Conditioning intensity and peritransplant flow cytometric MRD dynamics in adult AML.

In acute myeloid leukemia (AML), measurable residual disease (MRD) before or after allogeneic hematopoietic cell transplantation (HCT) is an established independent indicator of poor outcome. To address how peri-HCT MRD dynamics could refine risk assessment across different conditioning intensities, we analyzed 810 adults transplanted in first or second remission after myeloablative conditioning (MAC; n = 515) or non-MAC (n = 295) who underwent multiparameter flow cytometry-based MRD testing before as well as 20 to 40 days after allografting. Patients without pre- and post-HCT MRD (MRDneg/MRDneg) had the lowest risks of relapse and highest relapse-free survival (RFS) and overall survival (OS). Relative to those patients, outcomes for MRDpos/MRDpos and MRDneg/MRDpos patients were poor regardless of conditioning intensity. Outcomes for MRDpos/MRDneg patients were intermediate. Among 161 patients with MRD before HCT, MRD was cleared more commonly with a MAC (85 of 104; 81.7%) than non-MAC (33 of 57; 57.9%) regimen (P = .002). Although non-MAC regimens were less likely to clear MRD, if they did, the impact on outcome was greater. Thus, there was a significant interaction between conditioning intensity and "MRD conversion" for relapse (P = .020), RFS (P = .002), and OS (P = .001). Similar findings were obtained in the subset of 590 patients receiving HLA-matched allografts. C-statistic values were higher (indicating higher predictive accuracy) for peri-HCT MRD dynamics compared with the isolated use of pre-HCT MRD status or post-HCT MRD status for prediction of relapse, RFS, and OS. Across conditioning intensities, peri-HCT MRD dynamics improve risk assessment over isolated pre- or post-HCT MRD assessments in patients with AML.

High frequency of severe hyperglycemia observed during intensive hematological care: a prospective study using continuous glucose monitoring.

OBJECTIVES: During intensive hematological care, patients are exposed to high-dose chemotherapy, corticosteroids, immunosuppressants and total parenteral nutrition. Combined with physiological stress and increased release of cytokines and hormones, this can lead to dysglycemia, which is associated with adverse clinical outcomes. This prospective study aims to investigate continuous glucose monitoring (CGM) to identify dysglycemia during intensive hematological care. METHODS: Patients receiving chimeric antigen receptor (CAR) T-cell therapy, allogeneic or autologous stem cell transplantation (SCT) were eligible. Throughout the study, glucose levels were concurrently monitored using CGM and point-of-care (POC) glucose measurements in sixty patients (71% male, median age of 64 (IQR [58-68]) years and 10% with diabetes). RESULTS: Hyperglycemia (glucose >10mmol/L) was prevalent in 93% of patients, of which 90% had no history of diabetes. Severe hyperglycemia (glucose >13.1mmol/L) was present in 38%. Additionally, hyperglycemia was associated with prolonged hospitalization in patients undergoing CAR T-cell treatment (ß=0.19, 95% CI=0.04-0.35) and autologous SCT (ß=0.16, 95% CI=0.01-0.32). CGM outperformed POC in detecting hyperglycemia (>10 mmol/L: 1060 vs. 124, detected 2.8 hours (IQR [0.7-4.0]) earlier). Mean absolute relative difference between CGM and POC was 21.5% with 99.8% of measurements in the clinical acceptable zones A+B of the Clarke Error Grid. CONCLUSION: These findings emphasize the potential and importance of glucose monitoring with CGM for improved and earlier detection of hyperglycemia, in this patient population, which seems feasible. Our results suggest a need for further studies into CGM as method to optimize glucose levels, which could improve outcomes in patients receiving intensive hematological care.

Emotional distress in cancer survivors from various ethnic backgrounds: Analysis of the multi-ethnic HELIUS study.

