Changes in Visual Impairment due to Diabetic Retinopathy During 1980-2019 Based on Nationwide Register Data.

OBJECTIVE: To evaluate changes in the incidence, prevalence, severity, and onset age of visual impairment (VI) due to diabetic retinopathy (DR) and compare these trends in the screening and treatment of diabetes during 40 years based on Finnish national register data. RESEARCH DESIGN AND METHODS: We included people with VI with nonproliferative DR (NPDR; n = 2,490, 73% women) or proliferative DR (PDR; n = 2,026, 53% women) as the main diagnosis for VI during 1980-2019 in the Finnish Register of Visual Impairment. The number of patients with treated diabetes during 1986-2019 was obtained from the Social Insurance Institution of Finland registers based on reimbursed medication data. RESULTS: The annual incidence of reported VI due to DR has decreased since it peaked in the 1990s: regarding NPDR, it decreased from 102.3 to 5.5 per 100,000 patients with treated diabetes between the 1990s and 2010s; regarding PDR, the respective change was from 39.9 to 7.4. The incidence of patients with diabetes treated for DR increased during this period. Annual prevalence of reported VI and differences between sexes steadily decreased in the 2000s and 2010s. The severity of reported VI has decreased, and the age at the onset of reported VI increased during the 40 years. CONCLUSIONS: Prevalence and incidence of VI due to DR have dramatically decreased and shifted to older age during the 40 years despite the increasing prevalence of diabetes. These positive trends highlight the successful development and effectiveness of screening and therapies for diabetes and DR.

Prevalence and 11-Year Incidence of Cataract and Cataract Surgery and the Effects of Socio-Demographic and Lifestyle Factors.

Purpose: To assess the impact of cataract in ageing population by evaluating the prevalence, incidence, and background factors of cataract and cataract surgery. Patients and Methods: Two health examination surveys representing Finnish population in 2000 and 2011 included 7380 and 5930 participants aged 30 years or older with cataract status known. An 11-year follow-up included 4840 persons who participated in both the surveys. The data include information on physician-made diagnoses, socio-demographic factors, and lifestyle factors based on self-reported assessment. Cataract diagnoses and surgeries recorded in the Finnish Care Register for Health Care were linked to the survey data. Cataract patients were compared to those without cataract using logistic regression. Differences in cataract surgery age were evaluated using linear regression. Univariable and multivariable models were included. Results: During 2000-2011, the prevalence of cataract increased from 8.8% to 13.6% and cataract surgery from 5.7% to 8.9% in a representative sample of the Finnish adult population. Cataract and cataract surgery were associated with age, smoking, and high alcohol consumption. Cataract was also associated with female gender and low income in 2000, but this association declined during the 11 years. Smoking and high alcohol consumption were associated with younger surgery age. Conclusion: The prevalence of cataract and cataract surgery is increasing with the ageing of the population. The increase in cataract surgery is likely also reflecting the improvements in eye care. The possibility to equally use health-care services throughout a country can reduce the impact of socio-demographic status. Healthy lifestyle delays the development of cataract, whereas smoking and high alcohol consumption are associated with earlier cataract development. Therefore, the availability of cataract services and promotion of healthy lifestyle will be the key to prevent the detrimental effects of cataract on patients and the society in countries where the population is rapidly ageing.

Improving health-related quality of life in glaucoma during 11 years and its association with vision loss and treatment of the disease.

