Delayed diagnosis of endometriosis disadvantages women in ART: a retrospective population linked data study.

STUDY QUESTION: Do the outcomes and use of ART differ between women with and without endometriosis? SUMMARY ANSWER: ART use and outcome do not appear to differ for women with and without endometriosis, as long as endometriosis is diagnosed prior to commencing ART. WHAT IS KNOWN ALREADY: Approximately 40% of women with endometriosis have infertility and ART is the recommended treatment option for these women. However, diagnosis of endometriosis can be complex and lengthy, and a delay in diagnosis can reduce the likelihood of achieving a live birth. STUDY DESIGN, SIZE, DURATION: This retrospective national cohort study used longitudinal self-report data (collected 1996-2018) from women born in 1973-1978 who are participants in the Australian Longitudinal Study on Women's Health (ALSWH). The study also used linked administrative data on Endometriosis (1970-2018), ART (1996-2020) and births (1996-2018). PARTICIPANTS/MATERIALS, SETTING, METHODS: The outcome measures were: age at first ART cycle; use of ART treatments (IVF only; IUI only/and IVF); number of ART cycles (1-3; 4-10; 11-36); and births after first ART (no; yes) (note that births could not be tied to ART). MAIN RESULTS AND THE ROLE OF CHANCE: One in three (34.7%, n = 459/1322) women using ART had endometriosis, with 65.6% of these diagnosed before first ART and 34.4% after. Adjusted regression analyses showed women with endometriosis diagnosed before first ART were not significantly different to women without endometriosis on any outcome. However, women with endometriosis diagnosed after first ART were more likely to use IUI (adjusted odds ratio (aOR) 2.14, 95% CI 1.48, 3.09) and do more cycles (11-36 cycles: aOR 4.09, 95% CI 2.41, 6.95), and less likely to report a birth (aOR 0.67, 95% CI 0.45, 0.99), compared to women without endometriosis, despite no significant difference in starting age (coefficient = -0.62, 95% CI -1.36, 0.13). LIMITATIONS, REASONS FOR CAUTION: We did not have information on the severity of endometriosis, or the reasons for using ART, which can influence treatment and outcomes. We were not able to reliably link births with ART treatment. Finally, it is possible that some of the women in our 'no endometriosis' group did have endometriosis and were unaware of it, although prevalence rates match population estimates. WIDER IMPLICATIONS OF THE FINDINGS: These findings support previous studies that have found no difference in outcome of ART for women with endometriosis, but add the new insight that this is only true if endometriosis is diagnosed prior to commencing ART. A delayed diagnosis can create disadvantage during ART treatment. Early recourse to IVF may be advantageous for pregnancy prospects for women with endometriosis. STUDY FUNDING/COMPETING INTEREST(S): The ALSWH is funded by the Australian Government Department of Health. G.D.M. is supported by an NHMRC Principal Research Fellowship (APP11218449). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Prevalence and incidence of endometriosis in Australian women: a data linkage cohort study.

OBJECTIVE: To estimate the prevalence and incidence of endometriosis among Australian women. DESIGN: Population-based cohort study linked to administrative health records. SETTING: Secondary analysis of seven surveys collected between 2000 and 2018 from a population-based cohort study. POPULATION: A total of 13 508 Australian women, born 1973-78, from a prospective cohort study of 14 247 women conducted between 1996 and 2018. METHODS: During 2000 and 2018, self-reported longitudinal survey data were linked to three administrative health databases to separately identify women with clinically confirmed or suspected endometriosis across the multiple data sources. MAIN OUTCOME MEASURES: Prevalence and incidence of clinically confirmed endometriosis in the cohort were first estimated using national hospital data. Data were then combined with other administrative health databases and the survey data to capture all clinically confirmed and suspected diagnoses of endometriosis. RESULTS: The cumulative prevalence of clinically confirmed endometriosis was 6.0% (95% CI 5.8-6.2%) by age 40-44 years. The cumulative prevalence increased to 11.4% (95% CI 11.1-11.7%) when adding diagnoses of clinically suspected endometriosis. Age-specific incidence estimates peaked to 6 per 1000 person-years at age 30-34 years. CONCLUSIONS: Among 13 508 Australian women followed for 20 years, one in nine women had clinically confirmed or suspected endometriosis by the age of 44, with most diagnosed during their early thirties. Endometriosis is a significant public health issue requiring increased surveillance, clinical awareness and management. Efforts to expand knowledge on the aetiology of the disease and optimal methods for disease management are crucial to women's health. TWEETABLE ABSTRACT: In a national study of 13 508 Australian women, one in nine women were diagnosed with endometriosis by age 44.

