Glaucoma Agreement in New Zealand (GAINZ).

CLINICAL RELEVANCE: With an ageing population, ophthalmologists are becoming burdened with glaucoma management, and patient care can be delayed. Therefore, the use of optometrists in glaucoma management can help alleviate the burden. BACKGROUND: The ageing population and subsequent rise of glaucoma prevalence are putting a strain on the public health system in New Zealand. Glaucoma collaborative care between optometrists and ophthalmologists has been gaining support with the aim to reduce this burden on ophthalmologists. There has been little investigation of the agreement in care and management of mild-to-moderate severity glaucoma patients by optometrists and ophthalmologists. METHODS: One hundred and three glaucomatous eyes were used in a survey where clinical history and examination, intraocular pressures (IOPs), visual field testing and optical coherence tomography (OCT) imaging were evaluated for glaucoma progression and decision-making regarding subsequent management by four participants. Two participants were glaucoma-credentialled optometrists (Group 1), and the other two were glaucoma specialists (Group 2). RESULTS: With respect to glaucoma progression, Spearman coefficients identified strong agreement between the two groups for IOP, visual fields and overall status and moderate agreement for OCT imaging. A confusion matrix was used to analyse management and found 80% ± 10% agreement between the two groups. Review periods gave an agreement of 55% ± 20% between the two groups. CONCLUSION: There was strong agreement in the assessment of glaucoma progression between the two groups. The 80% level of agreement for subsequent management between the two groups is comparable to other published reports. These results provide some reassurance that a collaborative care system can perform safely and as intended.

Volumetric comparison of mandibular condyles and mandibles in the different skeletal classes in the Saudi population.

Background: Assessing the relationship between the condyle and mandible volume and the various skeletal classes is essential in orthodontic diagnosis. The current study evaluated this relationship using volumetric cone-beam computed tomography (CBCT), cephalometric methods, and the correlations between them. Materials and Methods: The study examined 37 full-head CBCTs (74 condyles) from adults in the Saudi population. The condyle and mandible were separated from within the CBCT images. The volume of each segment was compared to measurements from multiple cephalometric analyses. Results: The combined total condylar volume has a moderate correlation with the maxillomandibular differential in each of the genders and in the total sample. Mandibular volume has a significant correlation with the Wits appraisal (sagittal classification) in males. It was also significantly correlated with the vertical classification using gonial angles in females and in the total sample. Conclusion: The relationship between mandible and condyle volume and cephalometric measurements is both dimensional and within the maxillomandibular complex rather than positional or related to the cranial base. Also, the correlation between the condylar and mandibular volumes and the sagittal and vertical dimensions in the orthodontic skeletal classes provides better insight into the mandibular complex.

Real-world effectiveness of COVID-19 vaccines: A retrospective cohort study of vaccinated individuals in Jazan, Saudi Arabia.

BACKGROUND: COVID-19 (Coronavirus Disease 2019) vaccinations are a critical control measure for the coronavirus pandemic that began in 2019. Several COVID-19 vaccines have been developed, and their effectiveness will almost certainly vary. OBJECTIVE: This study aimed to assess how effective two doses of the Pfizer and Oxford-AstraZeneca vaccines were in preventing SARS-CoV-2 infection six months after administration. METHODS: This is a retrospective cohort study of adult individuals from the Jazan Region of Saudi Arabia who received their second dose of the COVID-19 vaccine [Pfizer and Oxford-AstraZeneca (ASZ)] between April and June 2021. The monitoring and follow-up period continued until the end of January 2022. Data were retrieved from the Health Electronic Surveillance Network and National Vaccination Records. Logistic regression was performed to assess the risk of COVID-19 infection among the vaccinated subjects. RESULTS: This study included randomly enrolled 4458 participants in Jazan who received two doses of the COVID-19 vaccine during the research period. The majority of them received the Pfizer vaccine (3136/4458; 70.3%), while the remaining received the ASZ vaccine (1322/4458; 29.7%). The study participants' mean age was 59.7 years, with a male-to-female ratio of 1.9:1.0 (2920:1538). The results showed that the Pfizer and ASZ vaccines' protection against infection decreased from 93.2% and 90.2%, respectively, during the first three months, to 68.5% and 68.1% after a six-month interval. In the current study population, being Saudi Arabian, younger as well as having longer intervals between vaccines or crossing a 6-month period after the second vaccine dose were factors linked to higher rates of breakthrough infections. CONCLUSION: Our findings revealed variations in the efficacy of different COVID-19 vaccine types against COVID-19 breakthrough infections. The Pfizer (mRNA-based) vaccine was found to be relatively more effective than the ASZ (DNA-based) vaccine.

