Eliciting preferences in glaucoma management-a systematic review of stated-preference studies.

BACKGROUND: In most cases, glaucoma patients require long-term medical and/or surgical treatment. Preference studies investigate how different aspects of glaucoma management, such as health or process outcomes, are valued and herewith help stakeholders make care more responsive to patients' needs. As, to our knowledge, no overview of these studies is currently available, this study aims to systematically review and critically appraise these studies. METHODS: A systematic literature review was conducted using keywords for stated-preference studies and glaucoma up to October 2021. Studies were included if they were original research and used a stated-preference methodology to investigate preferences in patients or healthcare professionals for different aspects of glaucoma management. Data were extracted and summarized. Furthermore, a quality appraisal of the included studies was performed using two validated checklists. RESULTS: The search yielded 1214 articles after removal of duplicates. Of those, 11 studies fulfilled the inclusion criteria. Studies aimed to elicit preferences for glaucoma treatment (27%), glaucoma related health state valuation (36%), and services (36%) from the patient (91%) or ophthalmologists' perspective (9%). Altogether studies included 69 attributes. The majority of attributes were outcome related (62%), followed by process (32%) and cost attributes (6%). Outcome attributes (e.g., effectiveness) were most often of highest importance to the population. CONCLUSIONS: This systematic review provides an up-to-date and critical review of stated-preference studies in the field of glaucoma, suggesting that patients have preferences and are willing to trade-off between characteristics, and revealed that outcome attributes are the most influential characteristics of glaucoma management.

Increased ratios of complement factors C3a to C3 in aqueous humor and serum mark glaucoma progression.

INTRODUCTION: We recently performed a combined analysis of publicly available proteomic studies of aqueous humor (AH) of patients with primary open angle glaucoma (POAG). This analysis revealed changes in complement protein concentrations in the AH of progressive POAG patients, which suggested that the complement system may play a role in POAG progression. As the proteomic studies could not provide information on the activity of the complement system, we addressed this question in the current study. METHODS: Blood serum and AH were obtained from 30 patients: 10 progressive POAG, 10 stable POAG and, as controls, 10 cataract patients. Glaucoma patients with a visual field Mean Deviation (MD) change of at least 1.0 dB/year were considered progressive; a MD change of less than 0.5 dB/year was considered stable. The ratio between the levels of complement factors C3a and C3 was used as indicator for activation of the complement cascade. The factors were measured with commercially available ELISA kits. RESULTS: AH levels of complement factors C3 and C3a did not significantly differ between groups. In serum, complement factor C3 did not differ between groups whereas C3a was significantly elevated in progressive POAG patients compared to controls (p < 0.05). The resulting complement C3a/C3 ratio was significantly higher in progressive POAG patients in both AH (p < 0.05) and serum (p < 0.01), and this ratio significantly correlated between the two body fluids (p < 0.001). Furthermore, there was a strong correlation between disease progression and C3a/C3 activation ratio both in AH (p < 0.01) and in serum (p < 0.001). The higher the complement C3a/C3 ratio, the faster the disease progression. CONCLUSION: Significant increases in AH and serum complement C3a/C3 ratios were observed in progressive POAG patients but not in stable POAG patients. Furthermore, the complement C3a/C3 ratio correlated strongly with the rate of disease progression in both AH and serum. These findings suggest that activation of the complement system plays a role in glaucoma progression and that progressive glaucoma patients may have systemic changes in complement activation.

The relationship between visual field loss in glaucoma and health-related quality-of-life.

