Symptoms In Japanese Patients Research Articles

Longitudinal long COVID symptoms in Japanese patients after COVID-19 vaccinations

We conducted a subgroup analysis of a study on the long-term effects of COVID-19 (long COVID) in Japan to assess the effect of vaccination on long COVID symptoms. We assessed the clinical course of 111 patients with long COVID at the time of vaccination. The follow-up period was one year from the onset of COVID-19 or until the administration of the third vaccine dose. Of the 111 patients, 15 (13.5%) reported improvement, four (3.6%) reported deterioration, and 92 (82.9%) reported no change in their long COVID symptoms after vaccination. The most common long COVID symptoms before vaccination were alopecia, dyspnea, muscle weakness, fatigue, and headache among participants whose symptoms improved. Reduced dyspnea and alopecia were the most frequently reported improvements in symptoms after vaccination. Some symptoms persisted, including sleep disturbance, myalgia, and hypersensitivity. Vaccination did not appear to have a clinically important effect on patients with long COVID symptoms.

Effectiveness of Long-Term Treatment with Brodalumab on Anxiety or Depressive Symptoms in Japanese Patients with Psoriasis: The ProLOGUE Study.

Evidence on treatment effectiveness in patients with psoriasis having anxiety or depressive symptoms helps shared decision-making. This single-arm, open-label, prospective study-ProLOGUE-was conducted to assess the effectiveness of brodalumab on self-assessed anxiety and depressive symptoms in Japanese patients with psoriasis. Patients aged ≥ 18years with plaque psoriasis without peripheral arthritis symptoms who had responded inadequately to current therapies were enrolled at 15 Japanese facilities and received brodalumab 210mg subcutaneously. A total of 73 patients were enrolled (male, 82%; median age, 54years). The proportion of patients without anxiety symptoms changed significantly from baseline (72.6%) to weeks 12 (88.9%, p = 0.008) and 48 (87.7%, p = 0.02); the proportion of patients without depressive symptoms did not change significantly. The Generalized Anxiety Disorder-7 score (median [quartile(Q)1-Q3], 1.0 [0.0-5.0] at baseline; 0.0 [0.0-2.0] at week12, p = 0.008; and 0.0 [0.0-1.0] at week 48, p = 0.007) and Patient Health Questionnaire-8 score (median [Q1-Q3], 2.0 [0.0-4.0] at baseline; 1.0 [0.0-4.0] at week12, p = 0.03; and 0.0 [0.0-2.0] at week48, p = 0.004) significantly decreased after treatment. The median Psoriasis Area and Severity Index scores after treatment were < 1, irrespective of the presence of baseline anxiety or depressive symptoms. At week 12, the health-related quality of life was more impaired in patients with versus without baseline depressive symptoms, which largely resolved at week48. Brodalumab treatment resulted in the reduction of the levels of self-assessed anxiety and depressive symptoms in Japanese patients with psoriasis. Unlike anxiety symptoms, depressive symptoms did not resolve completely with brodalumab treatment. Patients with psoriasis having depressive symptoms may require long-term treatment. UMIN Clinical Trials Registry identifier: UMIN000027783, Japan Registry of Clinical Trials identifier: jRCTs031180037.

The prevalence and associated factors of seasonal exacerbation of subjective symptoms in Japanese patients with restless legs syndrome

ObjectivesTo elucidate the prevalence of seasonal exacerbation in patients with restless legs syndrome (RLS) and identify its associated factors. MethodsWe investigated the presence/absence of seasonal exacerbation of RLS by distributing self-administered questionnaires with an interval of three years. Patients who reported having seasonal exacerbation in both surveys were defined as having seasonal exacerbation. RLS severity was determined using the International Restless Legs Syndrome Rating Scale (IRLS). ResultsAmong 180 patients, 89 reported having seasonal exacerbation in the first survey. Among them, only two reported not having seasonal exacerbation in the second survey; thus, 87 (48.3%) patients were considered to have a seasonal exacerbation. Although many of them (68 out of 87, 78.2%) experienced exacerbation in spring or summer, 19 out of 87 (21.8%) reported that their symptoms worsened in fall or winter. All the patients in this study had mild to moderate degrees of RLS severity according to the IRLS score. Multiple logistic regression analyses revealed that having a family history of RLS (p < 0.05) and moderate RLS (p < 0.001) were significantly associated with the presence of seasonal exacerbation. ConclusionsThis study revealed that approximately half of all RLS patients had seasonal exacerbation of the symptoms and that about 80% of the exacerbation was observed during the spring/summer season. Moreover, seasonal exacerbation is likely to be present even in patients whose symptoms had been improved to moderate severity with pharmacological treatment.

