The importance of benign urological disease in communities.
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Adult↗
Biomedical subjects
P Boyle
Publications and source records attributed to P Boyle.
The prevalence of lower urinary tract symptoms in men and women in four centres. The UrEpik study.
OBJECTIVE: To evaluate the epidemiology of lower urinary tract symptoms (LUTS) among men and women, as there are significant unanswered questions about the prevalence and impact of LUTS in different populations. SUBJECTS AND METHODS: A population-based, cross-sectional survey was completed in Boxmeer (the Netherlands), Auxerre (France), Birmingham (UK) and Seoul (Republic of Korea), using culturally and linguistically validated versions of the International Prostate Symptom Score (IPSS). The aim was to estimate the distribution of symptoms of LUTS in men and women. Stratified random samples of men aged 40-79 years in each community were collected. Postal questionnaires were used in Europe and direct interviews in Korea. RESULTS: In all, 4979 index men and 3790 women were recruited, with age-adjusted response rates among men of 72% in Boxmeer, 28% in Auxerre, 60% in Birmingham and 68% in Seoul. The percentages of men and women with an IPSS of 8-35, indicating moderate to severe symptoms, were, respectively, 20.7 and 18.0 (Boxmeer); 19.2 and 12.6 (Auxerre); 25.1 and 23.7 (Birmingham); 16.2 and 19.9 (Seoul). Among women the relationship between symptoms and age was not as strong as in men. The percentages of men and women with moderate to severe symptoms were by age group, respectively, 10.6, 15.5 (40-49); 19.0, 18.2 (50-59); 30.5, 23.8 (60-69); 40.4, 28.7 (70-79). Among those aged 40-49 the main differences between men and women were in the questions about frequency of urination during the day and holding back urine. Among the older groups men reported more symptoms on all questions apart from urination at night and difficulty in holding back urine, both of which were equally prevalent among men and women. CONCLUSIONS: The overall prevalence of LUTS was high and showed no marked cultural variation. Prevalence increased with age, with severe LUTS commoner in older men. Women reported similar levels of the symptoms traditionally associated with LUTS in men. In each age group there were no major cultural differences in the frequency of LUTS. There were differences with age between men and women; younger men had a lower prevalence of LUTS than younger women but older men a much higher prevalence than older women. These findings emphasize that the IPSS should be confined to within-patient comparisons and not used as a diagnostic tool. The IPSS performs very similarly regardless of gender.
Adult↗
The relationship between lower urinary tract symptoms and health status: the UREPIK study.
OBJECTIVES: To assess the hypothesis that as lower urinary tract symptoms (LUTS) increase in severity, the impact as measured by the BPH impact index (BII) would also increase. SUBJECTS AND METHODS: The UREPIK survey collected information on this relationship from men and their partners in the Netherlands, Korea, France and the UK. Culturally and linguistically validated versions of three standard questionnaires, the SF-12, the BII and the International Prostate Symptom Score (IPSS) were used to assess the distribution of symptoms and the impact on health status. Stratified random samples of men aged 40-79 years in each community were recruited. Response rates were 72% in Boxmeer, 28% in Auxerre, 60% in Birmingham and 68% in Seoul. Regression analyses were undertaken on total SF-12, BII and IPSS. RESULTS: In all, 4800 index men and 3674 women responded; the BII increased with increasing IPSS. The correlation coefficients were; Boxmeer 0.69, Auxerre 0.56, Birmingham 0.60 and Seoul 0.68. For women, the correlations were slightly lower except in Birmingham, at 0.65 (Boxmeer), 0.44 (Auxerre), 0.71 (Birmingham), 0.57 (Korea). BII scores were higher in women than in men with the same level of IPSS. Adjusting for IPSS there was no association between age and BII. There was an association between IPSS quality-of-life (QoL) score and BII; for men the correlation was 0.62 and for women 0.60. Men and women with the same score on the IPSS QoL reported the same bother. Among those with an IPSS of 20-35 women expressed significantly more bother (P < 0.001). The SF-12 scores decreased as the IPSS and the BII increased in both men and women. Furthermore, the SF-12 mental score decreased with increasing symptoms in the partner. CONCLUSIONS: The relationship between the severity of LUTS and BII was similar in all centres. There is a clear association between the BII and the IPSS QoL question in men and women. The BII discriminates between people who are unhappy about their urinary condition compared with those who are pleased. Although designed for use in men with benign prostatic hyperplasia, the index also appears to be a useful among women. The severity of symptoms of LUTS has an adverse effect on the health status of the individual and his/her partner.
