Economic and health implications of routine CBCT examination before surgical removal of the mandibular third molar in the Danish population.

OBJECTIVES: This epidemiological study aimed to analyse economical and societal consequences in Denmark if CBCT is used routinely as a diagnostic method before removal of the mandibular third molar. Furthermore, the aim was to calculate the excess cancer incidence from this practice. METHODS: 17 representative dental clinics in the regions of Denmark were visited by two observers, who registered the total number of patients in each clinic, the number of removed mandibular third molars from patients' files together with the age and gender of these patients. The data were collected from 2008 to 2014. The total number of removed mandibular third molars in Denmark each year was derived from the collected data and information on patients' contacts with dentists from Statistics Denmark as a sum of contributions from each region. The contribution of a region was obtained as the number of removed mandibular third molars in the selected clinics in the region times the ratio of the number of patients in the selected clinics in the region to the total number of patients with contact to a general practitioner in the region in 2011. Existing knowledge on the costs for panoramic and CBCT imaging was used to calculate total costs. The cancer incidence was calculated from lifetime attributable risk curves based on linear risk assumptions. RESULTS: The selected clinics included 109,686 patients, and 1369 mandibular third molars had been surgically removed. Using data from Statistics Denmark gave an estimated annual number of removed mandibular third molars of 36,882 at a total cost of €6,633,400. The additional cancer incidence was estimated to be approximately 0.46 per year. CONCLUSIONS: The data should be used in a cost-effectiveness analysis of the clinical efficacy of CBCT imaging before removal of mandibular third molars.

Image and surgery-related costs comparing cone beam CT and panoramic imaging before removal of impacted mandibular third molars.

OBJECTIVES: The aim of this prospective clinical study was to derive the absolute and relative costs of cone beam CT (CBCT) and panoramic imaging before removal of an impacted mandibular third molar. Furthermore, the study aimed to analyse the influence of different cost-setting scenarios on the outcome of the absolute and relative costs and the incremental costs related to surgery. METHODS: A randomized clinical trial compared complications following surgical removal of a mandibular third molar, where the pre-operative diagnostic method had been panoramic imaging or CBCT. The resources implied in the two methods were measured with health economic tools. The primary outcome was total costs defined as the sum of absolute imaging costs and incremental surgery-related costs. The basic variables were capital costs, operational costs, radiological costs, radiographic costs, overheads and patient resource utilization. Differences in resources used for surgical and post-surgical management were calculated for each patient. RESULTS: Converted to monetary units, the total costs for panoramic imaging equalized €49.29 and for CBCT examination €184.44. Modifying effects on this outcome such as differences in surgery time, treatment time for complications, pre- and post-surgical medication, sickness absence, specialist treatment and hospitalization were not statistically significant between the two diagnostic method groups. CONCLUSIONS: Costs for a CBCT examination were approximately four times the costs for panoramic imaging when used prior to removal of a mandibular third molar. The use of CBCT did not change the resources used for surgery, post-surgical treatment and patient complication management.

Association between refill compliance to oral bisphosphonate treatment, incident fractures, and health care costs--an analysis using national health databases.

SUMMARY: The study estimates the cost of poor and suboptimal refill compliance by estimating fracture costs and assessing the association between refill compliance with oral bisphosphonates and incident fractures using Danish health registers. Patients with poor and suboptimal refill compliance had more major osteoporotic fractures, and the direct costs related to hospital care, primary care, and pharmaceutical treatment for these excess fractures reached almost 14 M DKK (2.5 M USD) for the study population which compares to a national annual excess cost of around 17 M DKK (3.1 M USD) using 2011 prescription prevalence. INTRODUCTION: Adherence to oral anti-osteoporosis treatment has been shown in several studies to be relatively low and the potential impact on fracture burden is high. The aim of the study was to assess the association between refill compliance and all-cause health care costs. METHODS: A national dataset was extracted with all treatment-naive patients who began oral bisphosphonate (BP) treatment for osteoporosis in Denmark between 1997 and 2006 (N = 54,876, 87 % women). Patients who survived for at least 2 years (N = 47,176) were divided into groups based on Medication Possession Ratio (MPR). Logistic regressions were used to derive difference in the probability of incident fractures between the three MPR groups. Fracture costs (related to medication use, primary care practice, specialists, and hospitals) were derived by comparing cost 12 months before and after fracture. RESULTS: For alendronate, the adjusted risk of major osteoporotic fractures was significantly reduced (OR 0.768; 0.686-0.859), including fractures of the hip (0.718; 0.609-0.846) and humerus (0.54; 0.431-0.677) with MPR ≥ 0.8. The risk reduction was lower with etidronate. Over 2 years, a total of 171 hip fractures and 53 other major osteoporotic fractures were attributed to suboptimal or poor refill compliance, with an excess cost of 13.7 M DKK (2.5 M USD). CONCLUSIONS: Poor refill compliance is not unusual in patients on oral bisphosphonates, and we demonstrate that this is accompanied by excess major osteoporotic fractures and health care costs at the societal level.