Galcanezumab Effects on Migraine Severity and Symptoms in Japanese Patients with Episodic Migraine: Secondary Analysis of a Phase 2 Randomized Trial.

Galcanezumab, a humanized monoclonal antibody against calcitonin gene-related peptide, is a preventive migraine treatment. In global, randomized, placebo-controlled trials, galcanezumab reduced migraine headache severity and the frequency of migraine headaches associated with nausea and/or vomiting, photophobia and phonophobia, prodromal symptoms, or aura. We report secondary analyses from a Japanese phase 2 trial that assessed the effect of galcanezumab on migraine headache severity, frequency of migraine-associated symptoms, and frequency of migraine headaches during menstrual periods in Japanese patients with episodic migraine. Adults with migraine (International Classification of Headache Disorders, 3rd edition; 4-14 migraine headache days/month) were randomized (2:1:1) to amonthly placebo (n = 230), 120mg galcanezumab (240mg loading dose; n = 115), or 240mg galcanezumab (n = 114) for 6months (double-blind). Patients recorded migraine headache days, severity, and symptoms in an electronic diary. Changes from baseline were analyzed (mixed model for repeated measures). Both galcanezumab doses significantly reduced the number of monthly moderate-to-severe and severe migraine headache days compared with placebo, overall (difference in least-squares mean change from baseline, 120mg/240mg versus placebo: moderate-to-severe, -1.9/-1.8days; severe: -0.4/-0.4days) and in each month;mean severity score was significantly reduced in the 240mg group. Both galcanezumab doses significantly reduced the number of migraine headache days with nausea/vomiting (-1.1/-1.0days), photophobia/phonophobia (-2.3/-1.7days), prodromal symptoms (-0.7/-0.8days), and aura (-0.7/-0.7days). In most cases, the proportion of migraine headache days with these symptoms was reduced by galcanezumab. Both galcanezumab doses reduced the number of migraine headache days occurring during menstrual periods (n = 269; -0.8/-0.9days). Once-monthly galcanezumab significantly reduced the frequency of migraine headache days with moderate-to-severe or severe headache, migraine headache days with migraine-associated symptoms, and migraine headache days during menstrual periods in Japanese patients with episodic migraine, consistent with results from global studies. ClinicalTrials.gov (NCT02959177).

Therapeutic Potential of Vortioxetine for Anhedonia-Like Symptoms in Depression: A Post Hoc Analysis of Data from a Clinical Trial Conducted in Japan.

AimAnhedonia in major depressive disorder may be resistant to first-line antidepressants. We examined the effect of vortioxetine, a multimodal antidepressant, on anhedonia-like symptoms in Japanese patients with major depressive disorder.MethodsThis was a post hoc analysis of an 8-week, randomized, double-blind, placebo-controlled, phase 3 study of vortioxetine (10 mg or 20 mg) in Japanese patients aged 20–75 years with recurrent major depressive disorder and a Montgomery–Åsberg Depression Rating Scale (MADRS) total score of at least 26. The primary outcome was the mean change from baseline to week 8 in anhedonia-like symptoms as measured by MADRS anhedonia factor score, composed of: Q1, apparent sadness; Q2, reported sadness; Q6, concentration; Q7, lassitude; and Q8, inability to feel. Mean change in MADRS total score and anhedonia factor score were compared among treatment groups, with data categorized by median baseline anhedonia factor score (0–17 or ≥18).ResultsData were available for 489 patients. The least-squares mean difference in MADRS anhedonia factor score change from baseline to week 8 versus placebo was −1.34 for vortioxetine 10 mg (P = 0.0300) and −1.77 for vortioxetine 20 mg (P = 0.0044). The least-squares mean difference between vortioxetine and placebo in MADRS total score change from baseline to week 8 was −3.11 (10 mg dose) and −3.37 (20 mg dose) for patients with a higher baseline anhedonia factor score (≥18), and −2.08 (10 mg) and −2.61 (20 mg) for patients with a lower baseline score (0–17).ConclusionThis post hoc analysis suggests that vortioxetine may have therapeutic potential in patients with anhedonia-like symptoms of major depressive disorder. ClinicalTrials.gov identifier for primary study: NCT02389816.