Height loss in elderly women is preceded by osteoporosis and is associated with digestive problems and urinary incontinence.

SUMMARY: This study explores risk factors for height loss and consequences in terms of health and wellbeing, in older women. Osteoporosis, low body-mass index, being born in Europe and using medications for both sleep and anxiety were risk factors for height loss. Height loss was associated with digestive problems; excessive height loss was also associated with urinary stress-incontinence and a decline in self-rated health. INTRODUCTION: Height loss is associated with osteoporosis, but little is known about its consequences. We aimed to examine the risk factors for height loss and the symptoms associated with height loss. METHODS: Elderly participants of the Australian Longitudinal Study on Women's Health (aged 70-75 in 1996) who provided data on height at any two consecutive surveys (held in 1996, 1999, 2002, and 2005) were included (N = 9,852). A regression model was fitted with height loss as the outcome and sociodemographics, osteoporosis, and other risk factors as explanatory variables. Symptoms related to postural changes or raised intra-abdominal pressure were analyzed using height loss as an explanatory variable. RESULTS: Over 9 years, average height loss per year was -0.12% (95% confidence intervals [95% CI] = -0.13 to -0.12) of height at baseline. Height loss was greater among those with osteoporosis and low body mass index and those taking medications for sleep and anxiety. After adjusting for confounders, symptoms associated with height loss of > or =2% were heartburn/indigestion (odds ratio [OR] = 1.19, 95% CI = 1.01 to 1.40), constipation (OR = 1.18, 95% CI = 1.01 to 1.37), and urinary stress incontinence (OR = 1.20, 95% CI = 1.02 to 1.41). CONCLUSION: These findings highlight the importance of monitoring height among the elderly in general practice and targeting associated symptoms.

Monitoring dendritic cells in clinical practice using a new whole blood single-platform TruCOUNT assay.

Dendritic cells (DC) from distinct DC subsets are essential contributors to normal human immune responses. Despite this, reliable assays that enable DC to be counted precisely have been slow to evolve. We have now developed a new single-platform flow cytometric assay based on TruCOUNT beads and the whole blood "Lyse/No-Wash" protocol that allows precise counting of the CD14(-) blood DC subsets: CD11c(+)CD16(-) DC, CD11c(+)CD16(+) DC, CD123(hi) DC, CD1c(+) DC and BDCA-3(+) DC. This assay requires 50 microl of whole blood; does not rely on a hematology blood analyser for the absolute DC counts; allows DC counting in EDTA samples 24 h after collection; and is suitable for cord blood and peripheral blood. The data is highly reproducible with intra-assay and inter-assay coefficients of variation less than 3% and 11%, respectively. This assay does not produce the DC-T lymphocyte conjugates that result in DC counting abnormalities in conventional gradient-density separation procedures. Using the TruCOUNT assay, we established that absolute blood DC counts reduce with age in healthy individuals. In preliminary studies, we found a significantly lower absolute blood CD11c(+)CD16(+) DC count in stage III/IV versus stage I/II breast carcinoma patients and a lower absolute blood CD123(hi) DC count in multiple myeloma patients, compared to age-matched controls. These data indicate that scientific progress in DC counting technology will lead to the global standardization of DC counting and allow clinically meaningful data to be obtained.