PURPOSE: Insight into emotional distress of cancer survivors from ethnic minority groups in Europe is scarce. We aimed to compare distress levels of survivors from ethnic minorities to that of the majority population, determine whether the association between having cancer (yes vs. no) and distress differs among ethnic groups and investigate sociocultural correlates of distress. METHODS: Cross-sectional data were derived from HELIUS, a multi-ethnic cohort study conducted in the Netherlands. Of 19,147 participants, 351 were diagnosed with cancer (n = 130 Dutch, n = 75 African Surinamese, n = 53 South-Asian Surinamese, n = 43 Moroccan, n = 28 Turkish, n = 22 Ghanaian). Distress (PHQ-9, MCS-12) and correlates were assessed by self-report. Cancer-related variables were derived from the Netherlands Cancer Registry. RESULTS: Survivors were on average 7 years post-diagnosis. Survivors from South-Asian Surinamese, Moroccan, Turkish and Ghanaian origin reported more distress than survivors from Dutch origin (effect sizerange : 0.44-1.17; adjusted models). The association between having cancer or not with distress differed in direction between Dutch and the non-Dutch ethnic groups: Non-Dutch cancer patients tended to have more distress than their cancer-free peers, whereas Dutch cancer patients tended to have less distress than their cancer-free peers. For Moroccan and Turkish patients, the acculturation style of separation/marginalization, compared to integration/assimilation, was associated with higher depressive symptoms. In analyses pooling data from all ethnic minorities, lower health literacy, lower emotional support satisfaction and younger age at the time of migration were associated with higher depressive symptoms. Lower health literacy, fewer emotional support transactions, and more frequent attendance at religious services were associated with worse mental health. CONCLUSION: Cancer survivors from ethnic minorities experience more distress than those from the majority population. Culturally sensitive supportive care should be considered.

Effect of ruxolitinib on the oral mucosa of patients with steroid-refractory chronic Graft-versus-Host disease and oral involvement.

BACKGROUND: Chronic Graft-versus-Host Disease (cGVHD) can impact quality of life, especially in patients with oral involvement. Half of the patients with cGVHD do not respond to first-line therapy with corticosteroids and calcineurin inhibitors. Ruxolitinib is effective in steroid-refractory (SR)-cGVHD cases, but the long-term effects of ruxolitinib on the oral mucosa are unknown. OBJECTIVE(S): This study aims to assess the effect of ruxolitinib on the oral mucosa of SR-cGVHD patients with oral involvement. MATERIALS AND METHODS: An observational longitudinal patient study was conducted in 53 patients with SR-cGVHD and oral involvement who were treated with ruxolitinib. The baseline condition of the oral mucosa was compared to its condition at 4 and 12 weeks after starting ruxolitinib. RESULTS: The overall response was 81% (43/53), with a complete response in 53% (28/53) and partial response in 28% (15/53) after 12 weeks (p < 0.001). Men and patients concurrently using immunosuppressive therapy responded better than women (p = 0.005) and patients with ruxolitinib monotherapy (p = 0.02), respectively. At a longer follow-up (median 20 months), oral symptoms were comparable to the 12-week symptoms (p = 0.78), regardless of ruxolitinib use (p = 0.83). CONCLUSION: Ruxolitinib treatment of SR-cGVHD patients with oral involvement was associated with a significant response of the oral manifestations at 12 weeks. CLINICAL RELEVANCE: The oral mucosa of SR-cGVHD patients is likely to improve after 4 and 12 weeks of ruxolitinib treatment. Symptom severity at baseline does not affect the response of the oral mucosa.

Founder effects facilitate the use of a genotyping-based approach to molecular diagnosis in Swedish patients with familial hypercholesterolaemia.

