Low attendance by non-native women to human papillomavirus vaccination and cervical cancer screening - A Danish nationwide register-based cohort study.

BACKGROUND: Cervical cancer is preventable through human papillomavirus vaccination and cervical cancer screening. However, possibly due to systemic, individual (e.g. low socio-economic staus) and socio-cultural barriers, it is likely that non-natives, especially non-westerns, are more prone to attend neither vaccination nor screening (combined non-attendance). This is disturbing as the non-native population in Denmark is predicted to rise to 21% by 2060. We aimed to investigate differences in combined non-attendance by nativity and region of origin, and to analyse the association between country of origin and combined non-attendance adjusted for socio-economic status. SETTING: 1.6.2007-31.12.2016 Denmark. METHODS: Logistic regression was performed to estimate crude and adjusted odds ratios with 95% confidence intervals for combined non-attendance. RESULTS: 170,158 women were included. Overall combined non-attendance was 11.8% [11.7-12.0]; 10.0% [9.8-10.1] for native women and 27.1% [26.4-27.7] for non-native women, with highest degrees among Middle-Eastern and North-Africans (30.1% [29.2-30.9]). Even when adjusted for socio-economics, women from Middle-East and North-Africa had substantially higher odds of combined non-attendance than natives (adj. OR = 7.5 [6.3-8.9] for Somali women). CONCLUSION: Denmark has a relatively low degree of combined non-attendance. However, cervical cancer preventive programmes seem to be better tailored to the needs of native women and do not appear to cater sufficiently to the needs of the fast-growing non-native populations, particularly not to the needs of Middle-Eastern and North African women. In order to secure more just cervical cancer prevention, future studies are recommended to develop tailored intervention sensitive to the need of non-native women.

Influence of Prior Psychiatric Disorders on the Treatment Course of Gynaecological Cancer - A Nationwide Cohort Study.

AIMS: To examine the influence of pre-existing psychiatric disorder on the choice of treatment in patients with gynaecological cancer. MATERIALS AND METHODS: The analyses were based on all patients who underwent surgical treatment for endometrial, ovarian or cervical cancer who were registered in the Danish Gynecological Cancer Database in the years 2007-2014 (3059 patients with ovarian cancer, 5100 patients with endometrial cancer and 1150 with cervical cancer). Logistic regression model and Cox regression model, adjusted for relevant confounders, were used to estimate the effect of pre-existing psychiatric disorder on the course of cancer treatment. Our outcomes were (i) presurgical oncological treatment, (ii) macroradical surgery for patients with ovarian cancer, (iii) radiation/chemotherapy within 30 days and 100 days after surgery and (iv) time from surgery to first oncological treatment. RESULTS: In the group of patients with ovarian cancer, more patients with a psychiatric disorder received macroradical surgery versus patients without a psychiatric disorder, corresponding to an adjusted odds ratio of 1.24 (95% confidence interval 0.62-2.41) and the chance for having oncological treatment within 100 days was odds ratio = 1.26 (95% confidence interval 0.77-2.10). As for patients with endometrial cancer, all outcome estimates were close to unity. The adjusted odds ratio for oncological treatment within 30 days after surgery in patients with cervical cancer with a history of psychiatric disorder was 0.20 (95% confidence interval 0.03-1.54). CONCLUSIONS: We did not find any significant differences in the treatment of ovarian and endometrial cancer in patients with pre-existing psychiatric diagnoses. When it comes to oncological treatment, we suggest that increased attention should be paid to patients with cervical cancer having a pre-existing psychiatric diagnosis.

Is it possible to define an optimal time for chemotherapy after surgery for ovarian cancer?