Maxillary sinus volume in patients with canted occlusal plane: A cone-beam computed tomography study.

OBJECTIVES: To compare the maxillary sinus volume between both sides in adult patients with upper occlusal canting (>2 mm cant) and a control group (≤2 mm cant) using cone-beam computed tomography scans. MATERIALS AND METHODS: This retrospective study included a total of 84 scans (42 scans per group) according to predetermined selection criteria. OnDemand 3-D™ software was used for volumetric and linear measurements of the maxillary sinus. Maxillary occlusal canting was determined at the level of the maxillary first molars. It was defined as the vertical difference between right and left sides relative to the Frankfort horizontal plane. Non-parametric tests were applied. RESULTS: The median difference in the maxillary sinus volume between the sides was statistically significant between the control and cant groups (P < 0.001). Also, the median difference in the maxillary sinus craniocaudal height and apex sinus distance between the sides was statistically significant between the control and cant groups (P < 0.05 and P < 0.001, respectively). CONCLUSION: In adult patients, maxillary occlusal canting of more than 2 mm was associated with asymmetric maxillary sinus volumes. In the cant group, maxillary first molars on the canted-down side were in close proximity to the sinus floor, which suggests a limited leeway for molar intrusion.

Neuropilin 2/Plexin-A3 Receptors Regulate the Functional Connectivity and the Excitability in the Layers 4 and 5 of the Cerebral Cortex.

The functions of cortical networks are progressively established during development by series of events shaping the neuronal connectivity. Synaptic elimination, which consists of removing the supernumerary connections generated during the earlier stages of cortical development, is one of the latest stages in neuronal network maturation. The semaphorin 3F coreceptors neuropilin 2 (Nrp2) and plexin-A3 (PlxnA3) may play an important role in the functional maturation of the cerebral cortex by regulating the excess dendritic spines on cortical excitatory neurons. Yet, the identity of the connections eliminated under the control of Nrp2/PlxnA3 signaling is debated, and the importance of this synaptic refinement for cortical functions remains poorly understood. Here, we show that Nrp2/PlxnA3 controls the spine densities in layer 4 (L4) and on the apical dendrite of L5 neurons of the sensory and motor cortices. Using a combination of neuroanatomical, ex vivo electrophysiology, and in vivo functional imaging techniques in Nrp2 and PlxnA3 KO mice of both sexes, we disprove the hypothesis that Nrp2/PlxnA3 signaling is required to maintain the ectopic thalamocortical connections observed during embryonic development. We also show that the absence of Nrp2/PlxnA3 signaling leads to the hyperexcitability and excessive synchronization of the neuronal activity in L5 and L4 neuronal networks, suggesting that this system could participate in the refinement of the recurrent corticocortical connectivity in those layers. Altogether, our results argue for a role of semaphorin-Nrp2/PlxnA3 signaling in the proper maturation and functional connectivity of the cerebral cortex, likely by controlling the refinement of recurrent corticocortical connections.SIGNIFICANCE STATEMENT The function of a neuronal circuit is mainly determined by the connections that neurons establish with one another during development. Understanding the mechanisms underlying the establishment of the functional connectivity is fundamental to comprehend how network functions are implemented, and to design treatments aiming at restoring damaged neuronal circuits. Here, we show that the cell surface receptors for the family of semaphorin guidance cues neuropilin 2 (Nrp2) and plexin-A3 (PlxnA3) play an important role in shaping the functional connectivity of the cerebral cortex likely by trimming the recurrent connections in layers 4 and 5. By removing the supernumerary inputs generated during early development, Nrp2/PlxnA3 signaling reduces the neuronal excitability and participates in the maturation of the cortical network functions.

Effects of COVID-19 lockdown on the mental health of dental students: A longitudinal study.

