Assessing the role of regulatory bodies in managing health professional issues and errors in Europe.

OBJECTIVE: This paper explores how medical regulatory bodies in nine European countries manage professional issues involving quality and patient safety, to build on limited existing information on procedures for regulating medical professionals in Europe. DESIGN: Twelve vignettes describing scenarios of concerns about standards of physicians were developed, covering clinical, criminal and administrative matters. Medical regulatory bodies in nine European countries were asked what action they would normally take in each situation. Their responses were related to their regulatory mandate. RESULTS: Responses varied greatly across participating countries. Regulators are always involved where patients are at risk or where a criminal offence is committed within the clinical setting. Non-criminal medical issues were generally handled by the employer, if any, at their discretion. Countries varied in the use of punitive measures, the extent to which they took an interest in issues arising outside professional activities, and whether they dealt with issues themselves or referred cases to another regulatory authority or took no action at all. CONCLUSIONS: There is little consistency across Europe on the regulation of medical professionals. There is considerable diversity in the range of topics that regulatory bodies oversee, with almost all covering health care quality and safety and others encompassing issues related to reputation, respect and trust. These inconsistencies have significant implications for professional mobility, patient safety and quality of care.

Effectiveness of dinoprostone gel, misoprostol vaginal insert and dinoprostone vaginal insert for induction of labour in twin pregnancies.

OBJECTIVES: To compare the effectiveness and safety of Dinoprostone Gel (DG), Misoprostol Vaginal Insert (MVI) and Dinoprostone Vaginal Insert (DVI) for induction of labour (IOL) in twin pregnancies. STUDY DESIGN: Retrospective cohort study of twin pregnancies > 34 + 0 weeks gestation that underwent induction of labour (IOL) with DG, MVI or DVI between December 2016 and November 2019 in a Tertiary NHS hospital, North West England, UK. Delivery characteristics, maternal complications and neonatal outcomes were compared between the three groups. RESULTS: A total of 87 twin pregnancies were included for analysis. 27 women received DG, 34 received MVI and 26 DVI. The MVI cohort had a higher proportion of nulliparous women (55.9%) compared to the DG and DVI cohorts, 29.6% and 38.5% respectively. No other differences amongst demographic characteristics were considered clinically significant. DG demonstrated a significantly quicker time to delivery (minutes) compared to DVI (1021 ± 556 versus 1649 ± 852; P = 0.0026). Significantly fewer women required terbutaline for hyperstimulation/tachysystole in the DG group compared to MVI (0% vs 32%; RR 0.05; 95% CI 0.003-0.88). Both DG and MVI groups required significantly less oxytocin following artificial rupture of membranes compared to DVI (33% vs 65%; RR 0.51; 95% CI 0.28-0.93) and (29% vs 65%; RR 0.45; 95% CI 0.25-0.81). There were no significant differences in mode of delivery, maternal complications and neonatal outcomes. CONCLUSION: Our data suggests that for women with a twin pregnancy considering a planned labour that induction with DG, MVI and DVI appear to be equally safe and effective IOL methods. These results should be interpreted with caution due to the study being underpowered to detect significant adverse outcomes. In order to determine the optimal method of IOL in twins, direct randomised comparison is needed.

Jaguar (Panthera onca) density and tenure in a critical biological corridor.

We estimated jaguar density and tenure, and investigated ranging behavior, using camera traps across the Maya Forest Corridor, a human-influenced landscape in central Belize that forms the only remaining connection for jaguar populations inhabiting two regional forest blocks: the Selva Maya and the Maya Mountain Massif. Jaguars were ubiquitous across the study area. Similar to the neighboring Selva Maya, mean density ranged from 1.5 to 3.1 jaguars per 100 km2, estimated by spatial capture-recapture models. Cameras detected almost twice as many males as females, probably reflecting detection bias, and males ranged more widely than females within the camera grid. Both sexes crossed two major rivers, while highway crossings were rare and male-biased, raising concern that the highway could prevent female movement if traffic increases. Jaguars were more transient where the landscape was fragmented with settlements and agriculture than in contiguous forest. Compared with jaguars in the protected forests of the Maya Mountains, jaguars in central Belize displayed a lower potential for investment in intraspecific communication, indicative of a lower quality landscape; however, we did detect mating behavior and juveniles. Tenure of individuals was shorter than in the protected forests, with a higher turnover rate for males than females. At least three-quarters of reported jaguar deaths caused by people were male jaguars, and the majority was retaliation for livestock predation. Jaguars seem relatively tolerant to the human-influenced landscape of central Belize. However, intensification of game hunting and lethal control of predators would threaten population persistence, while increased highway traffic and clear-cutting riparian forest would severely limit the corridor function. Our results show that the viability of the corridor, and thus the long-term survival of jaguar populations in this region, will depend on appropriate land-use planning, nonlethal control of livestock predators, enforcement of game hunting regulations, and wildlife-friendly features in future road developments.