Adult↗
The association between lower urinary tract symptoms and erectile dysfunction in four centres: the UrEpik study.
OBJECTIVE: To report a large-scale multinational investigation of lower urinary tract symptoms (LUTS) and sexual function, designed to investigate the independent association between them, as recent small-scale epidemiological studies suggest an association between benign prostatic hyperplasia and sexual dysfunction; both conditions are strongly associated with age and no study has been able to exclude age as a confounding factor in this relationship. SUBJECTS AND METHODS: Culturally and linguistically validated versions of standard questionnaires were used to estimate the prevalence of LUTS (using the International Prostate Symptom Score, IPSS) and erectile dysfunction (ED) score (using O'Leary's Sexual Function Inventory) in regions of the UK (Birmingham), the Netherlands (Boxmeer), France (Auxerre) and Korea (Seoul). In each centre, stratified random samples were selected from population registers to provide representative samples of the population of men aged 40-79 years (and their partners) in each community. Direct interviews were held in Seoul and postal questionnaires used in the three European centres. The samples were selected randomly, providing representative samples in each community. RESULTS: In all, 4800 men and 3674 women responded; the response rates among men were 77% in Boxmeer, 21% in Auxerre, 42% in Birmingham and 65% in Seoul. The overall prevalence of ED for men aged 40-79, estimated as an ED score of 0-4, was 21.1%. There was evidence of a linear increase with age (P < 0.001) and the pattern was very similar in the four centres. From the weighted logistic model, there was evidence of an association between sexual dysfunction, other self-reported diseases and lifestyle. From the ED score, after adjusting for age and country, men with diabetes were more likely to score of 0-4 (odds ratio 1.57, 95% confidence interval 1.09-2.25), as were those with high blood pressure (1.38, 1.09-1.75) and with an IPSS of 8-35 (1.39, 1.10-1.74). For lifestyle, smokers were more likely to score 0-4 (1.54, 1.23-1.92), while physical activity during leisure time was slightly associated with a reduction in the chance of scoring 0-4 (0.87, 0.77-0.99). The analysis gave the same results when repeated using self-reported ED instead of the dichotomised score. CONCLUSIONS: ED is clearly age-related and a problem for a large proportion of men in the community. It can have a profound impact on the quality of life of the man and on his partner. Were all men with this problem to seek medical help there would be a large burden on healthcare systems. There are cultural and age effects on the assessment of this problem.
Adult↗
Cancer mortality in Ireland, 1926-1995.