OBJECTIVES: Many countries have enforced lockdowns on their populations due to the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to assess the effects of the lockdown on dental students. METHODS: A longitudinal, repeated cross-sectional study was conducted to evaluate psychological problems experienced by dental students during the COVID-19 lockdown in Saudi Arabia. The dental students were selected from different universities using 2-stage cluster sampling. The validated Arabic version of the 21-item depression, anxiety, and stress scale questionnaire was distributed at the beginning and end of the lockdown. Mann-Whitney U and Kruskal-Wallis tests were used as appropriate. Chi-square test was used to compare the proportions between the sociodemographic data, and logistic regression analysis was used to identify variables associated with the students' responses. RESULTS: A total of 1287 respondents participated in this study (695 first-survey respondents, 592 second-survey respondents). There were longitudinally significant differences in the students' mental health outcomes based on gender, university, class year, and survey time during the COVID-19 lockdown. The lockdown increased the likelihood of female, single, and junior students experiencing stress. The students who lived alone recorded a high chance of elevated levels of depression, anxiety, and stress, which showed a significant longitudinal reduction during the lockdown. Moreover, the lockdown increased the likelihood of mental health problems among the students staying in households of two persons or two-five persons. CONCLUSIONS: This study indicates the importance of considering the detrimental mental health consequences on dental students in the event of future pandemics.

Coronavirus Disease in Children: A Single-Center Study from Western Saudi Arabia.

INTRODUCTION: Local data in Saudi Arabia regarding pediatric SARS-CoV-2 infection is limited. This study is aimed at adding insight regarding the effect of the novel coronavirus on pediatric patients by studying the presentation, laboratory parameters, and disposition of SARS-CoV-2-infected pediatric patients in one center in Jeddah, Saudi Arabia. Methodology. A retrospective study was conducted at the International Medical Center (IMC) in Jeddah, Saudi Arabia, to assess features of pediatric patients admitted with COVID-19 from April 2020 to September 2020. RESULTS: A total of 43 patients were found to meet the study inclusion criteria. The most common presenting symptom was fever (53.5%) in study participants followed by complaints of cough, runny nose, and shortness of breath (37.2%). Lymphocytopenia was evident among 60% of those studied. Elevated C-Reactive Protein was remarkable in 24.9%. More than half of those (53.5%) studied required only supportive treatment. CONCLUSION: COVID-19 disease for the most part is mild in children with a varying clinical picture and nonspecific laboratory parameters. Further, large-scale national-based studies are needed to help in the early identification of pediatric cases at risk of complication due to COVID-19 infection hence providing proper and timely management, identifying population-specific disease pattern and perhaps targeted immunization.

Investigating Principal Working Memory Features in Generalized, Panic, and Social Anxiety Spectrum Disorders.

Anxiety spectrum disorders are characterized by excessive and uncontrollable worrying about potential negative events in the short- and long-term future. Various reports linked anxiety spectrum disorders with working memory (WM) deficits despite conflicting results stemming from different study approaches. It remains unclear, however, how different anxiety spectrum disorders such as generalized anxiety disorder (GAD), social anxiety disorder (SAD), and panic disorder (PD), differ in WM function. In this study, we utilized verbal, numerical, and sequential evaluations of WM to cover most possible facets of the WM data space. We used principal component analysis to extract the uncorrelated/whitened components of WM based on these measures. We evaluated medication-free patients with GAD, SAD, and PD patients as well as matched healthy individuals using a battery that measures WM duration and load. We found that patients with GAD and SAD, but not PD, exhibited poor performance only in the WM principal component that represents maintenance. There were no other significant differences between the four groups. Further, different WM components significantly predicted the severity of anxiety symptoms in the groups. We explored the clinical utility of WM components for differentiating patients with anxiety spectrum disorders from healthy individuals. By only using the WM components that represent maintenance and encoding, we managed to differentiate patients from controls in 84% of cases. For the first time, we present multiple novel approaches to examine cognitive function and design cognitive screening, and potentially diagnostics, for psychiatric disorders.

Depression Reduces Accuracy While Parkinsonism Slows Response Time for Processing Positive Feedback in Patients with Parkinson's Disease with Comorbid Major Depressive Disorder Tested on a Probabilistic Category-Learning Task.

