Self-sampling of vaginal fluid and high-risk human papillomavirus testing in women aged 50 years or older not attending Papanicolaou smear screening.

OBJECTIVES: To study the value of self-sampling of vaginal fluid at home in combination with high-risk human papillomavirus (HPV) testing in a cohort of older women not attending Papanicolaou (Pap) smear screening. DESIGN: Women (n = 3618), aged 50-65 years, who had not attended screening for at least 6 years were offered self-sampling of vaginal fluid at home (study cohort). The collected material was analysed for the presence of high-risk HPV (using Hybrid capture 2; Hc2). Women with a positive HPV test were referred for colposcopy. These results were compared with the results of Pap smear screening in a corresponding age group of women (controls). The end point of the study was identification of a histological cervical intraepithelial neoplasia stage 2 (CIN2) and above (CIN2+). RESULTS: In all, 39.4% (n = 1426) women participated and 4.6% (n = 66) were high-risk HPV positive. Of the HPV-positive women 56 chose to attend a surgery (84.8%) after a mean time of 2.1 months and ten of these women (17.9%) showed CIN2+, corresponding to 0.70% of all participating women. In the controls, who participated in organised Pap smear screening, the prevalence of CIN2+ was 0.25% (15/6048). The odds ratio for identification of CIN2+ in women aged 50 years or older performing self-sampling and HPV test in comparison with Pap smear was: 2.84 (95% CI 1.14-6.77, P = 0.0174). In older women primary high-risk HPV testing (Hc2) and Pap smear screening showed equal specificity of around 96%. CONCLUSIONS: Self-sampling of vaginal fluid in combination with high-risk HPV testing appears to be an attractive method to improve screening coverage and decrease the prevalence of cervical cancer in women aged 50 years or older.

Short-time repeat high-risk HPV testing by self-sampling for screening of cervical cancer.

BACKGROUND: Testing for high-risk human papillomavirus (HPV) in primary screening for cervical cancer is considered more sensitive, but less specific, in comparison with Pap-smear cytology. Women with persistent HPV infections have a higher risk of developing cervical intraepithelial neoplasia 2+ (CIN2+) lesions. This study was performed to evaluate the gain in specificity for detection of histologically confirmed CIN2+ lesions achieved by short-time repeat testing for high-risk HPV in women aged 30-65 years, with the primary sample for HPV analysis taken by self-sampling. METHODS: A total of 8000 women in Uppsala County, aged 30-65 years, who had not attended organised screening for 6 years or longer, were offered self-sampling of vaginal fluid at home and the samples sent for HPV typing. Of these, 8% (669) were not possible to contact or had performed hysterectomy. Women positive for high-risk HPV in the self-sampling test were invited for a follow-up HPV test and a cervical biopsy on average 3 months after the initial HPV test. RESULTS: In all, 39% (2850/7331) of invited women chose to perform self-sampling of vaginal fluid at home. High-risk HPV infection was found in 6.6% (188) of the women. In all, 89% of the women testing HPV positive performed a follow-up examination, on average 2.7 months, after the first test and 59% of these women were HPV positive in the follow-up test. The prevalence of CIN2+ lesions in women with an initial HPV-positive test was 23% (95% CI 18-30%) and in women with two consecutive HPV-positive tests was 41% (95% CI 31-51%). In women with two positive HPV tests, the prevalence of CIN2+ lesions varied from 49% in women at age 30-39 years to 24% in women at age 50-65 years. Short-time repeat HPV testing increased the specificity for detection of CIN2+ lesions from about 94.2% to 97.8%. The most prevalent HPV types were HPV16 (32%), followed by HPV18/45 (19%) and HPV 33/52/58 (19%). CONCLUSION: The short-time persistence of high-risk HPV infection in this age group was about 60%. Repeat testing for high-risk HPV using self-sampling of vaginal fluid can be used to increase the specificity in the screening for cervical cancer in women aged 30-65 years.

Self-sampling and HPV testing or ordinary Pap-smear in women not regularly attending screening: a randomised study.