Utilizando trampas-cámara, se estimó la densidad, permanencia y desplazamiento de jaguares a través del Corredor del Bosque Maya, un paisaje dominado por humanos en la zona central de Belice y que actualmente representa la única posibilidad de conectividad para las poblaciones de jaguares que habitan en dos grandes bloques boscosos regionales: La Selva Maya y El Macizo de las Montañas Mayas. Los jaguares estuvieron presentes en toda el área de estudio. De igual forma que en la vecina Selva Maya, la densidad media varió de 1.5 a 3.1 jaguares por cada 100 km2, estimada con modelos espaciales de captura-recaptura. Las cámaras detectaron casi el doble de machos que hembras, probablemente reflejando un sesgo de detección; y los machos se desplazaron más ampliamente que las hembras a lo largo de la cuadrícula de las cámaras. Jaguares de ambos sexos cruzaron dos ríos principales, mientras que el cruce de carreteras no fue común y estuvo sesgado hacia los machos, generando la preocupación de que las carreteras puedan impedir el movimiento de hembras si el tráfico vehicular aumenta. Los jaguares fueron más transitorios en paisajes fragmentados por asentamientos humanos y agricultura que en áreas de bosque continuo. Comparando con los jaguares de los bosques protegidos de las Montañas Mayas, los jaguares de la zona central de Belice mostraron menor potencial para invertir en comunicación intraespecífica, indicador de un paisaje de menor calidad; sin embargo, se detectó comportamiento de apareamientos y la presencia de juveniles. La permanencia de individuos fue más corta que en los bosques protegidos, con una tasa de recambio más alta para machos que para hembras. Al menos las tres cuartas partes de las muertes reportadas de jaguares causadas por humanos correspondieron a jaguares machos, la mayoría como retaliación por la muerte de ganado. Los jaguares parecen relativamente tolerantes del paisaje dominado por humanos en la zona central de Belice. Sin embargo, el aumento de la cacería de especies presa y el control letal de predadores amenazaría la persistencia de la población, mientras que el aumento del tráfico vehicular y la deforestación de bosques de galería reducirían severamente la funcionalidad del corredor. Nuestros resultados muestran que la viabilidad del corredor y por lo tanto la sobrevivencia de jaguares a largo plazo en esta región dependerá de la planificación apropiada del uso del suelo, de un control no letal de predadores de ganado, una mejor regulación de la cacería, y de una infraestructura amigable con la vida silvestre en las futuras carreteras.

The number of people with glaucoma worldwide in 2010 and 2020.

AIM: To estimate the number of people with open angle (OAG) and angle closure glaucoma (ACG) in 2010 and 2020. METHODS: A review of published data with use of prevalence models. Data from population based studies of age specific prevalence of OAG and ACG that satisfied standard definitions were used to construct prevalence models for OAG and ACG by age, sex, and ethnicity, weighting data proportional to sample size of each study. Models were combined with UN world population projections for 2010 and 2020 to derive the estimated number with glaucoma. RESULTS: There will be 60.5 million people with OAG and ACG in 2010, increasing to 79.6 million by 2020, and of these, 74% will have OAG. Women will comprise 55% of OAG, 70% of ACG, and 59% of all glaucoma in 2010. Asians will represent 47% of those with glaucoma and 87% of those with ACG. Bilateral blindness will be present in 4.5 million people with OAG and 3.9 million people with ACG in 2010, rising to 5.9 and 5.3 million people in 2020, respectively. CONCLUSIONS: Glaucoma is the second leading cause of blindness worldwide, disproportionately affecting women and Asians.

Neuronal death in glaucoma.

