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Prevalence of genotypic and phenotypic HIV-1 drug-resistant strains among patients who have rebound in viral load while receiving antiretroviral therapy in the UNAIDS-Drug Access Initiative in Abidjan, Côte d'Ivoire.

OBJECTIVE: To determine the prevalence of genotypic and phenotypic antiretroviral (ARV) drug-resistant HIV-1 strains among patients with viral load rebound while receiving ARV therapy in Abidjan, Côte d'Ivoire. METHODS: Between August 1998 and April 2000, we selected all patients (n = 241) who had received ARV drug therapy for at least 6 months in the UNAIDS-Drug Access Initiative (DAI), in Abidjan. We analyzed for genotypic and phenotypic drug resistance among 97 (40%) of the 241 patients who had a rebound in plasma viral load, defined as an initial decrease of > 0.5 log10 copies/ml followed by a subsequent increase of > 0.25 log10 copies/ml. RESULTS: Of the viruses isolated from the 97 patients, 86 (88.7%) had usable sequences and 68 (79%) of the 86 patients had genotypic resistance to at least one reverse transcriptase inhibitor (RTI) or protease inhibitor (PI). Resistant mutations were found for zidovudine in 50 (78%) of 64 patients who had received the drug, 11 (68.7%) of 16 patients on lamivudine, for nevirapine in two (2%), for indinavir in one (1%), and for ritonavir in one (1%). Phenotypic resistance to at least one nucleoside RTI was seen in 45 (56%) of the 80 patients tested, to non-nucleoside RTIs in eight (10%), and to PIs in one (1.3%). Multivariate regression analysis showed factors associated with resistance to be initial treatment with dual therapy (P = 0.04) compared with highly active antiretroviral therapy, and maximal initial viral load response (P = 0.006). CONCLUSION: Our results demonstrate a high prevalence of ARV drug resistance associated with dual ARV therapy. These results indicate the limited role for dual ARV therapy.

Adult↗

Environmental factors in inflammatory bowel disease: a co-twin control study of a Swedish-Danish twin population.

BACKGROUND: Genetics and environmental factors are implicated in the etiology of inflammatory bowel disease (IBD). We studied environmental factors in a population-based Swedish-Danish twin cohort using the co-twin control method. SUBJECTS AND METHODS: A questionnaire was sent to 317 twin pairs regarding markers of exposures in the following areas: infections/colonization and diet as well as smoking, appendectomy, and oral contraceptives. Odds ratios (OR) were calculated by conditional logistic regression. When confounding appeared plausible, multivariate conditional logistic regression was added. The questions were also divided into topic groups, and adjustment was made for multiple testing within each of the groups. RESULTS: The response rate to the questionnaire was 83%. In consideration of the study design, only discordant pairs were included (Crohn's disease [CD], n = 102; ulcerative colitis [UC], n = 125). Recurrent gastrointestinal infections were associated with both UC (OR, 8.0; 95% confidence interval [CI], 1.0-64) and CD (OR, 5.5; 95% CI, 1.2-25). Hospitalization for gastrointestinal infections was associated with CD (OR, 12; 95% CI, 1.6-92). Smoking was inversely associated with UC (OR, 0.4; 95% CI, 0.2-0.9) and associated with CD (OR, 2.9; 95% CI, 1.2-7.1). CONCLUSIONS: The observed associations indicate that markers of possible infectious events may influence the risk of IBD. Some of these effects might be mediated by long-term changes in gut flora or alterations in reactivity to the flora. The influence of smoking in IBD was confirmed.

Adult↗

Family communication and mental health after breast cancer.

In the context of a traumatic event, such as a breast cancer diagnosis, talking with others about the event can facilitate emotional adjustment and meaning-finding. Among women with a history of breast cancer, open communication is likely to be of particular importance in the family setting, as the family is frequently a primary source of support. The goal of this cross-sectional survey study was to determine the association between open family communication about cancer and breast cancer survivors' mental health. Responses from 230 women at various stages post-treatment suggest that the majority of women are able to talk openly with their family about breast cancer. Multivariate regression analysis further indicates that open family communication is independently associated with better mental health outcomes. Given that many women live long after a breast cancer diagnosis, maintaining mental health functioning is an important long-term goal. Efforts to enhance productive communication between patients and their family members may help women cope with and overcome the challenges of breast cancer survivorship.