Difference in health‐related quality of life between anxiety and depressive symptoms in Japanese patients with plaque psoriasis: the ProLOGUE study

Anxiety symptoms and depressive symptoms are observed in approximately 20%-50% and 30% of patients with psoriasis, respectively.1,2 To date, however, evidence for the association of these symptoms with patients' direct perception of their disease (called patient-reported outcomes [PROs]) remains limited. We assessed the association of anxiety symptoms and depressive symptoms with the severity of psoriasis, psoriatic symptoms, health-related quality of life (HRQoL), and satisfaction levels in Japanese patients with psoriasis using baseline data of participants from a single-arm, open-label, multicenter, prospective cohort study-ProLOGUE (Japan Registry of Clinical Trials identifier: jRCTs031180037).3 Patients (aged ≥18 years) who had plaque psoriasis without peripheral arthritis symptoms and were eligible for self-administration of brodalumab were enrolled at 15 facilities across Japan (study period, October 2017-March 2020).3.

Characteristics of Neurological Symptoms in Adult Japanese Patients with Fabry Disease.

Objective Fabry disease (FD) is a hereditary lysosomal storage disease that has been highlighted as a possible etiology of stroke at a young age and presents with other various neurological symptoms. Since FD is rare, limited information is currently available on the prevalence of neurological symptoms in Japanese patients with FD. Therefore, we examined the characteristics of neurological symptoms and brain magnetic resonance imaging (MRI) findings in adult Japanese patients with FD. Methods This was a retrospective, single-center study. We reviewed neurological symptoms and brain MRI findings in the medical records of 12 adult Japanese patients with FD diagnosed by a gene analysis of the α-galactosidase gene. Results Ten out of 12 patients with FD presented with the following neurological symptoms: acroparesthesia (n=6), headache (n=5) [migraine (n=4)], hypohidrosis (n=5), and cerebral infarction (n=3). Two and three of the patients with migraine were complicated by ischemic stroke and coronary spastic angina, respectively. Five and 10 patients presented with periventricular hyperintensity and deep white matter hyperintensity, respectively, on brain MRI. Two out of eight patients had cerebral microbleeds. Seven out of 11 patients had a dilated basilar artery diameter on magnetic resonance angiography. There were no patients with the pulvinar hyperintensity sign. Conclusion Patients with FD present with various neurological symptoms. Headache, particularly migraine, might be a major neurological symptom in patients with FD. Since migraine, ischemic stroke, and coronary spastic angina might occur together in FD, caution is needed when administering triptan to FD patients with migraine.

Treatment Satisfaction With Current Medications for Chronic Constipation: An Internet Survey of Japanese Patients.

This survey aims to determine relevant patient characteristics, treatment satisfaction, and bothersome symptoms in Japanese patients with chronic constipation (CC) treated at medical institutions. Epidemiological surveys of Japanese patients with CC are limited. This internet survey, conducted in 2017, included 500 adults (selected from 589 respondents to match age composition ratio in Japan) who experienced constipation-like symptoms for ≥6 months, were treated at medical institutions for symptoms, and were taking any prescribed medication. Of 500 patients, 65.6% were female and 62.6% had experienced constipation for >10 years. Abdominal bloating, infrequent bowel movement, hard consistency of stool, and difficulty of defecation were the most frequently reported and most bothersome symptoms in males and females. Overall, 29% of patients were satisfied with treatment (36% of males, 26% of females); the individual major CC symptom with the highest level of treatment satisfaction was infrequent bowel movement (31% of total, 45% of males, 26% of females). The level of treatment satisfaction for most individual major CC symptoms was lower in females than in males, and overall treatment satisfaction by therapeutic categories ranged from 16% to 46%. Mean overall treatment satisfaction, as well as mean treatment satisfaction for each major symptom, decreased with increasing number of treatments. The survey results suggest that conventional treatment options were not effective enough to improve bothersome symptoms or treatment satisfaction. Treatment selection that is tailored to individual symptoms and takes patient characteristics into consideration may be key to improving patients' treatment satisfaction.

Efficacy, tolerability, and safety of lurasidone for acute schizophrenia: A systematic review and network meta-analysis of phase 3 trials in Japan.