Glaucoma is recognized to have its major detrimental effect upon the eye by killing retinal ganglion cells. The process of cell death appears to be initiated at the optic nerve head, though other sites of injury are possible but unsubstantiated. At present the injury at the nerve head seems related to the level of the eye pressure, but its detailed mechanism is as yet unexplained. There is a greater loss of ganglion cells from some areas of the eye, and this feature of glaucoma seems related to the regional structure of the supporting connective tissues of the optic nerve head. Larger retinal ganglion cells have been consistently shown to have somewhat greater susceptibility to injury in glaucoma, though all cells are injured, even early in the process. Ganglion cells die by apoptosis in human and experimental glaucoma, opening several potential areas for future therapies to protect them from dying. Neurotrophin deprivation is one possible cause of cell death and replacement therapy is a potential approach to treatment.

Undetected eye disease in a primary care clinic population.

BACKGROUND: Population-based data have indicated that a significant proportion of persons with undiagnosed ocular disease in the community are regular users of general medical services. This, combined with the high prevalence of chronic medical disorders known to be risk factors for ocular disease in such clinics, makes them an attractive site for screening. METHODS: The prevalence of ocular disease was estimated in a sample of 405 general medicine patients attending an adult primary care clinic in an urban teaching hospital. RESULTS: Overall, 205 (50.6%) of 405 patients were found to have clinically important ocular pathology. One third of those affected (n = 68) were unaware of their eye disease, and 26% (n = 18) of these 68 patients required immediate medical or surgical intervention. Patients 65 years or older (odds ratio [OR], 1.76), in fair or poor general health (OR, 1.78), with diabetes mellitus (OR, 2.07), or with self-reported fair or poor vision (OR, 3.03), were at increased risk for the presence of ocular disease. Among patients with eye disease, those who had no insurance coverage for eye care (OR, 3.45), those who had not had an eye examination during the previous 2 years (OR, 4.03), and those whose last eye examination was performed by an optometrist (OR, 7.25, reference ophthalmologist) were more likely to not be aware of their eye disease. CONCLUSIONS: Our results underscore the importance of screening for ocular disease in primary health care settings, especially for patients who are older than 65 years, are in poor health, report poor vision, have had infrequent eye examinations, or have inadequate insurance coverage for eye care.

Gap junctions between optic nerve head astrocytes.

Astrocytes of the primate and human optic nerve head are joined to each other by the gap junction type of intercellular membrane specialization. Although the precise function of these contacts is not fully determined, they may serve such diverse roles as adhesive bonding and intercellular electrical and chemical coupling.

Models of open-angle glaucoma prevalence and incidence in the United States.

PURPOSE: To estimate the prevalence and incidence of open-angle glaucoma among black and white persons in the United States and to characterize quantitatively their life experience with glaucoma using a life table approach to estimate disease duration. METHODS: Review of published data on glaucoma combined with statistical models to estimate prevalence and incidence. RESULTS: The association of open-angle glaucoma with age was examined separately for white and black persons. By the year 2000, the number of persons in the United States with primary open-angle glaucoma is estimated to be 2.47 million (1.84 million white and 619,000 black Americans). A model using derived incidence rates for open-angle glaucoma (OAG) and United States mortality data indicated that the average black American has OAG 27% longer than the average white American (16.3 years compared to 12.8 years). CONCLUSIONS: Meta-analysis to obtain pooled prevalence estimates for glaucoma provides useful information on length of disease and age distribution of those affected. It may assist in estimating treatment effects and associated costs to derive data that effect health care decisions.

Laser energy levels for trabecular meshwork damage in the primate eye.

The authors treated the trabecular meshwork of 17 primate eyes with the argon laser by a variety of protocols in an attempt to cause moderate, consistent intraocular pressure elevation. This was achieved most satisfactorily with deliveries of 0.5 to 1.0 seconds and a total energy of at least 50 joules. The method allows production of a satisfactory laser-induced model of chronic glaucoma with one treatment session in most eyes. This experience provides a measure of the upper limit of acceptable total laser energy for therapeutic procedures in humans with this instrument. Delivery durations longer than 0.1 sec should be used with caution in trabeculoplasty.

Chronic experimental glaucoma in primates. I. Production of elevated intraocular pressure by anterior chamber injection of autologous ghost red blood cells.