BACKGROUND: Investigation of long time series of cancer data can still be very useful in helping to identify Cancer Control priorities and achievements. Since the partition of Ireland into the independent Republic of Ireland and Northern Ireland, which remained part of the United Kingdom, cancer mortality data have been published in an essentially similar format in both countries. The information presented here will contribute to providing a basis for the collaborative Cancer Research programme initiated recently. PATIENTS AND METHODS: Cancer mortality data have been assembled and analysed separately for the Republic of Ireland and Northern Ireland: the data have then been combined to present mortality rates for the whole of Ireland, covering the period from 1926 to 1995. Several rubrics had to be aggregated to provide data continuously over the time span (e.g. colon and rectum and cervix and body of the uterus). When data were only available in 10-year classes of age, the EM algorithm was employed to obtain 5-year age-specific rates. All rates presented are age-standardised, employing the World Standard Population. RESULTS: In women, the death rate from all neoplasms combined increased very slightly from 117 per 100 000 in 1946-1950 to 120 per 100 000 in 1991-1995. In men, the death rate increased from 127 per 100 000 to 172 per 100 000 over the same time period. The overall cancer death rate in Ireland is currently similar to the European average in men, although in women it is among the top fifth of national cancer mortality rates in European countries. While cancer is a major cause of death in Ireland, there is no evidence of an evolving epidemic building up: the death rates from most forms of cancer are declining towards the end of the time period considered. CONCLUSIONS: As demonstrated by falling death rates from Hodgkin's disease and testicular cancer, major treatment advances appear to have been incorporated effectively into clinical practice in Ireland. Progress is apparent in tobacco control and further initiatives in this area must be undertaken since tobacco appears to be the only major new carcinogen introduced recently into the Irish environment during the period covered by this study. Effective population-based screening programmes for cervix and breast cancer and, more controversially, consideration of a National Prostate Cancer Screening programme, offer scope for further improvement in mortality. Examination of this long time series of mortality data from Ireland provides information about the evolving cancer pattern and provides the necessary background to evaluate the impact of the cross-border cancer research activities now being launched.
Adult↗
Mortality from major cancer sites in the European Union, 1955-1998.
After long-term rises, over the last decade age-standardised mortality from most common cancer sites has fallen in the European Union (EU). For males, the fall was 11% for lung and intestines, 12% for bladder, 6% for oral cavity and pharynx, and 5% for oesophagus. For females, the fall was 7% for breast and 21% for intestines. There were also persisting declines in stomach cancer (30% in both sexes), uterus (mainly cervix, -26%) and leukaemias (-10%). Mortality rates for other common neoplasms, including pancreas for both sexes, prostate and ovary, tended to stabilise. The only unfavourable trends were observed for female lung cancer (+15%). Lung cancer rates in women from the EU are approximately one-third of those in the USA, and 50% lower than breast cancer rates in the EU. Lung cancer rates in European women have also tended to stabilise below the age of 75 years. Thus, effective interventions on tobacco control could, in principle, avoid a major lung cancer epidemic in European women.
Adolescent↗
European Code Against Cancer and scientific justification: third version (2003).
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Adult↗
Cancer mortality trends in the EU and acceding countries up to 2015.
BACKGROUND: Examination of trends in cancer mortality in Europe over the past 30 years has shown that, after long-term rises, age-standardised mortality from most common cancer sites has fallen in the EU since the late 1980s. This study aimed to examine trends in the age-specific and age-standardised cancer mortality rates and numbers of cancer deaths up to 2020 for all cancers and various specific sites for all 15 EU countries, the 10 acceding countries, Bulgaria and Romania (currently applicant countries, along with Turkey), and Iceland, Norway and Switzerland of the four EEA countries. PATIENTS AND METHODS: Mortality rates were modelled as a function of age, calendar period and birth cohort. Birth cohort was calculated as age subtracted from calendar period. RESULTS: As a consequence of the generally decreasing trends in the age-standardised rates, the best estimate is that there will be approximately 1.25 million cancer deaths in 2015, which is almost 130,000 (11%) more deaths than in 2000, but 155,000 (11%) fewer deaths than the 1.4 million projected in 2015 on the basis of demographic changes alone. The increases in the forecast numbers of cancer deaths in 2015 are proportionally larger in males than in females (13% and 10%, respectively) and proportionally larger in the acceding countries than in the current EU member countries (14% and 11%, respectively). CONCLUSIONS: Our forecasts are conservative best estimates of future cancer mortality. There is clearly scope for large improvements in survival, and hence reductions in cancer mortality, in some countries, through eliminating these differences using existing knowledge and treatment regimes.
Adolescent↗
Global summit on mammographic screening.
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Breast Neoplasms↗
Measuring progress against cancer in Europe: has the 15% decline targeted for 2000 come about?