IntroductionConsidering that the efficacy results of the Japan lurasidone phase 3 trials for acute schizophrenia were inconsistent, we conducted a systematic review and a random‐effect model network meta‐analysis of those trials to examine whether lurasidone was beneficial for the treatment of Japanese patients with acute schizophrenia.MethodsThe study included the double‐blind, randomized trial in Japan that included patients with acute schizophrenia. Efficacy outcomes were improvement of the Positive and Negative Syndrome Scale total score (PANSS‐T, primary), positive (PANSS‐P), negative (PANSS‐N), and general (PANSS‐G) subscale scores; and Clinical Global Impression‐Severity Scale (CGI‐S) score and response rate. Other outcomes were discontinuation rates and incidence of individual adverse events.ResultsWe included four studies (n = 1,608). Although both lurasidone 40 mg/d (LUR40) and 80 mg/d (LUR80) outperformed placebo in PANSS‐T [standardized mean difference (95% credible interval): LUR40 = −0.298 (−0.420, −0.176), LUR80 = −0.170 (−0.320, −0.019)], PANSS‐P, and CGI‐S scores, LUR40 but not LUR80 outperformed placebo in PANSS‐N and PANSS‐G scores and response rate. LUR40 outperformed LUR80 regarding PANSS‐G score. Both LUR40 and LUR80 were associated with a higher incidence of akathisia, somnolence, and increased body weight compared with placebo. Compared with placebo, LUR40 was associated with a higher incidence of weight gain (≥7%), and LUR80 was associated with a higher incidence of dystonia and weight loss (≥7%) and higher Drug‐Induced Extrapyramidal Symptoms Scale score.ConclusionsBoth LUR40 and LUR80 improved overall symptoms in Japanese patients with acute schizophrenia. However, LUR80 seemed to have a risk of extrapyramidal symptoms.

Time-dependent changes in lower urinary tract symptoms in Japanese patients who undergo bariatric and metabolic surgery.

Time-dependent changes in lower urinary tract symptoms in Japanese patients who undergo bariatric and metabolic surgery.

Evaluation of the dose and efficacy of ruxolitinib in Japanese patients with myelofibrosis.

Ruxolitinib, a potent JAK1/JAK2 inhibitor, improved splenomegaly and myelofibrosis-associated symptoms and prolonged survival compared with placebo and best available therapy in the phase 3 COMFORT studies. Although cytopenias were the most common adverse events associated with ruxolitinib treatment, a COMFORT-I analysis showed that they were managed effectively with dose modifications, without a negative impact on the efficacy of ruxolitinib. Subsequently, studies A2202 and AJP01 showed that ruxolitinib is an effective treatment for Japanese patients with myelofibrosis. We conducted a pooled analysis of these two studies (N=81) to evaluate the association between ruxolitinib dose and changes in spleen volume or symptoms in Japanese patients. Most patients began treatment at 15 or 20mg twice daily (BID); 70% received a final titrated dose≥10mg BID. Overall, 91% of patients exhibited spleen volume reductions; patients with final titrated doses≥10mg BID had larger spleen volume reductions. Similarly, 83% of patients showed improvements in symptom scores; those with a final titrated dose of 20 or 25mg BID had the greatest reductions. Consistent with COMFORT-I, this pooled analysis indicates that, despite dose adjustments, ruxolitinib provides spleen and symptom control in Japanese patients, with higher doses associated with better responses.

An observational study of duloxetine versus SSRI monotherapy for the treatment of painful physical symptoms in Japanese patients with major depressive disorder: primary analysis.

ObjectiveThe objective of this study was to assess the effectiveness of duloxetine monotherapy, in comparison with selective serotonin reuptake inhibitor (SSRI) monotherapy, in the treatment of painful physical symptoms (PPS) in Japanese patients with major depressive disorder (MDD) in real-world clinical settings.MethodsThis was a multicenter, 12-week prospective, observational study. This study enrolled MDD patients with at least moderate PPS, defined as a Brief Pain Inventory-Short Form (BPI-SF) average pain score (item 5) ≥3. Patients were treated with duloxetine or SSRIs (escitalopram, sertraline, paroxetine, or fluvoxamine) for 12 weeks, and PPS were assessed by BPI-SF average pain score. The primary outcome was early improvement in the BPI-SF average pain score at 4 weeks post-baseline.ResultsA total of 523 patients were evaluated for treatment effectiveness (duloxetine N=273, SSRIs N=250). The difference in BPI-SF average pain score between the two groups was not statistically significant at 4 weeks post-baseline, the primary endpoint (least-squares mean change from baseline [95% confidence interval]: duloxetine, −2.8 [−3.1, −2.6]; SSRIs, −2.5 [−2.8, −2.3]; P=0.166). There was a numerical advantage for duloxetine in improvement from 4 to 12 weeks post-baseline, and the difference was statistically significant at 8 weeks post-baseline (least-squares mean change from baseline [95% confidence interval]: duloxetine, −3.6 [−3.9, −3.3]; SSRIs, −3.1 [−3.4, −2.8]; P=0.023). The 30% and 50% responder rates were significantly higher in patients treated with duloxetine at 4 and 8 weeks post-baseline. There were no serious adverse events experienced by duloxetine-treated patients. The rate of discontinuations due to adverse events was similar for duloxetine and the SSRIs (1.0% and 0.8% of patients, respectively).ConclusionIn this observational study, BPI-SF improvement was not significantly different at 4 weeks, the primary endpoint; however, patients treated with duloxetine tended to show better improvement in PPS compared to those treated with SSRIs.