PURPOSE: To evaluate the impact of glaucoma on health-related quality of life (HRQoL) and mental health in the ageing population of Finland. METHODS: Altogether 7380 and 5774 Finnish individuals aged 30 years and older with known eye disease status were studied in 2000 and 2011, respectively, in two population-based surveys, including an 11-year follow-up of 4683 participants. Data on HRQoL (EQ-5D-3L, 15D), depression (BDI), psychological distress (GHQ-12) and eye disease diagnoses were obtained from self-reported assessments. Information on glaucoma was complemented with the medication, diagnosis and eye surgery data obtained from the Finnish Health Registries. Distance visual acuity was assessed using the Snellen eye chart test. In logistic regression analyses, data were corrected for age, gender and the most common comorbidities. RESULTS: Glaucoma patients with verified diagnosis (n = 192 in 2000, n = 202 in 2011) and individuals with self-suspected glaucoma (n = 100 in 2000, n = 41 in 2011) showed a significant decrease in their HRQoL. Glaucoma was also associated with worsened overall mental health based on BDI and GHQ-12 results. Visual impairment associated with glaucoma is the major determinant of the reduced HRQoL and mental health. Neither glaucoma medication nor glaucoma surgery affected these parameters. The impact of glaucoma on HRQoL and mental health diminished between 2000 and 2011 in a cross-sectional setting. The newly diagnosed glaucoma during the 11-year follow-up had a minimal effect on them. CONCLUSION: Glaucoma patients show reduced HRQoL and mental health, which is associated with vision loss regardless of the awareness or treatment of the disease. However, this effect seems to be diminishing over time, and the newly diagnosed glaucoma did not show a significant effect on either HRQoL or mental health.

Prevalence and 11-year incidence of common eye diseases and their relation to health-related quality of life, mental health, and visual impairment.

PURPOSE: To study the prevalence and incidence of the most common eye diseases and their relation to health-related quality of life (HRQoL), depression, psychological distress, and visual impairment in the aging population of Finland. METHODS: Our study was based on two nationwide health surveys conducted in 2000 and 2011. Eye disease status data were obtained from 7379 and 5710 individuals aged 30 + years, of whom 4620 partook in both time points. Both surveys included identical indicators of HRQoL (EuroQol-5 Dimension [EQ-5D], 15D), depression (Beck Depression Inventory [BDI]), psychological distress (General Health Questionnaire-12 [GHQ-12]), visual acuity, and self-reported eye diseases. We assessed the impact of known eye diseases on these factors, adjusted for age, gender, and co-morbidities. RESULTS: Prevalence of self-reported eye diseases was 3.1/2.7% for glaucoma, 8.1/11.4% for cataract, and 3.4/3.8% for retinal degeneration in 2000 and 2011, and the average incidence between 2000 and 2011 was 22, 109, and 35 /year/10,000 individuals, respectively. These eye diseases were associated with a significant decrease in EQ-5D and 15D index scores in both time points. BDI and GHQ-12 scores were also worsened, with some variation between different eye diseases. Impaired vision was, however, the strongest determinant of declined HRQoL. During the 11-year follow-up the effect of eye diseases on HRQoL and mental health diminished. CONCLUSION: Declined HRQoL associated with eye diseases is more related to impaired vision than the awareness of the disease itself, and this declining effect diminished during the follow-up. Therefore, information directed to the public on the risks and prevention of blindness can and should be strengthened to prevent the deleterious effects of visual impairment.

The decline in joint replacement surgery in rheumatoid arthritis is associated with a concomitant increase in the intensity of anti-rheumatic therapy: a nationwide register-based study from 1995 through 2010.

BACKGROUND AND PURPOSE: Drug-based treatment of rheumatoid arthritis (RA) has evolved markedly over the past 2 decades. Using nationwide register data, we studied how this has affected the rates of hip, knee, shoulder, and elbow replacement from 1995 to 2010. METHODS: The number of primary joint replacements was obtained from the Finnish Arthroplasty Register. To test the hypothesis that improvements in medical treatment of RA reduce the need for joint replacements, we also collected data about purchases of different disease-modifying anti-rheumatic agents (DMARDs) and biological drugs from the nationwide drug registers. RESULTS: The annual incidence of primary joint replacements for RA declined from 19 per 10(5) in 1995 to 11 per 10(5) in 2010. The decline was greater for upper-limb operations than for lower-limb operations. At the same time, the numbers of individuals using methotrexate, hydroxychloroquine, and sulfasalazine (the most commonly used DMARDs) increased 2- to 4-fold. INTERPRETATION: Our results are in accordance with observations from other countries, and indicate that the use of joint replacements in RA has decreased dramatically. Our data suggest that effective medical therapy is the most likely explanation for this favorable development.

Incidence of rheumatoid arthritis-related ankle replacement and ankle arthrodesis: a Finnish nationwide register-based study from 1997­2010.

