Outcomes for women without conventional treatment for stage 1A (microinvasive) carcinoma of the cervix.

BACKGROUND: An unethical clinical study that entailed withholding treatment from women diagnosed with cervical intraepithelial neoplasia 3 (CIN3) was conducted at National Women's Hospital, Auckland, New Zealand. Women with microinvasive carcinoma of the cervix also had treatment withheld. AIMS: To describe the management and outcomes for women with microinvasive carcinoma for many of whom conventional treatment was withheld. MATERIALS AND METHODS: Retrospective cohort study of women with a diagnosis of stage 1A cervical carcinoma at National Women's Hospital. Medical records, cytology and histopathology were reviewed and data linked with cancer and death registries up to December 2000. RESULTS: Between 1955 and 1976, 62 women were initially diagnosed with stage 1A cervical cancer and 20 were diagnosed during follow up (to 1995). Sixty of the 82 women had initial management characterised as 'probably non-curative'; 20 of these received only a small diagnostic excision. Women in the latter group were more likely to: (i) subsequently have positive cytology (P < 0.0005), (ii) have untreated positive cytology (P = 0.02), and (iii) undergo multiple biopsies after initial management (P = 0.001). Of the women who received only a small diagnostic excision, eight of 20 developed invasive carcinoma of the cervix (≥ stage 1B) or vaginal vault, compared to two of 22 women who received initial treatment characterised as 'probably curative'. CONCLUSIONS: Women with microinvasive carcinoma were included in a natural history study of CIN3; they underwent numerous procedures designed to observe rather than treat their condition, and had a substantial risk of invasive cancer.

Vaccine mandates in the time of Omicron.

Nil.

Nocturnal enuresis in patients taking clozapine, risperidone, olanzapine and quetiapine: comparative cohort study.

BACKGROUND: Nocturnal enuresis has been reported in patients taking clozapine, but the incidence has not been accurately established. The incidence of enuresis in patients taking risperidone, olanzapine or quetiapine is unknown. Aims To compare nocturnal enuresis in patients taking clozapine with that in patients taking risperidone, olanzapine or quetiapine. METHOD: Observational cohort study using prescription event monitoring methods. Patients prescribed atypical antipsychotic medicines were followed up by questionnaires that were sent to their medical practitioner. Practitioners were asked to directly ask their patients about bed-wetting. RESULTS: Nocturnal enuresis was reported by 17 of 82 (20.7%) patients taking clozapine, 11 of 115 (9.6%) taking olanzapine, 7 of 105 (6.7%) taking quetiapine and 12 of 195 (6.2%) taking risperidone. Compared with clozapine, the risk of nocturnal enuresis was significantly lower in patients taking olanzapine (odds ratio, OR = 0.43, 95% CI 0.19-0.96), quetiapine (OR = 0.33, 95% CI 0.13-0.59) or risperidone (OR = 0.27, 0.12-0.59), with odds ratios adjusted for age, gender and duration of treatment. CONCLUSIONS: Approximately one in five patients prescribed clozapine experienced bed-wetting. This was significantly higher than the rate of nocturnal enuresis in patients taking olanzapine, quetiapine or risperidone.

Consequences in women of participating in a study of the natural history of cervical intraepithelial neoplasia 3.

BACKGROUND: A retrospective cohort study was performed in 1063 women diagnosed with cervical intraepithelial neoplasia grade 3 (CIN3) (previously termed carcinoma in situ- CIS) in the National Women's Hospital, Auckland, New Zealand. The study describes the clinical management and outcomes for women with CIN3 diagnosed in the decade of 1965-1974, when treatment with curative intent was withheld in an unethical clinical study of the natural history of CIS. A comparison is made with women who were diagnosed earlier (1955-1964) and later (1975-1976). AIMS: The aim of the study is to record the medical encounters, frequency and management of cytological abnormalities and the occurrence of invasive cancers. The medical records, cytology and histopathology were reviewed and data linked with cancer and death registers. RESULTS: Women diagnosed with CIN3 in 1965-1974 (n = 422), compared with those diagnosed earlier (n = 385) or later (n = 256): (i) were less likely to have initial treatment with curative intent (51% vs 95 and 85%, respectively); (ii) had more follow-up biopsies (P < 0.0005); (iii) were more likely to have positive cytology during follow-up (P < 0.005) and positive smears that were not followed within six months by a treatment with curative intent (P < 0.005); and (iv) experienced a higher risk of cancer of the cervix or vaginal vault (RR = 3.3 compared with the first period, 95% CI: 1.7-5.3). Among women diagnosed in 1965-1974, those initially managed by punch or wedge biopsy alone had a cancer risk ten times (95% CI: 3.9-25.7) higher than women initially treated with curative intent. CONCLUSIONS: During the 'clinical study' (1965-1974), women underwent numerous interventions that were aimed to observe rather than treat their condition, and their risk of cancer was substantially increased.