Patient complexity and GPs' income under mixed remuneration.

Because of problems with recruiting GPs to deprived areas in Denmark, it has been discussed whether the mixed remuneration scheme is flexible enough to compensate GPs serving patients with high need for services. The objective is to assess how patient heterogeneity affects list size, income and total utility of GPs operating under a mixed remuneration scheme. We adapt the model by Iversen (2004) as a theoretical framework for analysing the consequences of patient heterogeneity in a mixed remuneration system. We use a data set of Danish solo practitioners to analyse the effect of patient complexity on list size and income. From the theoretical model we find that higher levels of patient complexity lead GPs to choose a lower list size, whereas the effect on income is ambiguous. The effect on total utility (income and leisure) is, however, shown to be negative. Using empirical data from 1039 solo practices we find that patient complexity reduces both list size and income and conclude that a mixed per capita and fee for service remuneration system does not fully compensate practices with more complex patients. Differentiated per capita payment may represent a means of ensuring fair and equal income of GPs.

The effectiveness of nationally implemented smoking interventions in Denmark.

OBJECTIVE: The present study aimed to investigate the effectiveness of smoking cessation interventions at a national level. METHOD: A systematic follow-up was made of 3628 adults who participated in smoking cessation groups or in individual interventions in different settings in Denmark from January 2001 to March 2002. RESULTS: The rates of continued abstinence from smoking were estimated as 18% and 16% after 6 and 12 months, respectively, for the 3628 participants from 101 smoking cessation units. Among participants, who accomplished at least 75% of the intervention, the rates of non-smokers after six and twelve months were 23% and 19%, respectively. Five of the investigated factors influenced continued abstinence after 12 months: gender, age, degree of nicotine dependence, the format and the setting of the cessation service. CONCLUSIONS: The study shows that it is possible to implement uniform smoking cessation interventions at a national level keeping the same abstinence rates as previously achieved in randomized clinical trials. The successful cessation interventions were run by nurses and equivalent staff that had received only 3 days of training and had no other particular therapeutic skills.

Traumatic macular hole: observations, pathogenesis, and results of vitrectomy surgery.

PURPOSE: To review our experience with vitrectomy surgery techniques for the treatment of traumatic macular holes and the biomicroscopic and surgical findings. DESIGN: Retrospective noncomparative, multicenter, case series. PARTICIPANTS AND INTERVENTION: Twenty-five patients with traumatic macular hole underwent surgical repair. INTERVENTION: Vitrectomy with membrane peeling and gas injection followed by prone positioning for 7 to 14 days. MAIN OUTCOME MEASURES: Postoperative evaluation included visual acuity testing, closure of the macular hole, and ocular complications. RESULTS: The macular hole was successfully closed in 24 of 25 cases (96%). The visual acuity improved two or more lines in 21 (84%) cases, and 16 (64%) achieved 20/50 or better vision. CONCLUSIONS: Vitrectomy surgery can successfully close macular holes associated with trauma and improve vision.

Dose rate effect of 125I irradiation on normal rabbit eyes and experimental choroidal melanoma.

