End Of Long-term Follow-up Research Articles

Cardiac fatty acid binding protein as a biomarker for long-term prognosis of clinically manifested heart failure and severe post-infarction left ventricular myocardial remodeling

The aim of the study is to evaluate cardiac fatty acid binding protein as a prognostic biomarker for the occurrence of severe post-infarction structural and functional remodeling of the left ventricular myocardium and heart failure with clinical manifestations in patients with acute myocardial infarction during long-term follow-up. Material and methods. The study included 95 patients with acute myocardial infarction and ST-segment elevation (mean age 56.8 ± 9.8 years). Upon admission to the emergency room, all patients underwent clinical and laboratory studies to determine cardiac fatty acid binding protein (cFABP) and high-sensitivity troponin T (hs-TnT). At the end of the long-term follow-up (Me = 36 months), the patients were examined for clinically evident heart failure (NYHA functional class II and higher), high-sensitivity C-reactive protein (hsCRP) was determined in the blood, and echocardiography was performed. According to the echocardiography data, the presence and severity of structural and functional remodeling of the left ventricle myocardium (SFR LV) were established. Results. It was determined that the presence of clinically evident heart failure is directly associated with age, the Charlton comorbidity index, cFABP ≥10 ng/ml upon admission to the hospital and has a direct tendency to be associated with hs-TnT upon admission to the hospital. The presence of severe structural and functional remodeling of the left ventricle myocardium is directly associated with age, obesity, creatinine, cFABP ≥ 10 ng/ml and hs-TnT upon admission to hospital, and there is also a direct tendency towards an association with age. It was revealed that hs-TnT upon admission to hospital is directly associated with hsCRP ≥ 2 mg/l at the end of long-term followup. Conclusions. the presence of cFABP ≥ 10 ng/ml in the blood of patients with acute myocardial infarction upon admission to hospital is associated with an increase in the probability of developing clinically evident heart failure during long-term follow-up by 4.27 times, and severe structural and functional remodeling of the left ventricle myocardium is 3.07 times more likely, which is due to the size of the infarction lesion and the subsequent development of myocardial fibrosis.

Long-Term Outcomes of Early Surgery vs Endoscopy First in Chronic Pancreatitis

Patients with painful chronic pancreatitis and a dilated pancreatic duct can be treated by early surgery or an endoscopy-first approach. To compare long-term clinical outcomes of early surgery vs an endoscopy-first approach using follow-up data from the ESCAPE randomized clinical trial. Between April 2011 and September 2018, 88 patients with painful chronic pancreatitis were randomly assigned to early surgery or an endoscopy-first approach in 30 hospitals in the Netherlands collaborating in the Dutch Pancreatitis Study Group as part of the ESCAPE randomized clinical trial. For the present cohort study, long-term clinical data were collected after the initial 18-month follow-up. Follow-up was completed in June 2022, and data analysis was performed in June 2023. Patients with chronic pancreatitis were randomly assigned to early surgery or an endoscopy-first approach. The primary end point was pain, assessed by the Izbicki pain score; secondary end points included patient-reported complete pain relief and satisfaction. Predefined subgroups included patients who progressed from endoscopy to surgery and those with ductal clearance obtained by endoscopy. Analysis was performed according to the intention-to-treat principle. In this cohort study, 86 of 88 overall patients could be evaluated, with a mean (SD) follow-up period of 98 (16) months. Of 88 initial patients, 21 patients (24%) were female, and mean (SD) patient age was 61 (10) years. At the end of long-term follow-up, the mean (SD) Izbicki pain score was significant lower (33 [31] vs 51 [31]) in the early surgery group, as was the rate of patient-reported complete pain relief (14 of 31 patients [45%] vs 6 of 30 patients [20%]), compared to the endoscopy-first group. After the initial 18-month follow-up, 11 of 43 patients in the early surgery group (26%) underwent reinterventions vs 19 of 43 patients in the endoscopy-first group (44%). At the end of follow-up, more patients in the early surgery group were "very satisfied" with their treatment (22 of 31 patients [71%] vs 10 of 30 patients [33%]). Patients who progressed from endoscopy to surgery (22 of 43 patients [51%]) had significantly worse mean (SD) Izbicki pain scores (33 [31] vs 52 [24]) compared to the early surgery group and had a lower rate of complete pain relief (55% for early surgery vs 12% for endoscopy first). In the endoscopy-first group, patients with endoscopic ductal clearance had similar mean (SD) Izbicki pain scores as the remaining patients (49 [34] vs 53 [28]). In this cohort study evaluating long-term outcomes of the ESCAPE randomized clinical trial, after approximately 8 years of follow-up, early surgery was superior to an endoscopy-first approach in patients with painful chronic pancreatitis and a dilated main pancreatic duct in pain scores and patient satisfaction. Notably, patients who progressed from endoscopy to surgery had worse outcomes compared to patients undergoing early surgery, and obtaining endoscopic ductal clearance did not improve outcomes.

