Clinical utility of late-night and post-overnight dexamethasone suppression salivary cortisone for the investigation of Cushing's syndrome.

INTRODUCTION: There is a pressing need to identify diagnostic testing for Cushing's syndrome that can be achieved with ease and at low cost. This study aimed to explore the usefulness of late-night and post-overnight 1-mg dexamethasone suppression salivary cortisone, as measured by liquid chromatography-tandem mass spectrometry, for investigation of hypercortisolism. METHODS: Salivary cortisone data of subjects were investigated according to a pre-specified protocol. Subjects were classified as having 'hypercortisolism' or 'eucortisolism' on the basis of histological or biochemical criteria. Receiver operating characteristic curves were drawn to identify the cut-off values and study their performance characteristics. We measured 24-hour urinary free cortisol; late-night salivary cortisol and cortisone; and post-overnight 1-mg dexamethasone suppression serum cortisol, and salivary cortisol and cortisone. Saliva and urine samples were assayed by liquid chromatography-tandem mass spectrometry. RESULTS: In this study, 21 subjects were classified as having hypercortisolism and 78 as having eucortisolism. A late-night salivary cortisone cut-off of 13.50 nmol/L had a sensitivity of 94.7% and a specificity of 87.2%. After taking 1-mg dexamethasone the night before, a salivary cortisol cut-off of 0.85 nmol/L had a sensitivity of 76.2% and a specificity of 96.2%; a salivary cortisone cut-off of 7.45 nmol/L had a sensitivity of 85.7% and a specificity of 94.9%, while a salivary cortisone cut-off of 3.25 nmol/L had a sensitivity of 95.2% and a specificity of 79.5%. Many salivary cortisol samples were below the detection limit of liquid chromatography-tandem mass spectrometry. In comparison with salivary cortisol, salivary cortisone had a better correlation with total serum cortisol and better diagnostic performance following dexamethasone suppression. CONCLUSIONS: Both late-night and post-overnight dexamethasone suppression salivary cortisone levels are of diagnostic value in the investigation of hypercortisolism.

Euthyroid graves' ophthalmopathy in a Chinese population: A cross-sectional follow-up study.

OBJECTIVES: A subtype of patients with thyroid eye disease (TED) were found to be euthyroid without prior thyroid dysfunction or treatment, known as Euthyroid Graves' Ophthalmopathy (EGO). We report the prevalence, clinical and serological phenotypes of EGO in a Chinese population. METHODS: A cross-sectional follow-up study. Ethnic Chinese TED patients were managed at the Thyroid Eye Clinic(TEC), Prince of Wales Hospital and TEC, the Chinese University of Hong Kong between September 2007 and July 2021. RESULTS: A total of 66 (5%) patients among the 1266 ethnic Han Chinese TED cohort were diagnosed as EGO, and 6 (9%)of them become dysthyroid over an average of 74-month follow-up. EGO patients were associated with a longer duration between onset of the symptoms to our first consultation (P < 0.0001), a higher male-to-female ratio (P = 0.0045) and a higher age of disease onset (P = 0.0092). Family history of thyroid disease was more common in TED patients (P = 0.0216) than in EGO patients. EGO patients were more likely to present unilaterally (P < 0.0001), and they have a larger difference in MRD1 (P < 0.0001), and extraocular motility (P < 0.0001) between the 2 eyes when compared to the TED patients. Notably, the extraocular motility restriction of the worst eye was more affected in EGO patients (P = 0.0113). The percentages of patients who received IVMP, ORT and emergency or elective surgeries(decompression or squint operation) between EGO and TED were similar. CONCLUSIONS: Understanding the important clinical phenotypes of EGO may help the clinician to make the correct diagnosis. Further study to compare EGO and TED is warranted.

Hypertriglyceridaemia-induced pancreatitis: a contributory role of capecitabine?

Capecitabine is an orally administered pro-drug of 5-fluorouracil that confers superior disease-free survival and presumably has a more favourable side-effect profile. Here we report on a patient who developed acute necrotising pancreatitis and very high triglyceride levels as well as hand-foot syndrome after receiving capecitabine for colonic cancer. Increased awareness of this potential side-effect and close monitoring of lipid levels may be warranted, especially in patients who have other conditions predisposing them to severe secondary hyperlipidaemia when using this drug.