Adaptation, Psychological↗

Oxidized LDL and small LDL particle size are independently predictive of a selective defect in microcirculatory endothelial function in type 2 diabetes.

AIM: To explore the associations of LDL (low-density lipoprotein) particle size and oxidized LDL with endothelium-dependent function of the forearm microcirculation in diabetes. METHODS: Endothelium-dependent function was examined in 43 middle-aged men and women with type 2 diabetes and 10 age-matched controls. All received aspirin to inhibit endothelial cyclo-oxygenase. Forearm blood flow (FBF) was measured using venous occlusion plethysmography with separate administration of acetylcholine (ACh) and bradykinin (BK) into the brachial artery. Endothelium-independent function was assessed using sodium nitroprusside (SNP). N(G)-monomethyl-L-arginine (L-NMMA) was co-infused with ACh (ACh + L-NMMA) and BK (BK + L-NMMA) to assess non-NO-mediated contributions to endothelium-dependent function. RESULTS: Subjects with diabetes had impaired endothelium-dependent and endothelium-independent function compared with controls (p < 0.01 for ACh, BK and SNP). In multivariate regression analysis, LDL size (r = 0.41 and p = 0.007), oxidized LDL (r = -0.41 and p = 0.007) and duration of diabetes (r = -0.37 and p = 0.02) predicted FBF response to ACh independently of age, gender and systolic blood pressure. There were no associations between LDL size, oxidized LDL, duration of diabetes and FBF response to BK, SNP, ACh + L-NMMA or BK + L-NMMA. CONCLUSION: In type 2 diabetes, small dense LDL particles, duration of diabetes and oxidized LDL may independently contribute to endothelial dysfunction of the microcirculation. These disturbances may occur via a selective defect, because ACh and BK activate endothelial NO synthase via different G-protein signal transduction pathways.

Acetylcholine↗

Mortality of Swedish horses with complete life insurance between 1997 and 2000: variations with sex, age, breed and diagnosis.

The aim of this study was to evaluate the potential usefulness of the database maintained by the Swedish insurance company Agria for providing mortality statistics on Swedish horses. Mortality statistics (incidence rates and survival) were calculated, both crudely and stratified by sex, age, breed, breed group and diagnosis, for the horses with complete life insurance, which covers most health problems. The total mortality was 415 (95 per cent confidence interval [CI] 399 to 432) deaths per 10,000 horse-years at risk, and the diagnostic mortality, including only deaths with an assigned diagnosis, was 370 (95 per cent CI 355 to 386) deaths per 10,000 horse-years at risk. The diagnostic mortality of geldings was 459 (95 per cent CI 431 to 487), of mares 345 (95 per cent CI 322 to 365) and of stallions 214 (95 per cent CI 182 to 247) deaths per 10,000 horse-years at risk. The mortality rates increased with age and differed widely between breeds. Survival analysis showed that the median age at death of the horses enrolled before they were one year of age was 18.8 years. The most common cause of death or euthanasia was joint problems, which were responsible for 140 (95 per cent CI 130 to 149) deaths per 10,000 horse-years at risk. The results of multivariable models developed by using Poisson regression generally agreed well with the crude results.

Age Distribution↗

Prognostic significance of changes in short-term prostate volume and serum prostate-specific antigen after androgen withdrawal in men with metastatic prostate cancer.

OBJECTIVE: Endocrine therapy is the standard treatment for metastatic prostate cancer although progression to androgen independence is inevitable. To evaluate prognostic factors in metastatic prostate cancer, patients who had been treated with endocrine therapy were investigated especially for the change in prostate volume. METHODS: Fifty-nine patients with untreated metastatic prostate cancer who received endocrine therapy were included in the present study. Blood chemistry, histological grade, extent of bony metastasis, clinical response to hormone therapy including the short-term change in prostate volume and serum prostate-specific antigen (PSA), and prognosis of the patients were evaluated. RESULTS: With univariate analysis, hemoglobin concentration, serum alkaline phosphatase, lactate dehydrogenase (LDH), histological grade, extent of bony disease, the short-term change of prostate volume and response of PSA at 3 months were shown to be significant prognostic factors. Response of PSA, LDH and the change in prostate volume were significant for predicting prognosis with multivariate analyses. Five-year survival rate in patients whose prostate had regressed 20% or more at 1 month and whose PSA had been normalized at 3 months was 67%, whereas that in patients whose prostate had regressed less than 20% and whose PSA had not been normalized was 0%. CONCLUSIONS: The patients in whom PSA had not been normalized at 3 months and the prostate volume had regressed less than 20% at 1 month were in the high-risk group. New or more aggressive treatment should be considered.

