Fixed-dose combination of tafluprost and timolol in the treatment of open-angle glaucoma and ocular hypertension: comparison with other fixed-combination products.

A new preservative-free fixed-dose combination of 0.0015% tafluprost, a prostaglandin F2α analog, and 0.5% timolol (TAF/TIM; Santen Oy, Tampere, Finland), a beta-adrenergic antagonist has recently been developed. The intraocular pressure (IOP) reduction with TAF/TIM in open-angle glaucoma and ocular hypertension is similar to that of other prostaglandin-timolol fixed-combination products. Patients with high IOP responded well to TAF/TIM with reductions of up to 40% (>13 mmHg) and beyond. Compared to previous controlled and double-masked clinical trials with DuoTrav(®) (Alcon, Fort Worth, USA) and Ganfort(®) (Allergan, Irvine, USA), TAF/TIM caused less superficial ocular side effects and less conjunctival hyperemia. Plausible explanations for the differences in side effects between the fixed-combination products are discussed.

Assessment of information to substantiate a health claim on the prevention of prostate cancer by lignans.

Lignans and their in vivo metabolites, especially enterolactone (ENL), have attracted substantial interest as potential chemopreventive agents for prostate cancer. Preclinical and clinical interventions performed with lignan-rich flaxseed that use surrogate biomarkers as endpoints suggest that lignans may attenuate prostate carcinogenesis in individuals with increased risk or with diagnosed cancer. No unequivocal prostate cancer risk reduction has been found for lignans in epidemiological studies, suggesting that lignan concentrations found in populations consuming a regular non-supplemented diet are not chemopreventive in prostate cancer. Presumably, the main obstacles in assessing the efficacy of food lignans is limited knowledge of the serum and tissue lignan concentrations required for the putative prevention. Further clinical studies performed with the purified compounds are required to substantiate a health claim.

Nasal insulin to prevent type 1 diabetes in children with HLA genotypes and autoantibodies conferring increased risk of disease: a double-blind, randomised controlled trial.

BACKGROUND: In mouse models of diabetes, prophylactic administration of insulin reduced incidence of the disease. We investigated whether administration of nasal insulin decreased the incidence of type 1 diabetes, in children with HLA genotypes and autoantibodies increasing the risk of the disease. METHODS: At three university hospitals in Turku, Oulu, and Tampere (Finland), we analysed cord blood samples of 116 720 consecutively born infants, and 3430 of their siblings, for the HLA-DQB1 susceptibility alleles for type 1 diabetes. 17 397 infants and 1613 siblings had increased genetic risk, of whom 11 225 and 1574, respectively, consented to screening of diabetes-associated autoantibodies at every 3-12 months. In a double-blind trial, we randomly assigned 224 infants and 40 siblings positive for two or more autoantibodies, in consecutive samples, to receive short-acting human insulin (1 unit/kg; n=115 and n=22) or placebo (n=109 and n=18) once a day intranasally. We used a restricted randomisation, stratified by site, with permuted blocks of size two. Primary endpoint was diagnosis of diabetes. Analysis was by intention to treat. The study was terminated early because insulin had no beneficial effect. This study is registered with ClinicalTrials.gov, number NCT00223613. FINDINGS: Median duration of the intervention was 1.8 years (range 0-9.7). Diabetes was diagnosed in 49 index children randomised to receive insulin, and in 47 randomised to placebo (hazard ratio [HR] 1.14; 95% CI 0.73-1.77). 42 and 38 of these children, respectively, continued treatment until diagnosis, with yearly rates of diabetes onset of 16.8% (95% CI 11.7-21.9) and 15.3% (10.5-20.2). Seven siblings were diagnosed with diabetes in the insulin group, versus six in the placebo group (HR 1.93; 0.56-6.77). In all randomised children, diabetes was diagnosed in 56 in the insulin group, and 53 in the placebo group (HR 0.98; 0.67-1.43, p=0.91). INTERPRETATION: In children with HLA-conferred susceptibility to diabetes, administration of nasal insulin, started soon after detection of autoantibodies, could not be shown to prevent or delay type 1 diabetes.

Histological characteristics of basal cell carcinoma of the eyelid.