BACKGROUND: Most women with cervical cancer have not participated in Pap-smear screening. Self-sampling of vaginal fluid in combination with high-risk HPV testing may be a method to increase the attendance rate. METHODS: A total of 4060 women, 39-60 years old, who had not attended the organised Pap-smear screening for 6 years or more were randomised into two equal groups. A study group was offered to self-sample vaginal fluid (Qvintip) at home and/or recommended to attend the Pap-smear screening. The collected fluid after self-sampling was examined for the presence of high-risk HPV (Hybrid Capture 2 method). Controls were only recommended to attend the Pap-smear screening. The end point was a histological identification of CIN2-3. RESULTS: The participation rate was 39% (771 out of 2000) in the self-sampling group and 9% (188 out of 2060) in the conventional cytology (P<0.001). The number of histological CIN2-3 alterations detected was 0.4% (8 out of 2000) among women offered self-sampling of vaginal fluid and 0.07% (3 out of 4060) in women offered Pap-smears. The odds ratio (OR) for offering self-sampling and HPV testing instead of Pap-smear screening for detection of CIN2-3 was OR=5.42 (95% CI: 1.30-31.8). CONCLUSION: Offering self-sampling of vaginal fluid followed by a high-risk HPV test was considerably more effective for detection of histological CIN2-3 lesions in comparison with offering Pap-test in a midwife reception in women not regularly attending organised screening.

Self-sampling of the vaginal fluid at home combined with high-risk HPV testing.

BACKGROUND: Around 65% of women with cervical carcinoma in Sweden have not attended an organised screening. We therefore investigated the value of using self-sampling at home in combination with a test for high-risk human papilloma virus (HPV) to increase participation. METHODS: A total of 2829 women 30-58 years old, who had not attended the organised screening for > or = 6 years, were recruited. They were offered self-sampling at home (Qvintip) and recommended to send the collected vaginal fluid to a laboratory for analysis of the presence of high-risk HPV (Hybrid Capture 2 method). RESULTS: A total of 39.1% of the women accepted home sampling. These women disclosed a relatively high prevalence of high-risk HPV, which decreased with age, from 11.1% in women 30-39 years old to 2.9% in women > or =50 years . Follow-up disclosed histological cervical intraepithelial neoplasm (CIN) 2-3 lesions in 43.2% of the women with a persistent HPV infection, corresponding to 2.0% of the total number of participating women. The sensitivity of a single smear to detect the histological CIN 2-3 lesions were only 52.6%, even if all abnormal smears (atypical squamous cells of unknown significance (ASCUS)-CIN 3)) were included. CONCLUSION: The use of self-sampling at home in combination with testing for high-risk HPV increases the participation rate of the organised screening and detects almost twice as many women with pre-malignant cell alterations (CIN 2-3) in comparison those with a single cytological smear.

Difficulties in performing leisure activities among persons with newly diagnosed rheumatoid arthritis: A prospective, controlled study.

OBJECTIVE: To compare leisure activities and associated factors in a group with recent onset RA and matched community derived controls, to examine whether leisure activities are altered during the early years of disease and to seek predictors. METHODS: One hundred and forty-seven consecutive persons with early RA were followed for 0.9-5.9 yr. One hundred and forty-four RA patients were compared cross-sectionally at baseline with community-derived controls matched for age, gender and residential area. Leisure activities were evaluated with an interest checklist (20 domains). Socio-demographic variables, disease activity (DAS) and disability (HAQ) were evaluated as possible predictors for loss of participation in leisure activities at baseline and longitudinally (using area under the curve analyses). RESULTS: At baseline (mean disease duration 7 months) RA patients performed less (8.2 vs 9.9 domains, P < 0.001) but did not have significantly less interest (10.9 vs 11.4 domains, P = 0.15) in leisure activities compared with controls. Decrease in performed leisure activities was only significant in those with a low level of education. At baseline, in RA patients, low education (P = 0.035), age (P = 0.019) and HAQ (P < 0.001) significantly predicted performed leisure activity. No loss in performed leisure activities was seen during follow-up and no significant predictors were found for individual change. CONCLUSION: Loss of performed leisure activities occurs early in RA and chiefly in those with low formal education. Disability was associated with early loss, but not with change during follow-up. Other factors, possibly related to individual personality and resources, may be more important for predicting changes in leisure activities.