BACKGROUND: Against a background of increasing cancer rates in the mid-1980s, Europe Against Cancer launched an ambitious programme aiming to reduce cancer mortality by 15% by the year 2000. A programme of activities and research, focussing on three major themes [prevention (particularly tobacco control), screening, and education and training], was developed together with the European Code Against Cancer. METHODS: To evaluate the outcome of the programme, all cancer mortality data were abstracted for each member state of the European Union (EU) until the most recent year available. For each gender group in each member state, age-specific rates were estimated for 2000. For each country-gender grouping, the standardized mortality rate (SMR) and expected numbers of deaths in 2000 were calculated based on the age-specific rates for 1985 and the population estimates for 2000. The ratio of the SMR in 2000 to that of 1985, was used as the measure to compare mortality rates. RESULTS: In 1985, there were 850 194 cancer deaths in the EU. Based solely on demographic considerations, this number was expected to rise to 1 033 083 in the year 2000. Between 1985 and 2000, the number of cancer deaths increased in both men (+12%) and women (+9%). The target of a 15% reduction in the expected numbers of cancer deaths in the EU was not met, although the 10% reduction in number of deaths expected in men and 8% in women, along with a 11% reduction in risk of cancer death in men and a 10% reduction in women, was noteworthy. Only Austria and Finland achieved the 15% reductions in deaths in both men and women. The UK and Luxembourg (where the small population and annual number of deaths make interpretation difficult) came close to meeting these targets, as did Italy. Portugal and Greece had the poorest performance, with increases in each gender group. CONCLUSIONS: Cancer deaths in the EU were expected to rise from 850 194 in 1985 to 1 033 083 in 2000. It is estimated that there will be 940 510 cancer deaths that year, due to the decline in risk observed since 1985. The Europe Against Cancer programme appears to have been associated with the avoidance of 92 573 cancer deaths in the year 2000. With few exceptions, most countries are experiencing declining trends in cancer death rates, which seem set to continue, at least in the near future. Renewed tobacco control efforts are clearly needed for women, and there is a strong case for the introduction of organized breast and cervix screening programmes in all member states. Continuing to emphasize prevention within cancer control will help to promote the continuing decline in death rates in the future.
Adolescent↗
Androgenetic alopecia in men aged 40-69 years: prevalence and risk factors.
BACKGROUND: The epidemiology of androgenetic alopecia (AGA) is not fully understood. Although a strong genetic basis has long been identified, little is known of its non-genetic causes. OBJECTIVES: To estimate the prevalence of and to determine risk factors for AGA in men aged 40-69 years in Australia. METHODS: Men (n = 1390) were recruited at random from the electoral rolls to serve as controls in a population-based case-control study of prostate cancer. All were interviewed in person and direct observations of AGA were made. Men were grouped into the following categories; no AGA, frontal AGA, vertex AGA and full AGA (frontal and vertex AGA). Epidemiological data collected from these men were used for an analysis of risk factors for each AGA category using unconditional logistic regression with AGA category as the response variable adjusting for age, education and country of birth. RESULTS: The prevalence of vertex and full AGA increased with age from 31% (age 40-55 years) to 53% (age 65-69 years). Conversely, the proportion of men with only frontal AGA was very similar across all age groups (31-33%). No associations were found between pubertal growth spurt or acne, reports of adult body size at time of interview, urinary symptom score, marital status, or current smoking status or duration of smoking and the risk of any form of AGA. The consumption of alcohol was associated with a significant increase in risk of frontal and vertex AGA but not full AGA. Men with vertex AGA had fewer female sexual partners but average ejaculatory frequency did not differ between men in different AGA categories. Reported weight and lean body mass at reaching maturity at about 21 years of age were negatively associated with vertex balding (P for trend < 0.05) but not with frontal AGA or full AGA. CONCLUSIONS: Evidence for environmental influences on AGA remains very slight. Our study failed to confirm previously reported or hypothesized associations with smoking and benign prostatic hypertrophy. The associations that we found with alcohol consumption and with lean body mass at age 21 years would be worthy of further research if they were able to be replicated in other studies.