Long-term impact of an integrated HIV/non-communicable disease care intervention on patient retention in care and clinical outcomes in East Africa.

To describe rates of retention in care and control of hypertension, diabetes and HIV among participants receiving integrated care services for a period of up to 24 months in East Africa. Between 5 October 2018 and 23 June 2019 participants enrolled into a prospective cohort study evaluating the feasibility of integrated care delivery for HIV, diabetes and hypertension from a single point of care in Tanzania and Uganda (MOCCA study). Integrated care clinics were established in 10 primary healthcare facilities and care was provided routinely according to national guidelines. Initial follow-up was 12 months. Outcomes were rates of retention in care, proportions of participants with controlled hypertension (blood pressure <140/90 mmHg), diabetes (fasting blood glucose <7.0 mmol/L) and HIV (plasma viral load <1000 copies/ml). The study coincided with the COVID-19 pandemic response. Afterwards, all participants were approached for extended follow-up by a further 12 months in the same clinics. We evaluated outcomes of the cohort at the end of long-term follow-up. The MOCCA study enrolled 2273 participants of whom 1911 (84.5%) were retained in care after a median follow-up of 8 months (Interquartile range: 6.8-10.7). Among these, 1283/1911 (67.1%) enrolled for a further year of follow-up, 458 (24.0%) were unreachable, 71 (3.7%) reverted to vertical clinics (clinics providing services dedicated to study conditions), 31 (1.6%) died and 68 (3.6%) refused participation. Among participants who enrolled for longer follow-up, mean age was 51.4 ± 11.7 years, 930 (72.5%) were female and 509 (39.7%) had multiple chronic conditions. Overall, 1236 (96.3%) [95% confidence interval 95.2%-97.3%] participants were retained in care, representing 1236/2273 (54.3%) [52.3%-56.4%] of participants ever enrolled in the study. Controlled hypertension, diabetes and HIV at the end of follow-up was, 331/618 (53.6%) [49.5%-57.5%], 112/354 (31.6%) [26.8%-36.8%] and 332/343 (96.7%) [94.3%-98.4%] respectively. Integrated care can achieve high rates of retention in care long term, but control of blood pressure and blood sugar remains low.

ExTENSION: Long-Term Follow-up Study of an Endoscopic versus a Surgical Step-up Approach for Infected Necrotizing Pancreatitis

Introduction: In 2018, the TENSION trial found that the endoscopic step-up approach is preferred over the surgical approach for necrotizing pancreatitis, because of fewer pancreaticocutaneous fistulas and shorter hospital stay. However, it remains unclear whether long-term outcomes (> 6 months) differ between both approaches. Method: TENSION trial participants were prospectively re-evaluated after a follow-up period of at least 5 years. The composite primary endpoint, similar to the TENSION trial, consisted of mortality and major complications occurring between randomization and the end of long-term follow-up. Results: The mean follow-up period was 7 years (84 ± 11 months). The primary endpoint occurred in 27 patients (53%) in the endoscopy group and 27 patients (57%) in the surgery group (RR 0.93, 95% CI 0.65 to 1.32, P=0.69). Mortality did not differ (15 patients (29%) vs. 7 (15%); RR 1.89, 95% CI 0.89 to 4.42). The endoscopy group had fewer pancreaticocutaneous fistulas (8% vs. 34%; RR 0.23, 95% CI 0.08–0.83) and fewer drainages during long-term follow-up (7% vs. 24%; RR 0.29, 95% CI 0.09 - 0.99). No differences were found in exocrine insufficiency (57% vs. 66%, RR 0.86, 95% CI 0.63 - 1.18) or endocrine insufficiency (31% vs. 34%, RR 0.92, 95% CI 0.52 - 1.63). QoL scores did not differ between group at long-term follow-up. Conclusion: In this long-term follow-up study, we found the endoscopic step-up approach to result in fewer pancreaticocutaneous fistulas and reinterventions. No differences were found in mortality, major complications and quality of life at the end of long-term follow-up.