PURPOSE: To evaluate the histological subtypes of basal cell carcinoma (BCC) of the eyelid and to determine their effect on the size, depth of invasion and need of retreatment of a nonselected patient material seen in south-western Finland. METHODS: We studied the case records and the histological characteristics of BCC of the eyelid treated at the Turku University Eye Clinic during the years 1988 through 1997. The material consisted 103 patients (103 BCC tumors of the eyelid). All tumors were surgically excised. Histological slides were reviewed by a pathologist and the material was divided into histopathological subtypes. RESULTS: In 78.3% of the cases, the diameter of the lesion was smaller than 10 mm. The most frequent histological subtype was nodular (84.5%) followed by sclerosing (5.8%), micronodular (4.9%), keratotic (2.9%) and superficial (1.9%) types of BCC of the eyelid. Only patients of the nodular subtype showed recurrences (11 cases). The size of the tumor and the depth of invasion correlated directly with each other. However, some nodular types of BCC tumors smaller than 10 mm in diameter extended to a depth of more than 4.0 mm. CONCLUSIONS: The nodular subtype of BCC should be regarded as a potentially invasive and recurrent tumor. Histopathological examination and subtyping of all BCC tumors is recommended.

Basal cell carcinoma of the eyelid in Finland during 1953-97.

PURPOSE: To study the incidence of basal cell carcinoma (BCC) of the eyelid in Finland. METHODS: We studied 6241 cases of BCC of the eyelid reported to the nationwide Finnish Cancer Registry during 1953-97. We determined the age- and sex- specific incidence rates and overall rates adjusted for age to the world standard population, and social class- and occupation-specific standardized incidence ratios, with the total Finnish population as reference. RESULTS: The incidence rates of BCC of the eyelid varied between 0.7 and 3.0 per 100 000 person-years in men and between 0.5 and 2.8 per 100 000 person-years in women during the study period. The age-adjusted incidence rates of BCC of the eyelid increased during 1953-87 (p < 0.0001). The incidence of BCC of the eyelid rose significantly with age. There were no significant differences in standardized incidence ratios (SIRs) for BCC of the eyelid between different social class and occupation categories. CONCLUSION: Age-adjusted incidence rates showed that BCC of the eyelid was more than twice as frequent during 1978-97 than before 1968. Ageing may partly explain the increased incidence of BCC of the eyelid, whereas there were no differences in the SIRs for BCC of the eyelid between different social class and occupation categories in Finland.

Efficacy and systemic side-effects of topical 0.5% timolol aqueous solution and 0.1% timolol hydrogel.

PURPOSE: The objective of this randomized, double-blind, controlled crossover trial was to compare 0.1% timolol hydrogel formulation eyedrops with 0.5% timolol aqueous solution in terms of systemic effects, hypotensive efficacy and pharmacodynamics. METHODS: Twenty-four healthy subjects underwent careful ocular, cardiovascular and pulmonary function evaluation before and after 2 weeks of topical treatment with 0.1% timolol hydrogel or 0.5% aqueous timolol maleate. Intraocular pressure (IOP), heart rate, blood pressure, forced expiratory volume and plasma levels of timolol were measured. RESULTS: There was a statistically significant difference in the systemic absorption of timolol between these two ophthalmic timolol solutions. The peak concentration and mean area under the plasma drug concentration-time curve (AUC) were about 10-fold higher after 0.5% timolol aqueous solution. The mean peak heart rate during exercise was reduced by 19 bpm (SD 6.4 bpm) after 0.5% timolol aqueous solution and by only 4.6 bpm (SD 3.8 bpm) after 0.1% timolol hydrogel (p < 0.0001). There was no difference between the two formulations in efficacy in reducing IOP. No differences between treatments were found in respect of pulmonary function. CONCLUSIONS: The lower timolol concentration in the hydrogel vehicle and its better bioavailability resulted in reduced systemic absorption and side-effects without loss of efficacy.

Impaired left ventricular diastolic function in newborn infants of mothers with pregestational or gestational diabetes with good glycemic control.

THE AIM OF THE STUDY: We assessed by echocardiography the left ventricular systolic and diastolic function in newborn infants of mothers with well-controlled pregestational type 1 or gestational diabetes (IDM) in comparison to normal term neonates. SUBJECTS AND METHODS: Two-dimensional/M-mode and Doppler transmitral flow velocity measurements were performed in 18 IDM and 26 control infants of non-diabetic mothers (gestational ages 36-40 and 36-41 weeks, respectively) between days 2 and 5 after birth. In the IDM, there were nine mothers with pregestational (White class C or D) and nine mothers with gestational diabetes (White class A or A/B). Peak early and atrial filling velocity, early deceleration time, early acceleration time, early, atrial and total time velocity integrals were used to examine the left ventricular diastolic performance. We also calculated the early/atrial velocity ratio, early/atrial integral ratio and early/total integral ratio. The fractional shortening, fractional shortening area, midwall fractional shortening (mFS), left ventricular mass and indexed left ventricular mass for body surface area (BSA) and birth weight were used in assessment of left ventricular systolic performance. RESULTS: The early deceleration time was longer, resulting in higher early integral and early filling fraction (EFF) in the IDM than in the control infants (p<0.01). In the IDM, the fractional shortening was somewhat greater and the left ventricular mass/body surface area ratio was higher than in the control group (p<0.05), although the measures of systolic performance were within the normal range. There were no significant differences in the systolic or diastolic function parameters between the gestational and pregestational groups. CONCLUSION: In the infants of mothers with well-controlled pregestational or gestational diabetes, we found prolonged deceleration time of early left ventricular diastolic filling, probably reflecting an impaired left ventricular relaxation rather than compliance. The mechanism for the findings may be maternal hyperglycemia during the third trimester and subsequent fetal hyperinsulinaemia leading to neonatal cardiac hypertrophy.