Adult↗
The prevalence of male urinary incontinence in four centres: the UREPIK study.
OBJECTIVES: To report the results of the prevalence and health status associated with male urinary incontinence (UI) in a population-based, multicentre study in four countries, and to assess the epidemiology of this condition. SUBJECTS AND METHODS: A standard questionnaire asking about frequency and amount of urine loss, use of pads and stress incontinence, was used to measure the prevalence of UI among men in four countries (Boxmeer, The Netherlands; Auxerre, France; Birmingham, UK; and Seoul, Korea). Self-reported urinary leakage was also recorded, with details of visits to the doctor for the symptoms. The samples were selected randomly from population registers of men aged 40-79 years, which provided representative samples in each community. RESULTS: In all, 4979 men responded; from incontinence symptom scores, 7.3% of men aged 40-79 years in Auxerre, 16.3% in Boxmeer, 14.4% in Birmingham and 4.3% in Seoul reported mild to severe UI. On a self-reported question, 14.8% and 14.5% of men in Birmingham and Boxmeer thought that they had urinary leakage, compared with 7.5% and 7.1% of men in Auxerre and Seoul, but typically the reported incontinence was leaking drops of urine a few times a week. Of men with urinary leakage in the three European centres, 25.9% visited the doctor with this problem, compared with only 9.0% of men in Seoul. Of men in the European centres, 5.9% used pads at least occasionally, compared with only 1.6% of men in Seoul. UI was age-related and the reporting of it varied among centres, with 14.4% of men in Birmingham and 12.7% of men in Boxmeer aged 40-49 years reporting mild to severe UI, compared with 5.2% in Auxerre and 1.9% in Seoul. Among men aged 60-69 years the corresponding percentages were 13.7% in Birmingham, 22.6% in Boxmeer, 9.2% in Auxerre and 8.0% in Seoul. CONCLUSIONS: UI is more common in older men and relatively uncommon among younger men. Some men reported no problems on the symptom questionnaire but replied positively to a direct question. Surprisingly many men wear protective pads at least occasionally as a result of their problem. UI appears to be a problem for men and which remains largely untreated; this may partly be a result of cultural differences.
Adult↗
Screening.
Screening for cancer is currently entering a very promising period as new technologies become available for assessment. However, this great opportunity also presents significant problems, starting with how do you select the likeliest method for evaluation? How do you do trials where the technology will be out-moded by the time the result is known? Indeed, how can all promising technologies be evaluated? There is a need for a renewal of methodological thinking on this topic at present. Randomised trials, which currently rely on death as the primary outcome, are very long and very complicated to undertake and run. There is an urgent need for biological markers, which are true surrogate end-points, to help reduce sample size and make trials more feasible, so that more trials can be done. For those screening modalities of demonstrated effectiveness, the key issue at present is how to maximise the outcome in population screening when the technology is transferred from the research setting to the public health setting. It is essential to remember that screening, per se, has never prevented a cancer nor prevented a cancer death. It is impossible to separate the issues of screening with those of adequate treatment: the best results in a screening programme will come when treatment is excellent. Screening is the first, and sometimes key, stage in a global management programme for the cancer in question. As the aim at present is to strive to maximise the effectiveness of population-based programmes, this aspect should be foremost in all thought processes.
Biomarkers, Tumor↗
Meta-analysis of clinical trials of Cyclo 3 Fort in the treatment of chronic venous insufficiency.