OBJECTIVE: The aims of this study are to investigate the actual time from primary surgery for epithelial ovarian cancer (OC) to initiation of chemotherapy (TI) amongst Danish women in 2005-2006, and to compare the survival for groups with early initiation (≤median TI) and late initiation of adjuvant chemotherapy (>median TI). METHODS: All Danish women who underwent surgery for OC in the period 1 January 2005 to 31 December 2006 and recorded in the Danish Gynaecological Cancer Database (DGCD) were included. The five-year survival was estimated overall and by TI exposure. The Cox proportional hazard regression analysis was used to compute the adjusted hazard ratio (HR). RESULTS: The median TI was 32days (25-75% quartile: 24days; 41days). The strongest prognostic factors for death were residual tumour and the International Federation of Obstetrics and Gynecology (FIGO) stage. The unadjusted HR for death in patients with TI>32days compared with TI≤32days was 0.85 (95% CI: 0.70; 1.04), p-value 0.12. When adjusted for residual tumour and FIGO-stage the HR was 1.13 (95% CI: 0.92; 1.39), p-value 0.26. The overall five-year survival was 42.8%, (95% CI: 38.9%; 46.5%). CONCLUSIONS: This nationwide population-based cohort study revealed a non-significant increased risk of death for patients with TI>32days compared with the reference TI≤32days. The strongest prognostic factors were residual tumour after surgery and FIGO-stage. The overall five-year survival was 42.8% (95% CI: 38.9%; 46.5%).

Oral contraceptive use and impact of cumulative intake of estrogen and progestin on risk of ovarian cancer.

PURPOSE: Oral contraceptive use decreases the risk of ovarian cancer, but no previous studies have assessed the impact of cumulative intake of estrogen and progestin on ovarian cancer risk. METHODS: We used data from a population-based case­control study conducted in Denmark in 1995­1999 among women aged 35­79 years; 554 women with epithelial ovarian cancer and 1,564 age-matched controls were included in the analyses. Data were analyzed in multiple logistic regression models. RESULTS: The use of combined oral contraceptives only and the mixed use of combined and progestin-only pills decreased the risk of ovarian cancer, while no association was found with exclusive use of progestin-only pills. No major differences in risk were found for users of combined oral contraceptives with high- and low-potency estrogen and progestin. There was no effect of cumulative progestin intake, but decreased risks of ovarian cancer with increasing cumulative intake of estrogen (OR = 0.82; 95 % CI 0.67­0.99, per 100 mg estrogen) and increasing duration of oral contraceptive use (OR = 0.95; 95 % CI 0.92­0.98, per year of use) were found. No effect of cumulative estrogen intake was found, however, after adjustment for duration of oral contraceptive use. CONCLUSIONS: The protective effect of oral contraceptives against ovarian cancer may be sufficiently explained by duration of anovulation. This suggests that if the estrogen and progestin doses are sufficient to cause anovulation, a higher intake of estrogen or progestin confers no extra protection against ovarian cancer.

Hoping for the best, preparing for the worst: the lived experiences of women undergoing ovarian cancer surgery.

In this study, the lived experiences of women undergoing ovarian cancer surgery were explored, aiming to provide a patient perspective on being newly diagnosed and starting treatment for ovarian cancer. The study period ran from the first visit in the outpatient clinic, till 8 weeks later, when the women had either begun chemotherapy or completed their recovery. Ten women participated in two qualitative research interviews each, before and after surgery. By applying a phenomenological-hermeneutic text interpretation methodology, the findings were systematically identified, put into meaning-structures, interpreted and discussed. This process constituted the theme: 'Hoping for the best, preparing for the worst'. Final diagnostics and treatment start were extensive life events, where life itself was threatened, although hope and will were present. The women intuitively prepared themselves for the diagnosis and treatment. However, the ability to prepare was influenced by personal lifestyle, social conditions, coping strategies, and experiences of hope. The ability to prepare could be strengthened by providing adjusted information, psychosocial support and physical optimisation during the perioperative period. By offering targeted family counselling and taking good care of the women's general health and well-being, hope could be sustained and early cancer rehabilitation initiated.

Preoperative serum tetranectin, CA125 and menopausal status used as single markers in screening and in a risk assessment index (RAI) in discriminating between benign and malignant ovarian tumors.