The dose rate effect of radiation by 125I plaque on choroidal melanoma and normal intraocular tissue was studied. In the first part of the experiment, high activity plaques (HAP) and low activity plaques (LAP) were implanted on rabbit eyes with experimental Greene choroidal melanoma to deliver a total dose of 10,000 cGy to the tumor apex. The mean dose rate calculated at 0.5 mm from the inner sclera in eight eyes with high activity plaques was 3341.5 cGy hr-1 (1 cGy = 1 rad) while that in ten eyes with low activity plaques was 239.9 cGy hr-1. For tumors less than 1.0 mm in height, both groups showed complete tumor regression at the tumor implantation site after plaque treatment. For tumors more than 1.0 mm in height, two out of two eyes in the low activity plaque group and one of four eyes in the high activity plaque group failed to show complete tumor regression. Both LAP and HAP were effective in eradicating tumors, but logistic regression analysis demonstrates that HAP was more effective than LAP when adjustment was made for initial tumor height (P = 0.032). Nine tumor control eyes without 125I plaque implantation demonstrated marked tumor growth within 3 weeks. In the second part of the experiment, 125I plaques were implanted on the sclera of 12 normal rabbits' eyes. Six received high dose rate plaque treatment, while the other six received low dose rate plaque treatment. Clinical and histologic examinations demonstrated more damaging effects to the normal chorioretinal tissues at the plaque implantation site in the high dose rate plaque group at 24 weeks of follow-up. These results suggest that high dose rate plaques are more effective than low dose rate plaques when tumor height is statistically controlled. However, high dose rate delivery increases the damaging effects on normal intraocular tissue.

Tissue plasminogen activator thrombolysis during surgical evacuation of experimental subretinal hemorrhage.

To assess the role for intraoperative thrombolysis during surgical evacuation of massive subretinal hemorrhage, the authors studied the ability of tissue plasminogen activator (tPA) to facilitate removal of an experimental subretinal blood clot through a small drainage retinotomy. In rabbit eyes, a single subretinal injection of tissue plasminogen activator in concentrations of up to 250 micrograms/ml failed to produce significant (greater than 50%) clot dissolution during a 3-hour period. However, repetitive subretinal lavage and aspiration with tPA (50 micrograms/ml) resulted in progressive intraoperative clot dissolution in rabbits and allowed complete evacuation of blood through a small drainage retinotomy in 6 (100%) of 6 cat eyes. Repetitive vigorous subretinal irrigation with saline solution had no discernible effect on clot size in rabbit eyes. Histopathologic examination of cat eyes following tPA-assisted surgical evacuation of subretinal blood showed preservation of the outer retina in 2 eyes and severe atrophy of the outer retina in 4 eyes.

Measurement of cellular proliferation within the vitreous during experimental proliferative vitreoretinopathy.

Cellular proliferation is an important component in the pathogenesis of complex retinal detachments caused by proliferative vitreoretinopathy (PVR). We used flow cytometry to measure the proliferation of cells recovered from the vitreous cavity in an experimental model of tractional retinal detachment induced by homologous fibroblast injection. Two distinct populations of cells were detected. One population comprised smaller, dense cells representing mostly leukocytes. A second population of larger cells contained not only the injected fibroblasts but also high concentrations of host-derived cells with significant proliferative activity, whose number increased for 3 days following injection. Flow cytometry was useful for analysis of the recovered cells for concentration, morphologic features and proliferation. This technique may be applicable in the identification of patients at high risk for the development of PVR.

Results and complications in treated retinal breaks.

One hundred sixty-four patients (171 eyes) were treated for retinal breaks and the treatment outcomes were studied. One hundred two eyes were acutely symptomatic, 22 eyes were chronically symptomatic, and 47 eyes were asymptomatic. The reasons for further treatment in 38 of the 171 eyes (22%) included the following: (1) inadequate closure of the original break without detachment in eight eyes (5%), (2) new breaks without detachment in 15 eyes (9%), (3) an operation for retinal detachment caused by the original break in seven eyes (4%), or (4) retinal detachment caused by a new break in eight eyes (5%). Failure rates of treatment among acutely symptomatic, chronically symptomatic, and asymptomatic subgroups were not statistically significant. The risk of treatment failure was higher for aphakic and pseudophakic eyes, and in eyes with peripheral retinal abnormalities in the fellow eye. Among 38 patients with failed treatments, 20 (52%) returned for further examination within one month of initial treatment, whereas eight of the 38 patients with failed treatments (21%) returned six months or more after initial treatment. Peripheral retinal abnormalities were recognized initially in 65 of the 171 fellow eyes (38%) and subsequently developed in nine of the fellow eyes (5%) during the follow-up interval. Further treatment is often necessary after initial treatment of peripheral retinal breaks, emphasizing the need for careful long-term follow-up care.