The Chinese version of the pelvic pain and urgency/frequency symptom scale: a useful assessment tool for street-ketamine abusers with lower urinary tract symptoms.

OBJECTIVE: To investigate the use of a translated Chinese version of the pelvic pain and urgency/frequency symptom scale as an assessment and prognostic tool to evaluate the severity of street-ketamine-associated lower urinary tract symptoms and their reversibility after abstinence. DESIGN: Cross-sectional study. SETTING: A special designated out-patient clinic in a regional hospital in Hong Kong. PARTICIPANTS: There were 50 patients with street-ketamine-associated lower urinary tract symptoms and 20 healthy individuals. MAIN OUTCOME MEASURES: Reliability and validity of the questionnaire; frequency of individual lower urinary tract symptoms, cystoscopic, urodynamic and radiological abnormalities, and their correlation with pelvic pain and the urgency/frequency score. RESULTS: The test-retest reliability coefficient was 0.755 (P<0.001). Cronbach's alpha was 0.974. Mann-Whitney U test proved the discriminatory ability of the questionnaire (P<0.001). Patients with specific lower urinary tract symptoms had a higher mean pelvic pain and urgency/frequency total score compared to those without them: frequency (23.8 vs 17.3), nocturia (22.4 vs 14.0), urgency (22.5 vs 15.1), dysuria (22.7 vs 13.3), and haematuria (24.8 vs 16.2). The number of daytime voids and nocturia episodes correlated well with pelvic pain and urgency/frequency scores. With an increasing score, the likelihood of having cystitis changes, urodynamic abnormalities and hydronephrosis increased, while the cystometrically determined bladder capacity decreased. None of the patients with a score of 16 or below had urodynamic abnormality or hydronephrosis. The mean score change in the abstinence group was -4.33, versus +3.33 in their counterparts. CONCLUSIONS: The Chinese version of the pelvic pain and urgency/frequency questionnaire is reliable and valid for assessment in patients with street-ketamine-associated lower urinary tract symptoms. The pelvic pain and urgency/frequency score correlates well with symptom severity as well as endoscopic, urodynamic and radiological abnormalities in patients with street-ketamine-associated lower urinary tract symptoms. A cut-off total pelvic pain and urgency/frequency score of 17 may suggest more serious urological sequelae from ketamine abuse. Abstinence from ketamine reduced lower urinary tract symptoms, but the extent of reversibility of urinary tract damage is yet to be evaluated.

Structural and magnetic properties of ZnO nanocrystals in (Zn, Al)O films using pulse laser deposition.

In this manuscript, we reported that the room temperature ferromagnetism was observed in (Zn0.70, Al0.30)O film, which was fabricated by a novel physical method (pulse laser deposition (PLD)). The film was deposited from (Zn0.80, Al0.20)O ceramic target onto quartz (110) substrate by PLD at 400 degrees C under an oxygen partial pressure of 10(-4) torr. TEM result shows ZnO NCs with diameter of 4-5 nm and they are quite uniformly embedded into amorphous ZnO-Al2O3 phase. The SAED shows clearly that ZnO NCs possess polycrystalline structure. The SQUID measurement shows that the film has room temperature ferromagnetism (saturation magnetization = 3.6 emu/cm3) with Curie temperature above 300 K. The magnitude of magnetic moment of the films can be changed by tuning ZnO NCs size. Both oxygen partial pressure and film thickness studies show that the origin of ferromagnetism is possibly related to the oxygen defects at the surface of ZnO NCs.

Associations of pre-pregnancy body mass index, middle-upper arm circumference, and gestational weight gain.