Gastroschisis: can prenatal sonography predict neonatal outcome?

OBJECTIVE: Gastroschisis is associated with significant neonatal morbidity, and occasionally mortality. Previous studies looking at ways to prognosticate this condition by antenatal ultrasound have shown conflicting results. The aim of this study was to evaluate the usefulness of prenatal sonographic parameters to predict neonatal outcome of gastroschisis. METHODS: The charts, photographs, and videotapes of all fetuses with gastroschisis who were assessed during pregnancy at the Mater Mothers' Hospital, Brisbane over an 8.5-year period (Jan 1993-May 2001) were reviewed. Adverse neonatal outcome was defined as death, severe bowel complications (atresia, perforation, necrotic segments), need for multiple bowel operations, or a combination of these. Various sonographic parameters assessed included: gestation at first diagnosis, maximum bowel diameter, maximum bowel wall thickness, presence of other anomalies, evidence of growth restriction, and polyhydramnios. RESULTS: Forty-five patients met the entry criteria during the study period. Six neonates died, 12 had severe bowel complications, and 15 had a combination of the adverse outcomes. Polyhydramnios was most significantly associated with severe bowel complications, with a likelihood ratio of 11.7 (P = 0.001). Other ultrasound parameters were not significantly correlated with neonatal outcome. CONCLUSION: Most standard ultrasound parameters assessed antenatally in fetal gastroschisis were not significantly associated with adverse neonatal outcome, except for polyhydramnios, which was strongly predictive of severe bowel complications in the neonatal period. This information is important both for parents and for health professionals managing pregnancies with fetal gastroschisis.

Minimum acceptable standards for digital compression of a fetal ultrasound video-clip.

If the Internet could be used as a method of transmitting ultrasound images taken in the field quickly and effectively, it would bring tertiary consultation to even extremely remote centres. The aim of the study was to evaluate the maximum degree of compression of fetal ultrasound video-recordings that would not compromise signal quality. A digital fetal ultrasound videorecording of 90 s was produced, resulting in a file size of 512 MByte. The file was compressed to 2, 5 and 10 MByte. The recordings were viewed by a panel of four experienced observers who were blinded to the compression ratio used. Using a simple seven-point scoring system, the observers rated the quality of the clip on 17 items. The maximum compression ratio that was considered clinically acceptable was found to be 1:50-1:100. This produced final file sizes of 5-10 MByte, corresponding to a screen size of 320x240 pixels, running at 15 frames/s. This study expands the possibilities for providing tertiary perinatal services to the wider community.

Surgical and physical stress increases circulating blood dendritic cell counts independently of monocyte counts.

Dendritic cells (DCs) are specialized antigen-presenting cells that have the unique ability to initiate a primary immune response. The effect of physiologic stress on circulating blood DCs has thus far not been studied. In this study, we applied a recently developed method of counting blood DCs to test the hypothesis that significant stress to the body such as surgery and exercise might induce measurable changes in the DC numbers, subsets, phenotype, and function. Twenty-six patients scheduled for elective laparoscopic cholecystectomy, 4 for elective hysterectomy, 56 controls, and 5 volunteers who underwent a stress exercise test were enrolled in the study. Absolute DC counts increased acutely (71.7% +/- 11% [SEM], P =.0001) in response to the stress of surgery and dropped below preoperative levels (-25% +/- 14% [SEM], P =.05) on days 2-3. The perioperative DC subset balance remained constant. Interestingly, DC counts changed independently of monocyte counts. Exercise also induced a rise in DC counts but coincidentally with monocyte counts. Surprisingly, no phenotypic or functional activation of DCs was seen in either stress situations in vivo. DCs are rapidly mobilized into the circulation in response to surgical and exercise stress, which may serve to prepare the host's immune defenses against trauma. The independent regulation of the DC and monocyte counts reinforces the distinction between these 2 cell populations.