Chronic elevations of intraocular pressure (IOP) were produced in rabbit and monkey eyes by anterior chamber injection of autologous fixed red blood cells. The method confirms the possibility of secondary glaucoma due to trabecular obstruction by ghost cells in eyes with intraocular hemorrhage. In primates, decreased aqueous outflow may result from direct obstruction by free cells and macrophages as well as swelling of trabecular endothelium following phagocytosis of cellular debris. IOP elevations for from 2 days to greater than 1 month were produced in order to study the effects of elevated IOP on ocular tissues. The model has the advantages of producing IOP elevation easily and without associated intraocular inflammation. The extensive filling of the anterior chamber necessary to produce IOP rises in healthy animal eyes leads to the disadvantage of poor visibility of the optic disk. In rabbit eyes, chronic IOP elevation leads to corneal enlargement and ectasia, making IOP measurements difficult.

Chronic experimental glaucoma in primates. II. Effect of extended intraocular pressure elevation on optic nerve head and axonal transport.

Intraocular pressure (IOP) elevations lasting from 2 to 42 days were produced in 13 primate eyes by anterior chamber injections of autologous, fixed red blood cells. The retina, optic nerve head, and optic nerves were studied by electron microscopy, and ganglion cell rapid axonal transport was examined after IOP elevations for various durations. Transport of axonal material was blocked at the scleral lamina cribrosa by IOP elevations to 50 mm Hg. With IOP elevation for less than 1 week, return to normal IOP restored normal transport in some axons. However, in other axons IOP elevation for less than 1 week intiated ganglion cell degeneration. The process of cellular death involved a rapid ascending degeneration from nerve head to brain, followed 3 to 4 weeks later by descending degeneration of the ganglion cell body and its attached axon. Axons of the superior and inferior optic nerve head and nerve seem to be damaged more extensively than those in the nasal and temporal optic nerve. Two to four days after IOP elevation, axons of the superficial optic nerve head were swollen with accumulating axonal material, leading to histologic disk edema. In those eyes with IOP elevation longer than 1 week, the loss of anterior disk nerve fibers combined with posterior and lateral movement of the lamina cribrosa lead to an increase in optic disk cupping. Astrocytes and capillaries of the optic nerve head seem to tolerate elevated IOP well and were relatively spared.

Distribution of axonal transport blockade by acute intraocular pressure elevation in the primate optic nerve head.

We studied the degree of axonal transport blockade in various areas of the optic nerve head with acute intraocular pressure (IOP) elevation in 19 squirrel monkey eyes. When IOP was raised to 20 to 50 mm. Hg for 7 hr., mild axonal transport blockade occurred in each area of the disk, most prominently in nerve fiber bundles of the superior pole. With 7 hr. IOP elevations between 50 and 90 mm. Hg, a somewhat greater degree of transport blockade occurred throughout the nerve head, although again the superior and inferior poles were somewhat more affected. The distribution of short-term transport blockade over the entire nerve head corresponds to the diffuse damage of acute glaucoma, but the pattern hints at the preference for damage near the poles of the disk seen in chronic glaucoma. However, before these results can be fully evaluated, further information is needed on axonal pathways through the optic nerve head and on the relationship between transport obstruction and ganglion cell death.

Retinal ganglion cell loss is size dependent in experimental glaucoma.

Thirty-two areas located in the temporal midperipheral retina were evaluated in whole-mount preparations from four monkeys with monocular experimental glaucoma. Diameter frequency distributions of remaining ganglion cells in the glaucomatous eye were compared with corresponding areas in the normal fellow eye. Large cells were significantly more vulnerable at each stage of cell damage as determined by linear-regression analysis. The magnitude of size-dependent loss was moderate at an early stage (20% loss), peaked at 50% total cell loss, and decreased in advanced damage (70% loss). In glaucomatous eyes, the lower retina had significantly more large cell loss than the corresponding areas of the upper retina. In optic nerve zones that matched the retinal areas studied, large axons selectively were damaged first. Psychophysical testing aimed at functions subserved by larger ganglion cells is recommended for detection and follow-up of early glaucoma; however, assessment of functions unique to small cells is more appropriate for detecting change in advanced glaucoma.

Foveal ganglion cell loss is size dependent in experimental glaucoma.