OBJECTIVES: An optimal gestational weight gain is essential for maternal health and to reduce adverse birth outcomes. Current guidelines to monitor gestational weight gain are based on pre-pregnancy body mass index (BMI). However, middle-upper arm circumference (MUAC) is increasingly used as an alternative nutritional status measure for pregnant women. Hence, this study aimed to determine associations of MUAC and pre-pregnancy BMI with gestational weight gain rate among Malaysian pregnant women. STUDY DESIGN: A cross-sectional study was conducted among 444 pregnant women (≥20 weeks gestation). MAIN OUTCOMES MEASURES: Women completed questionnaires on sociodemographic data, maternal characteristics and pre-pregnancy weight. Height, current weight and MUAC were measured at study visit (from 1st February 2016 to 31st January 2017). RESULTS: About a third (34.24%) of pregnant women were overweight or obese prior to pregnancy. MUAC was inversely associated with an inadequate rate of gestational weight gain (OR = 0.77; 95% CI: 0.68, 0.87) as compared to normal gestational weight gain. In contrast, a higher MUAC was associated with a higher odds ratio (OR = 1.28; 95% CI: 1.11, 1.49) of having excessive rate of gestational weight. No associations were found for pre-pregnancy BMI categories for gestational weight gain rate. CONCLUSION: Our findings revealed that women with low MUAC were more likely to have an inadequate gestational weight gain rate during pregnancy whereas higher MUAC was associated with an excessive gestational weight gain rate. MUAC may be a useful indicator of nutritional status associated with GWG. Routine measurement of MUAC in pregnant women may help health professionals, particularly in middle-income countries, to counsel women about gestational weight gain.

Prevalence and significance of white-coat hypertension and masked hypertension in type 2 diabetics.

OBJECTIVES: To explore the prevalence of various categories of hypertension in diabetic patients, and assess any corresponding associations with end-organ complications. DESIGN: Cross-sectional study. SETTING: Tertiary centre of a regional hospital in Hong Kong. PATIENTS: All ambulatory type 2 diabetic patients attending our clinics from January 2002 to November 2004 were invited to participate in the protocol. RESULTS: A total of 133 diabetic patients were included; 82 had normal clinic blood pressures, 15 (18%) of whom had masked hypertension, the remaining 67 (82%) had 'normotension'. The remaining 51 patients had high clinic blood pressures, of whom 28 (55%) had white-coat hypertension and 23 (45%) had sustained hypertension. Urinary albumin excretion rate was higher in patients with masked hypertension (10 mg/day; range, 7-580 mg/day) and sustained hypertension (7 mg/day; 7-3360 mg/day) in comparison to those with white-coat hypertension (7 mg/day; 7-109 mg/day) or 'normotension' (7 mg/day; 7-181 mg/day) [P<0.01]. Likewise, the prevalence of albuminuria was significantly higher in patients with masked hypertension (40%) and sustained hypertension (26%) than in those with 'normotension' (6%) and white-coat hypertension (11%) [P<0.01]. The prevalence of left ventricular hypertrophy was significantly higher in subjects with masked hypertension (38%) and sustained hypertension (26%) compared to patients with 'normotension' (8%) or white-coat hypertension (11%) [P<0.01]. Left ventricular diastolic dysfunction was more prevalent in patients with masked hypertension (46%), sustained hypertension (48%), and white-coat hypertension (43%) in comparison to subjects with 'normotension' (18%) [P=0.01]. CONCLUSION: Masked hypertension is associated with a higher prevalence of albuminuria, left ventricular diastolic dysfunction, and hypertrophy. White-coat hypertension carries a more benign prognosis than sustained hypertension and masked hypertension. Our cross-sectional study supports the recommendation to performing ambulatory blood pressure measurements in type 2 diabetic patients.

Bilateral epidural extension of thoracic capillary vertebral (intraosseous) hemangioma mimicking spinal meningioma.

We describe a rare case of vertebra (intraosseous) hemangioma with bilateral and symmetrical epidural extension causing cord compression in a 24-year-old woman. The epidural component was isointense to cord on both T1 and T2 sequences, and enhanced markedly and homogenously following gadolinium administration. The gradual in onset and progressive nature with the typical enhancing pattern lead the neurosurgeon to the more common diagnosis of spinal meningioma. Epidural extension of vertebral hemangiomas causing cord compression is rarely reported. Review of literatures reveal that cases that have been reported are of unilateral extension into epidural space and of cavernous type. This is the first case report of capillary vertebral (intraossous) hemangioma with bilateral extension through both intervetebral foramen into the epidural space causing myelopathy.

Use of lithium in the treatment of thyrotoxicosis.