Major depressive disorder (MDD) is the most common non-motor manifestation of Parkinson's disease (PD) affecting 50% of patients. However, little is known about the cognitive correlates of MDD in PD. Using a computer-based cognitive task that dissociates learning from positive and negative feedback, we tested four groups of subjects: (1) patients with PD with comorbid MDD, (2) patients with PD without comorbid MDD, (3) matched patients with MDD alone (without PD), and (4) matched healthy control subjects. Furthermore, we used a mathematical model of decision-making to fit both choice and response time data, allowing us to detect and characterize differences between the groups that are not revealed by cognitive results. The groups did not differ in learning accuracy from negative feedback, but the MDD groups (PD patients with MDD and patients with MDD alone) exhibited a selective impairment in learning accuracy from positive feedback when compared to the non-MDD groups (PD patients without MDD and healthy subjects). However, response time in positive feedback trials in the PD groups (both with and without MDD) was significantly slower than the non-PD groups (MDD and healthy groups). While faster response time usually correlates with poor learning accuracy, it was paradoxical in PD groups, with PD patients with MDD having impaired learning accuracy and PD patients without MDD having intact learning accuracy. Mathematical modeling showed that both MDD groups (PD with MDD and MDD alone) were significantly slower than non-MDD groups in the rate of accumulation of information for stimuli trained by positive feedback, which can lead to lower response accuracy. Conversely, modeling revealed that both PD groups (PD with MDD and PD alone) required more evidence than other groups to make responses, thus leading to slower response times. These results suggest that PD patients with MDD exhibit cognitive profiles with mixed traits characteristic of both MDD and PD, furthering our understanding of both PD and MDD and their often-complex comorbidity. To the best of our knowledge, this is the first study to examine feedback-based learning in PD with MDD while controlling for the effects of PD and MDD.

Epidemiology, management and outcomes of Graves' disease-real life data.

PURPOSE: Treatment options in Graves' disease are clearly defined, but management practices and the perceptions of success are varied. The outcomes of treatment in large consecutive cohorts of Graves' disease have not been well characterised. The study describes the epidemiology, management strategies and medium term outcomes following anti-thyroid drug treatment, radio-iodine ablation and surgery in Graves' disease. METHODS: All patients (n = 659) who received treatment for a new diagnosis of Graves' disease in secondary care over a 5 year period were included with a median (interquartile range) follow-up of 42.9 (29-57.5) months. RESULTS: The age adjusted incidence of adult onset Graves' disease in Sheffield, UK was 24.8 per 100,000 per year. Excluding 35 patients lost to follow-up, 93.1% (n = 581) were controlled on anti-thyroid drug treatment. Of these, 73.6% went into remission following withdrawal of anti-thyroid drugs; 5.2% were still undergoing initial therapy; 13.3% lost control whilst on anti-thyroid drugs; and 7.9% went on to have either surgery or radio-iodine ablation whilst controlled on anti-thyroid drugs. Of the 428 patients who achieved remission, 36.7% relapsed. Of 144 patients who had radio-iodine ablation treatment, 5.6% relapsed and needed further treatment. Of 119 patients having surgery, 5.2% had long-term hypoparathyroidism and none had documented long-term recurrent laryngeal nerve palsy. CONCLUSIONS: In the follow-up, 39.9% of patients underwent surgery or radio-iodine ablation with little morbidity. Up to two-thirds of patients who achieved remission did not relapse. Data on effectiveness and risks of treatments for Graves' disease presented in this study will help clinicians and patients in decision making.

Generalized Anxiety Disorder and Social Anxiety Disorder, but Not Panic Anxiety Disorder, Are Associated with Higher Sensitivity to Learning from Negative Feedback: Behavioral and Computational Investigation.

Anxiety disorders, including generalized anxiety disorder (GAD), social anxiety disorder (SAD), and panic anxiety disorder (PAD), are a group of common psychiatric conditions. They are characterized by excessive worrying, uneasiness, and fear of future events, such that they affect social and occupational functioning. Anxiety disorders can alter behavior and cognition as well, yet little is known about the particular domains they affect. In this study, we tested the cognitive correlates of medication-free patients with GAD, SAD, and PAD, along with matched healthy participants using a probabilistic category-learning task that allows the dissociation between positive and negative feedback learning. We also fitted all participants' data to a Q-learning model and various actor-critic models that examine learning rate parameters from positive and negative feedback to investigate effects of valence vs. action on performance. SAD and GAD patients were more sensitive to negative feedback than either PAD patients or healthy participants. PAD, SAD, and GAD patients did not differ in positive-feedback learning compared to healthy participants. We found that Q-learning models provide the simplest fit of the data in comparison to other models. However, computational analysis revealed that groups did not differ in terms of learning rate or exploration values. These findings argue that (a) not all anxiety spectrum disorders share similar cognitive correlates, but are rather different in ways that do not link them to the hallmark of anxiety (higher sensitivity to negative feedback); and (b) perception of negative consequences is the core feature of GAD and SAD, but not PAD. Further research is needed to examine the similarities and differences between anxiety spectrum disorders in other cognitive domains and potential implementation of behavioral therapy to remediate cognitive deficits.