Change in and predictors of leisure activities among patients with rheumatoid arthritis: a prospective study.

OBJECTIVE: To describe factors associated with leisure activities, changes in leisure activities over time, and predictors of such changes among persons with rheumatoid arthritis (RA). METHODS: A prospective study was conducted of 80 consecutive persons with RA, recruited while participating in a 3-week, rehabilitation day-care programme. The number of leisure activities was assessed through a structured interview. Sociodemographic variables, measures of disease activity [pain, patient's global assessment, C-reactive protein (CRP)], disability [Health Assessment Questionnaire (HAQ), Signals of Functional Impairment (SOFI), grip strength], quality of life at baseline, as well as disease activity [mean erythrocyte sedimentation rate (ESR)] and treatment (proportion of follow-up time on anti-rheumatic drugs during follow-up) were evaluated as possible predictors of change in leisure activities. RESULTS: Active leisure activities increased, while 'not obviously active or passive' leisure activities were unchanged during the follow-up period. The change in active leisure activities did not correlate with the predictors evaluated. CONCLUSION: The increase in active leisure activities was not predicted to a substantial degree by disease activity, disability, or medication. The results suggest that factors other than those evaluated influence changes in leisure activities.

Health-related quality of life in primary Sjögren's syndrome, rheumatoid arthritis and fibromyalgia compared to normal population data using SF-36.

OBJECTIVE: To investigate the health-related quality of life in women with primary Sjogren's syndrome (prim SS) and compare with normative data and the health-related quality of life in women with rheumatoid arthritis (RA) and women with fibromyalgia. METHODS: A questionnaire including the MOS Short-Form 36 (SF-36) was completed by 42 prim SS women, 59 RA women, and 44 women with fibromyalgia. RESULTS: All three patient groups experienced a decreased quality of life level ranging from 5 to 65 % in all SF-36 scales compared to normative data. Differences between groups were seen in 7 of the 8 scales (p< or = 0.004). The prim SS patients experienced a higher quality of life level with regard to physical function than the women with RA and fibromyalgia, whereas in the psychological dimensions the quality of life level was comparable to that of the two other groups. CONCLUSION: The health-related quality of life was significantly decreased as compared to norms in prim SS women and comparable to the levels of women with RA and fibromyalgia.

The influence of hearing and age on speech recognition scores in noise in audiological patients and in the general population.

OBJECTIVE: To describe the influence of pure-tone audiometry and age on the speech recognition score in noise, both in audiological patients and also in a random population sample. DESIGN: In a cross-sectional study, speech recognition scores (SRS) using monosyllabic words presented in a fixed background noise were evaluated on 1895 audiological patients of both genders with normal hearing or sensorineural hearing losses. The background noise was speech weighted and presented with a signal to noise ratio of +4 dB. In 291 participants, SRS in quiet was estimated as well. A female random population sample also was tested (N = 513). RESULTS: The major predictor for the SRS-noise was high-frequency hearing thresholds. If hearing was normal, age had no effect on speech recognition. Young persons with hearing loss had higher SRS-noise than older persons with the same degree of hearing loss. The difference between young and old persons became larger the greater the hearing loss. Predictive SRS-noise with consideration taken to hearing function and age are presented. SRS-noise correlated stronger with pure-tone audiometry and age than SRS-quiet. Controls performed better (by 10 to 20%) than their same-aged peers with similar hearing loss. CONCLUSION: It is recommended that speech recognition tests be performed in background noise. SRS-noise is a valuable tool for audiologists and audiological physicians to identify patients in need of pedagogic rehabilitation programs or further diagnostic investigations.

Evaluation of a structured multidisciplinary day care program in rheumatoid arthritis. A similar effect in newly diagnosed and long-standing disease.