Childhood poisoning in Queensland: an analysis of presentation and admission rates.

OBJECTIVE: To determine the presentation rates for paediatric poisoning by ingestion and the determinants of hospital admission. METHODOLOGY: Cross-sectional survey using an injury surveillance database from emergency departments in South Brisbane, Mackay and Mt Isa, Queensland, from January 1998 to December 1999. There were 1516 children aged 0-14 years who presented following ingestional poisoning. RESULTS: The presentation rates for poisoning were 690, 40 and 67 per 100000 population aged 0-4, 5-9 and 10-14 years, respectively. The admission rates to hospital for poisoning were 144, 14 and 22 per 100000 population aged 0-4, 5-9 and 10-14 years, respectively. Although presentation rates for poisoning were higher in the rural centres the admission rates were disproportionately high for the 0-4 years age group. The agents most frequently ingested were paracetamol, Dimetapp, rodenticides and essential oils. CONCLUSION: There is a need to design and implement interventions aimed at reducing poison exposures and unnecessary hospital admissions in the 0-4 years age group.

Mutation of a nuclear receptor gene, NR2E3, causes enhanced S cone syndrome, a disorder of retinal cell fate.

Hereditary human retinal degenerative diseases usually affect the mature photoreceptor topography by reducing the number of cells through apoptosis, resulting in loss of visual function. Only one inherited retinal disease, the enhanced S-cone syndrome (ESCS), manifests a gain in function of photoreceptors. ESCS is an autosomal recessive retinopathy in which patients have an increased sensitivity to blue light; perception of blue light is mediated by what is normally the least populous cone photoreceptor subtype, the S (short wavelength, blue) cones. People with ESCS also suffer visual loss, with night blindness occurring from early in life, varying degrees of L (long, red)- and M (middle, green)-cone vision, and retinal degeneration. The altered ratio of S- to L/M-cone photoreceptor sensitivity in ESCS may be due to abnormal cone cell fate determination during retinal development. In 94% of a cohort of ESCS probands we found mutations in NR2E3 (also known as PNR), which encodes a retinal nuclear receptor recently discovered to be a ligand-dependent transcription factor. Expression of NR2E3 was limited to the outer nuclear layer of the human retina. Our results suggest that NR2E3 has a role in determining photoreceptor phenotype during human retinogenesis.

Finding bile duct injuries using record linkage: a validated study of complications following cholecystectomy.

Laparoscopic cholecystectomy was introduced to Western Australia in 1991 and has become the method of choice for this procedure, although there are concerns about complications, particularly bile duct injuries. Previous studies have investigated this problem but have not confirmed the accuracy of coded information. We used Record Linkage to link operative admissions to subsequent admissions for all people who underwent cholecystectomy between 1988 and 1994. Using ICD9-CM discharge codes, we identified patients with an associated complication. We validated these patients' medical notes to obtain the proportion of complications in the period encompassing the introduction of laparoscopic cholecystectomy. We found 48 bile duct injuries in 413 patients. Of these 43% were found using complication codes on the operative admission, 79% using linked records of subsequent admissions, and 90% by adding lists of complicated cases from the three teaching hospitals. Any epidemiological research that uses surgical complication codes from operative admissions, particularly in the absence of a specific ICD9-CM code, will lead to significantly underestimating the prevalence of complications. By using record linkage, and validating medical records, we captured a significant proportion of complications.

Analysis of myocilin mutations in 1703 glaucoma patients from five different populations.