Aged↗

Gender, weight concerns, and adolescent smoking.

This study examined the beliefs that adolescents' hold regarding smoking and weight. In particular, this study examined the relationship between smoking status and self-perceptions of body weight. In addition, it examined gender and age differences in adolescent male and female smokers' beliefs about smoking and weight control. Analyses were conducted on the telephone interview responses of 1,200 adolescent smokers and nonsmokers between the ages of 12 and 17. Chi-square analyses were utilized for univariate comparisons, and logistic regression for multivariate comparisons. Results revealed gender and age differences in perceptions of body weight. In addition, female smokers were more likely than male smokers to adhere to the belief that smoking controlled weight. While no relationship was observed between males' perceived weight and their smoking status, females who perceived themselves to be either overweight or underweight were more likely to smoke. Findings suggest a gender bias in processing social/environmental cues linking smoking and weight control.

Adolescent↗

DNA-ploidy abnormalities are a reflection of the metastatic potential of malignant melanoma. Microfluorometric DNA analysis.

Using DAPI (4',6-diamidino-2-phenylindole)-DNA microfluorometry, we examined the nuclear DNA-ploidy abnormalities of 15 primary malignant melanomas and their 20 corresponding metastases. They all presented the aneuploid DNA histographic pattern. When the DNA index value was calculated as the reflection of DNA-ploidy abnormalities, it was found to be significantly higher in the metastases (2.07 +/- 0.50) than in the primary tumors (1.76 +/- 0.50) (p < 0.01). Sixteen (80%) of the metastatic tumors had a higher DNA index value than their primary tumors, whereas the remaining four (20%) had a lower value. The difference in the DNA index values between the primary and metastatic tumors did not correlate to any other conventional prognostic variables (e.g. histologic type, level, and thickness). When we added 15 non-metastatic melanomas to the above 15 primary melanomas and evaluated the predictors for metastasis using multivariate stepwise logistic regression analysis, the DNA index value of the primary melanomas was found to be the most reliable risk factor. These results suggest that primary melanoma cell populations, having high DNA index values, are usually responsible for subsequent metastasis, and that hence, DNA-ploidy abnormalities of primary melanomas are likely to provide useful information for patient potential with regard to metastasis.

Adult↗

Work-to-family spillover and fruit and vegetable consumption among construction laborers.

PURPOSE: Spillover is the effect of one role on another as working adults attempt to integrate demands from work and family. We conducted a survey to understand how worker, job, and family characteristics were related to negative work-to-family spillover and how spillover was related to fruit and vegetable consumption to inform intervention design. DESIGN: A combined mail and telephone survey. SETTING: A national random sample in the United States. SUBJECTS: 1108 (44% response) unionized construction laborers. MEASURES: Personal characteristics, job factors, family factors, work-to-family spillover, and fruit and vegetable consumption. ANALYSIS: Multivariable logistic and least-squares regression. RESULTS: A range of 20% to 50% of respondents reported negative work-to-family spillover, agreeing that work demands, time, fatigue, and stress interfered with family meals or food choices. Higher spillover was associated with job factors, being of white race/ethnicity, and having children at home. Lower fruit and vegetable consumption was associated with higher work-to-family spillover (p = .002), being of white race or ethnicity (p < .0001), and working the graveyard or day shift (p = .02). CONCLUSION: Negative experience of work-to-family spillover may link employment to fruit and vegetable consumption and thus to worker health. Understanding the contribution of spillover to fruit and vegetable consumption aids understanding of how work experience affects health.