Neodymium:YAG laser surgery in the hospital district of southwestern Finland during the years 1987 to 1998.

BACKGROUND AND OBJECTIVE: To investigate the annual incidence rates of Neodymium:YAG laser procedures in the treatment of eye diseases. PATIENTS AND METHODS: In this population-based retrospective study, we evaluated 6,040 patients treated with a Nd:YAG laser in the hospital district of southwestern Finland during the years 1987 to 1998. The corresponding annual incidence rates of different Nd:YAG laser procedures were calculated using the corrected population statistics of the hospital district. RESULTS: The annual incidence rates of all Nd:YAG laser procedures rose significantly (P < 0.0001) from 32.1 per 100,000 patients in 1987 to 169.0 per 100,000 people in 1998. A great majority of Nd:YAG patients were females with a higher median age than the males in the study (P < 0.0001). CONCLUSION: The rise of the annual population-based incidence rates of cataract surgery with a 7% to 29% need of Nd:YAG laser capsulotomies explained the increase of all Nd:YAG laser procedures.

Advance information improves user satisfaction with the levonorgestrel intrauterine system.

OBJECTIVE: To evaluate parameters associated with and the impact of advance information given in a regular outpatient setting on user satisfaction with the levonorgestrel-releasing intrauterine system. METHODS: A questionnaire was sent to 23,885 women in Finland who had had a levonorgestrel intrauterine system inserted between 1990 and 1993. The number of returned questionnaires was 17,914 (response rate 75%). Cumulative logistic regression analysis was based on the five-grade scale of satisfaction as a dependent variable. RESULTS: Most users of the levonorgestrel-releasing intrauterine system (74%) were very or fairly satisfied with it, although over 70% of them had chosen it because of dissatisfaction with their previous method of contraception. User satisfaction increased with age and was associated with the amount of information about different symptoms (menstrual, greasiness of hair/skin, pregnancy, pelvic inflammatory disease, and missed periods) regardless of whether the symptom in question was actually experienced. The women who received information about the possibility of absence of menstruation were more satisfied than the less informed women (odds ratio 5.0, 95% confidence interval 4.1, 5.9). CONCLUSION: Information received at the insertion visit is strongly associated with increased user satisfaction among the users of the levonorgestrel intrauterine system. The association between high user satisfaction and advance information was strongest regarding the possibility of missing periods.

Ovarian function and regulation of the hypothalamic-pituitary-ovarian axis after tubal sterilization.

OBJECTIVE: To assess the effects of laparoscopic tubal sterilization with Hulka or Filshie clip on ovarian function and regulation of the hypothalamic-pituitary-ovarian axis. STUDY DESIGN: Hormonal changes were evaluated in 33 women undergoing sterilization with Hulka (n = 16) or Filshie clips (n = 17). All participants were healthy, with regular menstrual cycles. The levels of estradiol, follicle-stimulating hormone, luteinizing hormone, sex hormone binding globulin, prolactin, testosterone and androstenedione were measured in one cycle immediately before and 3 and 12 months after sterilization on cycle days 3-7 and 20-24. Repeated measures analysis of variance, paired t test and nonparametric Friedman two-way analysis of variance were used for statistical analysis. RESULTS: The follicular phase estradiol values increased after sterilization. The highest values were observed three months after the procedure (204.8 +/- 119.1 pmol/L vs. 170.3 +/- 111.7 pmol/L) (P = .0407). The values declined to the presterilization level by 12 months (150.3 +/- 71.3 pmol/L). The luteal phase estradiol values did not change significantly. No change in any of the other hormones studied took place, with the exception of a slight increase in follicular phase luteinizing hormone levels (4.4 +/- 1.4 U/L in the first cycle, 5.1 +/- 1.3 U/L in the second cycle and 5.2 +/- 1.8 U/L in the third cycle) (P = .0553). CONCLUSION: Laparoscopic tubal sterilization increases follicular phase estradiol levels, but the change seems to be only temporary.