypertension vs. those with normotension (157.1 vs. 161.2 measuring units, P < 0.001). In forward multivariable-adjusted regression analysis, only CRAE was negatively related to masked hypertension [adjusted R2 = 0.267, ß = -0.097 (95% CI = -0.165; -0.029), P = 0.005], but other retinal microvascular parameters were not associated with masked hypertension. In multivariable logistic regression analyses, masked hypertension [OR = 2.333, (95% CI = 1.316; 4.241), P = 0.004] was associated with a narrower CRAE. In young healthy adults, masked hypertension was associated with retinal arteriolar narrowing, thereby reflecting early microvascular alterations known to predict cardiovascular outcomes in later life.

Postoperative aqueous outflow in the human eye after glaucoma filtration surgery: biofluidmechanical considerations.

To evaluate the possible postoperative outflow from the anterior chamber of the eye after filtration surgery, a mathematical model based on fluid mechanical principles and clinical data is proposed. Two ophthalmic surgical procedures, non-penetrating deep sclerectomy and trabeculectomy, were analyzed. Based on mathematical modeling, the amount of postoperative outflow through the fistula (after trabeculectomy) or membrane (after non-penetrating surgery) as well as the outflow through residual natural drainage pathways were calculated and compared. From our model, the following results were obtained: 1) if trabeculectomy is carried out in an eye with preoperative intraocular pressure (IOP) of 30 mm Hg and postoperative IOP=10 mm Hg, only 10% of aqueous utilizes the natural outflow pathway via the trabecular meshwork, whereas if non-penetrating surgery is carried out in the same eye with postoperative IOP=16 mm Hg, the outflow through the trabecular meshwork amounts to 35%. Thus, non-penetrating surgery provides more aqueous outflow along the natural outflow pathways than trabeculectomy. 2) Generally, the higher the postoperative IOP and/or the lower the preoperative IOP, the higher the amount of aqueous, which will utilize the natural outflow pathways postoperatively. 3) The reestablishment of aqueous production postoperatively in addition to other factors, such as wound healing, may be a reason for IOP increase during the postoperative period.

Effect of aging on retinal artery blood column diameter measured along the vessel axis.

PURPOSE: To determine whether retinal branch arteries of healthy persons in different age groups show different longitudinal vessel profiles at baseline and during dynamic reaction to flicker stimulation. METHODS: Thirty-three healthy subjects (age groups: 21-27 years, 40-59 years, and 60-85 years) were examined with the use of a retinal vessel analyzer. A monochromatic flicker of 12.5 Hz was applied for 60 seconds. Arterial diameters were measured in vessel segments of 1 mm in length to obtain the longitudinal vessel profile. Differences in amplitude and frequency of arterial width changes were characterized by the parameter spectral edge frequency (SEF). RESULTS: SEF was significantly different between the young group and the senior group in each phase of the arterial reaction to flicker (baseline, dilation, constriction, relaxation; P < 0.05; Mann-Whitney U test). No significant difference within any age group was found in any phase of the arterial reaction. No significant difference between the middle-aged and either young or elderly subjects was found at baseline. However, after stimulation, the middle-aged group displayed a significant difference compared with the young group, with values resembling those of the elderly group. CONCLUSIONS: In healthy elderly subjects, retinal arteries assumed a significantly less regular longitudinal vessel profile than those of young subjects. Middle-aged subjects assumed a more irregular profile only in the stimulated states of dilation, constriction, and relaxation. Early age-related changes in vessel profile are noted only after metabolic demand. These changes might be a cause for impaired blood flow and blood-vessel wall interaction.

Arterial and retinal vascular changes in hypertensive and prehypertensive adolescents.

INTRODUCTION: Increasing evidence suggests that arterial hypertension (AHT) may begin in childhood and result in the premature development of cardiovascular disease. In view of this, we believed it would be important to investigate the early vascular changes related to early hypertension at the micro- and macrovascular levels both under normal circumstances and after cold-induced sympathetic stimulation. METHODS: In a cohort of 121 adolescent subjects, we measured peripheral and central blood pressure (pBP and cBP, respectively), pulse pressure (PP), and the augmentation index (AIx), as well as retinal vascular diameters, at baseline and during a cold pressor test (CPT). We measured the central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) and calculated the retinal arteriolar-to-venular ratio (AVR). We compared macro- and microvascular alterations among normotensive (NT), prehypertensive (PHT), and hypertensive (HT) adolescents. RESULTS: Of the adolescent subjects in the study, 54.5% were NT, 25.6% were PHT, and 19.8% were HT. With regard to BMI, central systolic BP (cSBP), aortic pulse pressure (AoPP), and CRAE, the PHT adolescents had values similar to those in the HT group but significantly different than those in the NT group. In the studied population, there was a positive and significant correlation of AIx with cSBP and a negative association of CRAE with both cSBP and peripheral SBP (pSBP). We describe the evolution of these parameters during and after sympathetic stimulation. CONCLUSION: As compared with the prevalence of hypertension and prehypertension in large studies, involving teenagers and children, an alarming percentage (45.5%) of the adolescents in our study were HT or PHT. Higher pSBP and cSBP were associated with narrower retinal arterioles but not with changes of arterial elasticity. With particular regard to CRAE, the PHT group was more closely related to the HT group than to the NT group. There were no differences among the NT, PHT, and HT groups in the results of the CPT.