A glaucoma locus, GLC1A, was identified previously on chromosome 1q. A gene within this locus (encoding the protein myocilin) subsequently was shown to harbor mutations in 2-4% of primary open angle glaucoma patients. A total of 1703 patients was screened from five different populations representing three racial groups. There were 1284 patients from primarily Caucasian populations in Iowa (727), Australia (390) and Canada (167). A group of 312 African American patients was from New York City and 107 Asian patients from Japan. Overall, 61 different myocilin sequence variations were identified. Of the 61 variations, 21 were judged to be probable disease-causing mutations. The number of probands found to harbor such mutations in each population was: Iowa 31/727 (4.3%), African Americans from New York City 8/312 (2.6%), Japan 3/107 (2.8%), Canada 5/167 (3.0%), Australia 11/390 (2.8%) and overall 58/1703 (3. 4%). Overall, 16 (76%) of 21 mutations were found in only one population. The most common mutation observed, Gln368Stop, was found in 27/1703 (1.6%) glaucoma probands and was found at least once in all groups except the Japanese. Studies of genetic markers flanking the myocilin gene suggest that most cases of the Gln368Stop mutations are descended from a common founder. Although the specific mutations found in each of the five populations were different, the overall frequency of myocilin mutations was similar ( approximately 2-4%) in all populations, suggesting that the increased rate of glaucoma in African Americans is not due to a higher prevalence of myocilin mutations.

Variation of clinical expression in patients with Stargardt dystrophy and sequence variations in the ABCR gene.

OBJECTIVE: To report the spectrum of ophthalmic findings in patients with Stargardt dystrophy or fundus flavimaculatus who have a specific sequence variation in the ABCR gene. PATIENTS: Twenty-nine patients with Stargardt dystrophy or fundus flavimaculatus from different pedigrees were identified with possible disease-causing sequence variations in the ABCR gene from a group of 66 patients who were screened for sequence variations in this gene. METHODS: Patients underwent a routine ocular examination, including slitlamp biomicroscopy and a dilated fundus examination. Fluorescein angiography was performed on 22 patients, and electroretinographic measurements were obtained on 24 of 29 patients. Kinetic visual fields were measured with a Goldmann perimeter in 26 patients. Single-strand conformation polymorphism analysis and DNA sequencing were used to identify variations in coding sequences of the ABCR gene. RESULTS: Three clinical phenotypes were observed among these 29 patients. In phenotype I, 9 of 12 patients had a sequence change in exon 42 of the ABCR gene in which the amino acid glutamic acid was substituted for glycine (Gly1961Glu). In only 4 of these 9 patients was a second possible disease-causing mutation found on the other ABCR allele. In addition to an atrophic-appearing macular lesion, phenotype I was characterized by localized perifoveal yellowish white flecks, the absence of a dark choroid, and normal electroretinographic amplitudes. Phenotype II consisted of 10 patients who showed a dark choroid and more diffuse yellowish white flecks in the fundus. None exhibited the Gly1961Glu change. Phenotype III consisted of 7 patients who showed extensive atrophic-appearing changes of the retinal pigment epithelium. Electroretinographic cone and rod amplitudes were reduced. One patient showed the Gly1961Glu change. CONCLUSIONS: A wide variation in clinical phenotype can occur in patients with sequence changes in the ABCR gene. In individual patients, a certain phenotype seems to be associated with the presence of a Gly1961Glu change in exon 42 of the ABCR gene. CLINICAL RELEVANCE: The identification of correlations between specific mutations in the ABCR gene and clinical phenotypes will better facilitate the counseling of patients on their visual prognosis. This information will also likely be important for future therapeutic trials in patients with Stargardt dystrophy.

Complications of cholecystectomy: risks of the laparoscopic approach and protective effects of operative cholangiography: a population-based study.