AIM: To investigate whether genotyping could be used as a cost-effective screening step, preceding next-generation sequencing (NGS), in molecular diagnosis of familial hypercholesterolaemia (FH) in Swedish patients. METHODS AND RESULTS: Three hundred patients of Swedish origin with clinical suspicion of heterozygous FH were analysed using a specific array genotyping panel embedding 112 FH-causing mutations in the LDLR, APOB and PCSK9 genes. The mutations had been selected from previous reports on FH patients in Scandinavia and Finland. Mutation-negative cases were further analysed by NGS. In 181 patients with probable or definite FH using the Dutch lipid clinics network (DLCN) criteria (score ≥ 6), a causative mutation was identified in 116 (64%). Of these, 94 (81%) were detected by genotyping. Ten mutations accounted for more than 50% of the positive cases, with APOB c.10580G>A being the most common. Mutations in LDLR predominated, with (c.2311+1_2312-1)(2514)del (FH Helsinki) and c.259T>G having the highest frequency. Two novel LDLR mutations were identified. In patients with DLCN score < 6, mutation detection rate was significantly higher at younger age. CONCLUSION: A limited number of mutations explain a major fraction of FH cases in Sweden. Combination of selective genotyping and NGS facilitates the clinical challenge of cost-effective genetic screening in suspected FH. The frequency of APOB c.10580G>A was higher than previously reported in Sweden. The lack of demonstrable mutations in the LDLR, APOB and PCSK9 genes in ~1/3 of patients with probable FH strongly suggests that additional genetic mechanisms are to be found in phenotypic FH.

The Clinical Utility of Neuron-Specific Enolase (NSE) Serum Levels as a Biomarker for Merkel Cell Carcinoma (MCC).

BACKGROUND: No adequate biomarker for Merkel cell carcinoma (MCC) has been identified. Serum neuron-specific enolase (NSE) has been tested and is commonly used as a biomarker for several other small cell malignancies. However, the role of NSE in MCC is still unclear. The purpose of this study was to investigate the role of NSE as a biomarker in MCC. METHODS: A prospective cohort of MCC patients was analyzed using Kaplan-Meier curves with log-rank test, ROC curves, Cox regression, and mixed models. A separate evaluation was performed for patients treated with immunotherapy. RESULTS: Eighty-four patients were included [47 males, median age 71 years, stages I & II, III, and IV MCC in respectively 39 (46%), 42 (50%), and 4 (3%) patients at time of diagnosis] with 565 NSE samples (median 15; interquartile range 12.6-22 ng/ml). Baseline NSE had no association with prognosis. NSE correlated with extent of disease (P = 0.01) and increased with 15 ng/ml per class (no tumor load, localized MCC, regional or distant metastases, respectively). NSE was able to detect progression (AUC 0.89). A NSE of 18.2 ng/ml was considered the most optimal level for clinical use (sensitivity 91%, specificity 78%, PPV 48%, NPV 98%). During immunotherapy (N = 23; 248 NSE values), all complete responders (N = 10) had a normalized NSE (< 18.2 ng/ml), all partial responders (N = 5) had a decreasing NSE. In nonresponders (N = 8), all NSE levels remained elevated. CONCLUSIONS: NSE could be a valuable biomarker in MCC. NSE correlates with extent of disease; it is able to rule out progression and distinguishes responders from nonresponders during immunotherapy.

Driver mutations occur frequently in metastases of well-differentiated small intestine neuroendocrine tumours.

AIMS: To investigate the clinicopathological significance of driver mutations in metastatic well-differentiated small intestine neuroendocrine tumours (SI-NETs). METHODS AND RESULTS: Whole genome sequencing (WGS) of 35 metastatic SI-NETs and next-generation sequencing (NGS) of eight metastatic SI-NETs were performed. Biopsies were obtained between 2015 and 2019. Tumours were classified according to the 2019 World Health Organization classification. WGS included assessment of somatic mutations in all cancer-related driver genes, the tumour mutational burden (TMB), and microsatellite status. NGS entailed a cancer hotspot panel of 58 genes. Our cohort consisted of 21% grade 1, 60% grade 2 and 19% grade 3 SI-NETs. Driver mutations were identified in ~50% of SI-NETs. In total, 27 driver mutations were identified, of which 74% were in tumour suppressor genes (e.g. TP53, RB1, and CDKN1B) and 22% were in proto-oncogenes (e.g. KRAS, NRAS, and MET). Allelic loss of chromosome 18 (63%), complete loss of CDKN2A and CDKN1B (both 6%) and CDKN1B mutations (9%) were most common. Potential targetable genetic alterations were detected in 21% of metastasised SI-NETs. All tumours were microsatellite-stable and showed low TMBs (median 1.10; interquartile range 0.87-1.35). The Ki67 proliferation index was significantly associated with the presence of driver mutations (P = 0.015). CONCLUSION: Driver mutations occur in 50% of metastasised SI-NETs, and their presence is associated with a high Ki67 proliferation index. The identification of targetable mutations make these patients potentially eligible for targeted therapy.