BACKGROUND AND PURPOSE: For 20 years, medical treatment of rheumatoid arthritis (RA) has been improving and the incidence of joint surgery has decreased. We investigated the rates of primary ankle joint arthrodesis and total ankle arthroplasty in patients with RA in Finland between 1997 and 2010 to establish whether trends have changed during that period. METHODS: The annual figures for primary ankle joint arthrodeses and total ankle replacements performed in patients with RA were obtained from nationwide population-based registries. Incidences were calculated per population of 10(5) and they are reported in 2-year periods. RESULTS: During the study period, 593 primary ankle joint arthrodeses and 318 total ankle arthroplasties were performed in patients with RA. The incidence of ankle joint arthrodesis reached its highest value (2.4/10(5)) in 1997-1998 and it was lowest in 2001-2002 (1.1/10(5)). After 2002, the incidence increased slightly but did not reach the level in 1997-1998, even though total ankle replacements almost ended in Finland during the period 2009-2010. From 1997, total ankle replacements increased until 2003-2004 (incidence 1.5/10(5)) and then gradually decreased. In 2009-2010, the incidence of total ankle replacements was only 0.4/10(5). INTERPRETATION: During the observation period 1997-2010, while total ankle replacements generally became more common in patients with RA, the incidence of primary ankle joint arthrodesis decreased and did not increase in the period 2009-2010, even though total ankle replacement surgery almost ended in Finland. No change in the incidence of these operations, when pooled together, was observed from 1997 to 2010.

Comorbid diseases as predictors of survival of primary total hip and knee replacements: a nationwide register-based study of 96 754 operations on patients with primary osteoarthritis.

OBJECTIVES: To examine how comorbid diseases (cardiovascular diseases, hypertension, diabetes, cancer, pulmonary diseases, depression, psychotic disorders and neurodegenerative diseases) affect survival of hip and knee replacements. METHODS: Data for this register-based study were collected by combining data from five nationwide health registers. 43 747 primary total hip and 53 007 primary total knee replacements performed for osteoarthritis were included. The independent effects of comorbid diseases on prosthesis survival were analysed using multivariate Cox regression analysis. RESULTS: Occurrence of one or more of the diseases analysed was associated with poorer survival of hip (HR for revision 1.16, 95% CI 1.08 to 1.23) and knee replacements (1.23, 1.16 to 1.30). Cardiovascular diseases and psychotic disorders were associated with increased risk of revision after both hip (1.19, 1.06 to 1.34 and 1.41, 1.04 to 1.91, respectively) and knee replacement (1.29, 1.14 to 1.45 and 1.41, 1.07 to 1.86, respectively). Hypertension and diabetes were associated with early revision (0-5 years after primary operation) after knee replacements (1.14, 1.01 to 1.29 and 1.27, 1.08 to 1.50, respectively). Cancer was associated with poorer survival of hip replacements (1.27, 1.05 to 1.54) and late revision (>5 years) of knee replacements (2.21, 1.31 to 3.74). Depression affected the risk of early revision after hip replacement (1.50, 1.02 to 2.21). Neurodegenerative and pulmonary diseases did not affect prosthesis survival. CONCLUSIONS: Comorbid diseases may play an important role in predicting survival of primary hip and knee replacements. The mechanisms underlying these findings and their effect on cost-effectiveness of joint replacements, merit further research.

Incidence of prosthetic joint infections after primary knee arthroplasty.

We report the 1-year incidence of postoperative infections in an unselected series of 2647 consecutive primary knee arthroplasties (3137 knees) performed in a modern specialized hospital dedicated solely to joint arthroplasty surgery in 2002 to 2006. The rates of superficial and prosthetic joint infections were 2.9% and 0.80%, respectively. Prospective surveillance by hospital infection register failed to detect 6 of the 24 prosthetic joint infections. Increased rate of prosthetic joint infections was associated with complex surgery and with several patient-related factors, for example, comorbidity, obesity, and poor preoperative clinical state. The rate of prosthetic joint infections in contemporary knee arthroplasty is low and mainly related to patient-related factors, of which patient comorbidity has the most profound effect on the infection rate.