OBJECTIVES: To improve the poor survival in ovarian cancer (OC) patients, the research has been focused on new OC markers. One aim is to find markers to identify the cancers in early preclinical stages by screening. Another aim is to find new diagnostic markers, which may select patients at high risk for OC for quick referral to highly specialized centers in gynecologic oncology. These aims were addressed in the present study by evaluating serum tetranectin (TN) and serum CA125 on a large number of pre- and postmenopausal women with ovarian tumors and controls. METHODS: The potential ability of the markers to discriminate between the four groups (208 benign ovarian tumor, 153 borderline ovarian tumor (BOT), 445 OC and 1333 age matched controls) in OC screening was examined. We also constructed a risk assessment index (RAI) for discrimination between tumor groups based on these variables and menopausal status. RESULTS: Highly significant differences in both TN and CA125 levels were found between all the four groups as well as between the different FIGO stages of OC patients. A very high probability of having OC or a benign tumor, respectively, was predicted by the RAI. CONCLUSIONS: In the case-control part of the study, we found that TN and CA125 deserve to be validated on pre-clinical samples by inclusion in future marker panels. The RAI is also a potential new candidate for a diagnostic tool for selecting patients at high risk for having OC; hence it deserves further evaluation in a prospective clinical study.

Tagging single-nucleotide polymorphisms in candidate oncogenes and susceptibility to ovarian cancer.

Low-moderate risk alleles that are relatively common in the population may explain a significant proportion of the excess familial risk of ovarian cancer (OC) not attributed to highly penetrant genes. In this study, we evaluated the risks of OC associated with common germline variants in five oncogenes (BRAF, ERBB2, KRAS, NMI and PIK3CA) known to be involved in OC development. Thirty-four tagging SNPs in these genes were genotyped in approximately 1800 invasive OC cases and 3000 controls from population-based studies in Denmark, the United Kingdom and the United States. We found no evidence of disease association for SNPs in BRAF, KRAS, ERBB2 and PIK3CA when OC was considered as a single disease phenotype; but after stratification by histological subtype, we found borderline evidence of association for SNPs in KRAS and BRAF with mucinous OC and in ERBB2 and PIK3CA with endometrioid OC. For NMI, we identified a SNP (rs11683487) that was associated with a decreased risk of OC (unadjusted P(dominant)=0.004). We then genotyped rs11683487 in another 1097 cases and 1792 controls from an additional three case-control studies from the United States. The combined odds ratio was 0.89 (95% confidence interval (CI): 0.80-0.99) and remained statistically significant (P(dominant)=0.032). We also identified two haplotypes in ERBB2 associated with an increased OC risk (P(global)=0.034) and a haplotype in BRAF that had a protective effect (P(global)=0.005). In conclusion, these data provide borderline evidence of association for common allelic variation in the NMI with risk of epithelial OC.

Do risk factors for epithelial ovarian cancer have an impact on prognosis? Focus on previous pelvic surgery and reproductive variables.

OBJECTIVES: The prognostic impact of risk factors for ovarian cancer development is sparsely explored, but previous sterilisation has been shown to have a negative impact on survival. METHODS: Ovarian cancer cases were from the Danish MALOVA study. Information on previous pelvic surgery as well as reproductive variables was obtained from a personal interview conducted closely after primary surgery. Cox regression models were used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) for ovarian cancer specific death in relation to previous pelvic surgery and reproductive variables including lifetime number of ovulation years. RESULTS: A total of 295 women with Stage III ovarian carcinomas were identified and followed to death or for a median of 7.3 years (range 5.4-9.5 years). Previously sterilised or hysterectomised women seemed to have a slightly decreased risk of ovarian cancer death (HR = 0.62; 95% CI: 0.36-1.08 and HR = 0.82; 95% CI: 0.55-1.21), although none of these associations reached statistical significance. The prognostic impacts of the individual reproductive variables followed the same pattern as the impact of the variables on ovarian cancer development, although significance was only reached for age at menarche (HR = 0.91 per year; 95% CI: 0.84-0.99). By accumulation of the possible minor effects of the reproductive variables in calculation of the total lifetime number of ovulation years, we found that survival decreased significantly with increasing number of ovulations (HR = 1.53 per 10 years; 95% CI: 1.09-2.14). CONCLUSION: Increasing lifetime number of ovulations was a negative prognostic factor for ovarian cancer specific survival. Previous sterilisation or hysterectomy seemed to be associated with improved survival.