Recommendations on how to provide cardiac rehabilitation services during the COVID-19 pandemic.

The ongoing coronavirus disease 2019 (COVID-19) crisis is having a large impact on acute and chronic cardiac care. Due to public health measures and the reorganisation of outpatient cardiac care, traditional centre-based cardiac rehabilitation is currently almost impossible. In addition, public health measures are having a potentially negative impact on lifestyle behaviour and general well-being. Therefore, the Working Group of Cardiovascular Prevention and Rehabilitation of the Dutch Society of Cardiology has formulated practical recommendations for the provision of cardiac rehabilitation during the COVID-19 pandemic, by using telerehabilitation programmes without face-to-face contact based on current guidelines supplemented with new insights and experiences.

Cardiac telerehabilitation as an alternative to centre-based cardiac rehabilitation.

Multidisciplinary cardiac rehabilitation (CR) reduces morbidity and mortality and increases quality of life in cardiac patients. However, CR utilisation rates are low, and targets for secondary prevention of cardiovascular disease are not met in the majority of patients, indicating that secondary prevention programmes such as CR leave room for improvement. Cardiac telerehabilitation (CTR) may resolve several barriers that impede CR utilisation and sustainability of its effects. In CTR, one or more modules of CR are delivered outside the environment of the hospital or CR centre, using monitoring devices and remote communication with patients. Multidisciplinary CTR is a safe and at least equally (cost-)effective alternative to centre-based CR, and is therefore recommended in a recent addendum to the Dutch multidisciplinary CR guidelines. In this article, we describe the background and core components of this addendum on CTR, and discuss its implications for clinical practice and future perspectives.

Aids to management of headache disorders in primary care (2nd edition) : on behalf of the European Headache Federation and Lifting The Burden: the Global Campaign against Headache.

The Aids to Management are a product of the Global Campaign against Headache, a worldwide programme of action conducted in official relations with the World Health Organization. Developed in partnership with the European Headache Federation, they update the first edition published 11 years ago.The common headache disorders (migraine, tension-type headache and medication-overuse headache) are major causes of ill health. They should be managed in primary care, firstly because their management is generally not difficult, and secondly because they are so common. These Aids to Management, with the European principles of management of headache disorders in primary care as the core of their content, combine educational materials with practical management aids. They are supplemented by translation protocols, to ensure that translations are unchanged in meaning from the English-language originals.The Aids to Management may be individually downloaded and, as is the case for all products of the Global Campaign against Headache, are available without restriction for non-commercial use.

Headache service quality: the role of specialized headache centres within structured headache services, and suggested standards and criteria as centres of excellence.

In joint initiatives, the European Headache Federation and Lifting The Burden have described a model of structured headache services (with their basis in primary care), defined service quality in this context, and developed practical methods for its evaluation.Here, in a continuation of the service quality evaluation programme, we set out ten suggested role- and performance-defining standards for specialized headache centres operating as an integral component of these services. Verifiable criteria for evaluation accompany each standard. The purposes are five-fold: (i) to inspire and promote, or stimulate the establishment of, specialized headache centres as centres of excellence; (ii) to define the role of such centres within optimally structured and organized national headache services; (iii) to set out criteria by which such centres may be recognized as exemplary in their fulfilment of this role; (iv) to provide the basis for, and to initiate and motivate, collaboration and networking between such centres both nationally and internationally; (v) ultimately to improve the delivery and quality of health care for headache.