PURPOSE: The purpose of this study was to study the pattern of foveal ganglion cell loss in experimental glaucoma. METHODS: Retinal ganglion cell size and number in the foveal region of seven monkey eyes with experimental glaucoma was determined and compared to normal monkey eyes. Serial sections of macular retina were studied in two regions: the plateau of peak density of ganglion cells (800-1100 microns from the fovea), and within 500 microns of the foveal center. RESULTS: In normal eyes, cell densities were 37,900 +/- 2700 in the foveal plateau and 17,200 +/- 1800 cells/mm2 in the foveal center. There was selective loss of larger ganglion cells in glaucoma eyes. The degree of foveal ganglion cell loss was significantly correlated to the degree of nerve fiber loss in the temporal optic nerve of the same eye. CONCLUSIONS: Detection of early, central visual function loss in glaucoma could be enhanced by testing functions subserved by larger retinal ganglion cells.

Repeatability of the Glaucoma Hemifield Test in automated perimetry.

PURPOSE: To examine the concordance of the Glaucoma Hemifield Test and other global visual field indexes between two consecutive automated visual field tests. METHODS: Normal subjects, subjects with ocular hypertension, and subjects with glaucoma had two automated visual field tests on the Humphrey Field Analyzer. The Glaucoma Hemifield Test results, mean deviation, and corrected pattern standard deviation of the two consecutive visual field tests were compared. RESULTS: Forty-one normal subjects were tested within 1 and 2 years of each other. Four hundred seven subjects with ocular hypertension and 95 subjects with glaucoma were tested 1 year apart. The proportion of normal subjects who met a criterion for abnormality on two consecutive tests was 2.4%. The proportion of subjects with glaucoma with normal results of two tests was 10.5%. The specificity of automated visual field testing was improved from 80.8% to 89.9%, with a modest loss of sensitivity if two rather than one abnormal test result was required for entry into a clinical trial enrolling patients with glaucomatous field loss. Similarly, specificity increased from 84.2% to 89.5% if two normal tests were required for entry into an ocular hypertensive clinical trial. Among subjects with more closely spaced tests, the agreement between consecutive tests was similar for tests spaced 4 versus 12 months apart. CONCLUSIONS: Although there is concordance of Glaucoma hemifield Test results on consecutive testing, there is enough disagreement to result in improved specificity from the use of a second test in a clinical trial setting.

The effect of biogenic monomines on rapid axonal transport in the rabbit optic nerve.

Since L-dopa and serotonin have been reported to increase the rate of axonal transport in rat sciatic nerve, we decided to study the effect of these monoamines on rapid orthograde transport in the rattit optic nerve. To do this, tritiated leucine was injected into the vitreous of both eyes of 56 albino rabbits, and arrival of radioactive labeled proteins at the superior colliculus was measured at various intervals by liquid scintillation counting. Rabbits were studied 24 hr after intraperitoneal injections of (1) Sinemet + L-dopa, (2) Sinemet + 5-hydroxytryptophan, or (3) pargyline. There were 14 rabbits in each group compared to 14 controls that received no monoamies. In the monoamine-treated groups, transported labeled proteins arrived at the superior colliculus earlier, and an increased amount of radioactivity accumulated during the next several hours. The maximum amount of radioactive proteins accumulating in drug-treated animals did not differ significantly from the maximum amount in control animals. As judged by autoradiographic densitometry, retinal ganglion cell synthesis was similar in control and drug-treated animals. We suspect that the rate of rapid axonal transport is increased by monoamines, although an increased rate of ganglion cell protein synthesis is another possibility.

Analysis of progressive change in automated visual fields in glaucoma.