Extension: Long-term Follow-up Study of an Endoscopic versus Surgical Step-up Approach for Infected Necrotizing Pancreatitis

Introduction: The TENSION trial (published in 2018) found that the endoscopic step-up approach in patients with infected necrotizing pancreatitis does not reduce mortality or major complications. However, it prevents pancreatic fistulas and shortens hospital stay, as compared to the surgical step-up approach. Nonetheless, the question remains whether long-term outcomes (>6 months) differ between both approaches. The aim of this study is to compare long-term clinical outcomes after the endoscopic and surgical step-up approach. Methods: TENSION trial participants were prospectively evaluated by interviews and pancreatic function measurements after a follow-up period of at least 5 years. Endpoints were similar to those of the original TENSION trial. The primary endpoint was composed of death and major complications, occurring between randomization and end of long-term follow-up. Secondary endpoints included the individual components of the primary endpoint, pancreatic fistula, exocrine and endocrine insufficiency, total hospital stay, reinterventions, and quality of life (QoL). Results: The mean follow-up period was 7 years (84±11 months). The primary endpoint occurred in 29 patients (57%) from the endoscopy group and in 27 patients (57%) from the surgery group (RR 0.99, 95% CI 0.70–1.40). No difference was found in overall mortality (15 patients (29%) vs. 7 (15%) respectively; RR 1.89, 95% CI 0.89–4.42). During long-term follow-up, the first patient died 2.5 years after randomization, and all but one deaths were not related to pancreatitis (5 out of 6 (83%) vs. 1 (100%); RR 0.83, 95% CI 0.58–1.19). In the endoscopy group, fewer pancreatic fistulas (8% vs. 36%; RR 0.25, 95% CI 0.09–0.69) and additional drainages were observed during follow-up (7% vs. 24%; RR 0.29, 95% CI 0.09–0.99). The endoscopy group reported higher physical health scores (SF-36) at 3 months after randomization (42±11 vs. 36±10, P=0.04), however, long-term QoL scores did not differ (EQ-5D 0.80±0.23 vs. 0.86±0.17, P=0.24). Conclusion: During the long-term follow-up of TENSION trial participants, we found no differences in mortality and major complications between the endoscopic and surgical step-up approach for infected necrotizing pancreatitis. However, the endoscopic step-up approach results in fewer pancreatic fistulas, additional drainage procedures, and a faster physical recovery. These results confirm that, if both techniques are feasible, the endoscopic approach should be preferred.

90Y Radiosynovectomy in Persistent Synovitis Caused by Knee Replacement: Long-Term Outcome.