Merkel cell carcinoma: Clinical outcome and prognostic factors in 351 patients.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine carcinoma of the skin. AIM: To describe clinical outcome and prognostic factors of MCC patients in two expert-centers. METHOD: Patients with histologically confirmed MCC in 1990-2014 were included. Data on patient, tumor characteristics and treatment were retrospectively collected. RESULTS: A total of 351 Patients were evaluated, 153 (44%) males, median age 74 years (range 28-94). Median follow-up time was 28 months (IQR 13-58). Median primary tumor size was 17 mm (range 2-135). At time of diagnosis 112 (32%) patients had lymph node metastases. The cohorts' 5-year overall survival (OS) was 58%. Using a competing risk analysis the 5-year relapse and MCC related death was 42% and 22%. Adjuvant radiation therapy (XRT) was associated with reduced recurrence (SDH 0.54; CI 0.3-0.9). Nodal involvement (SDH 2.7; CI 1.1-6.6) and the male gender were associated with higher MCC related death (SDH 3.1; CI 1.2-7.9) CONCLUSION: In a large cohort a low MCC related death, in the presence of a low OS was seen. This indicates that a significant number of MCC patients die due to other causes than MCC. Adjuvant XRT was associated with relapse. Male gender and nodal metastasis were associated with MCC related death.

Recommendations for radioembolisation after liver surgery using yttrium-90 resin microspheres based on a survey of an international expert panel.

INTRODUCTION: Guidelines on how to adjust activity in patients with a history of liver surgery who are undergoing yttrium-90 radioembolisation (90Y-RE) are lacking. The aim was to study the variability in activity prescription in these patients, between centres with extensive experience using resin microspheres 90Y-RE, and to draw recommendations on activity prescription based on an expert consensus. METHODS: The variability in activity prescription between centres was investigated by a survey of international experts in the field of 90Y-RE. Six representative post-surgical patients (i.e. comparable activity prescription, different outcome) were selected. Information on patients' disease characteristics and data needed for activity calculation was presented to the expert panel. Reported was the used method for activity prescription and whether, how and why activity reduction was found indicated. RESULTS: Ten experts took part in the survey. Recommendations on activity reduction were highly variable between the expert panel. The median intra-patient range was 44 Gy (range 18-55 Gy). Reductions in prescribed activity were recommended in 68% of the cases. In consensus, a maximum DTarget of 50 Gy was recommended. CONCLUSION: With a current lack of guidelines, large variability in activity prescription in post-surgical patients undergoing 90Y-RE exists. In consensus, DTarget ≤50 Gy is recommended. KEY POINTS: • BSA method does not account for a decreased remnant liver volume after surgery. • In post-surgical patients, a volume-based activity determination method is recommended. • In post-surgical patients, a mean D Target of ≤ 50Gy should be aimed for.

Migraine associated with altitude: results from a population-based study in Nepal.

BACKGROUND AND PURPOSE: A 1988 pilot study in Peru suggested an association between migraine and chronic exposure to high altitude. This study provides epidemiological evidence corroborating this. METHODS: In a cross-sectional nationwide population-based study, a representative sample of Nepali-speaking adults were recruited through stratified multistage cluster sampling. They were visited at home by trained interviewers using a culturally adapted questionnaire. The altitude of dwelling of each participant was recorded. RESULTS: Of 2100 participants, over half [1100 (52.4%)] were resident above 1000 m and almost one quarter [470 (22.4%)] at ≥2000 m. Age- and gender-standardized migraine prevalence increased from 27.9% to 45.5% with altitude between 0 and 2499 m and thereafter decreased to 37.9% at ≥2500 m. The likelihood of having migraine was greater (odds ratio, 1.5-2.2; P ≤ 0.007) at all higher altitudes compared with <500 m. In addition, all symptom indices increased with altitude across the range <500 m to 2000-2499 m, i.e. median attack frequency from 1.3 to 3.0 days/month (P < 0.001), median duration from 9 to 24 h (P < 0.001) and pain intensity [the proportion reporting 'bad pain' (highest intensity)] from 35.5% to 56.9% (P = 0.011). Each of these showed a downward trend above 2500 m. CONCLUSIONS: Dwelling at high altitudes increases not only migraine prevalence but also the severity of its symptoms.

