RESUMEN
BACKGROUND: There is little information regarding gender-specific measurements of colonic transit and anorectal function in patients with defecation disorders (DD). To compare overall colonic transit by gender in DD. METHODS: In 407 patients with constipation due to DD diagnosed by a single gastroenterologist (1994-2012), DD was characterized by anorectal manometry, balloon expulsion test, and colonic transit by scintigraphy. The primary endpoint was overall colonic transit (geometric center, GC) at 24 h (GC24). Effects of gender in DD on colonic transit, and comparison with transit in 208 healthy controls were assessed by Mann-Whitney rank sum test. Secondary endpoints were maximum anal resting (ARP) and squeeze (ASP) pressures. We also tested association of the physiological endpoints among DD females by pregnancy history and among DD patients by colectomy history. KEY RESULTS: The DD patients were 67 males (M) and 340 females (F). Significant differences by gender in DD patients were observed in GC24 (median: M: 2.2; F: 1.8; P = 0.01), ARP (median: M: 87.8 mmHg; F: 82.4 mmHg; P = 0.04), and ASP (median: M: 182.4 mmHg; F: 128.7 mmHg; P < 0.001). GC24 was slower in DD compared with same-gender healthy controls. GC24 did not differ among DD females by pregnancy history. Anorectal functions and upper GI transit did not differ among DD patients by colectomy history. CONCLUSIONS & INFERENCES: Patients with DD have slower colonic transit compared with gender-matched controls. Among DD patients, males have higher ARP and ASP, and females have slower colonic transit. Although the clinical significance of these differences may be unclear, findings suggest that interpretation of these tests in suspected DD should be based on same-gender control data.
Asunto(s)
Canal Anal/fisiopatología , Colon/fisiopatología , Estreñimiento/fisiopatología , Defecación/fisiología , Tránsito Gastrointestinal/fisiología , Adulto , Femenino , Humanos , Masculino , Manometría , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Quantitative hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) assays are emerging as effective tools of on-treatment predictors of response to antiviral agents, in addition to monitoring serum HBV DNA levels. However, the dynamic relationship between quantitative HBsAg, as well as HBeAg and HBV DNA, and the predictability of subsequent clinical outcomes during entecavir (ETV) therapy remain unclear. Eighty-two patients with HBeAg-positive chronic hepatitis B (CHB) received ETV therapy for ≥3 years. Virologic response (VR) after 3 years of ETV therapy was achieved in 73 (89.0%) patients. Among baseline and on-treatment factors, on-treatment HBV DNA levels performed better with respect to the prediction of response than HBsAg and HBeAg levels. Especially, the performance of absolute values of HBV DNA with respect to response was superior to HBV DNA decline from the baseline. The best predictive value was an absolute HBV DNA level of 2.3 log(10) IU/mL at month 6 (areas under the curve [AUROC], 0.977; 95% CI, 0.940-1.000; P < 0.001). HBeAg seroconversion after 3 years of therapy was achieved in 26 (31.7%) patients. On-treatment HBeAg levels performed better with respect to the prediction of seroconversion than HBsAg and HBV DNA levels. The best cut-off value for the HBeAg level at month 12 for the prediction of seroconversion was 0.62 log(10) PEIU/mL. Although the HBsAg level at baseline is often used to predict the antiviral potency of entecavir, on-treatment HBV DNA and HBeAg levels are more helpful for prediction of subsequent clinical outcomes in HBeAg-positive CHB patients with entecavir treatment.
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Antivirales/administración & dosificación , ADN Viral/sangre , Monitoreo de Drogas/métodos , Guanina/análogos & derivados , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Hepatitis B Crónica/tratamiento farmacológico , Adulto , Femenino , Guanina/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Resultado del TratamientoRESUMEN
BACKGROUND: Gastric emptying (GE) is measured in pharmacodynamic and diagnostic studies. Our aim was to assess inter- and intra-subject coefficients of variation (COV) of scintigraphic GE measurements in healthy subjects, and associations of GE with gender and body mass index (BMI). METHODS: Data from participants with scintigraphic measurements of gastric emptying of solids were analyzed. Primary endpoints were gastric emptying T(1/2) (GE T(1/2) ) and GE at 1, 2, 3, and 4 h. KEY RESULTS: The patient cohort consisted of 105 males and 214 females; at least two studies were performed in 47 subjects [16 males (M), 32 females (F)]. Inter-subject COV (COV(inter) ) for GE T(1/2) were similar in M and F: overall 24.5% (M 26.0%, F 22.5%); COV are predictably lowest for GE at 4 h (COV(inter) 9.6%). COV(intra) for T(1/2) and GE at 4 h were overall 23.8% and 12.6%, and were similar to COV(inter) values. Gender (but not age or BMI) was significantly associated with GE T1/2 [P < 0.001, F 127.6 ± 28.7 (SD) min; M 109.9 ± 28.6 min] and with GE at 1 h and 2 h. Repeat GE T(1/2) values in 47 participants were significantly correlated (r = 0.459, P < 0.001) with median difference of -6 min (mean -1.6, range -56 to 72 min). Bland-Altman plots showed Δ GE T(1/2) similarly distributed across mean GE T(1/2) 100-155 min, and across studies conducted 90-600 days apart. CONCLUSIONS & INFERENCES: Inter-subject variations in scintigraphic GE results are only slightly higher than the intra-subject measurements, which are also reproducible over time in healthy volunteers. Gender, but not BMI, is significantly associated with GE results.