PURPOSE: to investigate the relationship between visual field loss and health-related quality-of-life (HRQOL) in patients with ocular hypertension (OHT) or primary open-angle glaucoma (POAG). METHODS: we conducted a cross-sectional study among 537 OHT and POAG patients from seven hospitals in The Netherlands. Clinical information was obtained from medical files. Patients completed a questionnaire, containing generic HRQOL instruments (EQ-5D and Health Utilities Index mark 3), vision-specific National Eye Institute Visual Functioning Questionnaire (VFQ-25), and glaucoma-specific Glaucoma Quality-of-Life questionnaire (GQL-15). The impact of visual field loss on HRQOL scores was analysed with multiple linear regression analyses. RESULTS: a relationship between mean deviation (MD) and HRQOL was found after adjusting for age, gender, visual acuity, medication side effects, laser trabeculoplasty, and glaucoma surgery. We found interaction between MD in both eyes for GQL and VFQ-25 scores. The relationship between MD and utility was non-linear, with utility only affected at MD-values below -25 dB in the better eye. Visual acuity, side effects, and glaucoma surgery independently affected HRQOL. Binocular MD and MD in the better eye had similar impacts on HRQOL, whereas MD in the worse eye had an independent effect. HRQOL was affected more by binocular defects in the inferior than in the superior hemifield. CONCLUSION: visual field loss in progressing glaucoma is independently associated with a loss in both disease-specific and generic quality-of-life. It is important to prevent progression, both in early and in advanced glaucoma, especially in patients with inferior hemifield defects and severe defects in either eye.

Knowledge base and preferred methods of obtaining knowledge of glaucoma patients.

PURPOSE: To gather information regarding patient's understanding of glaucoma and the manner in which patients wish to learn about the disease with the intent of improving patient education. METHODS: Forty-four of sixty randomly selected ophthalmologists (73%) asked four of their patients consecutively to complete a questionnaire about glaucoma. The selection of questions was based on focus group interviews and suggestions from several experts. Topics included knowledge about glaucoma and its treatment, the need for information, and preferred providers and methods of patient education. RESULTS: Fifty percent of the patients had 49% or less correct answers to questions about glaucoma or its treatment. Per item the correct answers ranged from 5% to 90%. Lack of knowledge was associated with low level of education, short duration of glaucoma, high age, and no preference for the Internet as method of supplying information. These variables, however, did not identify groups with a considerable lack of knowledge sufficiently accurately to target patient education. A high need for information was observed and included information about the patient's own glaucoma. Almost all patients preferred the ophthalmologist and many also a nurse or a representative of the Glaucoma Patient Society as providers of information. Written material was the preferred method. CONCLUSIONS: Patient education should address all patients. A patient education program should cover a wide range of topics with a focus on general information through written material and information tailored to the individual glaucoma patient's needs. The ophthalmologist is a key- person, but others could play an important role in patient education.

Phacotrabeculectomy.

The outcome of combined same-site phacoemulsification, posterior chamber lens implantation and trabeculectomy was retrospectively studied in patients with cataract and moderately controlled glaucoma, with a follow-up of at least 6 months. Primary phacotrabeculectomy without antimetabolites was performed in 74 patients. Mean IOP decreased from 22.8 to 14.3 mm Hg (35.3%). A maximum IOP of 19 mm Hg without glaucoma medication was reached in 66.2%. Mean logMAR visual acuity increased from 0.58 to 0.30. Primary phacotrabeculectomy has been shown to be a safe and effective procedure with good IOP control and rapid visual rehabilitation.

Effect of chlorhexidine varnish on Actinomyces naeslundii genospecies in plaque from dental fissures.

This study describes the effects of varnish containing 40% chlorhexidine diacetate on Actinomyces naeslundii populations in plaque from human molar fissures. In each of 15 subjects two dental fissures with high levels of mutants streptococci were selected. The experimental treatment consisted of the single application of a small amount of chlorhexidine varnish onto the selected fissures. The varnish was removed 15 min after application. One month after varnish application a significant increase was observed in A. naeslundii counts while the number of mutans streptococci had decreased significantly compared with preexperimental levels. From 85 randomly selected Actinomyces isolates taken from blood agar plates before varnish application, 44% belonged to A. naeslundii genospecies 1 and 56% to A. naeslundii genospecies 2. From 106 isolates taken 1 month after chlorhexidine varnish application, 42% belonged to A. naeslundii genospecies 1 and 58% to A. naeslundii genospecies 2. At baseline 28% of A. naeslundii genospecies 1 strains were catalase-positive, but 1 month after varnish application 4% of the strains were catalase-positive (p < 0.05). It is concluded that chlorhexidine varnish application caused an increase of A. naeslundii in dental plaque, but induced no significant changes in the distribution of the two A. naeslundii genospecies.

Sympathetic innervation of the rat choroid: an autoradiographic tracing and immunohistochemical study.