After knee replacement, therapy resistant, persistent synovitis is a common issue, which causes effusion and pain, and leads to loosing. It has been hypothesized that radiosynovectomy (RSO) is useful in these patients. A cohort of 55 patients with 57 knee replacements and persistent synovitis underwent RSO using 4.9 ± 0.24 mCi (182 ± 9 MBq) of Y-citrate. The number of RSOs ranged from 1 to 4. Bone scans before and 3 months after every RSO were performed. Long-term follow-up ranged from 0.8 to 7.6 years with a mean of 23.2 months. For qualitative analysis, an established 4 steps scoring was used. For quantification, the uptake was determined within the Tc-MDP scintigraphy blood pool phase before and after therapy. Long-term response was in 27% with excellent, 24% good, 30% weak, and 20% no response. The duration of response was 12.0 ± 12.0 months (maximum, 54 months). In patients with repeated treatment, the effect after the first therapy was lesser than in patients who received a single treatment in total. However, 3 months after the last RSO, patients with repeated treatment showed a similar effectiveness than single treated patients. At the end of long-term follow-up, patients with repeated RSOs had a higher effectiveness at similar duration response. In bone scan, 65% of patients showed a reduction of uptake. When comparing subjective and objective response, 78% of patients showed a concordance in both symptoms and scintigraphy. Pilot histological analysis revealed that the synovitis is triggered by small plastic particles. We concluded that RSO is an effective therapy in patients with knee replacement and persistent synovitis with high long-term response. Repeated treatment leads to a stronger long-time response.

An age-stratified follow-up of complications and clinical benefit of posterior lumbar intervertebral fusion procedure in middle-aged and older patients

To compare the complications and clinical scores of posterior lumbar intervertebral fusion (PLIF) in middle-aged and older patients of different ages, and to assess the risk of complications of PLIF in different ages, providing a reference for clinical treatment. The clinical data of 1 136 patients, who were more than 55 years old and underwent PLIF between June 2013 and June 2016, were retrospectively analyzed. According to the age of patients undergoing surgery, they were divided into 3 groups as 55-64 years old, 65-74 years old, and ≥75 years old. The general characteristics, comorbidities, and surgical data of the three groups were compared, with comparison the morbidity of complications. According to the minimal clinical important difference (MCID), the improvement of patient's pain visual analogue scale (VAS) score and the Oswestry disability index (ODI) score were compared. Univariate logistic regression analysis was used to analyze the difference of complications and the improvement of VAS and ODI scores. Multivariate logistic regression analysis was performed for the risk factors of complications. There were significant differences in the number of surgical fusion segments and osteoporosis between groups ( P<0.05); there was no significant difference in gender, body mass index, operation time, preoperative American Society of Anesthesiologists (ASA) classification, and comorbidities between groups ( P>0.05). All patients were followed up 6-62 months with an average of 27.4 months. Among the results of postoperative complications, there were significant differences in the total incidence of intraoperative complications, systemic complications, minor complications, and the percentage of improvement of ODI score to MCID between groups ( P<0.05); but there was no significant difference in the total incidence of complications at the end of long-term follow-up and the percentage of improvement of VAS score to MCID between groups ( P>0.05). Univariate logistic regression analysis showed that after adjusting the confounding factors, there were significant differences in intraoperative complications and the percentage of improvement of ODI score to MCID between 55-64 and 65-74 years old groups ( P<0.05); systemic complications, minor complications, complications at the end of long-term follow-up, and the percentage of improvement of ODI score to MCID in ≥75 years old group were significantly different from those in the other two groups ( P<0.05). Multivariate logistic regression analysis showed that age was a risk factor for systemic complications, minor complications, and complications at the end of long-term follow-up. Except for age, long operation time was a risk factor for intraoperative complications, increased number of fusion segments was a risk factor for systemic complications, the number of comorbidities was a risk factor for minor complications, and osteoporosis was a risk factor for complications at the end of long-term follow-up. The risk of surgical complications is higher in the elderly patients (≥75 years) with lumbar degenerative diseases than in the middle-aged and older patients (<75 years), while the improvements of postoperative VAS and ODI scores were similar. Under the premise of fully assessing surgical indications, PLIF has a positive effect on improving the elderly patients' quality of life.