KIF5C: a new binding partner for protein kinase CK2 with a preference for the CK2alpha' subunit.

Protein kinase CK2 is a highly conserved serine/threonine kinase that is ubiquitously expressed in eukaryotic cells. CK2 is a constitutively active tetrameric enzyme composed of two catalytic alpha and/or alpha'-subunits and two regulatory beta-subunits. There is increasing evidence that the individual subunits may have independent functions and that they are asymmetrically distributed inside the cell. To gain a better understanding of the functions of the individual subunits, we employed a yeast-two-hybrid screen with CK2alpha and CK2alpha'. We identified the motor neuron protein KIF5C as a new binding partner for CK2. The interaction found in the yeast-two-hybrid screen was confirmed by co-sedimentation analysis on a sucrose density gradient and by co-immunoprecipitation analysis. Pull-down experiments and surface plasmon resonance spectrometry revealed a direct binding of KIF5C to CK2alpha'. Co-localization studies with neuroblastoma cells, bone marrow and with primary neurons confirmed the biochemical analysis that KIF5C preferentially bound to CK2alpha'.

Survival of the AGC total knee arthroplasty is similar for arthrosis and rheumatoid arthritis. Finnish Arthroplasty Register report on 8,467 operations carried out between 1985 and 1999.

We report the survival of AGC knee endoprosthesis from the Finnish Arthroplasty Register for 2 indications, osteoarthrosis (OA, 6,306 knees) and rheumatoid arthritis (RA, 2,161 knees) during 1985-1999. Survivorship analysis was performed with revision as an endpoint. We found similar survival rates. In the OA group, survival after 5 years was 97% and it was 94% after 10 years. In the RA group the corresponding figures were 97% and 96%, respectively. There was no significant difference in survival whether or not cement was used for fixation. The revision rates were higher in men and in younger patients.

Souter arthroplasty for elbows with severe destruction.

One hundred fifty-eight primary Souter elbow arthroplasties were done on 134 patients (121 women) with severe joint destruction (Larsen Grade 5) or large bone defects or both. Joint replacement operations were done at our institution from 1985-1997. The study group comprised 156 joints in 132 patients with rheumatoid arthritis or other variants of chronic inflammatory joint disease, one in a patient with osteoarthritis, and one patient with posttraumatic arthrosis. The mean age of the patients at the time of surgery was 57 years (range, 26-81 years) and the mean disease duration was 27 years (tinge, 2-70 years). Radiographically, severe bone defects were detected in 100 humeri and 134 ulnas. Retentive (snap-fit) ulnar components were implanted in 110 joints, and bone grafts were used on 26 humeri and 14 ulnas. Major complications led to five early and 16 late reoperations in 19 patients. Four reoperations were done because of dislocation and eight because of aseptic loosening. One reoperation was done because of early infection and five were done because of late infection. One patient had reoperation because of superficial infection in the bursa olecrani and one triceps tendon rupture also was repaired. One patient had wound repair because of marginal necrosis. In the survival analysis, the cumulative success rate without revision for aseptic loosening at 5 years followup was 97%. Despite the demanding nature of these arthroplasties, the primary results are encouraging. Technically, it is possible to do elbow replacement, even on elbows where the humeral condyles or olecranon or both are missing, if there is sufficient bone left on the diaphyseal areas for primary stem fixation. However, in these extreme cases, the poor general condition of the patient or the difficult soft tissue problems in the elbow region may prove to be a contraindication for joint replacement.

Stress fractures of the ankle and forefoot in patients with inflammatory arthritides.

Twenty-four stress fractures occurring in the metatarsal bones and ankle region were examined in 17 patients with inflammatory arthritides. There were 16 metatarsal, four distal fibular, two distal tibial, and two calcaneus fractures. Radiographic analyses were performed to determine the presence of possible predisposing factors for stress fractures. Metatarsal and ankle region stress fractures were analyzed separately. Stress fractures occurred most frequently in the second and third metatarsals. In metatarsal fractures, there was a trend for varus alignment of the ankle to cause fractures of the lateral metatarsal bones and valgus alignment of the medial metatarsal bones. Valgus deformity of the ankle was present in patients with distal fibular fractures in the ankle region group. Calcaneus fractures showed neutral ankle alignment. Malalignment of the ankle and hindfoot is often present in distal tibial, fibular, and metatarsal stress fractures. Additionally, patients tend to have long disease histories with diverse medication, reconstructive surgery and osteoporosis. If such patients experience sudden pain, tenderness, or swelling in the ankle region, stress fractures should be suspected and necessary examinations performed.