Association between all-cause mortality and severity of depressive symptoms in patients with type 2 diabetes: Analysis from the Japan Diabetes Complications Study (JDCS)

ObjectiveThe aims of this study are to confirm whether the excess mortality caused by depressive symptoms is independent of severe hypoglycemia in patients with type 2 diabetes mellitus (T2DM) and to evaluate the association between all-cause mortality and degrees of severity of depressive symptoms in Japanese patients with T2DM. MethodsA total of 1160 Japanese patients with T2DM were eligible for this analysis. Participants were followed prospectively for 3years and their depressive states were evaluated at baseline by the Center for Epidemiologic Studies Depression Scale (CES-D). Cox proportional hazards model was used to evaluate the relative risk of all-cause mortality and was adjusted by possible confounding factors, including severe hypoglycemia, all of which are known as risk factors for both depression and mortality. ResultsAfter adjustment for severe hypoglycemia, each 5-point increase in the CES-D score was significantly associated with excess all-cause mortality (hazard ratio 1.69 [95% CI 1.26–2.17]). The spline curve of HRs for mortality according to total CES-D scores showed that mortality risk was slightly increased at lower scores but was sharply elevated at higher scores. ConclusionA high score on the CES-D at baseline was significantly associated with all-cause mortality in patients with T2DM after adjusting for confounders including severe hypoglycemia. However, only a small effect on mortality risk was found at relatively lower levels of depressive symptoms in this population. Further research is needed to confirm this relationship between the severity of depressive symptoms and mortality in patients with T2DM.

Prevalence of Irritable Bowel Syndrome-like Symptoms in Japanese Patients with Inactive Inflammatory Bowel Disease.

Background/AimsFew studies are available that have investigated the risk factors for overlapping irritable bowel syndrome (IBS)-like symptoms in patients with inactive inflammatory bowel disease (IBD). The present study has 3 objectives: (1) to assess the prevalence of IBS-like symptoms in Japanese patients with inactive IBD using Rome III criteria, (2) to examine the relationship of IBS-like symptoms to health related quality of life (HR-QOL), and (3) to investigate associations for developing IBS-like symptoms in patients with inactive IBD.MethodsIBS-like symptoms were evaluated using the Rome III questionnaire for functional gastrointestinal disorders. HR-QOL and hospital anxiety and depression scale were evaluated.ResultsIBS-like symptoms were found in 17.5% (7/40) of patients with inactive ulcerative colitis, 27.1% (29/107) of patients with inactive Crohn’s disease (CD), and 5.3% (23/438) of healthy control subjects. The QOL level was significantly lower and anxiety score was significantly higher in inactive CD patients with IBS-like symptoms than in those without such symptoms (P = 0.003, P = 0.009). Use of anti-anxiety drugs was associated with the presence of IBS symptoms (P = 0.045). HR-QOL score was lower and anxiety score was higher in patients with inactive ulcerative colitis, but the difference was not statistically significant.ConclusionsThe prevalence of IBS-like symptoms in inactive IBD patients was significantly higher than in healthy controls. Inactive CD patients with IBS-like symptoms has low QOL and anxiety; suggesting that anxiety may be associated with symptom development in such patients.

Preliminary evidence that rivastigmine-induced inhibition of serum butyrylcholinesterase activity improves behavioral symptoms in Japanese patients with Alzheimer's disease.

To investigate whether the inhibitory rate of serum butyrylcholinesterase (BuChE) activity in Japanese patients with Alzheimer's disease is correlated with cognitive function, behavioral symptoms and caregiver burden. A total of 61 patients with mild to moderately severe Alzheimer's disease who were not undergoing cholinesterase enzyme inhibitor/memantine combinatorial treatment received a rivastigmine (18 mg) patch for 24 weeks. The rate of inhibition of BuChE was correlated with scores obtained on cognitive (Mini-Mental State Examination), behavioral (the Japanese version of the modified Crichton Geriatric Behavioral Rating Scale [CGBRS] and Vitality Index [VI]) and burden (the Japanese version of Zarit Burden Inventory [ZBI]) scales; and the Clinical Global Impression of Change scale. The serum BuChE activity showed a significant decrease after 24 weeks compared with baseline (P < 0.001). Overall, significant effects were found in the Mini-Mental State Examination score, VI score and modified CGBRS score. We then divided patient groups into a high inhibitory rate (≥40%) group and a low inhibitory rate (<40%) group; there were significant improvements in the Mini-Mental State Examination score, VI score and modified CGBRS score in both groups. However, favorable results were seen in cooperation, restlessness and leisure on modified CGBRS subscales in the high inhibitory rate group (P < 0.001, P = 0.007, P < 0.001, respectively), and rehabilitation and other activities on VI subscales in the high inhibitory rate group (P = 0.005) compared with those in the low inhibitory rate group. Demonstrable significant improvements in behavioral symptoms, such as low cooperation, restlessness or low activities in patients with Alzheimer's disease, were achieved on inhibition of BuChE at a rate of 40% or more. Geriatr Gerontol Int 2017; 17: 1306-1312.