Male circumcision and serologically determined human papillomavirus infection in a birth cohort.

Circumcision has been reported to protect against infection with human papillomavirus (HPV) in men, but results have been inconsistent. We followed males in a birth cohort born in Dunedin, New Zealand, in 1972 and 1973 from age 3 to 32 years. Seropositivity at age 32 years for the oncogenic types HPV-16 and 18, and the nononcogenic types 6 and 11, was studied in relation to maternal reports of circumcision status at age 3 for 450 men. Seropositivity to any of these types was associated with lifetime number of sexual partners (P = 0.03), and lower moral-religious emphasis of the family of origin (P < 0.001). Circumcision was not found to be protective, with the adjusted odds ratio (95% confidence interval) for HPV6/11/16/18 seropositivity among the circumcised compared with the uncircumcised being 1.4 (0.89-2.2).

Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study.

BACKGROUND: The invasive potential of cervical intraepithelial neoplasia 3 (CIN3; also termed stage 0 carcinoma) has been poorly defined. At the National Women's Hospital, Auckland, New Zealand, treatment of CIN3 was withheld from a substantial number of women between 1965 and 1974 as part of an unethical clinical study. The resulting variation in management allows comparison of the long-term risk of invasive cancer of the cervix in women whose lesion was minimally disturbed with those who had adequate initial treatment followed by conventional management. We aimed to estimate the long-term risk of invasive cancer in these two groups of women. A judicial inquiry referred for independent clinical review in 1988 all women for whom there remained doubt about the adequacy of their management. METHODS: Between February, 2001, and December, 2004, medical records, cytology, and histopathology were reviewed for all women with CIN3 diagnosed between 1955 and 1976, whose treatment was reviewed by judicial inquiry and whose medical records could be located, and linkages were done with cancer and death registers and electoral rolls. To take into account the probability that the CIN3 lesion had been completely removed, we classified adequacy of treatment by type of procedure, presence of CIN3 at the excision margin, and subsequent cytology. The primary outcome was cumulative incidence of invasive cancer of the cervix or vaginal vault. Follow-up continued until death or Dec 31, 2000, whichever came first. Analyses accounted for procedures during follow-up. FINDINGS: 1229 women whose treatment was reviewed by the judicial inquiry in 1987-88 were included. Of these, 48 records (4%) could not be located and 47 women (4%) did not meet the inclusion criteria. At histopathological review, a further 71 (6% of 1134) women were excluded because the review diagnosis was not CIN3. We identified outcomes in the remaining 1063 (86% of 1229) women diagnosed with CIN3 at the hospital in 1955-76. In 143 women managed only by punch or wedge biopsy, cumulative incidence of invasive cancer of the cervix or vaginal vault was 31.3% (95% CI 22.7-42.3) at 30 years, and 50.3% (37.3-64.9) in the subset of 92 such women who had persistent disease within 24 months. However, cancer risk at 30 years was only 0.7% (0.3-1.9) in 593 women whose initial treatment was deemed adequate or probably adequate, and whose treatment for recurrent disease was conventional. INTERPRETATION: This study provides the most valid direct estimates yet available of the rate of progression from CIN3 to invasive cancer. Women with untreated CIN3 are at high risk of cervical cancer, whereas the risk is very low in women treated conventionally throughout.

Vitamin and mineral supplements in pregnancy and the risk of childhood acute lymphoblastic leukaemia: a case-control study.

BACKGROUND: An earlier case-control study from Western Australia reported a protective effect of maternal folic acid supplementation during pregnancy on the risk of childhood acute lymphoblastic leukaemia (ALL). The present study tested that association. METHODS: A national case-control study was conducted in New Zealand. The mothers of 97 children with ALL and of 303 controls were asked about vitamin and mineral supplements taken during pregnancy. RESULTS: There was no association between reported folate intake during pregnancy and childhood ALL (adjusted odds ratio (OR) 1.1, 95% confidence interval (CI) 0.5-2.7). Combining our results with the study from Western Australia and another study from Québec in a meta-analysis gave a summary OR of 0.9 (95% CI 0.8-1.1). CONCLUSION: Our own study, of similar size to the Australian study, does not support the hypothesis of a protective effect of folate on childhood ALL. Neither do the findings of the meta-analysis.