BACKGROUND: Previous studies suggest that laparoscopic cholecystectomy (LC) is associated with an increased risk of intraoperative injury involving the bile ducts, bowel, and vascular structures compared with open cholecystectomy (OC). Population-based studies are required to estimate the magnitude of the increased risk, to determine whether this is changing over time, and to identify ways by which this might be reduced. METHODS: Suspected cases of intraoperative injury associated with cholecystectomy in Western Australia in the period 1988 to 1994 were identified from routinely collected hospital statistical records and lists of persons undergoing postoperative endoscopic retrograde cholangiopancreatography. The case records of suspect cases were reviewed to confirm the nature and site of injury. Ordinal logistic regression was used to estimate the risk of injury associated with LC compared with OC after adjusting for confounding factors. RESULTS: After the introduction of LC in 1991, the proportion of all cholecystectomy cases with intraoperative injury increased from 0.67% in 1988-90 to 1.33% in 1993-94. Similar relative increases were observed in bile duct injuries, major bile leaks, and other injuries to bowel or vascular structures. Increases in intraoperative injury were observed in both LC and OC. After adjustment for age, gender, hospital type, severity of disease, intraoperative cholangiography, and calendar period, the odds ratio for intraoperative injury in LC compared with OC was 1.79. Operative cholangiography significantly reduced the risk of injury. CONCLUSION: Operative cholangiography has a protective effect for complications of cholecystectomy. Compared with OC, LC carries a nearly twofold higher risk of major bile, vascular, and bowel complications. Further study is required to determine the extent to which potentially preventable factors contribute to this risk.

[A methodological study in a space flight simulation context]. / Une etude methodologique lors d'une simulation espace.

To study the effects of isolation and confinement on small groups during long space flights, it is habitual to use closed hyperbaric ground chambers. For the first time, the European Space Agency made use of a nautral environment taking advantage of an Antarctic winter-over at the French Dumont d'Urville Station. The main objective of that study ("International Antarctic Psychological Programme"), was to compare different Russian tests used for training cosmonauts to a W. European approach validated during previous winter studies and European ground chamber simulations. Russian techniques appeared to be oriented to a narrow range of phenomena and unsuited to discern the adjustment to stress conditions.

Misclassification of social disadvantage based on geographical areas: comparison of postcode and collector's district analyses.

BACKGROUND: Analysis of socioeconomic status (SES), defined on the basis of geographical area, will always be subject to misclassification of individuals. We studied the relationship between SES and selected health-related measures when SES was defined firstly on the basis of postcode and secondly on the basis of the smaller spatial area of collector's district (CD). METHOD: A Census population of 1.4 million was used to investigate the misclassification of individuals to SES group using postcode as opposed to CD. A field survey of 1000 respondents and a mortality register of 1756 deaths were used to compare the relationship between SES and certain outcome variables, when SES group was assigned using postcode and CD. Misclassification probability matrices were used to try to adjust the postcode-based results to approximate CD-based results. RESULTS: The Census data showed that nearly 50% of residents were misclassified into SES groups by the postcode-based system compared with a CD-based system. In comparing the most socially disadvantaged group with the least disadvantaged group, the postcode analysis underestimated the absolute effects of SES by 58% for the increased prevalence of smoking, by 19% for the reduced prevalence of participation in junior sporting clubs and by 13% for the increased mortality rate at ages 0-64 years. Adjustment of postcode-based results using misclassification matrices proved fruitless due to differential misclassification and technical difficulties. CONCLUSIONS: Misclassification of individuals to SES groups on the basis of postcode has caused an underestimation of the true relationship between SES and health-related measures. A reduction of this misclassification by using smaller spatial areas, such as CD or census enumeration districts, will provide improved validity in estimating the true relationship.

European isolation and confinement study. Workload and stress: effects on psychosomatic and psychobiological reaction patterns.