The sympathetic innervation of the choroid was investigated by means of the anterograde tracer 3H-leucine, injected into the rostral part of the superior cervical ganglion. The tracer was autoradiographically visualized at the light- and electron-microscopic levels. Labelled unmyelinated fibres were found in the choroid and labelled terminals were observed in close proximity to the smooth muscle cells of arterioles. The labelled terminals contain granular vesicles of different size and clear vesicles; the mitochondria were of the electron-dense type and no cell-to-cell synaptic contacts were observed. In addition, tyrosine hydroxylase immunocytochemistry was performed. Immunostained terminals found in the choroid show ultrastructural features similar to those found in the tracing experiments: granular vesicles of different size, clear vesicles and electron-dense mitochondria. On the basis of previous studies and the present observations, it is concluded that the choroid has a dual innervation, a parasympathetic innervation from the pterygopalatine ganglion and a sympathetic innervation from the superior cervical ganglion. The dual innervation is most likely involved in maintaining the homeostasis of vasodilatation and vasoconstriction in the choroid.

Peripheral neural circuits regulating IOP? A review of its anatomical backbone.

The peripheral nervous system is classically separated into a somatic division containing both afferent and efferent pathways and an autonomic division composed of efferents only. The somatic afferent division is divided in A- and B-neurons. The B-neurons are supposed to be autonomic afferents as part of a reflex system involved in homeostasis. Recent data obtained by neuronal tracing and immunohistochemical experiments concerning the eye related peripheral nervous system endorse the existence of these peripheral reflex systems. Somatic afferents of trigeminal origin synaptically innervate parasympathetic neurons in the pterygopalatine ganglion. This probably represents a pathway mediating autonomically regulated ocular activity in response to sensory stimulation. In addition, it has been hypothesized that trigeminal sensory nerve fibres have an efferent function in response to noxious stimuli e.g. the ocular injury response. Sympathetic nerve fibres originating in the superior cervical ganglion course through the trigeminal and pterygopalatine ganglion without forming direct synaptic contacts. These fibres, however, contain clusters of vesicles suggesting some kind of interneural communication. Parasympathetic nerve fibres of pterygopalatine origin course through the ciliary ganglion. These nerve fibre terminals also contain clusters of vesicles without direct synaptic contacts. Experimental data concerning the distribution of neuropeptides revealed a more detailed knowledge of the anterior eye segment innervation. These experimental data are subject to some debate. The pros and cons of different techniques are discussed. Neural circuits regulating IOP have long been postulated. The possible role of peripheral reflex systems in the regulation of IOP is discussed.

The peripheral and central projections of the Edinger-Westphal nucleus in the rat. A light and electron microscopic tracing study.

The peripheral and central efferent projections of the rostral part of the Edinger-Westphal nucleus in the rat were investigated at the light and electron microscopic level by means of iontophoretic injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin and retrograde tracer injections of Fast blue and Nuclear yellow into the facial nucleus and into the principal olive. Two pathways leaving the rostral part of the Edinger-Westphal nucleus were studied, a peripheral and a central descending pathway. Fluorescent experiments demonstrated that the central pathway fibers originated from distinct individual Edinger-Westphal neurons. These neurons were mainly distributed throughout the rostral part of the Edinger-Westphal nucleus and had fusiform cell bodies. The neurons rarely form collateral projections. The central descending pathway left the Edinger-Westphal nucleus medially and terminated bilaterally in the principal olive, in the subnuclei A, B and C of the inferior olive and ipsilaterally in the medial accessory olive. The central pathway also terminated contralaterally in the lateral parabrachial nucleus, the facial nucleus, the trigeminal brainstem nuclear complex, the lateral reticular nucleus and the rostroventral reticular nucleus. The projection to the facial nucleus provides evidence for the existence of a polysynaptic loop forming the central part of the corneal blink reflex. Projections from the Edinger-Westphal nucleus to the cerebellar cortex or the deep nuclei, as described in cat and primate, could not be confirmed. The peripheral pathway left the Edinger-Westphal nucleus ventrally and terminated on dendrites of ciliary ganglion cells, along smooth muscle cells of ciliary ganglion associated arterioles and in the proximity of ciliary ganglion associated venules. The central and peripheral terminals that originate in the Edinger-Westphal nucleus all had similar ultrastructural features: clear, round vesicles and electron dense mitochondria. The terminals originating from the central descending pathway were often found to be arranged in glomerular-like structures. The central and peripheral terminals made asymmetric synaptic membrane specializations (Gray type one), except terminals innervating the ciliary ganglion associated vessels, which showed no synaptic contacts.