Relationship between the lesion location of acute ischemic stroke and early depressive symptoms in Japanese patients.

BackgroundApproximately one-third of stroke survivors suffer from post-stroke depression (PSD) in the acute or chronic stages. The presence of PSD in the acute stage after stroke is reportedly associated with poor patient prognosis; therefore, early recognition and treatment of PSD may alleviate these consequences. The aim of the current study was to examine the relationship between the lesion location and the presence of early depressive symptoms after acute ischemic stroke in Japanese patients.MethodsOur study included 421 patients who suffered from acute ischemic stroke. On the day of admission, the lesion location was determined using magnetic resonance imaging (MRI). Stroke severity was measured on the seventh day of hospitalization withat the National Institutes of Health Stroke Scale (NIHSS). On the tenth day of hospitalization, depressive symptoms were measured and functional assessments were performed with the Japan Stroke Scale (Depression Scale) (JSS-D) and functional independence measure (FIM), respectively.ResultsA total of 71 subjects (16.9 %) were diagnosed with depression. According to the multiple logistic regression analysis, the infarcts located at frontal and temporal lobes were found to be a significant independent risk factor of early depressive symptoms in the acute stage of stroke.ConclusionsPatients suffering from acute ischemic stroke, particularly in the frontal and temporal lobes, should be carefully assessed to detect and treat early depressive symptoms; such treatment may improve patient outcomes.

Prevalence of gastroesophageal reflux disease symptoms and effects of esomeprazole on the quality of life related to reflux and dyspepsia in patients on maintenance hemodialysis.

The prevalence of gastroesophageal reflux disease (GERD) symptoms has not been investigated in patients on maintenance hemodialysis in Japan, and few studies have reported the effect of proton pump inhibitors (PPIs) in hemodialysis patients with GERD symptoms. Here, we investigated the prevalence of GERD symptoms and the effects of the PPI esomeprazole on the quality of life related to reflux and dyspepsia in patients on maintenance hemodialysis. This was a cross-sectional/cohort study of hemodialysis outpatients implemented in 10 Japanese medical facilities from October 2012 to March 2014. The trial was registered in the UMIN Clinical Trial Registry (UMIN000009124). Forty-one of 385 patients (11%) reported GERD symptoms on the Global Overall Symptom (GOS) questionnaire. Multivariate logistic regression analysis identified the independent prognostic factors for GERD symptoms as a history of gastric ulcer and use of sevelamer hydrochloride or calcium polystyrene sulfonate. Participants with GERD symptoms completed the Quality of Life in Reflux and Dyspepsia, Japanese version (QOLRAD-J) questionnaire and were assigned to receive 4-week esomeprazole treatment (20 mg/day). This PPI therapy significantly improved all QOLRAD-J domains in the full analysis set (n = 28) and improved the GERD symptoms listed in the GOS questionnaire. Significantly impaired disease-specific quality of life (QOL) in the QOLRAD-J domains was observed in 44.4-74.1% of patients who had symptoms before treatment. The mean GOS and QOLRAD-J scores correlated significantly. Therapy with 20 mg/day esomeprazole appears to be efficacious for improving disease-specific QOL and GERD symptoms in Japanese patients on maintenance hemodialysis.

Association of severe hypoglycemia with depressive symptoms in patients with type 2 diabetes: the Fukuoka Diabetes Registry

ObjectiveAlthough many studies have investigated the clinical characteristics of patients with diabetes with depression in Western populations, there is a lack of information regarding other ethnicities. We studied the association...