Improved survival of patients with ovarian cancer in Northern Denmark, 1985-2004.

OBJECTIVE: Ovarian cancer is a serious disease with a high mortality. Our aim was to examine changes in the survival of patients with ovarian cancer in Northern Denmark. STUDY DESIGN AND SETTING: Patients (no. = 3,719) with an incident discharge diagnosis of ovarian cancer (1985-2004) from any hospital in four Danish counties (population, 1.6 million) were included and tracked for mortality through the Danish Civil Registration System. We determined survival and mortality rates stratified by age, and used Cox proportional hazard regression analyses to assess changes over time. RESULTS: Overall survival rate improved between 1985 and 2004. One-year survival increased from 61% to 73%, and five-year survival from 30% to 38%. Compared with the period 1985-1989 the age-adjusted one-year mortality rate ratio (MRR) was 0.65 (2000-2004) and the age-adjusted five-year MRR was 0.80 (1995-1999). The improvement was most pronounced in patients older than 40 years. CONCLUSION: The survival of ovarian cancer patients has improved in Denmark in recent decades. This change may be the result of improved treatment.

Increased risk of ovarian cancer in integrin beta3 Leu33Pro homozygotes.

We previously demonstrated that integrin beta(3) Leu33Pro homozygotes have an increased risk of cancer, possibly most pronounced for ovarian cancer. We now test the latter hypothesis in case-control and prospective studies. We genotyped 463 Danish women with ovarian cancer, and 4291 women from the Danish general population. Calculation of odds ratios by conditional logistic regression was performed in the case-control study (n = 463 + 3543), and of ovarian cancer incidence, log-rank statistics and hazard ratios by Cox regression in the prospective study (n = 4291) with 9.5-year follow-up. In the case-control study matched for age and marital status, the odds ratio for ovarian cancer in homozygotes versus non-carriers was 1.6 (95% confidence interval: 1.0-2.6). In the prospective study with 28 incident ovarian cancers, non-carriers and homozygotes had incidences of 7 (4-11) and 30 (10-92) per 10 000 person-years (log-rank P = 0.02). The age-adjusted hazard ratio for ovarian cancer in homozygotes versus non-carriers was 3.9 (1.1-13). Risk of ovarian cancer did not differ between heterozygotes and non-carriers in either study. Integrin beta(3) Leu33Pro homozygotes have an increased risk of ovarian cancer.

Simplified bladder training augments the effectiveness of tolterodine in patients with an overactive bladder.

OBJECTIVES: To compare the efficacy of tolterodine plus simplified bladder training (BT) with tolterodine alone in patients with an overactive bladder. PATIENTS AND METHODS: In a multicentre, single-blind study at 51 Scandinavian centres, 505 patients aged >or= 18 years with symptoms of urinary frequency (>or= 8 micturitions/24 h) and urgency, with or without urge incontinence, were randomized to oral treatment with either tolterodine 2 mg twice daily plus simplified BT or tolterodine alone. Changes in voiding diary variables were evaluated after 2, 12 and 24 weeks of treatment. The patients' perceptions of their bladder symptoms and tolerability (adverse events) were also determined. RESULTS: In all, 501 patients (75% women) were evaluable on an intention-to-treat basis (244 on tolterodine + BT and 257 on tolterodine alone). Tolterodine significantly reduced the voiding frequency and increased the volume voided per void at all sample times; these effects were significantly increased by adding BT. At the end of the study the median percentage reduction in voiding frequency was greater with tolterodine + BT than with tolterodine alone (33% vs 25%, P < 0.001), while the median percentage increase in volume voided per void was 31% with tolterodine + BT and 20% with tolterodine alone (P < 0.001). There was a median of 81% fewer incontinence episodes than at baseline with tolterodine alone, which was not significantly different from that with tolterodine + BT (- 87%). The two groups had comparable median percentage reductions in urgency episodes. Some 76% of patients on tolterodine + BT reported an improvement in their bladder symptoms relative to baseline, compared with 71% on tolterodine alone. Tolterodine was well tolerated; the most common adverse event was mild dry mouth. CONCLUSION: Tolterodine 2 mg twice daily is an effective and well tolerated treatment for an overactive bladder, the effectiveness of which can be augmented by a simplified BT regimen.