OBJECTIVES: To evaluate the efficacy and safety of lithium in the treatment of thyrotoxicosis, and to study the dose and serum levels at which therapeutic response occurs. DESIGN: Retrospective study. SETTING: Thyroid clinic of a regional hospital in Hong Kong. PATIENTS: Thirteen patients with thyrotoxicosis pending therapy with radioiodine or surgery, in whom thionamides were contra-indicated due to adverse reactions or failure of treatment. MAIN OUTCOME MEASURES: Free thyroxine levels, time to euthyroidism, and side-effects of lithium. RESULTS: A satisfactory response, defined as a fall by 40% or more in free thyroxine levels and clinical improvement, was achieved in eight patients within 1 to 2 weeks of lithium therapy. In four others, response occurred in 3 to 5 weeks. Response was slow and inadequate in one patient due to 'escape'. The median dosage of lithium was 750 mg daily, with a range of 500 to 1500 mg daily. The median serum lithium level was 0.63 mmol/L. Lithium toxicity was observed in one patient. CONCLUSIONS: A relatively low dose of lithium offers a safe and effective alternative means of controlling thyrotoxicosis in patients who cannot tolerate or do not respond to thionamides.

Combined orbital irradiation and systemic steroids compared with systemic steroids alone in the management of moderate-to-severe Graves' ophthalmopathy: a preliminary study.

OBJECTIVE: To assess the efficacy and safety of combined orbital irradiation and systemic steroids in the management of moderate-to-severe Graves' ophthalmopathy. DESIGN: Single-blind randomised prospective study. SETTING: Regional hospital, Hong Kong. PATIENTS: Sixteen patients with active moderate-to-severe Graves' ophthalmopathy who were randomly assigned to steroid therapy (ST group) or combination therapy of orbital irradiation and systemic steroids (SRT group) between June 2000 and June 2003. MAIN OUTCOME MEASURES: NOSPECS scoring system, total eye score, subjective eye score, and extra-ocular muscle thickness as determined by either computed tomographic or magnetic resonance imaging scans. RESULTS: The study was completed by 15 of 16 patients. Both groups experienced improvement in total eye score, soft tissue swelling, ocular motility, visual acuity, and subjective eye score at 52-week follow-up. Total eye score improved earlier in the SRT group, achieving statistical significance (P<0.05) at as early as 4 weeks of follow-up. Improvement in ocular parameters was greater and led to a significantly greater reduction in total eye score than in the ST group at weeks 16, 24, and 52. Maximum extra-ocular muscle thickness was significantly reduced in the SRT group only. No change was observed in proptosis in either group. No serious adverse effect was observed with the addition of orbital irradiation to steroid therapy. CONCLUSION: A combination of orbital irradiation and systemic steroids is well tolerated and more effective than steroids alone in the treatment of active moderate-to-severe Graves' ophthalmopathy. It achieves greater and more rapid improvement in soft tissue swelling, ocular motility, and visual acuity.

The effect of exogenous lymphokines on immunoglobulin production and lymphocyte proliferation in renal transplant patients.

Peripheral blood mononuclear cells from stable long-term kidney transplant patients were activated in vitro by Staphylococcus Aureus Cowan I (SAC) (a B cell mitogen). The effect of exogenous interleukin 2 and/or B cell growth factor (BCGF) on these cells was measured by 3H-thymidine incorporation and immunoglobulin production. Both proliferation and Ig production were lower in SAC-activated cells from transplanted patients compared to controls (P less than 0.01). BCGF significantly enhanced blastogenesis (P less than 0.01) and Ig production (P less than 0.01) in SAC-treated cells from either patients or controls; however, the SAC- and BCGF-treated cells of transplant patients did not reach normal proliferation or immunoglobulin production values (P less than 0.001, P less than 0.01, respectively). The addition of IL-2 to SAC-activated cells also increased proliferation and Ig production both in controls (P less than 0.05) and patients (P less than 0.005). However, cells from transplant patients treated with SAC and IL-2 did not reach the normal levels of proliferation or immunoglobulin production (P less than 0.05 for both). IL-2 did not enhance the increase of immunoglobulin production brought about by BCGF. SAC-activated B cells from transplant patients do not proliferate normally and do not produce normal amounts of Ig. The addition of IL-2 and BCGF results in a partial but subnormal improvement in both proliferation and Ig production. We conclude that the B cell abnormality in transplant patients may be due to lack of T cell lymphokines and an intrinsic B cell defect. These results suggest that the administration of exogenous lymphokines to transplant patients with B cell dysfunction may be clinically useful.

Pretransplant crossmatch status and immunoglobulin production in renal transplant recipients.