Facial parasympathetic innervation of the rat choroid, lacrimal glands and ciliary ganglion. An ultrastructural pterygopalatine tracing and immunohistochemical study.

The pterygopalatine parasympathetic innervation of the rat choroid, lacrimal glands and ciliary ganglion was ultrastructurally studied by anterograde 3H-leucine tracing. Numerous unmyelinated fibers and vesicle-containing terminals were labeled in these structures. No direct synaptic contacts were found. In the choroid, similar terminals were immunoreactive to vasoactive intestinal polypeptide (VIP). A regulatory feedback loop within the eye-related peripheral nervous system is endorsed by the present results. The finding of fibers and terminals of pterygopalatine origin in the lacrimal glands agrees with earlier studies in cats and monkeys. In the ciliary ganglion, pterygopalatine terminals most likely influence the ganglion cells by nonsynaptic release of neurotransmitters or neuromodulators including VIP.

Substance P in rat corneal and iridal nerves: an ultrastructural immunohistochemical study.

The distribution of substance P (SP) within the nerve fibers of the rat cornea and iris was studied using electron microscopic immunohistochemistry. Numerous SP-immunoreactive fibers were found throughout the corneal and iridal stroma. The most intense staining was found within varicosities containing numerous vesicles. Similar SP-immunoreactive varicosities were found in fibers in close proximity to the iris sphincter and dilator muscles. On account of previous ultrastructural work the SP-containing fibers and varicosities must be assumed to be of trigeminal origin. Additionally, the distribution of SP and calcitonin gene-related peptide (CGRP) in corneal and iridal fibers of rats is similar, suggesting that CGRP and SP are colocalized and may be coreleased from the same varicosities.

Ultrastructural identification of trigeminal nerve endings in the rat cornea and iris.

Trigeminal nerve terminals in the rat cornea and iris were ultrastructurally identified using anterograde tracing with Phaseolus vulgaris-leukoagglutinin (PHA-L). Electron microscopic immunohistochemistry was used to demonstrate the presence and localization of calcitonin gene-related peptide (CGRP) in cornea and iris. In the cornea and iris, nerve fibers were labelled with PHA-L throughout the stroma. Labelling was most obvious within varicosities, densely packed with mainly clear and a few granular vesicles and containing dark mitochondria. Numerous fibers in the stroma of cornea and iris were CGRP-positive. CGRP-positive staining was most intense within varicosities, containing mainly clear and incidentally granular vesicles and dark mitochondria, similar to the structures labelled with PHA-L. CGRP-positive varicosities packed with mainly clear and few granular vesicles also were demonstrated in fibers adjacent to the sphincter and dilator muscles of the iris. In the corneal epithelium, small terminals containing vesicles were CGRP-positive. Trigeminal nerve fibers innervating the rat cornea and iris contained numerous varicosities packed with vesicles. These areas are CGRP-positive, so it can be implied that CGRP is released from these varicosities as a response to triggering impulses. This agrees with the hypothesis that in addition to their afferent function, sensory fibers also exert an efferent modulating function.

Ultrastructural identification of trigeminal nerve terminals in the pterygopalatine ganglion of rats: an anterograde tracing and immunohistochemical study.

Trigeminal nerve terminals in the rat pterygopalatine ganglion (PPG) were ultrastructurally identified using anterograde tracing with Phaseolus vulgaris-leucoagglutinin (PHA-L). Electron microscopic immunohistochemistry was used to demonstrate the presence of substance P (SP) and calcitonin gene-related peptide (CGRP) in nerve terminals of the PPG. Adjacent to the rostral part of the PPG an additional minor area was described. Perikarya in this minor rostral part were more spherical and had irregular outlines. Ultrastructurally, the glial enwrapment of the nerve terminals seemed to be more loosely arranged in comparison to that in the major rostral part of the PPG. With PHA-L, numerous labelled nerve fibres and terminals were found in all parts of the PPG. The ultrastructure of these terminals was uniform, many of them showing synaptic contacts. Numerous terminals in the PPG were SP-positive, whereas only a few were CGRP-positive. Fibres stained positive for both neuropeptides. The PPG is shown to be synaptically innervated by sensory fibres arising in the trigeminal ganglion, with the strong suggestion of SP and CGRP acting as neurotransmitters. A modulatory interaction between the autonomic and sensory system, resembling an axon reflex mechanism in the peripheral nervous system is endorsed.