Six healthy males, the EMSInauts, were isolated in hyperbaric chambers for a period of 28 days at 5-msw overpressure. During that period they had to carry out meaningful operational and research tasks in addition to monitoring their psychological and physiological reactions. The actual workload was evaluated and compared with the planned workload, and its effects on symptomatology and psychobiology. The perceived workload and its effects on psychosomatic symptomatology and on some biological indices were monitored. Thus it was possible to evaluate how the workload carried during 4 weeks of isolation affected the psychological and biological well-being of the six EMSInauts. The following three types of assessments were performed: 1. Workload assessment: The objective workload was calculated based on the schedule which was revised daily, and the actual load calculated by the commander. A workload questionnaire was administered daily after each working session. 2. Psychosomatic assessment: Morning and evening questionnaires were administered daily. The state of health and of anxiety were also evaluated. 3. Biological indices: Cortisol, testosterone, adrenalin, and noradrenaline were determined once a week. In addition, cardiac activity was monitored every day. The workload assessment showed that on the average the planned workload was accomplished in slightly less than the scheduled time. The workload was not perceived as severe in terms of cognitive, emotional, and physical load. The group rated the support received from each other and from the mission control personnel as average, with minor changes during the isolation period. They gave a high rating to the amount of control they had over their activities. Fatigue and tension were scored in the middle range. The psychosomatic assessment showed that there were few symptoms, and these were mostly of low severity. The most common symptom was general fatigue. Furthermore, minor dizziness, headache and light tremor was in some cases reported. The sleep quality was good, but complaints about poor sleep increased somewhat with the passing of time. Few and mostly minor health problems were experienced during isolation. Only one EMSInaut had to miss one day of work due to a bout of flu. The state of anxiety was below that of the general population throughout the isolation period. The biological indices used showed no evidence of stress from the workload handled during the isolation period. The level of the "stress hormone" cortisol actually decreased during isolation. The adrenalin excretion, which tends to go up during acute stress, remained unchanged during this period. Neither was there any evidence of changes in cardiac activity throughout the isolation period.(ABSTRACT TRUNCATED AT 400 WORDS)

Screening for osteoporosis by bone densitometry: a stratified intervention approach.

We have performed computer modelling of the relationship between bone mass, age and hip fracture in a conditional probability model using a national population of 100,000 postmenopausal women aged 50 who have their bone density measured once. The computer model very closely reproduced the actual number of fractures in a Western Australian population. Intervention to bone loss completely in subjects with the lowest bone density (below 1 SD below the mean) would prevent 0.42 of a hip fracture per patient treated if the whole population were treated. Halving the rate of bone loss in the whole population would reduce hip fracture by two-thirds. These data suggest that hormone replacement therapy, which is the most effective therapy for preventing bone loss but which has the most side effects, should be focused on subjects with bone mass below 1 SD below the mean. The remainder of the population could be targeted with a public health campaign based on the lifestyle factors of increased dietary calcium and exercise which have been shown to slow but not stop bone loss.

Review of the benefits of treating hypertension.

The main points covered in this review are as follows: 1. Hypertension is a major determinant of cardiovascular disease (CVD). As such it is a major cause of mortality, potential years of life lost, morbidity and long-term disability. 2. The incidence of CVD is directly related to BP. It is likely that this extends over the full range of BP although some writers believe that a J-curve of risk exists for CHD. 3. The relationship between long-term disability from CVD and BP requires further study. 4. Because of regression dilution bias, the gradient in risk of stroke and CHD with BP has been underestimated in the past. Recent research suggests that the risk of stroke increases at least tenfold and CHD sixfold over a range of usual DBP of 30 mmHg (equivalent to approximately 50 mmHg baseline DBP). 5. The population attributable risk (PAR) of CVD related to general elevation of BP in the population from a mean daily excess of sodium intake of 100 mmol/day is at least 30%. In typical industrialised countries the PAR for stroke and CHD from clinical hypertension is 36% and 22%, respectively. These estimates of PAR provide a guide to the maximum benefit that could result from either restriction of sodium intake in the whole population or ideal management of all persons with hypertension. In practice such targets are unlikely to be realised. 6. Recent analyses of clinical trials of treatment of hypertension suggest that the risk of stroke is reduced at all levels of initial BP to the extent predicted from observational studies.(ABSTRACT TRUNCATED AT 250 WORDS)