The present study evaluated a multidisciplinary structured day-care programme in patients with rheumatoid arthritis of less than 2 years (n = 41) and more than 2 years disease duration (n = 46). During the 3 week intervention, outcome measures reflecting disability (HAQ, SOFI), the patient's perception of disease and pain (VAS for patient's global assessment and pain), Ritchie articular index (RAI), a 44 swollen joint count, and overall disease activity (DAS) improved significantly in the group as a whole. The improvements remained significant after 15 weeks and were of a similar magnitude in the patient groups with short and long disease duration. At week 3 and 15, the ACR and the EULAR criteria for individual response, for the total study group was fulfilled by 28% and 26%, and 36% and 52% respectively. Evaluation of a subgroup 6 weeks prior to admission indicated that the outcome measures were stable at the time of the intervention. Furthermore, administration of intraarticular glucocorticosteroids (GC) could only partly explain the observed improvement. This uncontrolled observational study supports that a multidisciplinary day-care rehabilitation program is beneficial and feasible for patients with rheumatoid arthritis of both short and long duration.

A problem-based education program for patients with rheumatoid arthritis: evaluation after three and twelve months.

OBJECTIVE: To develop and evaluate the effect of a new arthritis education program based on a previous study. METHODS: One hundred individuals with established rheumatoid arthritis randomized to an intervention group or a control group completed self-report questionnaires. RESULTS: Three months after the education program the patients in the intervention group had increased their knowledge about their disease. They reported increased practice of exercise and joint protection and reduction of disability and pain. After 12 months, increased knowledge and practice of joint protection was maintained. However, there was no longer any difference between the intervention group and the control group regarding reported pain, disability, and practice of exercise. At both intervals the individuals in the intervention group reported an increased ability to handle their pain and a reduction of problems with their disease. The control group remained stable except for a slight increase in pain. CONCLUSION: A structured patient education program had positive impact for 3 months, and some improvements were maintained for 12 months. We suggest that patient education should become an integrated part of the total management of rheumatoid arthritis.

Liquid chromatography-tandem mass spectrometry applied to a study of the metabolism of pentamidine. Discussion of possibilities and problems.

Tandem mass spectrometry is usually employed to achieve rapid screening or structure elucidation. We have used liquid chromatography-tandem mass spectrometry in order to detect metabolites of the antiprotozoal drug pentamidine in urine. Samples of urine from rat and man were analysed both by direct injection and after solid-phase extraction. The present paper discusses advantages and disadvantages of using direct injection of urine samples, optimization of chromatographic conditions with regard to the performance of the mass spectrometer, automation and stability of the entire system.

Metabolism is an important route of pentamidine elimination in the rat: disposition of 14C-pentamidine and identification of metabolites in urine using liquid chromatography-tandem mass spectrometry.

This study assesses the contribution of metabolism for the disposition of pentamidine in the rat. With the use of 14C-labelled compound, the excretion of radioactivity in urine and faeces has been studied in four rats during 44 days after a single intravenous injection of the drug. The urinary and faecal excretion of the radioactivity were of equal importance; 22 +/- 2% (mean +/- S.D.) and 25 +/- 4% being detected in urine and faeces, respectively. The activity in organs and tissues at 44 days after drug administration was also measured and amounted to 21 +/- 5% of the administered dose. Using HPLC the proportion of metabolites in urine in relation to unchanged pentamidine increased with time after dose, being 76 +/- 15% (mean +/- S.D.) of the total excreted radioactivity on day 1 and 97 +/- 1% on day 6. HPLC--tandem mass spectometry was used for identification of metabolites in urine obtained from four rats given unlabelled pentamidine. Using synthetic reference compounds and the selective MS/MS mode four oxidized metabolites of pentamidine were identified either by direct injection into the system or by analyses of extracted urine. Thus, a substantial part of pentamidine is excreted as metabolites in urine.

High-performance liquid chromatographic method for the enantioselective analysis of mefloquine in plasma and urine.