The factors responsible for B cell regulation in stable renal transplant patients are unknown. To examine these control mechanisms, the B cell responses to 4 mitogens (pokeweed, wheat germ agglutinin, lipopolysaccharide, and SAC-1), which are known to stimulate B cells by different mechanisms, were measured in two groups of stable long-term (greater than 1 year post-transplant) renal transplant recipients. The first group were patients who had been transplanted under conditions of a negative crossmatch on all available pretransplant sera (negative crossmatch group) and the second group were patients who might have a unique regulation of B cell function in that they had been successfully transplanted under the conditions of a negative crossmatch using sera at the time of transplant but with pretransplant sera that gave a positive donor-specific T cell crossmatch (positive crossmatch group). Stable transplant patients were found to have significantly impaired responses to all four mitogens tested. Furthermore there were no differences in the responses of the negative crossmatch patients as compared with the positive crossmatch patients. The lack of response to mitogens was not due to a lack of proliferation of cells or to a loss of viability in culture. The number of cells in culture was the same in negative crossmatch patients and controls but was significantly less than controls in positive crossmatch patients (P less than 0.001). These findings suggest an intrinsic B cell defect in all stable transplant patients, and that the degree of the impaired B cell responses is the same in positive and negative crossmatch patients. In addition in positive crossmatch patients, there is a decrease in the percentage B cells that resulted after separation on a Ficoll-Paque gradient.

Acute intestinal graft-versus-host disease in a syngeneic bone marrow transplant recipient.

BACKGROUND: We report a case of intestinal graft-versus-host disease (GVHD) in a syngeneic bone marrow transplant patient. METHODS: Several days after receiving a bone marrow transplant from his identical twin for treatment of non-Hodgkin's lymphoma, a 47-year-old man developed a skin rash and diarrhea. RESULTS: A colonic biopsy on day +15 revealed characteristic changes of acute intestinal GVHD. Molecular studies (microsatellite DNA and HLA sequence-specific primer polymerase chain reaction analyses) confirmed the genotypic identity of donor and host and the improbability of transfusion-associated GVHD. CONCLUSION: This case illustrates that pathological evidence of GVHD does not absolutely require the presence of genetic differences between host and donor and questions existing concepts about the nature of cyclosporine-induced GVHD.

HLA-C locus alleles in patients with psoriatic arthritis (PsA).

The aim of this investigation was to compare the frequency of alleles at the HLA-C locus in patients with psoriatic arthritis to that in the disease free population and to relate the HLA genes to disease phenotype in psoriatic arthritis (PsA). Ninety-four consecutive patients seen in the (PsA) clinic between April and July 1996 and 100 disease-free controls had HLA typing performed by both serologic and molecular techniques. Patients' disease was assessed according to a standard protocol. Fisher's exact test was used to compare the frequency of HLA alleles in the patients and controls. HLA-C determined by PCR-SSP decreased the frequency of non-identified, that is, "blank" (or null) alleles to 6% in patients and controls. HLA-Cw*0602 was present in 32 patients and 18 controls: allele frequency of 17% in the patients versus 9% in the controls (p < 0.01). Amongst patients with psoriatic arthritis, those who carried the HLA-Cw*0602 allele had a significantly earlier mean age of onset of their psoriasis (p = 0.003). This study confirms that molecular DNA techniques improve detection of C-locus alleles. The HLA-Cw*0602 is increased amongst patients with psoriatic arthritis compared to controls. The HLA-Cw*0602 is associated with an earlier age of onset of psoriasis.

HLA-DRB1*04 alleles in psoriatic arthritis: comparison with rheumatoid arthritis and healthy controls.

Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis usually seronegative for rheumatoid factor. An increased frequency of HLA-DR4 has been noted in PsA, particularly among patients with a rheumatoid arthritis like (RA) arthritis. The aim of the current investigation was to compare HLA-DRB1*04 alleles in patients with PsA, patients with RA, and healthy controls. Sample size calculations based on the frequency of HLA-DR4 suggested that 90 individuals in each patient group would be sufficient to address our question. Therefore, 90 HLA-DRB1*04 positive patients from each patient group underwent high resolution molecular typing and were included in this study. Although HLA-DRB1*0401 was the most frequent allele in all groups, its frequency among the PsA patients was lower than that of RA patients and controls. HLA-DRB1*0402 was higher among patients with PsA. Patients with RA were more likely to have more than one shared epitope allele than either PsA or the healthy control group. HLA-DQB1 alleles did not contribute further information. We suggest that the differences in the class II HLA epitope(s) may also be related to interaction specificity with another molecule functioning in the immune response to a putative arthritogenic antigen and result in differences in disease expression.