Air travel and fatal pulmonary embolism.

Although long-distance air travel is commonly regarded as a risk factor for venous thromboembolism, the risk of clinically important events has not been well defined. We estimated the absolute risk of dying from pulmonary embolism following long-distance air travel in a national population-based descriptive study of 121 men and women who were aged 15-59 years (the age range in which the majority of international arrivals are found) and whose underlying cause of death was certified as codes 415.1, 451, or 453 of the International Classification of Diseases (ninth revision). Eleven cases had undertaken long-distance air travel in the four weeks before the onset of the fatal episode. The estimated risks of fatal pulmonary embolism following a flight of at least three hours' duration were 0.5 (95% CI 0.2-1.2) and 0.6 (95% CI 0.2-1.4) per million arrivals for overseas visitors and New Zealand residents, respectively. For air travel of more than eight hours' duration, the risk in New Zealand residents was 1.3 (95% CI 0.4-3.0) per million arrivals. We also conducted a case-control study based on those cases who were normally resident in New Zealand and registered on the electoral roll (n = 99). For each case, four controls matched for sex, age, and electorate, were randomly selected from the electoral roll. In the key analysis (based on 88 cases and 334 controls), the adjusted odds ratio for travellers who had flown for more than eight hours was 7.9 (95% CI 1.1-55.1) compared with those who did not undertake a long-distance flight. Long-distance air travellers have a higher risk of dying from pulmonary embolism than non-travellers, but the absolute risk in people aged 15-59 years appears to be very small.

Review of cytologic slides from the national women's hospital, New Zealand, cohort of women with cervical intraepithelial neoplasia 3 diagnosed in 1955-1976.

OBJECTIVE: To review cytologic slides, mostly at least 25 years old, from women attending National Women's Hospital, Auckland, who had been diagnosed histologically with cervical carcinoma in situ in 1955-1976. STUDY DESIGN: Smears comprised all those from the 2 years following diagnosis as well as all subsequent smears for women who developed "microinvasive" or invasive lower genital tract cancer. The Victorian Cytology Service performed the review using the Australian Modified Bethesda System. was 0.97. RESULTS: Nine percent of 4,930 retrieved slides were technically unsatisfactory. Original (Papanicolaou) and review coding were available for 4,477 slides. Using categories of equivalence, smears coded as normal (original, 59.2%; review, 61.4%) or showing possible or definite high grade abnormalities (original, 25.9%; review, 29.6%) were found in similar proportions. The kappa statistic (0.79) indicated a high level of agreement between original and review coding. In comparison with the review, the sensitivity of the original coding in detecting high grade abnormalities was 0.80, while the ability of the original assessment to categorize smears as not high grade (specificity) CONCLUSION: This comprehensive review found nearly all archived cytology slides to be technically satisfactory and the broad diagnostic cytologic categories from earlier periods (apart from benign lesions) to be concordant with those currently used.

PSA testing and digital rectal examination in New Zealand.

OBJECTIVE: To investigate the use of digital rectal examination and prostate specific antigen (PSA) testing in a population-based sample of men in New Zealand. METHODS: A random selection of men aged 40-74 years, weighted by age, was chosen from the general electoral roll of New Zealand. Only men with a telephone who had been married at some time were eligible. Telephone interviews were conducted using a standard questionnaire. Crude and age-adjusted proportions were calculated. Logistic regression was used to explore associations between sociodemographic factors and digital rectal examination or PSA testing. RESULTS: Interviews were completed for 85% of the 1,486 eligible men and analyses were confined to the 1,225 European men. Many more men reported having a digital rectal examination (41%; 95% CI 33.8-48.2) than a PSA test (9%; 95% CI 4.2-14.2). Men in the lowest social class were significantly less likely to have had a digital rectal examination (OR 0.30; 95% CI 0.18-0.50) or PSA test (OR 0.25; 95% CI 0.11-0.60) compared with those in the highest social class. Men with vocational training or no post-school qualifications were approximately half as likely to report a digital rectal examination or a PSA test compared with men with degrees or diplomas. CONCLUSIONS: Although current New Zealand recommendations are that population screening for prostate cancer should not be introduced, many men are still having digital rectal examinations and PSA tests in the absence of symptoms. The frequency of PSA testing is considerably lower than in Australia and appears to be largely influenced by a man's social class.

Comparison of cancer mortality and incidence in New Zealand and Australia.