Adult↗

Vascular endothelial growth factor is associated with the efficacy of endocrine therapy in patients with advanced breast carcinoma.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a mediator of angiogenesis and is associated with a poor prognosis in patients with primary breast carcinoma. In the current study, the authors investigated whether there was an association between VEGF levels in tumor tissues and response rates to first-line, systemic therapy in patients with advanced breast carcinoma. METHODS: In 172 tumors from patients with primary breast carcinoma who developed distant metastases during follow-up, cytosolic levels of VEGF were measured using a quantitative enzyme-linked immunosorbent assay. Patients received either endocrine therapy (n = 96) or chemotherapy (n = 76) as first-line treatment after they were diagnosed with advanced disease. RESULTS: In univariate logistic regression analysis for response to endocrine therapy in 96 patients, an increasing level of VEGF, as a log-transformed, continuous variable, was correlated with a poor rate of response (P = 0.043). In multivariate analysis, a significantly lower rate of response to first-line endocrine therapy was found for patients who had high VEGF levels compared with patients who had low VEGF levels (P = 0.025). Similar results were found for the subgroup of 82 patients who received tamoxifen (P = 0.011). An association of VEGF with response to first-line endocrine therapy was found in addition to a predictive impact for estrogen receptor/progesterone receptor status (P = 0.027). VEGF levels did not predict the rate of response to first-line chemotherapy. CONCLUSIONS: The results demonstrated that the level of VEGF affects response to endocrine therapy independent of steroid hormone receptor status and may help to refine further the indication for this treatment in individual patients. Further studies are warranted to explain this underlying resistance to endocrine therapy.

Adult↗

Ingested inorganic arsenic and prevalence of diabetes mellitus.

To examine the association between ingested inorganic arsenic and prevalence of diabetes mellitus, in 1988, the authors studied 891 adults residing in villages in southern Taiwan where arseniasis is hyperendemic. The status of diabetes mellitus was determined by an oral glucose tolerance test and a history of diabetes regularly treated with sulfonylurea or insulin. The cumulative arsenic exposure in parts per million-years was calculated from the detailed history of residential addresses and duration of drinking artesian well water obtained through standardized interviews based on a structured questionnaire and the arsenic concentration in well water. The body mass index was derived from body height and weight measured according to a standard protocol, while the physical activity at work was also obtained by questionnaire interviews. Residents in villages where the chronic arseniasis was hyperendemic had a twofold increase in age- and sex-adjusted prevalence of diabetes mellitus compared with residents in Taipei City and the Taiwan area. There was a dose-response relation between cumulative arsenic exposure and prevalence of diabetes mellitus. The relation remained significant after adjustment for age, sex, body mass index, and activity level at work by a multiple logistic regression analysis giving a multivariate-adjusted odds ratio of 6.61 and 10.05, respectively, for those who had a cumulative arsenic exposure of 0.1-15.0 and greater than 15.0 ppm-year compared with those who were unexposed. These results suggest the chronic arsenic exposure may induce diabetes mellitus in humans.

Adult↗

Stochastic modeling of apoptosis tolerance distributions measured by multivariate flow analysis of human leukemia cells.

BACKGROUND: Cytofluorometric analysis allows single-cell resolution of all-or-none programmed cell death (apoptosis) responses and permits direct measurement of cumulative frequency distributions (CFDs) of apoptosis sensitivity from which the median apoptosis tolerance can be estimated. Robust estimation of susceptibility to apoptosis within neoplastic cell populations provides a means of either accurately determining pharmacologically induced changes in apoptosis sensitivity or comparing cell population responses to different apoptosis inducers. METHODS: Experimentally determined CFDs for VP-16 (etoposide)-induced apoptosis were measured by phosphotidylserine surface expression and mitochondrial membrane potential dissipation (DeltaPsi(m)) in BV173 leukemia cells. CFDs were modelled by a modified Hill equation using a four-parameter nonlinear regression from which median apoptosis tolerance (K) was estimated. RESULTS: Median apoptosis tolerance (K) was estimated from nonlinear regression analysis of CFDs for DeltaPsi(m) collapse and loss of membrane asymmetry. The error distribution of K determined from nonlinear regression analysis of 100 simulated CFDs was shown to exhibit an asymmetrical distribution. The asymmetrical likelihood intervals for K were computed iteratively, thereby providing a measure of experimental error. CONCLUSIONS: A distribution-based approach to apoptosis assay using multivariate flow analysis offers a powerful, quantitative technique for investigating the phenotypical basis of neoplastic cell responsiveness to apoptosis therapy, permitting separation of cell populations on the basis of apoptosis susceptibility.