Comparison of ropinirole controlled‐ and immediate‐release in Japanese patients with advanced Parkinson's disease

AbstractBackgroundIn Japan, ropinirole controlled‐release tabletsrecently became available for Parkinson's disease.AimWe compared the efficacy and safety of ropinirole controlled‐release with ropinirole immediate‐release.MethodsWe carried out a phase III clinical trial (randomized, double‐blind, double‐dummy), in which controlled‐release (n = 156) or immediate‐release (n = 146) was given to Japanese patients with advanced Parkinson's disease under L‐dopa treatment. First, we assessed the non‐inferiority of ropinirole controlled‐release to immediate‐release at week 24 by measuring change from week 0 in total score of the Unified Parkinson's Disease Rating Scale Part III. Then, during weeks 26–32, we evaluated the safety and efficacy of patients’ switching from ropinirole immediate‐release to controlled‐release, and a subset of patients continued on ropinirole controlled‐release though week 54.ResultsThe change in the Unified Parkinson's Disease Rating Scale Part III total score at week 24 was −10.8 for the controlled‐release group and −11.1 for the immediate‐release group (adjusted mean difference: 0.34, two‐sided 95% confidence interval −1.41 to 2.09), and the upper limit of the confidence interval was less than the predefined margin of 2.5, showing the non‐inferiority of ropinirole controlled‐release to immediate‐release. The efficacy did not change after overnight switching from ropinirole immediate‐release to controlled‐release, and lasted until week 54. Adverse events were comparable between the two groups during the whole study period.ConclusionsAs adjunctive therapy to L‐dopa, ropinirole controlled‐release improved motor symptoms in Japanese patients with advanced Parkinson's disease. The overnight switch from immediate‐release to controlled‐release did not result in any unexpected adverse event.

Noncirrhotic intrahepatic portal hypertension.