Studies of tumor-infiltrating lymphocytes from a human choroidal melanoma.

Cell suspensions prepared enzymatically from an ocular choroidal melanoma were cultured in vitro in an effort to generate (1) melanoma tumor cell lines and (2) tumor-infiltrating lymphocytes cytotoxic for ocular melanoma cells. Even though histologic study of the tumor did not show "significant" infiltrating bone marrow-derived cells, lymphocytes were generated readily in cultures to which interleukin-2 was added. Phenotypic analysis of the cultured lymphocytes indicated that T-cells, natural killer (NK) cells, and lymphokine-activated killer (LAK) cells were present. Moreover, functional studies of the cultured lymphocytes revealed NK activity, LAK activity, and most importantly, tumor antigen-specific cytotoxic T-cell activity. It was concluded that it is possible to obtain tumor cell lines and tumor-infiltrating lymphocytes from ocular tumors, both of which would be required if cellular immunotherapy of ocular tumors is contemplated. In addition, these results indicate that ocular melanomas can express unique tumor-specific antigens and that the immune system of a patient with such an ocular tumor can perceive these tumor antigens because antigen-specific precursor cytotoxic T-cells were present in the tumor-containing eye at the time of enucleation. The theoretic and therapeutic implications of these findings are discussed.

Retinal toxicity of human tissue plasminogen activator in vitrectomized rabbit eyes.

The retinal toxicity of human tissue plasminogen activator in normal rabbit eyes has recently been reported. We now report the retinal toxicity of tissue plasminogen activator in three groups of vitrectomized rabbit eyes. Group 1 underwent gas compression of the vitreous followed by tissue plasminogen activator injection in doses of 25, 50, and 100 micrograms (all doses were administered in 100 microL of fluid). Group 2 underwent lensectomy and vitrectomy followed by tissue plasminogen activator injection of 100 micrograms. Group 3 underwent lensectomy, vitrectomy, and complete fluid/gas exchange prior to injections of 12.5 and 25 micrograms of tissue plasminogen activator. Control eyes received 100 microL of balanced salt solution. In group 1, no retinal toxic reactions were observed after administration of 25 or 50 micrograms of tissue plasminogen activator, but all eyes receiving 100 micrograms demonstrated retinal damage on ophthalmoscopy, electroretinography, and light microscopy. In group 2, no retinal toxic reactions were seen after administration of 100 micrograms of tissue plasminogen activator. In group 3, two of 11 eyes receiving 25 micrograms of tissue plasminogen activator demonstrated toxic retinal changes by ophthalmoscopy, electroretinography, and light microscopy. These results suggest that gas compression of the vitreous does not significantly alter the toxic changes seen caused by tissue plasminogen activator. While lensectomy and vitrectomy appears to widen the therapeutic window for tissue plasminogen activator, the margin of safety is reduced with the addition of a large gas bubble.

Leber congenital amaurosis in siblings with diffuse dysmyelination.

Two brothers are described with the previously unrecognized combination of Leber amaurosis and abnormal myelin detected by magnetic resonance imaging. Both have evidence of delayed psychomotor development and one has autistic features. A possible relationship with infantile autism or a peroxisomal dysfunction syndrome is explored. No peroxisomal defect was found in these patients.

Tissue plasminogen activator treatment of experimental subretinal hemorrhage.