Prognostic value and kinetics of circulating endothelial cells in patients with recurrent glioblastoma randomised to bevacizumab plus lomustine, bevacizumab single agent or lomustine single agent. A report from the Dutch Neuro-Oncology Group BELOB trial.

BACKGROUND: Angiogenesis is crucial for glioblastoma growth, and anti-vascular endothelial growth factor agents are widely used in recurrent glioblastoma patients. The number of circulating endothelial cells (CECs) is a surrogate marker for endothelial damage. We assessed their kinetics and explored their prognostic value in patients with recurrent glioblastoma. METHODS: In this side study of the BELOB trial, 141 patients with recurrent glioblastoma were randomised to receive single-agent bevacizumab or lomustine, or bevacizumab plus lomustine. Before treatment, after 4 weeks and after 6 weeks of treatment, CECs were enumerated. RESULTS: The number of CECs increased during treatment with bevacizumab plus lomustine, but not during treatment in the single-agent arms. In patients treated with lomustine single agent, higher absolute CEC numbers after 4 weeks (log10CEC hazard ratio (HR) 0.41, 95% CI 0.18-0.91) and 6 weeks (log10CEC HR 0.16, 95% CI 0.05-0.56) of treatment were associated with improved overall survival (OS). Absolute CEC numbers in patients receiving bevacizumab plus lomustine or bevacizumab single agent were not associated with OS. CONCLUSION: CEC numbers increased during treatment with bevacizumab plus lomustine but not during treatment with either agent alone, suggesting that this combination induced the greatest vascular damage. Although the absolute number of CECs was not associated with OS in patients treated with bevacizumab either alone or in combination, they could serve as a marker in glioblastoma patients receiving lomustine single agent.

Blood pressure as a risk factor for headache and migraine: a prospective population-based study.

BACKGROUND AND PURPOSE: During the past decade, several population-based studies have found an inverse association between blood pressure (BP) and headache. However, most of them have a cross-sectional design or lack a validated definition of a headache-free population at baseline. Therefore, additional population-based studies using a clearly defined headache-free population and a prospective design are warranted. METHODS: Data from two large epidemiological studies, the Nord-Trondelag Health Survey 1995-1997 (HUNT 2) and 2006-2008 (HUNT 3), were used to evaluate the association between BP (systolic, diastolic and pulse pressure) at baseline and headache (migraine and tension type headache) at follow-up. RESULTS: An inverse relationship was found between all three BP measures at baseline in HUNT 2 and any headache in HUNT 3, more evident for systolic BP [odds ratio (OR) 0.90 per 10 mmHg increase in systolic BP, 95% confidence interval (CI) 0.87-0.93, P < 0.001] and pulse pressure (OR 0.84 per 10 mmHg increase in pulse pressure, 95% CI 0.80-0.89, P < 0.001) than for diastolic BP (OR 0.92 per 10 mmHg increase in diastolic BP, 95% CI 0.87-1.00, P = 0.036). The most robust finding, evident for both sexes, was that increased pulse pressure was linked to decreased prevalence of both migraine and tension type headache. CONCLUSION: An inverse relationship between BP and subsequent development of headache was confirmed in this large-scale population-based cohort study. Nevertheless, further research is needed to investigate the underlying mechanisms explaining these findings.

Measuring Neuroticism in Nepali: Reliability and Validity of the Neuroticism Subscale of the Eysenck Personality Questionnaire.