Watch a video presentation of this article Answer questions and earn CME Noncirrhotic portal hypertension comprises diseases of the liver manifesting with portal hypertension due to intrahepatic or prehepatic lesions in the absence of cirrhosis. Noncirrhotic portal fibrosis (NCPF) or idiopathic portal hypertension (IPH) is a common cause of noncirrhotic intrahepatic portal hypertension and has been reported worldwide. Other terms for this condition used throughout the world include obliterative venopathy, hepatoportal sclerosis, and idiopathic noncirrhotic portal hypertension (NCPH).1 The various denominations for noncirrhotic intrahepatic portal hypertension are outlined in Table 1. NCPF/IPH is characterized by the involvement of small and medium portal vein (PV) branches and periportal fibrosis.1 Extrahepatic portal vein obstruction (EHPVO) is an extrahepatic cause of NCPH and has been defined as “a vascular disorder of liver, characterized by obstruction of the extrahepatic PV with or without involvement of intrahepatic PV radicles or splenic or superior mesenteric veins.”2 Other causes of noncirrhotic intrahepatic portal hypertension are listed in Table 2. Systemic and intra-abdominal infections, toxin and medication exposure, immunological phenomena, and prothrombotic state are the broad etiological factors with a potential role in the disease (Table 3).3 The pathogenesis is not well understood, particularly for noncirrhotic intrahepatic portal hypertension. Sarin and Kumar3 presented a unifying common hypothesis for both NCPF/IPH and EHPVO wherein a major thrombotic event in the main PV at a young age results in EHPVO, whereas repeated microthrombotic events in smaller and medium-sized (<300 μm) branches lead to NCPF. Schouten et al.4 explained idiopathic noncirrhotic portal hypertension (INCPH) by presenting a dual theory of intrahepatic venous obstruction (obliterative venopathy) and increased splenic blood flow (due to high levels of endothelial nitric oxide synthase and inducible nitric oxide synthase). Sato and Nakanuma5 described a third concept of endothelial mesenchymal transition for IPH in which the vascular endothelial cells of portal venules acquire myofibroblastic features.5 NCPF usually presents in young males between the third and fourth decade of life, whereas IPH (in Japan) and INCPH (in the West) presents in the fifth decade of life with a female preponderance.6 The major presenting symptoms in Japanese patients with IPH are splenomegaly (88%), hepatomegaly (44%), gastrointestinal bleeding (35%), and ascites (12%). Patients with NCPF commonly present with splenomegaly (74%-97%), variceal bleed (65%-72%), anemia (90%), and ascites (10%-25%). INCPH in the West usually manifests with less common splenomegaly (26%-36%), variceal bleed (32%-55%), and more common ascites (34%) than NCPF and IPH. Variceal bleed is usually well tolerated. Ascites and hepatic encephalopathy are usually precipitated by bleed or shunt surgery. Jaundice and signs of chronic liver disease are rare. Anemia and thrombocytopenia are more common in NCPF than IPH. Coagulation and platelet function abnormalities are seen despite a procoagulant cause. A pilot study in NCPH (NCPF/EHPVO) showed that a latent hypercoagulable state may be evident on thromboelastographic evaluation.7 Hypersplenism is seen in 27%-87% of patients. Liver function tests are invariably normal. Endoscopy may reveal esophageal varices in 80%-90% of patients with NCPF/IPH and in 33%-43% of patients with INCPH. Esophageal varices are larger than those seen in patients with cirrhosis. Gastric and anorectal varices are more common, whereas portal hypertensive gastropathy is less common than cirrhosis.6 Imaging in NCPF reveals a normal, enlarged, or shrunken liver and large spleen with dilated and patent splenoportal axis, thickened PV (>3 mm), Gandy–Gamna bodies in the enlarged spleen. A withered tree appearance due to sudden narrowing of intrahepatic branches may also be seen. Spontaneous shunts are seen in 15.9% of patients and decrease the risk of variceal bleeding.8 Wedged hepatic venous pressure is usually normal, whereas intrasplenic and PV pressures are elevated.6 Nuclear imaging technetium-99m sulphur colloid scanning has been shown to differentiate NCPF from cirrhosis by demonstrating patchy uptake of colloids in cirrhosis and a significant colloid shift to bone marrow.9 ARFI elastography shows that liver stiffness in IPH is lower than cirrhosis and similar to chronic hepatitis whereas splenic stiffness is highest in IPH and lowest in chronic hepatitis.10 The major histological features in NCPH are shown in Fig. 1. Noncirrhotic intrahepatic portal hypertension needs to be differentiated from EHPVO and cirrhosis; the differences are outlined in Table 4. NCPF has a long-term survival of 100% with endoscopic eradication of varices and 80% with shunt surgery. However, up to one-third of patients may have progressive liver dysfunction, leading to decompensation and need for liver transplantation. Ascites and hepatic encephalopathy have been reported to occur in 26% and 7% of patients, respectively, with IPH on long-term follow up. The 1-year probability of developing portal vein thrombosis (PVT) is 9%, and 53% of patients show recanalization with anticoagulation. HIV and variceal bleeding at diagnosis are independent predictors of PVT in IPH.11 A study of explant liver from India showed that 9 (2.4%) out of 84 (22.6%) patients with cryptogenic cirrhosis had evidence of NCPF on pathological examination, emphasizing the natural course of decompensation in NCPF.12 NCPF accounts for 5% of end-stage liver disease patients who undergo liver transplantation.13 The probability of transplantation-free survival is 82% at 10 years in IPH, and the 1-year probability of first variceal bleed (in large varices) despite primary prophylaxis is 9%. Ascites at presentation and severe associated disorders are markers of poor survival.11 Liver transplantation has been done in severe cases of portal hypertension, advanced disease, and hepatopulmonary syndrome, but sufficient data are lacking. Treatment with endoscopic sclerotherapy and endoscopic variceal ligation are both effective in the eradication of varices. Endoscopic variceal ligation is faster in eradicating varices with less bleeding rates but with increased recurrence rates. The role of drug therapy alone or in combination in noncirrhotic intrahepatic portal hypertension is lacking. There are insufficient data at present to recommend the use of beta blockers for primary or secondary prophylaxis. However, Sarin et al.14 showed that for secondary prophylaxis, endoscopic variceal ligation was no more effective than beta blockers. Gastric varices as a cause of bleed are usually managed with cyanoacrylate glue injection, in contrast to esophageal varices, for which band ligation is the recommendation. Portosystemic shunting is indicated in cases of uncontrolled or recurrent portal hypertensive bleed and failed endotherapy. Transjugular intrahepatic portosystemic shunt or shunt surgery can be considered for failed endotherapy, ectopic variceal bleed, symptomatic hypersplenism, noncompliance with endoscopic therapy, severe growth retardation, and poor chance of follow-up.15 Shunts may be selective or nonselective. Shunt surgery is effective in NCPF with reduction in splenic pulp pressure and splenic size after a successful patent shunt surgery.16 Symptomatic hypersplenism is treated with shunt surgery with or without splenectomy. A recent retrospective analysis of surgery in hypersplenism over 10 years showed effective normalization of hypersplenism with splenectomy with or without shunt surgery. Shunt surgery, like proximal splenorenal shunt, also takes care of underlying portal hypertension.17 Anticoagulation is controversial and is currently not recommended for patients with NCPF/IPH and EHPVO; however, in noncirrhotic intrahepatic portal hypertension, it may be recommended for patients who develop PVT.