Water dynamics in channel hydrates investigated using H/D exchange.

The dynamics and interactions of water with different channel hydrates were studied. Caffeine 4/5-hydrate, theophylline monohydrate and sodium cromoglycate were used as model compounds. The hydrogen/deuterium (H/D) exchange of the different hydrates following exposure to deuterium oxide vapour was studied using FT-Raman spectroscopy. The aim of the work was to (1) investigate the potential for H/D exchange studies to provide information about channel hydrates and (2) correlate the mobility of the water molecules inside lattice channels with structural parameters of the specific hydrates. The rate of exchange in the three different compounds was shown to vary considerably with caffeine 4/5 hydrate undergoing exchange much more rapidly than either sodium cromoglycate or theophylline monohydrate, with exchange in the latter compound being extremely slow. Based on the known crystal structures, it was possible to rationalise the results and to draw conclusions about the mechanism of exchange for the model compounds. It was found that the mobility of the water molecules in a channel hydrate is very dependent on the dimensions of the hydrate channel. Thus H/D-exchange studies may provide very useful structural and energetic information about channel hydrates.

Revisions for aseptic loosening in Souter-Strathclyde elbow arthroplasty: incidence of revisions of different components used in 522 consecutive cases.

We present the prosthesis survival of the 7 most commonly used component types of 522 primary Souter elbow replacements performed in the Rheumatism Foundation Hospital during the years 1982-1997. The cohort comprised 370 female and 33 male patients with a mean age of 57 (20-81) years. 119 patients had a bilateral procedure. The indications for operation in all cases were rheumatoid arthritis and other chronic inflammatory joint disease. The mean duration of the disease at the time of operation was 25 (2-70) years. Elbows were often severely destroyed and, in one thiird of the joints, essential bone structures were missing. Therefore, in 178 cases, the ulnar components were retentive and in the remaining 344 elbows with better bone stock non-retentive. 47 patients had 51 operations for aseptic loosening up to the end of year 2000. In the survival analysis, the general cumulative success rates for the whole study cohort, without revision because of aseptic loosening 5 and10 years after surgery, were 96% and 84%, respectively. Revision was used as an end point. Cumulative success rates of the 7 most commonly used components are presented separately. The highest 5-year-survival rate was 100%, the lowest 93%. The corresponding 10-year-survival rates were 91% and 76%, respectively.

Bone destruction patterns of the rheumatoid elbow: a radiographic assessment of 148 elbows at 15 years.

A cohort of 74 patients with rheumatoid arthritis (RA) was followed prospectively for 15 years. At the end of the study, 148 elbows were radiographed with standard methods. The bone destruction of the humerus was measured from the anteroposterior (AP) radiograph as the bone attrition of the trochlea (TM) and the capitellum (CM). The bone destruction of the ulna was measured from the AP radiograph as the width (WO) and from the lateral radiograph as the thickness (TO) of the olecranon. Moreover, elbow joint destruction was graded by the Larsen system on a scale of 0 to 5. The relation of bone destruction to Larsen grade of the elbows was examined. The mean TM of the nonaffected (Larsen grades 0 to 1, n = 73) joints was 17.5 mm (SD, 2.1 mm; range, 10-22 mm), whereas the mean of Larsen grade 3 to 5 joints (n = 26) was 11.5 mm (SD, 5.2 mm). The mean CM of the nonaffected joints was 19.6 mm (SD, 2.6 mm; range, 15-25 mm), and the corresponding mean of Larsen grade 3 to 5 joints 15.5 mm (SD, 4.5 mm). The mean TO of the nonaffected joints was 18.9 mm (SD, 1.5 mm; range, 17-23 mm), and the mean of Larsen grade 3 to 5 joints was 13.9 mm (SD, 4.1 mm). The mean WO of the nonaffected joints was 23.3 (SD, 2.4 mm; range, 18-28 mm), and the mean of Larsen grade 3 to 5 joints was 22.4 mm (SD, 6.2 mm). Spearman correlation coefficients between TM, CM, and TO and Larsen grade of the joint were -0.45 (95% CI, -0.31 to -0.57), -0.38 (95% CI, -0.23 to -0.51), and -0.46 (95% CI, -0.31 to -0.57), respectively. Bone destruction in both the humerus and the olecranon appears to be a late consequence of rheumatoid elbow involvement. Bone loss is always present in the situation of rheumatoid elbow replacement, and it is most remarkable in Larsen grade 5 joints; the risk of preoperative and intraoperative complications due to bone destruction is significantly increased in this group.