Method for the detection of Shigella in foods.

A method for the detection of Shigella in foods was evaluated. The method consisted of selective enrichment at 37 degrees C in GN-broth supplemented with novobiocin (10 micrograms/ml) followed by subculture after 6 and 24 h incubation of 0.1 ml volumes to SS-agar with and without streptomycin (7.5 micrograms/ml). Test samples were contaminated by adding shigellae to 1:10 suspensions of foods (minced meat, fresh cut vegetables and cooked peeled shrimp) in the GN-broth with novobiocin. Shigella could be detected at a contamination level of 1 per 25 g in the presence of shrimp (in all 20 samples) and at 25 per 25 g in the presence of nearly all samples of fresh cut vegetables (in 13 out of 18 samples). Using this procedure Shigella could not be detected when the organism was present at a relatively high contamination level of 10(2) per 25 g in the presence of minced meat (with all 10 samples). However, the procedure described is an improvement on methods currently available for the detection of Shigella in foods.

A written test as an alternative to performance testing.

Performance tests are logistically complex and time consuming. To reach adequate reliability long tests are imperative. Additionally, they are very difficult to adapt to the individual learning paths of students, which is necessary in problem-based learning. This study investigates a written alternative to performance-based tests. A Knowledge Test of Skills (KTS) was developed and administered to 380 subjects of various educational levels, including both first-year students and recently graduated doctors. By comparing KTS scores with scores on performance tests strong convergent validity was demonstrated. The KTS failed discriminant validity when compared with a general medical knowledge test. Also the identification of sub-tests discriminating between behavioural and cognitive aspects was not successful. This was due to the interdependence of the constructs measured. The KTS was able to demonstrate differences in ability level and showed subtle changes in response patterns over items, indicating construct validity. It was concluded that the KTS is a valid instrument for predicting performance scores and could very well be applied as supplementary information to performance testing. The relative ease of construction and efficiency makes the KTS a suitable substitute instrument for research purposes. The study also showed that in higher ability levels the concepts which were meant to be measured were highly related, giving evidence to the general factor theory of competence. However, it appeared that this general factor was originally non-existent in first-year students and that these competencies integrate as the educational process develops.

Influence of xylitol on growth, establishment, and cariogenicity of Streptococcus mutans in dental plaque of rats.

The influence of xylitol on glucose metabolism of Streptococcus mutans C67-1S was studied in vitro and in rats in vivo. In vitro there was an inhibition by xylitol of the growth rate and acid production of S. mutans C67-1S, but in vivo no effect on the initial growth rate could be demonstrated. In vivo there was a delay in the start of growth of S. mutans which resulted in a 10-day delay of establishment. The isolated xylitol-resistant mutant of C67-1S, S. mutans C67-1S XR, showed no difference in glucose metabolism in batch cultures. S. mutans C67-1S and S. mutans C67-1S XR were both used to study caries development in SPF Osborne Mendel rats. The rats were housed under programmed feeding conditions and were fed a glucose or a glucose-xylitol diet. In the case of S. mutans C67-1S, there was a remarkable inhibition of fissure caries lesions in the presence of xylitol compared to the glucose group. But also in the S. mutans C67-1S XR groups there were fewer lesions in the presence of xylitol. These results indicated that the anticariogenic properties of xylitol do not only depend on an inhibition of bacterial metabolism, but in part on other mechanisms.

Incidence of Foodborne Diseases in The Netherlands: Annual Summary 1982 and an Overview from 1979 to 1982.