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Vaciamiento Gástrico/fisiología , Estómago/diagnóstico por imagen , Índice de Masa Corporal , Femenino , Humanos , Masculino , CintigrafíaRESUMEN
BACKGROUND: Tapentadol is a mu-opioid receptor agonist and norepinephrine reuptake inhibitor. In clinical trials, tapentadol provided somatic pain relief comparable to mu-opioids such as oxycodone, with significantly less gastrointestinal adverse effects. The acute effects of tapentadol on gastrointestinal and colonic transit are unclear. AIM: To compare acute effects of oral tapentadol and oxycodone on gastric, small bowel and colonic transit of solids in 38 healthy human subjects. METHODS: In a randomised, parallel-group, double-blind, placebo-controlled study of the effects of identical-appearing tapentadol immediate release (IR), 75 mg t.d.s., or oxycodone IR, 5 mg t.d.s., for 48 h, we measured gastric (GE), small bowel (SBT measured as colonic filling at 6 h) and colonic transit by validated scintigraphy. Drug was commenced on the evening before the start of the transit test. The primary endpoints were overall colonic transit (geometric centre, GC) at 24 h and GE half-time (t1/2 ). ancova of transit data included gender or BMI as covariates. Adverse effects were summarised. RESULTS: At the doses tested, oxycodone and tapentadol significantly delayed GE t1/2 and SBT, but not overall colonic transit, compared to placebo. Transit profiles in all regions were not significantly different between oxycodone and tapentadol at the doses tested. Both oxycodone and tapentadol were associated with nausea and central effects attributable to central opiate effects. CONCLUSIONS: Tapentadol significantly delayed gastric emptying t1/2 and small bowel transit, similar to oxycodone. These data suggest that acute administration of tapentadol may not have significant advantages over standard mu-opioids, in terms of the potential to avoid upper gastrointestinal motor dysfunction.
Asunto(s)
Analgésicos Opioides/efectos adversos , Tránsito Gastrointestinal/efectos de los fármacos , Oxicodona/efectos adversos , Fenoles/efectos adversos , Adulto , Analgésicos Opioides/administración & dosificación , Método Doble Ciego , Femenino , Humanos , Masculino , Náusea/inducido químicamente , Oxicodona/administración & dosificación , Fenoles/administración & dosificación , Receptores Opioides mu/agonistas , TapentadolRESUMEN
The efficacy of lamivudine re-treatment in chronic hepatitis B (CHB) patients who relapse after HBeAg seroconversion with lamivudine has not been investigated. The aim of this study was to evaluate the efficacy of lamivudine re-treatment in relapsed patients. Among 192 patients who had achieved HBeAg seroconversion with lamivudine at a dose of 100 mg/day, 121 patients discontinued lamivudine. Relapse occurred in 49 patients (40.5%). Thirty-three relapsed patients received lamivudine re-treatment for at least 6 months. The mean duration of lamivudine re-treatment was 16 months and the follow-up period was 8.9 months. HBeAg seroconversion was achieved in 23 patients (69.7%). The cumulative HBeAg seroconversion rates at 5, 9, and 12 months were 60, 64, and 67%, respectively. The mean time to HBeAg seroconversion in lamivudine re-treatment was shorter than that in the initial therapy (4.7 months vs. 9.7 months). Viral breakthrough occurred in six (18.2%) patients. All patients with viral breakthrough were accompanied by elevation of serum alanine aminotransferase (ALT) levels. Among 15 patients who discontinued lamivudine re-treatment after HBeAg seroconversion, relapse occurred in six patients (40%). All relapses occurred within 9 months after the discontinuation of lamivudine re-treatment. In conclusion, lamivudine re-treatment in relapsed patients after initial lamivudine therapy had a higher response rate and shorter duration to HBeAg seroconversion than during the initial therapy. However, HBeAg seroconversion induced by lamivudine re-treatment was not durable.