HLA-B8, immunoglobulins, and antibody responses in alcohol-related liver disease.

Ninety-two British, caucasian, alcoholic patients with liver disese were grouped on the basis of hepatic histology into fatty change, hepatitis with or without cirrhosis, and cirrhosis alone. Men with alcoholic hepatitis with or without cirrhosis showed an increased incidence of the histocompatibility antigen HLA-B8 (P less than 0.02). Increased measles antibody titres were found in patients without cirrhosis with or without hepatitis and were associated with the B8 phenotype in both sexes. Rubella antibody titres and percentage DNA-binding were raised in patients with cirrhosis and showed no association with the B8 phenotype. Concentrations of IgM and IgA were were raised in patients with stetosis and with hepatitis, while in patients with cirrhosis IgG concentrations were also increased. Low titres of autoantibodies were found in all histological groups. It is possible that the development of hepatitis in response to alcohol abuse may be influenced, at least in men, by a gene linked to the B locus. Otherwise, immune processes associated with alcohol-related liver disease are probably secondary phenomena.

Meta-analysis of streptokinase and heparin in deep vein thrombosis.

The efficacy and safety of streptokinase and heparin in deep vein thrombosis (DVT) were compared in a meta-analysis. Randomized trials in which streptokinase (followed by heparin) and heparin alone were compared in treating phlebographically documented acute DVT were identified from MEDLINE and other sources for a meta-analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) based on the logit method were computed for each study. A fixed-effect model was used to combine the study results, enabling differences between streptokinase recipients and recipients of heparin alone to be expressed as summary ORs with 95% CIs. Significantly more streptokinase recipients achieved thrombolysis than recipients of heparin alone (summary OR, 6.24; 95% CI, 3.62 to 10.78). One study was identified as an outlier and excluded from the analysis. The meta-analysis then showed that streptokinase recipients were significantly less likely to have postthrombotic changes (summary OR, 0.40; 95% CI, 0.18 to 0.88) and postphlebitic changes (summary OR, 0.32; 95% CI, 0.12 to 0.86) in phlebographic evaluation. The frequency of major bleeding was significantly higher among streptokinase recipients than recipients of heparin alone (summary OR, 3.78; 95% CI, 1.26 to 11.32). A meta-analysis showed that, compared with heparin alone, streptokinase therapy for DVT was associated with significantly more frequent thrombolysis and major bleeding; after exclusion of one outlying study, analysis showed that streptokinase therapy was associated less frequently than heparin alone with postthrombotic changes (assessed by phlebographic evaluation) and postphlebitic syndrome.

Novel hybrid GPU-CPU implementation of parallelized Monte Carlo parametric expectation maximization estimation method for population pharmacokinetic data analysis.

The development of a population PK/PD model, an essential component for model-based drug development, is both time- and labor-intensive. A graphical-processing unit (GPU) computing technology has been proposed and used to accelerate many scientific computations. The objective of this study was to develop a hybrid GPU-CPU implementation of parallelized Monte Carlo parametric expectation maximization (MCPEM) estimation algorithm for population PK data analysis. A hybrid GPU-CPU implementation of the MCPEM algorithm (MCPEMGPU) and identical algorithm that is designed for the single CPU (MCPEMCPU) were developed using MATLAB in a single computer equipped with dual Xeon 6-Core E5690 CPU and a NVIDIA Tesla C2070 GPU parallel computing card that contained 448 stream processors. Two different PK models with rich/sparse sampling design schemes were used to simulate population data in assessing the performance of MCPEMCPU and MCPEMGPU. Results were analyzed by comparing the parameter estimation and model computation times. Speedup factor was used to assess the relative benefit of parallelized MCPEMGPU over MCPEMCPU in shortening model computation time. The MCPEMGPU consistently achieved shorter computation time than the MCPEMCPU and can offer more than 48-fold speedup using a single GPU card. The novel hybrid GPU-CPU implementation of parallelized MCPEM algorithm developed in this study holds a great promise in serving as the core for the next-generation of modeling software for population PK/PD analysis.