PURPOSE: To detect and estimate the rate of progression of visual field loss in subjects with glaucoma who undergo long-term automated perimetric visual field testing. METHODS: Automated visual field data were obtained for subjects with glaucomatous visual field loss and a minimum of seven threshold field tests over at least 4.5 years. Univariate linear regression was performed with respect to mean deviation (MD), corrected pattern standard deviation (CPSD), mean thresholds of clusters corresponding to the Glaucoma Hemifield Test (GHT), and thresholds of 52 individual test locations. Subjects were classified as progressive or stable (unchanged or improved) based on the slope and statistical significance of these parameters. Adjusted P values were used to maintain the overall type 1 error at 5%. RESULTS: One hundred ninety-one subjects with a mean follow-up period of 7.1 years (range, 4.5 to 10.5 years) and a mean number of visual field tests of 9.5 (range, 7 to 16) were included. Twenty-four subjects (12.6%) showed progression in MD (mean slope [95% confidence interval], -1.26 [-1.50, -1.01] dB/year), and 27 (14.1%) showed progression in CPSD (mean slope [95% confidence interval], 0.71 [0.58, 0.84] dB/year). Thirty-five subjects (18.3%) had > or = 1 progressive GHT cluster. The mean slope in progressive clusters ranged from -1.51 [-1.82, -1.20] to -2.84 [-3.39, -2.29] dB/year. Thirty-six subjects (18.8%) had > or = 1 progressive individual test locations. Fifty-two subjects (27.2%) were classified as progressive based on progression of CPSD, > or = 1 cluster and/or > or = 1 point. CONCLUSIONS: Fewer than 1 in 3 subjects progressed by any one of the criteria for progression over an average of 7.1 years. Rates of progression that could be statistically confirmed were in the range of approximately 1 to 5 dB/year, depending on the number of fields, the variability over time, and the parameter assessed (global indices, GHT clusters, or individual points). No correlation between initial visual field status and the rate of progression was found. A minimum of approximately 5 years of follow-up with annual perimetry would be required to detect significant changes in the visual field by linear regression.

Selective effects of experimental glaucoma on axonal transport by retinal ganglion cells to the dorsal lateral geniculate nucleus.

Rapid-phase axonal transport to the dorsal lateral geniculate nucleus (dLGN) was determined autoradiographically in seven macaque monkey eyes with chronic intraocular pressure (IOP) elevation, in four eyes with an acute IOP elevation, and in three eyes with normal IOP. The monkeys with chronic IOP elevation showed a greater decrease in radioactive labeling of the magnocellular layers of the dLGN than the parvocellular layers by qualitative examination. Grain counts in selected specimens confirmed that transport to the magnocellular layers was less than to the parvocellular layers in monkeys with chronic IOP elevation. This selectivity was present in mildly damaged specimens and increased with greater ganglion cell loss. In monkeys with acute IOP elevation, qualitative evaluation suggested no consistent difference in transport among the dLGN layers; one animal in this group had less transport to the parvocellular than to the magnocellular layers by grain counts. Starting in early stages of the disease, chronic experimental glaucoma causes preferential damage to the ganglion cells that project to the magnocellular layers of the dLGN.

D-penicillamine and beta-aminopropionitrile effects on experimental filtering surgery.

We studied the effect of two compounds, beta-aminopropionitrile (BAPN) and D-penicillamine on the success of experimental glaucoma filtering surgery in cynomolgus monkeys. All animals had laser-induced glaucoma and underwent punch sclerectomy operations. Eyes treated with BAPN or D-penicillamine maintained successful filtration for at least 3 days longer than nondrug-treated controls. This effect, while statistically significant (P less than 0.05), was temporary. The lack of more substantial improvement in prolonging filtering patency may have resulted from an inadequate effective drug concentration. Alternatively, these drugs may have limited potency because their action on new collagen synthesis affects only a minor component of the healing process that causes filter failure.

The number and diameter distribution of axons in the monkey optic nerve.

Using an automated image analysis system, cross-sections from optic nerves of 17 normal cynomolgus monkeys were examined. The number of nerve fibers, their density, and the distribution of their diameters for whole nerves and for various regions of the nerve cross-section were estimated. The mean total number of fibers in the optic nerve was 1.2 million. The mean diameter of axons was 0.8 micron. The method of tissue fixation substantially affected the measurements. Histograms of fiber diameter suggested a trimodal distribution of fiber size with peaks at 0.5, 0.8, and 1.5 micron. The relative proportions of these fiber peaks differed significantly in different regions of the nerve. The highest proportion of large fibers was in the superior nerve periphery. The highest concentration of smallest fibers and the highest density of all fibers were located centrally in the infero-temporal quadrant. The observation that higher fiber density and smaller mean fiber diameter are skewed toward the inferior pole appears to coincide with the inferior position of the fovea with respect to the optic nerve head. This finding has importance for interpretation of pathologic changes in the optic disc.