Does increased blood pressure rather than aging influence retinal pulse wave velocity?

PURPOSE: It was demonstrated previously that retinal pulse wave velocity (rPWV) as a measure of retinal arterial stiffness is increased in aged anamnestically healthy volunteers compared with young healthy subjects. Using novel methodology of rPWV assessment this finding was confirmed and investigated whether it might relate to the increased blood pressure usually accompanying the aging process, rather than to the aging itself. METHODS: A total of 12 young 25.5-year-old (24.0-28.8) [median(1st quartile-3rd quartile)] and 12 senior 68.5-year-old (63.8-71.8) anamnestically healthy volunteers; and 12 senior 63.0-year-old (60.8-65.0) validated healthy volunteers and 12 young 33.0-year-old (29.5-35.0) hypertensive patients were examined. Time-dependent alterations of vessel diameter were assessed by the Dynamic Vessel Analyzer in a retinal artery of each subject. The data were filtered and processed using mathematical signal analysis and rPWVs were calculated. RESULTS: rPWV amounted to 1200 (990-1470) RU (relative units)/s in the hypertensive group and to 1040 (700-2230) RU/s in anamnestically healthy seniors. These differed significantly from rPWVs in young healthy group (410 [280-500] RU/s) and in validated healthy seniors (400 [320-510] RU/s). rPWV associated with age and mean arterial pressure (MAP) in the pooled cohort excluded validated healthy seniors. In a regression model these associations remain when alternately adjusted for MAP and age. When including validated healthy seniors in the pooled cohort only association with MAP remains. CONCLUSIONS: Both aging (with not excluded cardiovascular risk factors) and mild hypertension are associated with elevated rPWV. rPWV increases to a similar extent both in young mildly hypertensive subjects and in aged anamnestically healthy persons. Healthy aging is not associated with increased rPWV.

Pulse wave velocity in retinal arteries of healthy volunteers.

BACKGROUND/AIMS: Measurement of pulse wave velocity (PWV) in large vessels has been used extensively in clinical practice as an indirect measure of arterial stiffness and an indicator of cardiovascular risk factors. Arterial stiffness increases with age and in coronary artery disease. An in vivo clinical method to characterise arterial stiffness of the central microcirculation was developed. METHODS: Time-dependent alterations of retinal vessel diameter were examined by the dynamic vessel analyzer in a randomly chosen eye of 10 young (26.0 (23.5, 27.0) years old (median (1st quartile, 3rd quartile)) and 10 old (67.0 (61.3, 69.5)) years old) healthy volunteers. Two segments of a retinal artery were measured simultaneously. The distance between the segments was measured using retinal photographs. The data were filtered and analysed using signal analysis methods in order to calculate PWV in the assessed retinal artery (rPWV). RESULTS: rPWV differed significantly between young (21.5 (17.9, 4.6) mm/s) and old (243.8 (186.1, 347.7) mm/s) volunteers: (p=0.0001, Mann-Whitney test with Bonferroni correction). CONCLUSIONS: This study demonstrates a higher rPWV in elderly people than in young people. Therefore this new parameter resembles large artery PWV. This suggests that dynamic in vivo imaging of the central microcirculation enables the measurement of local microvascular stiffness with a commercially available medical device.

Dynamic retinal vessel response to flicker in age-related macular degeneration patients before and after vascular endothelial growth factor inhibitor injection.