Water diffusion in hydrated crystalline and amorphous sugars monitored using H/D exchange.

Water interacts with pharmaceutical materials in a number of different ways. The aim of this study was to investigate if exchange experiments with D(2)O can provide useful insights into the structure of hydrated materials. Raffinose pentahydrate, trehalose dihydrate, and sucrose were used as model compounds in conjunction with their amorphous counterparts. Following exposure to D(2)O vapor, the exchange of water of hydration and/or hydroxyl groups was monitored using Raman spectroscopy. For the amorphous materials, all of the sugar hydroxyl groups were found to exchange on exposure to D(2)O, providing evidence that water has no fixed site in amorphous materials, nor is access to different parts of the molecule restricted. For raffinose pentahydrate and trehalose dihydrate, exchange of both hydrate water and hydroxyls was incomplete, suggesting that there are specific pathways for diffusion into and within the crystal structure. The results are rationalized based on the known crystal structures. Using exchange experiments to investigate hydrates thus appears to be a useful probe of structure.

A comparison of postoperative C-reactive protein changes in primary and revision hip arthroplasty in patients with rheumatoid arthritis.

C-reactive protein (CRP) response was studied in 40 consecutive patients with rheumatoid arthritis undergoing primary (n = 20) or revision (n = 20) total hip arthroplasty (THA). In patients with primary THA, the median preoperative CRP concentration was 10 mg/L (interquartile range [IQR], 6-17 mg/L), and the median change in CRP was 69 mg/L (IQR, 43-69 mg/L) at the 1st or 2nd postoperative day (P< .001). In the patients with revision THA, the results were 8 mg/L (IQR, 0-32 mg/L) and 48 mg/L (IQR, 21-78 mg/L) (P< .001). Median change in CRP from preoperative to postoperative values did not differ significantly among the patients with primary and revision THA. No correlation was found between the preoperative and perioperative background variables and the change in CRP compared with patients with primary and revision THA. It seems that the revision operation has no significant additional influence on the postoperative CRP response. More detailed analyses are needed to evaluate the significance of endocrine, metabolic, and inflammatory responses in these patients.

Exocytotic mechanism studied by truncated and zero layer mutants of the C-terminus of SNAP-25.

The highly conserved SNARE proteins, SNAP-25, syntaxin and synaptobrevin, form a tight ternary complex, which is essential for exocytosis. Crystallization of this complex revealed a four-helix bundle with an unusual hydrophilic layer (zero layer) in its center. In order to evaluate the role of this layer in different kinetic components of secretion, we used the Semliki Forest virus (SFV) system to infect adrenal chromaffin cells with SNAP-25 Q174L, a point mutant in the zero layer. Using combined flash photolysis of caged calcium and membrane capacitance measurements, we investigated its effect on the exocytotic burst and sustained phase of exocytosis with high time resolution. Cells expressing SNAP-25 Q174L displayed a selective reduction in the sustained phase, while the two components of the exocytotic burst remained unaffected. Furthermore, the exocytotic response to the second flash was significantly reduced, indicating a decrease in refilling kinetics. We therefore conclude that the zero layer is critical for the formation of SNARE complexes, but that it plays no role in the dynamic equilibrium between the two exocytosis-competent vesicle pools.