AIM: Chronic venous insufficiency (CVI) of the lower limbs is a major cause of morbidity and varicose veins affect 20% to 60% of adults in the western world. The treatment of patients with CVI attempts to reduce both clinical symptoms and the development of chronic venous disease. A meta-analysis using data from all clinical trials and studies of Cyclo 3 Fort, a combination of root extract of the Ruscus aculeatus plant (150 mg per capsule), hesperidin methyl chalcone (150 mg) and ascorbic acid (100 mg), was carried out to estimate the overall effect on the symptoms and severity of chronic venous insufficiency. METHODS: The meta-analysis included 20 placebo controlled, randomised, double blind studies and 5 randomised studies against a comparator drug. There were 6 single arm studies of Cyclo 3 Fort alone with no placebo arm. In all studies the response to Cyclo 3 Fort was compared to baseline values. In total there was information from 10,246 subjects. RESULTS: On a 4 point symptom severity scale, where 0 corresponds to no symptoms and 3 to severe symptoms, Cyclo 3 Fort significantly reduces the severity of pain by 0.44 (0.12) points; cramps 0.26 (0.08), heaviness 0.53 (0.11), and paraesthesia 0.29 (0.10) compared to placebo. There is also a significant reduction in venous capacity of 0.70 (0.19) ml/100 ml with Cyclo 3 Fort compared to placebo. We also found reductions in the severity of oedema 0.43 (0.20) points, and decreases in calf and ankle circumference, 0.73 (0.37) cms and 1.17 (0.83) cm, respectively, among patients treated with Cyclo 3 Fort compared to placebo which were not statistically significant. CONCLUSION: Despite questions surrounding the variability of data quality and sample size of some of the studies, we conclude that in patients with CVI Cyclo 3 Fort significantly reduces the severity of the symptoms compared to placebo. This study is a strong and objective demonstration of the clinical efficacy of Cyclo 3 Fort in treating patients with CVI.
Adult↗
Alcohol, tobacco and breast cancer--collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease.
Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58,515 women with invasive breast cancer and 95,067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19-1.45, P<0.00001) for an intake of 35-44 g per day alcohol, and 1.46 (1.33-1.61, P<0.00001) for >/=45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1% per 10 g per day, P<0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers=1.03, 95% CI 0.98-1.07, and for current smokers=0.99, 0.92-1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver.
Adult↗
Trends in mortality from Hodgkin's disease in western and eastern Europe.
Hodgkin's disease mortality rates steadily declined by about 75% between the late 1960's and the late 1990's in the current European Union countries and the USA, and Japan. Eastern European countries, however, showed only an approximately 40% decline between the late 1960's and the early 1990's, and no further fall thereafter.
Adolescent↗
Tamoxifen for breast cancer among hysterectomised women.
Tamoxifen is a candidate drug for prevention of breast cancer, although findings from trials have not been consistent. In our extended follow-up (median 81.2 months, IQR 66.0-87.2) of the Italian Tamoxifen Trial, this drug did not significantly protect against breast cancer in women at usual or slightly reduced risk of the disease (p=0.215). Use of hormone replacement therapy increased risk of breast cancer, and users of such treatment who were randomly allocated to tamoxifen had a rate of breast cancer that was close to that of never-users. So far, no woman has died from breast cancer in this study. Decisions about introduction of tamoxifen to reduce risk of breast cancer remain important and open questions.
Anticarcinogenic Agents↗
[Prevalence of lower urinary tract disorders and incontinence in Auxerre. French segment of the UrEpik study].
OBJECTIVES: To estimate the prevalence of low urinary tract symptoms (LUTS) and urinary incontinence among men and women aged 40 to 79 years. METHODS: A postal survey was carried out in a community-dwelling random sample, in Auxerre, France. LUTS were assessed using the International Prostate Symptom Score (IPSS). Urinary incontinence (UI) was assessed using a score based upon four questions. RESULTS: 1216 men and 591 women participated in the survey. 19.2% of men and 13.7% of women reported moderate to severe LUTS (IPSS > 7). 73% of men and 29% of women suffered from UI. Among men and women reporting severe symptoms of UI (0.4 and 5.4% respectively), one third had been prescribed medications for urinary disorders within the previous six months. CONCLUSION: This survey confirms the high prevalence of LUTS and urinary incontinence among a community-dwelling sample of men and women, and highlights the need for management of these disorders.
Adult↗