BACKGROUND: The Neuroticism subscale of the Eysenck Personality Questionnaire Revised Short Form (12 items) (EPQRS-N) has proven to be a reliable and valid measure in multiple languages. OBJECTIVE: To develop a single-factor Nepali-language version of the EPQRS-N for use in the adult population of Nepal. METHOD: The original English version of EPQRS-N was translated into Nepali using a forward-backward translation protocol. The first set of translated items was modified after testing by factor analysis with principal component extraction in an outpatient sample. Items with low factor correlations or poor semantic consistencies were reworded to fit the gist of the original items in a Nepali cultural context; the revised version was then tested in a representative random sample from the general population. Again, the same statistical procedures were applied. RESULTS: The first trial gave three factors. Based on the factor distribution of the items or their semantic quality, five were reworded. In the second trial, a two-factor solution emerged; the second factor had only one item with high correlation, which also had modest correlation with the first factor. Accordingly, a forced one-factor solution was chosen. This gave an internal consistency (Cronbach's alpha) of 0.80, with item-to-factor correlations from 0.40 to 0.73, and item-to-sum correlations from 0.31 to 0.61. CONCLUSION: The final Nepali version of EPQRS-N achieved satisfactory internal consistency. The item distribution coincided with the original English version, providing acceptable construct validity. It is psychometrically adequate for use in capturing the personality trait of neuroticism, and has broad applicability to the adult population of Nepal because of the diversity of the participant samples in which it was developed.

Reliability and Validity of a Nepali-language Version of the Hospital Anxiety and Depression Scale (HADS).

BACKGROUND: In several languages and settings, the Hospital Anxiety and Depression Scale (HADS) has demonstrated reliable and valid screening properties in psychiatry. OBJECTIVE: To develop a Nepali version of HADS with acceptable reliability and construct validity for use among hospital patients and in the general population. METHOD: The original English version was translated into Nepali using a forward-backward translation protocol. Psychometric properties were tested by factor analysis and Cronbach's alpha. The translated scale was administered to three groups of adult in-patients in a university hospital in three trials, and to a sample of adults from the community in a fourth trial. Some of the 14 items were reworded reiteratively to achieve viable semantic and statistical solutions. RESULTS: The two-factor solution with anxiety and depression subscales eventually explained 40.3% of the total variance. Cronbach's alpha was 0.76 for anxiety (HADS-A) and 0.68 for depression (HADS-D). All seven HADS-A items showed at least acceptable item-to-factor correlations (range 0.44-0.74), and full construct validity was achieved for this subscale. Item-to-factor correlations for six HADS-D items were also at least acceptable (range 0.42-0.70); one item (D4) had persistently low correlations throughout all trials, although construct validity was still satisfactory. CONCLUSION: Reiterated rewording of items guided by statistical testing resulted in a Nepali version of HADS with satisfactory psychometric properties.

Undertreated Hypertension and its Implications for Public Health in Nepal: Nationwide Population-Based Survey.

BACKGROUND: Hypertension (HTN), a major risk factor for cardiovascular diseases (CVDs), is a substantial global public health problem. Occasional studies indicate a high prevalence of HTN in the Nepalese population, but no nationwide population-based data exist so far. We opportunistically used a survey of major disorders of the brain in Nepal to measure blood pressure (BP) in participants selected randomly from the adult general population. OBJECTIVE: To establish the prevalence of elevated BP (eBP), and factors associated with it, regardless of any antihypertensive therapy being taken. We took this to be indicative of unmet health-care need. METHOD: This was a cross-sectional study, conducted by unannounced household visits, employing multistage random cluster sampling. To achieve representativeness, 15 districts out of 75 in the country were investigated: one district from each of the three physiographic divisions in each of the five development regions of Nepal. One adult aged 18-65 years was selected from each household and interviewed by structured questionnaire. BP was recorded in a standardised manner by digital device (Microlife 3BM1-3®). RESULT: From 2,109 eligible households, 2,100 adults (99.6%) participated. The prevalence of eBP (>140/90 mmHg on ≥2 readings) was found to be 15.1%. Multivariate logistic regression showed significant and independent associations with demographic variables (higher age, male gender), with life-style factors (daily alcohol consumption, BMI ≥25), and with living at high altitude (≥2000 m). CONCLUSION: In the context of the survey we could not collect data on antihypertensive therapy being taken but, clearly, whatever this might have been, it was failing to meet treatment needs. Almost one in six adults met criteria for hypertension, carrying risk implications for CVDs and their substantial public-health consequences. Two remediable associated factors were identified, although in a cross-sectional survey we could not prove causation.