An HPLC method for analysis of the enantiomers of the antimalarial drug mefloquine is presented. A complete resolution of (-)-(11S,2'R) and (+)-(11R,2'S) erythro-mefloquine from plasma and urine was obtained on a commercial AGP column. Mefloquine enantiomers were detected by UV at 222 nm. The separation factor (alpha) at +20 degrees C was 1.50. The limit of determination (coefficient of variation 4.0%) for the enantiomeric ratio (11S,2'R)/(11R,2'S) is 15:1 at a total mefloquine concentration of 1.6 mM.

Prediction of high birthweight from maternal characteristics, symphysis fundal height and ultrasound biometry.

The possibility to predict a large infant during pregnancy was assessed using data from a prospective cohort study of 537 singleton pregnancies with term deliveries. Maternal characteristics, symphysis fundal height and ultrasound measurements were used in multivariate analyses for the prediction of an infant with a birthweight of > or = 4,500 or > or = 4,000 g. The positive predictive value was 55% for a birthweight > or = 4,000 g when only maternal characteristics were used, and increased slightly when symphysis fundal height was added. The corresponding value for a single ultrasound measurement at 37 gestational weeks was 52%. Using all available clinical data, positive predictive values of 45 and 80% could be achieved for birthweights of > or = 4,500 and > or = 4,000 g, respectively.

Maternal factors associated with high birth weight.

Maternal characteristics associated with high birth weight were studied in 473 mothers delivered of singleton infants at term with a birth weight of 4500 g or more. The controls were mothers who gave birth to singleton infants at term, with a normal birth weight +/- 1 SD for Swedish newborns. In the multivariate analysis the maximum symphysis-fundus height measurement and gestational duration were strongly significant (p less than 0.001), after correction for other variables, for the probability of being delivered of an infant of high birth weight. Maternal height, weight at beginning of pregnancy, total gestational weight increase and previous live birth of an infant weighing greater than or equal to 4500 g were also important (p less than 0.05) for high birth weight. The maternal characteristics included were evaluated in a prognostic model. With symphysis-fundus height measurement included, the sensitivity increased from 80.3 to 83.3% and specificity from 78.8 to 85.6%, compared with a model where symphysis-fundus measurement was not available.

Lack of relationship between glibenclamide metabolism and debrisoquine or mephenytoin hydroxylation phenotypes.

The pharmacokinetics of a single oral dose of 1.75 mg glibenclamide were studied in 15 healthy Caucasians including five poor metabolisers of debrisoquine and five poor metabolisers of S-mephenytoin. Plasma glibenclamide concentrations and the urinary concentrations of trans-4- and cis-3-hydroxyglibenclamide were analyzed by h.p.l.c. Thirty-six +/- 6% (mean +/- s.d., n = 15) of the given dose of glibenclamide was excreted in 48 h urine as hydroxylated metabolites, 27 +/- 4% as trans-4-hydroxyglibenclamide and 8 +/- 2% as cis-3-hydroxyglibenclamide. There were no differences in the plasma pharmacokinetics of glibenclamide or in the urinary excretion of the metabolites between poor and extensive metabolisers of debrisoquine, neither between the two mephenytoin hydroxylator phenotypes. The study thus indicates that the disposition of glibenclamide is not influenced by these two independent polymorphisms of drug oxidation.

Traumatic injury in large-for-date infants.

The risk of traumatic injury and low Apgar score was studied in 473 infants with a birth weight of 4500 g or more at term (LFD) and 473 infants with normal weight (NFD, birth weight +/- 1 SD of mean for the respective gestational age). The LFD group comprised 3.2% of all infants delivered during a 5-year period. Traumatic injuries were observed in 8.0% of the LFD versus 0.6% of the NFD group. The injuries in the LFD group were 28 fractured clavicles, four fractured humerus and 12 brachial plexus injuries. Six of the LFD infants had multiple injuries. The injuries in the NFD group were three fractured clavicles. All infants with traumatic injuries were delivered vaginally. Contributory obstetrical factors for traumatic injury were forceps, post-term pregnancy and vacuum extraction. High birth weight was correlated to a low Apgar score at one minute, as also was post-term pregnancy.