Analysis of Glaucoma Subtypes and Corresponding Demographics in a New Zealand Population.

PURPOSE: The aim of this paper was to determine the diagnosis distribution and demographic characteristics of glaucoma in a New Zealand population. METHODS: The clinical records of all patients presenting consecutively to the Auckland District Health Board Glaucoma Service over a 6-month period were reviewed. Demographic parameters including ethnicity, age at presentation, and gender were collected along with all clinical data. RESULTS: The case records of 857 patients were reviewed. Primary open-angle glaucoma (POAG) was the most common diagnosis (39.0%, n = 235), followed by primary-angle closure (PAC) diagnoses (24.8%, n = 149). This group was formed by the combination of narrow angle 18.1% (n = 109), narrow-angle glaucoma 0.3% (n = 2), PAC 2.1% (n = 13), and PAC glaucoma 4.2% (n = 25). Normal-tension glaucoma (NTG; 17.4%, n = 105), secondary glaucoma (SG; 11.5%, n = 69), ocular hypertension (5.0%, n = 30), and mixed mechanism (2.3%, n = 14) were also found. There was a significant difference in the ethnic distribution in the study population compared to the catchment population (p < 0.001). Caucasian and Indian ethnicities were overrepresented, whereas the Pacific Island Nation ethnicity was underrepresented in all groups except SG. The Maori ethnicity was underrepresented in all groups except PAC. The underrepresentation was most prominent in POAG (only 2 patients of Pacific origin and 1 Maori patient with POAG). Significant differences were identified in gender distribution including a higher preponderance of females in NTG and PAC. Significant differences in age at presentation were also identified between different glaucoma subtypes and ethnicities. Markers of glaucoma severity did not vary with respect to demographic characteristics. CONCLUSION: In a tertiary glaucoma service in New Zealand, Maori, Pacific peoples, and, to a lesser extent, Asians are underrepresented, while Caucasians and Indians are overrepresented in the glaucoma population.

Longitudinal relationship between insulin-like growth factor-1 levels and vertical facial growth.

BACKGROUND: Facial growth in the vertical dimension is the last to be completed and can often be detrimental to the success of dental implants, orthodontic treatment, and orthognathic surgery that young individuals undergo. AIM: The purpose of this study was to evaluate the longitudinal relationship between changes in total anterior facial height and insulin-like growth factor-1 (IGF-1) levels measured using blood-spot samples. METHODS: Our sample included 25 orthodontic patients from whom we had access to annual lateral cephalometric radiographs and IGF-1 measurements. Each subject was observed between 2 and 6 times, resulting in 43 annual intervals from a total of 77 observations. RESULTS: We noted a significant moderate positive correlation (+ 0.48) between the percentage of change in blood-spot IGF-1 levels and the percentage of change in total anterior face height (p = 0.01). CONCLUSION: Longitudinal changes in IGF-1 levels can be used to predict a patient's vertical facial growth. There was no significant correlation between changes in vertical facial development and a single cross-sectional IGF-1 measurement.

Oral squamous cell carcinoma and associated risk factors in Jazan, Saudi Arabia: a hospital based case control study.