Data on the incidence of foodborne disease in 1982 are presented. A total of 319 incidents affecting 1376 ill persons was analyzed. In 86 incidents (553 cases), the etiology was established. Microorganisms appeared to be the main causative agents: Bacillus cereus was responsible for 17 of these incidents (53 cases), Salmonella for 15 (83 cases), Campylobacter jejuni and Staphylococcus aureus for 11 (220 and 51 cases, respectively). Clostridium perfringens for 10 (96) and Yersinia enterocolitica for 1 (3). In 2 outbreaks (7 cases), several bacterial agents were detected without being able to discover which one had caused the symptoms. In 7 episodes (13 cases), illness resulted from ingestion of food contaminated with scombrotoxin. In one incident (4 cases), food had been contaminated with an excess of nutmeg and in 9 (20 cases) with monosodium glutamate. Two episodes (3 cases) were attributed to spoiled food. Cases of foodborne disease recorded by the Chief Medical Inspectorate, but not analyzed due to a lack of epidemiological information, included infections from Salmonella (6795), C. jejuni (1728) and Y. enterocolitica (274). Meat and meat products (24 incidents), fish and shellfish (25), snacks (21) and Dutch meals (23), but especially Chinese foods (132) were associated with incidents most frequently. About 70% of the incidents involved places where food is prepared for immediate consumption. Examples of outbreaks are presented.

Microbiology and food hygiene in mass catering.

Serious consequences can arise from lack of hygiene in mass catering. The uncritical use of routine microbiological tests purporting to measure hygiene merely creates a false sense of security. The microbiological safety of food is achieved by as far as possible ensuring the absence of pathogenic microorganisms and by all means preventing their multiplication. The Hazard Analysis Critical Control Point concept is used to identify microbiologically vulnerable points in the food production process and to determine the most appropriate methods of control to be applied, usually such methods as improved handling techniques, monitoring of temperature and more intensive supervision. Microbiological testing is of value in the initial analysis, at appropriate intervals for verifying the effectiveness of control measures, and in demonstrating to food handlers the reality of the microbial risk if good hygienic standards are not maintained.

The occurrence of salmonellae in kitchens of care institutions.

Sporadic cases of salmonellosis always by the same serotypes occurred in two different care institutions. In the first institution the cases had been caused by S. binza and S. eimsbuettel, in the second by S. mons and S. braenderup. The cases of salmonellosis prompted studies into the occurrence of these Salmonella serotypes in the kitchens of the relevant institutions, as well as into the occurrence of salmonellas in kitchens of care institutions in general. Using Moore's swabs the relevant Salmonella serotypes could be demonstrated in the kitchens of the institutions with sporadic cases of salmonellosis, while in kitchens of 15 other arbitrary chosen institutions Salmonella could not be detected at all. This demonstrated that the occurrence of sporadic cases of salmonellosis was related to the occurrence of salmonellas in the kitchens. Then investigations were started to establish the origin of the salmonellas. There was a mice plague in one institution. Mouse-dung was found positive for the relevant Salmonella serotype(s). Cases of salmonellas did not occur any more when the mice had been eradicated. It was concluded that the sporadic cases of salmonellosis in that institution were strongly associated with the presence of mice. In the other institution it appeared that disinfection was inadequate and that salmonellae were spread all over the kitchen environment during cleaning, leading to recontamination. After thorough disinfection and adaptation of cleaning and disinfection procedures sporadic cases of salmonellosis did not occur anymore. Results of these investigations demonstrated the important role of vermin and proper cleaning and disinfection in food hygiene. Moreover, the sporadic cases of salmonellosis came to light because gastro-enteritis was a reason for examination of faecal specimens of patients. This is not usual in many care institutions. However, in this way problems in hygiene can be traced, especially in the kitchen. For this reason it is recommended strongly to examine faecal specimens in cases of gastro-enteritis, even in sporadic cases.

Public health aspects of microbial contaminants in food.

Food-borne diseases affect the health and welfare of hundred thousands of people and result in considerable economic loss. Salmonella and Campylobacter are by far the most important causes of food-borne illness. Raw foods of animal origin are the major sources of these pathogens. Mishandling of foods in kitchens contributes to food-borne disease outbreaks. More education is necessary. But because of the inevitable risk of recontamination of cooked foods in every kitchen, more emphasis should be placed on pathogen-free raising of food animals and good manufacturing practices during slaughter. This will minimise contamination of raw foods of animal origin, thus reducing the contamination pressure in the kitchen and more effectively controlling food-borne diseases.