Incomplete endothelialization of WatchmanTM Device: Predictors and Implications from Two Cases

Initiation of antiarrhythmic drug therapy (AADx) for atrial fibrillation (AF) on an outpatient basis requires intensive ECG monitoring in order to assess antiarrhythmic efficacy as well as ECG signals of potential proarrhythmia. Dronedarone (DRO) reduces cardiovascular endpoints in AF patients fulfilling criteria of the ATHENA trial [1]. In the present study transtelephonic ECG monitoring was used to guide initiation of AADx in AF patients fulfilling the ATHENA criteria. In 19 consecutive patients (37% female; age 65+10 years; LVEF 62+7%; mean CHA2DS2-VASc score 2.9 + 1.6 (median=2), with symptomatic non-permanent AF and additional cardiovascular risk factors, DRO was prescribed as AADx of first choice. Initiation of therapy and follow-up were monitored by transtelephonic ECG recordings (VITAPHONE™100 IR; Vitaphone GmbH; Germany). In patients with persistent AF, electrical cardioversion was performed on an outpatient basis when DRO was started. Patients were followed for changes in QT intervals as well as AF recurrency. ECGs were transmitted according to a scheduled FU form as well as any time in case of pts symptoms. Patients in whom DRO did not prevent AF recurrence were switched to alternative AADx, or to pulmonary vein isolation (PVI), respectively. At the end of long-term follow-up, DRO alone was successful in preventing AF recurrence in 5 of 19 patients (26%). When pts who responded to AADx of second or third choice or who underwent PVI were included, SR could be maintained in 17/19 pts (89%). No patient required discontinuation of AADx due to ventricular depolarization abnormalities, symptomatic bradycardia or pathologic QT prolongation. In conclusion, transtelephonic ECG transmission is useful for close rhythm monitoring during initiation and follow-up of AADx, also during change from DRO to other AADx. DRO was effective to prevent AF recurrence in 26% of patients during a mean long-term follow-up of more than 30 months - which is well in line with data from the literature.

Calcium antagonists for acute ischemic stroke.

The sudden loss of blood supply in ischemic stroke is associated with an increase of calcium ions within neurons. Inhibiting this increase could protect neurons and might reduce neurological impairment, disability, and handicap after stroke. To assess the effects of calcium antagonists for reducing the risk of death or dependency after acute ischemic stroke. We investigated the influence of different drugs, dosages, routes of administration, time intervals after stroke, and trial design on the outcomes. The evidence is current to 6 February 2018. We searched the Cochrane Stroke Group Trials Register (6 February 2018), Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 2), MEDLINE Ovid (1950 to 6 February 2018), Embase Ovid (1980 to 6 February 2018), and four Chinese databases (6 February 2018): Chinese Biological Medicine Database (CBM-disc), China National Knowledge Infrastructure (CNKI), Chinese Scientific Periodical Database of VIP information, and Wanfang Data. We also searched the following trials registers: ClinicalTrials.gov, EU Clinical Trials Register, Stroke Trials Registry, ISRCTN registry, WHO International Clinical Trials Registry Platform, and Chinese Clinical Trial Registry, and we contacted trialists and researchers. Randomized controlled trials comparing a calcium antagonist versus control in people with acute ischemic stroke. Two review authors independently selected trials, extracted data, assessed risk of bias, and applied the GRADE approach to assess the quality of the evidence. We used death or dependency at the end of long-term follow-up (at least three months) in activities of daily living as the primary outcome. We used standard Cochrane methodological procedures. We included 34 trials involving 7731 participants. All the participants were in the acute stage of ischemic stroke, and their age ranged from 18 to 85 years, with the average age ranging from 52.3 to 74.6 years across different trials. There were more men than women in most trials. Twenty-six trials tested nimodipine, and three trials assessed flunarizine. One trial each used isradipine, nicardipine, PY108-608, fasudil, and lifarizine. More than half of these trials followed participants for at least three months. Calcium antagonists showed no effects on the primary outcome (risk ratio (RR) 1.05; 95% confidence interval (CI) 0.98 to 1.13; 22 trials; 22 studies; 6684 participants; moderate-quality evidence) or on death at the end of follow-up (RR 1.07, 95% CI 0.98 to 1.17; 31 trials; 7483 participants; moderate-quality evidence). Thirteen trials reported adverse events, finding no significant differences between groups. Most trials did not report the allocation process or how they managed missing data, so we considered these at high risk of selection and attrition bias. Most trials reported double-blind methods but did not state who was blinded, and none of the trial protocols were available. We found no evidence to support the use of calcium antagonists in people with acute ischemic stroke.