[Documentation problems in anesthesiology and gynecology?]. / Dokumentationsproblem i anaestesiologi og gynaekologi?

INTRODUCTION: The number of beds in surgical wards is declining. Whether the reason is more outpatient surgery or quicker recovery, owing to better perioperative care is unknown. MATERIALS AND METHODS: A questionnaire was sent to all gynaecological and anaesthetic departments in Denmark concerning the treatment of women who had had a hysterectomy for non-malignant disease. The following questions were asked: What were the numbers of patients operated on in 1998, the methods of operation, duration of admission, the surgeon in charge, information about admission and postoperative management of patients, choice of anaesthesia and treatment of postoperative pain. RESULTS: The chief surgical method was abdominal hysterectomy. There were relatively few vaginal or laparoscopically assisted hysterectomies. The duration of admission varied considerably. Patients mostly were given written information about admission and the postoperative course. Postoperative follow-up was relatively uncommon. The duration of admission was not influenced by the anaesthetic method. Seventeen of 31 anaesthetic departments knew the number of patients anaesthetised for hysterectomy in 1998 and the anaesthetic methods. DISCUSSION: This study cannot answer the question: How does the method of operation, choice of anaesthesia, postoperative analgesia, and information to the patient affect the duration of admission? Data allowing a discussion of the quality of the treatment were not available. There is a serious lack of registration.

Determination of serum tetranectin: technical and clinical evaluation of three sandwich immunoassays.

The performance of two sandwich-type immunoassays for the determination of the tumour marker tetranectin using monoclonal antibodies Hyb 130-13 and 130-14 as catching layer was compared with the performance of a polyclonal assay. Sensitivities were 0.4-0.6 microg/l, and intra- and inter-assay coefficients of variation were < 10% in all assays. One-hundred-and-ten blood donors were examined, and women had higher concentrations of tetranectin in serum than men when measured with monoclonal assays (P < 0.05). In preoperative serum samples from 43 patients with ovarian cancer, tetranectin concentrations were reduced (P < 0.001), and the mean tetranectin concentration decreased with increasing FIGO stage of the patients (P < 0.05). In sera from patients with ovarian cancer, tetranectin concentrations were lower in the polyclonal assay than in the monoclonal assays. This could, hypothetically, be explained by ligand-binding or other conformational changes in tetranectin, influencing the antigenicity of the molecule.

[Antibiotic prophylaxis in cesarean section]. / Antibiotikaprofylakse ved sectio caesarea.

We investigated the guidelines for patient selection and drug regimens for use of antibiotic prophylaxis in relation to Caesarean section in the maternity clinics in Denmark. A questionnaire was sent to all the Danish maternity clinics that perform Caesarean section, concerning indications for use of antibiotic prophylaxis and antibiotic regimens to patients undergoing acute and elective Caesarean section. All departments (n = 48) returned the questionnaire. Twenty departments (46%) provided written guidelines for antibiotic prophylaxis. Four departments (8%) used antibiotic prophylaxis in elective Caesarean sections, 25 departments (52%) used antibiotics in all emergency sections. In the presence of rupture of the membranes or prolongation of labour (> 12 hrs) 58 and 63% of the departments used antibiotic prophylaxis, respectively. The most frequent first choice drug was cefuroxim, employed by 27 departments (56%). Concerning timing, 21 departments (44%) gave antibiotics after cord clamping and 13 departments (27%) before incision. We propose a nation-wide prospective investigation on the rate of infections associated with Caesarean section to set up rational guidelines for antibiotic prophylaxis.

Antibiotic prophylaxis in cesarean section.