Apoptosis↗

Quality of life may be affected more by disease parameters and response to therapy than by haemoglobin changes.

Earlier studies showing a negative impact of anaemia on quality of life (QOL) lack adequate adjustment for confounding factors such as disease stage and tumour response. We examined the impact of haemoglobin concentration on QOL scores of 745 multiple myeloma patients followed from diagnosis, adjusting for objective disease parameters. Data from two Nordic studies with the EORTC QLQ-C30 questionnaire were analysed using linear regression analysis. Haemoglobin was independently related only to fatigue at baseline (P = 0.001) and at 12 months (P = 0.010). In multivariate analysis, extent of skeletal disease was at least as strong a predictor for fatigue at diagnosis as haemoglobin and was also related to other important QOL scores such as physical functioning, role functioning, global QOL and pain (P < 0.001). At 12 months' follow-up, response to therapy was related to physical functioning (P < 0.001) and pain (P = 0.001). In conclusion, haemoglobin and extent of skeletal disease were both predictors for fatigue in patients with newly diagnosed multiple myeloma, but extent of skeletal disease was also associated with other important QOL scores. During follow-up, response to therapy emerged as an important predictor variable. When examining the effect of haemoglobin on QOL, it is essential to adjust for disease parameters and response to therapy in order not to overestimate the impact of haemoglobin on QOL. Our findings imply that uncontrolled studies on the effect of erythropoietin (EPO) in cancer patients may be making exaggerated claims for the effect of EPO on QOL.

Adult↗

Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors.

Multivariable regression models are powerful tools that are used frequently in studies of clinical outcomes. These models can use a mixture of categorical and continuous variables and can handle partially observed (censored) responses. However, uncritical application of modelling techniques can result in models that poorly fit the dataset at hand, or, even more likely, inaccurately predict outcomes on new subjects. One must know how to measure qualities of a model's fit in order to avoid poorly fitted or overfitted models. Measurement of predictive accuracy can be difficult for survival time data in the presence of censoring. We discuss an easily interpretable index of predictive discrimination as well as methods for assessing calibration of predicted survival probabilities. Both types of predictive accuracy should be unbiasedly validated using bootstrapping or cross-validation, before using predictions in a new data series. We discuss some of the hazards of poorly fitted and overfitted regression models and present one modelling strategy that avoids many of the problems discussed. The methods described are applicable to all regression models, but are particularly needed for binary, ordinal, and time-to-event outcomes. Methods are illustrated with a survival analysis in prostate cancer using Cox regression.

Clinical Trials as Topic↗

Beliefs as predictors of condom use by injecting drug users in treatment.

This study was conducted to clarify (1) the extent to which health beliefs selected from Protection Motivation Theory can combine to correctly classify 72 injecting drug users (IDUs) as condom users or non-users and (2) which of the beliefs ('vulnerability to a regular partner', 'vulnerability to a casual partner', 'self-efficacy', 'response efficacy', 'response costs' and 'social norms') were most influential in this distinction. Results of a logistic regression indicated that these beliefs were significant predictors of condom use. Overall, 83.3% of participants were correctly classified according to condom use, with condom 'non-users' being more accurately predicted (94.0%) than 'users' (59.1%). 'Vulnerability to a regular partner' and 'social norms' were significant multivariate and univariate predictors of condom use, and 'response costs' were significant univariate predictors. IDUs were confident of their ability to use condoms, considered themselves highly vulnerable to HIV infection from casual partners and were confident in the efficacy of condoms to protect them from AIDS. However, the majority of IDUs were not condom users, particularly with 'regular' partners. Findings suggest that HIV prevention programmes should target beliefs regarding risks from known partners, perceived norms and negative consequences of condom use in order to increase condom use by IDUs in treatment.

Adult↗

Her-2/neu and EGFR tyrosine kinase activation predict the efficacy of trastuzumab-based therapy in patients with metastatic breast cancer.