BACKGROUND: Oral cancer is the third most common malignancy in Saudi Arabia, the highest incidence of which is reported from Jazan province. The objective of this study was to evaluate the association of various locally used substances, especially shamma, with oral cancer in the Jazan region of Saudi Arabia. MATERIALS AND METHODS: A hospital-based case-control study was designed and patient records were scanned for histologically confirmed oral cancer cases. Forty eight patients who were recently diagnosed with oral cancer were selected as cases. Two healthy controls were selected for each observed case and they were matched with age (+/-5 years) gender and location. Use of different forms of tobacco such as cigarettes, pipe-smoking and shamma (smokeless- tobacco) was assessed. Khat, a commonly used chewing substance in the community was also included. Descriptive analysis was first performed followed by multiple logistic regression (with and without interaction) to derive odds ratios (ORs) and 95% confidence interval (CIs). RESULTS: Mean age of the study sample (56% males and 44% females) was 65.3 years. Multinomial regression analysis revealed that shamma use increased the odds of developing oral cancer by 29 times (OR=29.3; 10.3-83.1). Cigarette (OR=6.74; 2.18-20.8) was also seen to have an effect. With the interaction model the odds ratio increased significantly for shamma users (OR=37.2; 12.3-113.2) and cigarette smokers (OR=10.5; 2.88-3.11). Khat was observed to have negative effect on the disease occurrence when used along with shamma (OR=0.01; 0.00-0.65). CONCLUSIONS: We conclude that shamma, a moist form of smokeless tobacco is a major threat for oral cancer occurrence in the Jazan region of Saudi Arabia. This study gives a direction to conduct further longitudinal studies in the region with increased sample size representing the population in order to provide more substantial evidence.

Predicting changes in mandibular length and total anterior facial height using IGF-1, cervical stage, skeletal classification, and gender.

BACKGROUND: The purpose of this study was to predict the annual growth rate of the mandible and total anterior facial height using IGF-1 levels together with cervical stage, skeletal classification, and gender. METHODS: Twenty-five orthodontic patients (12 females and 13 males) had their cervical stages, blood-spot IGF-1 levels, and cephalometric parameters measured at 1-year intervals. The number of years each patient was followed up varied between 1 and 5 years resulting in 43 12-month intervals collected from 77 observations. Descriptive, bivariate, and regression analyses were used to analyze this data. RESULTS: The linear regression model for predicting the annual mandibular growth rate was significant at p < 0.01 with an R-square value of 0.52. We found that the average IGF-1 level for the interval, the change in IGF-1 level, and the presence of a skeletal class III pattern were statistically significant predictors of mandibular growth. The regression model for predicting the annual change in anterior facial height was significant at p < 0.01 with an R-square value of 0.42. We found that the change in IGF-1 level was the only statistically significant predictor of this outcome. CONCLUSIONS: The proposed method which combines IGF-1 levels with information that is readily available to clinicians can be used to predict the timing and intensity of the growth spurt. These factors together explain more of the observed individual variation in growth rate than any of the factors used in isolation.

Nailfold capillaroscopy assessment in patients with glaucoma with a current optic disc hemorrhage.

OBJECTIVE: To determine whether there is an increased prevalence of nailfold hemorrhages in patients with glaucoma with a current optic disc hemorrhage (ODH) compared with those without a history of ODH. DESIGN: Prospective observational study. PARTICIPANTS: Group 1 (n = 40) consisted of patients with primary open-angle glaucoma or normal tension glaucoma (POAG/NTG) with a current ODH who met the specified inclusion/exclusion criteria. Group 2 (n = 20) consisted of age- and sex-matched patients with glaucoma without a history of ODH who met specified criteria (control group). METHODS: This study was performed in a clinical practice setting. Nailfold capillaroscopy was performed in each participant to determine the presence of nailfold hemorrhages and other capillary morphologic changes. RESULTS: There was no significant difference in mean age (68 ± 10 years for Group 1 vs 71 ± 12 years for Group 2; p = 0.20) or sex (62% female in Group 1 vs 59% female in Group 2; p = 0.80) between the groups. There was no significant difference in the proportion of patients with nailfold hemorrhage(s) between Group 1 (23%, 10/42) and Group 2 (26%, 11/42; p = 0.8). Subanalysis of Group 1 identified no significant difference in the prevalence of nailfold hemorrhages between patients with POAG (23%, 6/26) and NTG (25%, 4/16; p = 0.9). CONCLUSIONS: We report no increase in nailfold haemorrhages in patients with glaucoma with a current ODH compared with patients with glaucoma without a history of ODH. However, the prevalence of nailfold hemorrhages in patients with glaucoma either with or without an ODH is significantly greater than that identified in normal (nonglaucoma) control subjects in other studies.