BACKGROUND: To investigate the guidelines for patient selection and drug regimens for application of antibiotic prophylaxis in relation to cesarean section in the maternity clinics in Denmark. METHODS: A questionnaire to all the Danish maternity clinics that perform cesarean section, concerning indications for application of antibiotic prophylaxis and antibiotic regimens to patients undergoing acute and elective cesarean section. RESULTS: All departments (n = 48) returned the questionnaire. Twenty departments (46%) provided written guidelines for antibiotic prophylaxis. Four departments (8%) used antibiotic prophylaxis to elective cesarean sections, 25 departments (52%) applied antibiotics to all emergency sections. In the presence of the rupture of membranes or prolongation of labor (> 12 hrs) 58% and 63% of the departments applied antibiotic prophylaxis, respectively. The most infrequent first choice drug was cefuroxim, employed by 27 departments (56%). Concerning timing, 21 departments (44%) applied antibiotics after cord clamping and 13 departments (27%) before incision. CONCLUSION: We propose a nation-wide prospective investigation on the rate of infections associated with cesarean section to set up rational guidelines for antibiotic prophylaxis.

Immunoreactive inhibin concentration in blood tested under variable sampling conditions.

The stability of immunoreactive (i.r.) inhibin in blood samples drawn and handled under different conditions and at different time intervals were studied. Ten serum and plasma samples drawn in 1994 from healthy volunteers were compared to samples collected in 1986 from 10 healthy women admitted for laparoscopic sterilization and analysed 6 years later. All samples were drawn on the twelfth day of the menstrual cycle and handled under identical clinical conditions (22 degrees C). The concentrations in the 1986 samples were similar to the Se-i.r. inhibin levels from 1994. Different clotting temperatures, repetitive freezing and thawing or hemolysis had no effects on the i.r. inhibin values, whereas non-hemolysed samples left at room temperature (22 degrees C) for 3 days were significantly lower, which might be due to a statistical type 2 error. No differences in concentration between serum and plasma i.r. inhibin were demonstrated. In conclusion, i.r. inhibin is a very stable peptide hormone in both serum and plasma if drawn and handled under normal conditions.

Combined therapy trial with interferon alpha-2a and ablative therapy in the treatment of anogenital warts.

OBJECTIVE: To determine whether the combination of systemically administered interferon alpha-2a and ablative surgery for the treatment of genital and/or perianal warts produces a 30% or greater improvement in lasting response rate compared with a control group receiving a combination of placebo and ablative therapy. DESIGN: Randomised, triple-blind, placebo-controlled trial using 1 or 3 MIU of interferon alpha-2a or placebo administered subcutaneously three times weekly for 10 weeks in combination with ablative surgery. SETTING: International, multicentre study in 10 genitourinary medicine clinics. PATIENTS: Two hundred and fifty patients with anogenital warts. MAIN OUTCOME MEASURES: Lasting response at week 38. RESULTS: Standard efficacy analysis at week 38 showed a lasting response in 51% (35/68) of 3 MIU interferon-treated patients, 48% (30/63) of 1 MIU interferon-treated patients and 43% (29/67) of placebo-treated patients. CONCLUSIONS: With the doses and regime described, treatment with interferon alpha-2a in combination with ablative therapy is not significantly superior in the treatment of anogenital warts than placebo and ablative therapy.

[Laparoscopic sterilization. Late complications of the endocoagulation method]. / Laparoskopisk sterilisation. Senkomplikationer til endokoagulationsmetoden.

The objective of this analysis was to assess the failure rate and incidence of regret of tubal sterilization performed by the endocoagulation technique. The design was a register-based retrospective study. A total of 585 sterilizations were performed from January 1986 to December 1992 in the county hospital of Sønderborg. The patients who had undergone sterilization were identified by diagnosis from the database of "Kommune-data". Forty patients were excluded due to different reasons. The frequency of hospitalization from the operation to July 94 was registered. The actual case records were examined. The failure rate following endocoagulation was 0.92% (one intrauterine and four extrauterine pregnancies) corresponding to an incidence of 1.77/1000 women/year. Two women (0.37%) developed hydrosalpinx after the operation. Ten patients (1.8%) wanted a reversal of sterilization. It was concluded, that tubal sterilization by the endocoagulation method is cheap and safe. The failure rate is similar to that of other methods. Implantation in the peritoneal space is avoided. Thermic destruction is minimized, and the risk of peroperative burning of the tissue is therefore reduced.