PURPOSE: Retinal vessel responses to flickering light are different in various systemic and ocular diseases and can be improved after successful therapy. We investigated retinal vessel response to flickering light in age-related macular degeneration (AMD) patients before and after treatment with a single intravitreal bevacizumab (Avastin(®) ) injection. METHODS: In 10 patients with exudative AMD [age: median (1.quartile; 3.quartile) 76.0 (73.5; 80.0) years], retinal vessel reactions were examined by Dynamic Vessel Analyser (DVA) before and 3 months after a single intravitreal application of bevacizumab (1.25 mg). A baseline measurement was followed by three consecutive monochromatic flicker stimulations (530-600 nm, 12.5 Hz, 20 seconds). Temporal retinal vessel reaction was analysed and compared with the reaction in healthy controls. RESULTS: Mean arterial dilation at the end of flicker was not different in all groups. For veins this parameter amounted to: pre-treatment, 2.6 (1.7; 3.9)%; post-treatment, 2.9 (2.4; 4.0)%; control, 4.3 (3.2; 5.7)%; significant: pre-treatment - control (Dunnett's procedure, p < 0.05). Maximal dilation occurred in arteries at: pre-treatment, 17.5 (14.8; 32.5) seconds; post-treatment, 18.0 (16.6; 30.6) seconds; control, 14.5 (10.8; 17.3) seconds. Both AMD groups were slower (p < 0.05): in veins at 17.0 (14.5; 20.0) seconds, 12.8 (8.6; 14.8) seconds and 18.5 (17.1; 19.9) seconds, respectively; significant post-treatment - control (p < 0.05). In the post-treatment AMD group arterial constriction after stimulation occurred more slowly compared with the control group (p < 0.05). CONCLUSION: Dynamic retinal arterial and venous reactions to flickering light are altered in AMD compared with controls. Three months after a single injection of a vascular endothelial growth factor inhibitor, the investigated retinal dynamic vascular parameters were not altered in our study.

Functional in vivo assessment of retinal artery microirregularities in glaucoma.

PURPOSE: We investigated whether retinal branch arteries in healthy subjects, and non-treated and treated primary open-angle glaucoma (POAG) patients show irregular local patterns during dynamic reaction to acute increases of different magnitudes in intraocular pressure (IOP). METHODS: Nine POAG patients and nine age-matched normal volunteers were examined with the retinal vessel analyser (RVA) using a suprasystolic IOP increase (Study 1). Fourteen POAG patients and 13 age-matched controls were examined using a moderate IOP increase for 100 seconds (Study 2). Longitudinal arterial profiles were obtained for the chosen time intervals. The high-frequency waviness (HFW) of these profiles was analysed quantitatively. RESULTS: No significant changes in HFW were found in controls in different phases of the arterial reaction. Significant increases in HFW from baseline to dilation (Study 1, P < 0.03) and from dilation to constriction (Study 2, P < 0.05) were found in POAG patients. High-frequency waviness was higher in POAG patients than in controls during dilation (P < 0.05) in both studies. CONCLUSIONS: Our results indicate a local vessel wall difference in glaucoma patients compared with age-matched controls. Increasing HFW might worsen hydraulic resistance of the vessel segment to blood flow. Significant increase of arterial microirregularities in the POAG retina during vascular dilation might be an indication for vascular endothelial alterations in glaucoma, leading to impaired perfusion in response to IOP increase.

Retinal vessel reaction in response to chromatic flickering light.

BACKGROUND: Flickering light stimulation of the retina is known to increase retinal vessel diameter in animals and humans. The aim of the study was to quantify the response of retinal vessel diameter to red-green and blue-green flickering light. METHODS: In 11 normal healthy volunteers (mean age: 25.2+/-6.8 years) retinal arterial and venous diameters were examined by Retinal Vessel Analyzer (IMEDOS Ltd., Weimar, Germany) before, during and after red-green and blue-green flicker stimulation with a frequency of 12 Hz and duration of 10 and 30 s. RESULTS: For red-green flicker at 10 s there was a 2.4+/-1.4% arterial diameter increase at 9.1+/-3.3 s with a return to baseline after 30 s and a 2.4+/-1.1% venous diameter increase at 12.1+/-2.6 s with a return to baseline after 30 s. For red-green flicker at 30 s there was a 3.2+/-1.5% arterial diameter increase at 26.9+/-12.6 s with a return to baseline after 40 s and a 4.9+/-1.8% venous diameter increase at 31.4+/-7.6 s with a return to baseline after 40 s. For blue-green flicker at 10 s there was a 2.0+/-0.7% arterial diameter increase at 10.6+/-5.3 s with a return to baseline after 30 s and a 2.3+/-1.1% venous diameter increase at 12.0+/-5.5 s with a return to baseline after 30 s. For blue-green flicker at 30 s there was a 2.6+/-1.3% arterial diameter increase at 20.7+/-8.0 s with a return to baseline after 40 s and a 3.4+/-2.2% venous diameter increase at 28.8+/-10.5 s with a return to baseline after 40 s. CONCLUSIONS: Retinal vessel diameter dilation is a reproducible response to the applied flicker stimuli. This finding supports the existence of neurovascular coupling in the human retina. Flicker stimulation in either red-green or blue-green might be a useful stimulus for examination of retinal vessel behavior to regulatory demands.