Intraclass differences among antihypertensive drugs.

The four major classes of antihypertensive drugs­diuretics, ß-blockers, calcium channel blockers, and renin-angiotensin system inhibitors (including angiotensin-converting enzyme inhibitors and angiotensin receptor blockers)­have significant qualitative and quantitative differences in the adverse effects they cause. Structural and chemical differences have been identified within these classes, especially among the calcium channel blockers and, to a lesser extent, among the thiazide/thiazide-like diuretics. However, it has been more difficult to demonstrate that these differences translate into differential effects with respect to either the surrogate endpoint of blood pressure reduction or, more importantly, hypertension-related cardiovascular complications. Based on a hierarchy-of-evidence approach, differences are apparent between hydrochlorothiazide and chlorthalidone based on evidence of moderate quality. Low-quality evidence suggests atenolol is less effective than other ß-blockers. However, no significant intraclass differences have been established among the other classes of antihypertensive drugs.

GPER-independent effects of estrogen in rat aortic vascular endothelial cells.

GPER (aka GPR30) has been identified as an important mechanism by which estrogen mediates its effects. Previous studies from our laboratories and those of others have demonstrated that GPER activation mediates a range of vascular contractile and growth regulatory responses. However, the importance of GPER in mediating the actions of estradiol (E2) in rat aortic endothelial cells is unclear. Therefore, we sought to determine the importance of GPER vs. the "classical" estrogen receptor (ER) in mediating the endothelial growth regulatory effects of E2. To do this we assessed the effect of E2 in regulating phosphoERK content and apoptotic rates in rat aortic endothelial cells and the role of GPER in mediating these effects. E2 mediated a concentration-dependent inhibition of both ERK phosphorylation and serum deprivation-induced apoptosis with a maximal effect at a concentration of 10 nM. Pretreatment with the ER antagonist ICI 182780 abolished E2-mediated inhibition of both ERK phosphorylation and apoptosis. In contrast, pretreatment with GPER antagonist G15 had no significant effect on E2-mediated inhibition of ERK phosphorylation or on apoptosis. Further, downregulation of GPER expression with a GPER shRNA adenovirus did not block E2-mediated inhibitory effects on ERK phosphorylation and apoptosis. In fact, these inhibitory effects of E2 were further enhanced by GPER downregulation. Downregulation of ERα expression reversed the E2-mediated inhibitory effects to stimulatory effects. E2's phosphoERK and apoptosis stimulatory effects seen with ERα downregulation are attenuated by pretreatment with G15. In conclusion, in rat aortic endothelial cells, E2-mediated endothelial effects are predominantly driven by ER and not by GPER.

Economic analysis of the Ex-PRESS miniature glaucoma device versus trabeculectomy.

PURPOSE: Ex-PRESS shunt is an alternative filtration procedure to trabeculectomy. This study aimed to compare the 1-year cost differences between the 2 operations. METHODS: Subjects were enrolled in a randomized controlled trial comparing Ex-PRESS to trabeculectomy. Surgical cost difference and 1-year postoperative costs (follow-up visits, additional procedures, and medications) were determined and compared. The 95% confidence interval of incremental cost-effectiveness ratio was estimated using bootstrap method. RESULTS: Forty-three subjects with 1-year follow-up were included. Success rate was not significantly different for Ex-PRESS (65%) versus trabeculectomy (55%, P=0.49). Ex-PRESS had a net surgical cost of $956 greater than trabeculectomy. There was no significant difference in the overall postoperative cost [median (interquartile range); $485 (337, 822) vs. $609 (387, 820), P=0.78], cost of follow-up visits [$303 (275, 358) vs. $317 (275, 385), P=0.75], additional procedures [$182 (0, 365) vs. $182 (0, 365), P=0.69], or glaucoma medication [$0 (0, 68) vs. $0 (0, 90), P=0.8] for Ex-PRESS versus trabeculectomy, respectively. The overall 1-year cost was significantly greater for Ex-PRESS and the incremental cost-effectiveness ratio was $9625 (95% confidence interval, $2435-548,084). CONCLUSIONS: Ex-PRESS is associated with greater surgical cost compared with trabeculectomy. This needs to be considered in conjunction with efficacy and safety if Ex-PRESS is to supersede trabeculectomy.