Her-2/neu overexpression in human breast cancer leads to an aggressive biological behavior and poor prognosis. Although the anti-Her-2/neu antibody trastuzumab (Herceptin(R)) has become a valuable therapeutic option for patients with Her-2/neu-overexpressing breast cancer, many patients do not benefit from this therapy. To evaluate the effect of receptor activation on tumor response, we have investigated the phosphorylation status of Her-2/neu and EGFR in 46 Her-2/neu-overexpressing tumor samples from trastuzumab-treated metastatic breast cancer patients by immunohistochemistry. Activated (p)tyr-1248 Her-2/neu was detected in 9 of 46 breast cancers (20%), and activated (p)tyr-845 and (p)tyr-1173 EGFR were both present in 6 tumors (13%) while EGFR was present in 16 cases (35%). ptyr-1248 Her-2/neu showed a trend to correlate with increased response to trastuzumab (p = 0.063), while ptyr-845, ptyr-1173 EGFR and EGFR did not. The presence of ptyr-1248 Her-2/neu and ptyr-845 or ptyr-1173 EGFR, however, was a strong predictor of both response to trastuzumab-based treatment (OR = 8.0, p = 0.021 and OR = 8.0, p = 0.021) and clinical benefit (OR = 5.47, p = 0.041 and OR = 6.22, p = 0.028 multivariate logistic regression analysis). Furthermore, ptyr-845 EGFR and ptyr-1248 Her-2/neu were both independent predictors of progression-free survival (RR = 0.21, p = 0.01 and RR = 0.45, p = 0.026, multivariate analysis). Patients with ptyr-845 EGFR positive tumors also tended toward increased overall survival (RR = 0.17, p = 0.082). Taken together, we have demonstrated that the determination of activated EGFR improves the utility of ptyr-1248 Her-2/neu staining in predicting the clinical outcome of patients undergoing trastuzumab treatment. We hypothesize that the activation state of both Her-2/neu and EGFR are key determinants for trastuzumab efficacy.

Adult↗

Predictive factors for response to medical therapy in bacterial ulcerative keratitis.

BACKGROUND: Fifty-four consecutive cases of culture-positive bacterial ulcerative keratitis presenting at a major university hospital were reviewed to identify factors predictive of response to medical therapy for bacterial ulcerative keratitis (BUK). METHODS: Eleven patients (20%) failed medical therapy (defined as the need for surgical intervention or cyanoacrylate gluing). Using multivariate logistic regression, the following variables were evaluated: (1) predisposing ocular factors (e.g., contact lens wear), (2) pre-existing ocular diseases, (3) ulcer size, and (4) the number of topical ocular medications used at the time of presentation. RESULTS: We noted certain factors to be potentially predictive of medical therapy outcome. The average size of the ulcer at the time of presentation was 4.4 +/- 2.4 mm in the failure group but only 2.5 +/- 1.9 mm for the success group (P = 0.027). In addition, patients in the medical failure group used more topical ocular medications at the time of presentation (P = 0.0075). Further analysis of the individual topical ocular medications revealed that the use of corticosteroids was higher in the failure group (56% vs 12%, P = 0.0005 by Fisher's exact test). Other factors such as patient age, the type of organism(s), and the time elapsed between the onset of symptoms and the beginning of definitive therapy were not statistically significant. CONCLUSION: In this population, ulcer size at the onset of antibacterial treatment and the use of certain ocular medications, specifically corticosteroids, were significant predictive factors for failure of medical therapy for BUK.

Adolescent↗

Head-up tilt table test: how far and how long?

There is great variation between laboratories in the angle and duration of tilt used in the head-up tilt table test. We compared the hemodynamic response to three sequential randomized 20-min tilts of 60 degrees, 80 degrees and 90 degrees in 20 normal subjects. We studied 66 patients to determine the duration of tilt needed to document three types of orthostatic intolerance. Blood pressure and heart rate were monitored non-invasively. Thirty-nine patients with orthostatic hypotension of diverse causes and 17 patients with orthostatic tachycardia plus were tilted to 90 degrees for 10 min. Ten patients with vasovagal syncope were tilted to 90 degrees for 30 min. A multivariate analysis of variance performed to assess the hemodynamic responses to 60 degrees, 80 degrees and 90 degrees tilts did not show a statistically significant difference (F = 0.459). Logistic regression analyses revealed that the duration of tilt required to document orthostatic hypotension was 5 min (73% cases correctly identified), orthostatic tachycardia plus 10 min (86.5% cases correctly identified) and neurally mediated syncope 10 min (86.5% cases correctly identified). Tilt duration is a more important variable than tilt angle and the duration of the tilt should depend on the suspected cause of orthostatic intolerance.

Adult↗