AIMS: To compare cancer mortality and incidence data from New Zealand and Australia, in order to gauge the potential for reducing deaths from cancer in New Zealand. METHODS: For 1996 and 1997, numbers of deaths from cancer, numbers of new cases, and population data were stratified in 5-year age-groups. Numbers observed in New Zealand were compared with numbers expected from Australian rates. Age-standardized mortality and incidence rates for each sex were analysed. RESULTS: New Zealanders of both sexes experienced more deaths from cancer than expected in every age group. If Australian rates had applied, there would have been 215 fewer cancer deaths per year in New Zealand males, and 616 fewer in females. The largest differences related to breast cancer and lung cancer in women, and colorectal cancer in both sexes. The overall incidence of cancer was higher in New Zealand, but mortality/incidence ratios were also higher for many sites--suggesting that survival after treatment has been poorer in New Zealand than in Australia. CONCLUSIONS: Considerable scope exists for reducing cancer mortality in New Zealand. For a national cancer control strategy, it will be essential to clarify reasons for the high incidence of cancer and to study survival following treatment.

Body piercing, personality, and sexual behavior.

The associations of body piercing with other social characteristics, personality, and sexual behavior were investigated in a population-based sample of young adults, in light of the theory that body piercing has meaning in terms of a corporeal expression of the self. At age 26 years, 966 (95%) of 1019 members of the birth-cohort of the Dunedin Multidisciplinary Health and Development Study were asked about body piercing (at interview) and sexual behavior (questions presented by computer). Assessment of personality traits was conducted at ages 18 or 21 years. In total, 183 participants (9% of the men and 29% of the women) had piercings at a site other than the earlobes. People who lived outside New Zealand or who were of Maori descent were more likely to be pierced, but unemployment and low occupational status were not significantly related to piercing. Women who were pierced, compared with those without piercings, were more likely to have personality traits of low constraint or high negative emotionality. Women with piercings were also more likely to report having had, during the previous year, five or more heterosexual partners (odds ratio, 5.8, 95% CI: 2.3-14.6) or any same-sex partner involving genital contact (odds ratio, 10.3, CI: 2.9-37.2). The associations with sexual behavior in men were weaker and not statistically significant. In this population, body piercing in women was associated with sexual behavior. Having multiple heterosexual partners or any same-sex partner was very rare among women without piercings. The theory of meaning for body piercing was generally supported, offering the possibility of a richer understanding of this phenomenon in the general population.

Risk factors for prostate cancer: A national case-control study.

Statutory notification of cancer in New Zealand provided an opportunity to investigate risk factors for prostate cancer in a large national population-based case-control study. We analyzed data obtained from telephone interviews with 923 cases and 1,224 controls. For inclusion in the study, all subjects had to have been married at some time. We found an increased risk of prostate cancer among those with a history of prostate cancer in first degree relatives (RR 2.6; 95% CI, 1.9-3.7) and an increased risk of prostate cancer with length of marriage among men married only once and still married at interview. For a consecutive subgroup of 550 cases and 819 controls, data on height and weight at age 20 and at 5 years before interview were collected. Men less than or equal to 1.7 m in height at age 20 years had a lower risk of prostate cancer than men taller at that age. There was no association between weight or body mass index and risk of prostate cancer.

Psychotropic drugs and fatal pulmonary embolism.

PURPOSE: To examine the association between the use of psychotropic drugs and fatal pulmonary embolism. METHODS: We conducted a national case-control study of fatal pulmonary embolism. Cases were 75 New Zealand men and women aged 15-59 years who died between 1 January 1990 and 31 December 1998, where the underlying cause of death was certified as codes 415.1, 451 or 453 of the International Classification of Diseases (9th Revision). Four controls, matched for sex and age, were selected from the general practice to which each case had belonged. Information was abstracted from the records of general practitioners, family planning clinics and psychiatric services. Odds ratios and 95% confidence intervals (95% CI) were estimated using conditional logistic regression. The key analyses were restricted to cases (n = 62) and controls (n = 243) without major risk factors for venous thromboembolism. RESULTS: Compared to non-use, the adjusted odds ratio for current use of antipsychotic drugs was 13.3 (95% CI: 2.3-76.3). Low potency antipsychotics appeared to carry the highest risk (odds ratio: 20.8 [95% CI: 1.7-259.0]). The main drug involved was thioridazine. The odds ratio for current use of antidepressants was also increased, at 4.9 (95% CI: 1.1-22.5). CONCLUSIONS: Our results for conventional antipsychotics are consistent with previous studies of non-fatal venous thromboembolism. The finding for antidepressants needs to be replicated in other studies.