Previous investigators have suggested that subretinal blood damages the retina in part because of its solid fibrin meshwork. The role of fibrinolysis in facilitating the clearance of subretinal hemorrhage and preventing degeneration of the overlying retina was studied. Autologous whole blood (0.1 ml) was injected into the subretinal space of 20 rabbits. Twenty-four hours later, the animals were randomized to subretinal treatment with 2.5 micrograms of tissue plasminogen activator or a similar volume of physiologic saline. Mean subretinal hemorrhage thickness 3 days after treatment had decreased to 42% of pretreatment thickness in treated eyes and remained unchanged in control eyes (P less than 0.0005). By 7 days mean clot thickness was 9% in treated eyes and 60% in controls (P = 0.005). Light microscopy revealed severe progressive retinal degeneration in both groups. No histologic evidence of retinal toxicity was found in cat retina after subretinal injection of tissue plasminogen activator (50 micrograms/ml). Although treatment with tissue plasminogen activator accelerated the clearance of subretinal hemorrhage, it failed to prevent secondary retinal degeneration in this rabbit model.

Subretinal hemorrhage management by pars plana vitrectomy and internal drainage.

We reviewed 14 consecutive cases of subretinal hemorrhage involving the macula, in which surgery to remove the hemorrhage was performed by the authors between February 1984 and January 1989. All patients underwent pars plana vitrectomy and internal subretinal hemorrhage drainage. The causes of subretinal hemorrhages in group 1 were primary rhegmatogenous retinal detachments (three eyes), complications from scleral buckling procedures (three eyes), traumatic retinal detachments (two eyes), and sickle cell retinopathy associated with anticoagulation therapy after a pulmonary embolus (one eye). Group 2 consisted of five eyes with massive subretinal hemorrhage associated with age-related macular degeneration. In group 1, recurrent postoperative retinal detachment occurred in five eyes but reattachment was achieved in eight of the nine eyes, and final visual acuities were 20/400 or better in those eight eyes. In group 2, marked subretinal fibrosis occurred in two eyes. Although three eyes had improved visual acuities, final visual acuities were 5/200 or worse in all five eyes.

Retinal toxicity of recombinant tissue plasminogen activator in the rabbit.

We studied the dose-dependent retinal toxicity of the available commercial preparation of human recombinant tissue plasminogen activator in the normal rabbit eye. Tissue plasminogen activator was injected into the midvitreous cavity of albino rabbits in doses (per 100 microL) of 25, 50, 75, and 100 micrograms. Control eyes received 100 microL of balanced salt solution or tissue plasminogen activator vehicle. No evidence of a retinal toxic reaction was seen in eyes receiving 25 micrograms of tissue plasminogen activator. One of four eyes injected with 50 micrograms showed loss of photoreceptor cells by light microscopy. Severe retinal damage was seen by ophthalmoscopy, electroretinography, and light microscopy in three of four eyes receiving 75 micrograms of tissue plasminogen activator and in all eyes treated with 100 micrograms of tissue plasminogen activator or equivalent vehicle. These results suggest that the commercial recombinant tissue plasminogen activator formulation has a narrow margin of safety in nonvitrectomized eyes and that a component of the vehicle is the toxic factor.

MR technique for localization and verification procedures in episcleral brachytherapy.

Spatial definition of an intraocular tumor and subsequent determination of the actual position of an implanted eye plaque are essential for adequate ocular brachytherapy treatment planning. However, a method for verification of the plaque placement which would provide required 3-dimensional information is not available at present. In addition, tumor localization procedures, including ultrasonography and CT techniques, cannot always offer the precision needed for 3-dimensional definition of an intraocular target. This communication describes a magnetic resonance imaging technique specifically developed for both localization and verification procedures. A 1.5 Tesla magnetic resonance scanner, spin-echo pulse sequence (echo time 30 msec, repetition time 700 msec), and commercially available surface coil were used to obtain a series of transverse, coronal, and sagittal images of a slice thickness of 3 mm. Usually, eight scans in each of the three planes were needed for adequate coverage of the orbit. The required patient set-up and data acquisition time did not exceed 40 minutes. With a data matrix size of 256 X 256 pixels and 13 cm field of view, localization and verification were accomplished with a precision of 0.5 mm. Our results suggest that the magnetic resonance imaging technique permits precise integration of diagnostic and therapeutic procedures, and in addition provides adequate data for accurate treatment planning. We conclude that magnetic resonance imaging is the preferred diagnostic technique for episcleral brachytherapy.