Factors Associated With Early Loss of Hallux Valgus Correction

Recurrence is common after hallux valgus corrective surgery. Although many investigators have studied the risk factors associated with a suboptimal hallux position at the end of long-term follow-up, few have evaluated the factors associated with actual early loss of correction. We conducted a retrospective cohort study to identify the predictors of lateral deviation of the hallux during the postoperative period. We evaluated the demographic data, preoperative severity of the hallux valgus, other angular measurements characterizing underlying deformities, amount of hallux valgus correction, and postoperative alignment of the corrected hallux valgus for associations with recurrence. After adjusting for the covariates, the only factor associated with recurrence was the postoperative tibial sesamoid position. The recurrence rate was ~50% and ~60% when the postoperative tibial sesamoid position was >4 and >5 on the 7-point scale, respectively.

The Characteristics and Long-Term Course of Epilepsy in Lipoid Proteinosis: A Spectrum From Mild to Severe Seizures in Relation toECM1Mutations

Lipoid proteinosis (LP) is a rare autosomal recessive disease characterized by deposition of hyaline material in skin and mucosae. Epilepsy, as an extracutaneous manifestation associated with typical mesial temporal calcifications, has already been identified, but its characteristics and long-term prognosis have not been thoroughly investigated. We included 7 consecutive patients with LP with typical intracranial calcifications out of 16 patients with ECM1 mutations and investigated the semiologic features, ictal and interictal EEG findings, and long-term prognosis of epilepsy in this genodermatosis. Four of them had seizures (57.1%), and focal seizures with motionless staring were the most common seizure phenotype, originating from bilateral mesial temporal areas, but interictal spikes were scant. Auras were observed in three patients, mostly as epigastric sensation and déjà vu, which indicated mesial temporal lobe origin. Three patients with homozygous mutations in sixth and seventh exons of the ECM1 gene had a drug-resistant course at the end of long-term follow-up. Molecular genetic testing showed a rare compound heterozygous mutation in one patient, which was also associated with seizures but without drug-resistance. Our findings indicated a spectrum for epilepsy with a desperate drug-resistant course for decades in most patients with LP, which is still an underrecognized disease by neurologists.

Long-Term Effect of Maxillary Distraction Osteogenesis (DO) on Nasal Index in Adult Patients with Cleft Lip and Palate Deformities.

To test the hypothesis that there is no immediate and long-term effects of maxillary distraction osteogenesis (DO) on nasal index among adult subjects with cleft lip and palate deformities. Twelve adult subjects in the age range of 17-20years with complete unilateral cleft lip and palate underwent advancement of maxilla by DO. The immediate and long-term effects of maxillary DO on nasal index were evaluated from extra-oral full face frontal photographs recorded prior to DO (T0), at the end of active DO (T1) and at least 2-years after the DO (T2). The ANOVA, Post Hoc test (Bonferroni) and Pearson correlation coefficients were used. The probability value (P value) 0.05 was considered as statistically significant. SNM angle and Ptm-M distance increased significantly by DO (P<0.001). The nasal index increased significantly (P<0.01) by 13.85% from T0 value of 85.15±4.49 to 99.02±11.16% at the end of active distraction (T1) and by 12.69 to 97.84±9.14% at the end of long-term follow-up (T2). The correlation between sagittal maxillary advancement and nasal index was statistically significant (P<0.001). For each millimeter of maxillary advancement, the nasal index increased by 1.38 % and 1.8% at the end of active distraction and long-term follow-up respectively. The advancement of maxilla by distraction osteogenesis among subjects with cleft lip and palate deformities increased nasal index significantly.

Late HDV RNA relapse after peginterferon alpha-based therapy of chronic hepatitis delta

Interferon alpha is the only treatment option for hepatitis delta virus (HDV). Trials investigating the efficacy of pegylated interferon alpha (PEG-IFNa) showed HDV RNA negativity rates of 25-30% 24 weeks after therapy. However, the clinical and virological long-term outcome of HDV-infected patients treated with PEG-IFNa is unknown. We performed a retrospective-prospective follow-up of 77 patients treated for 48 weeks with either PEG-alfa-2a and adefovir (ADV) or either drug alone in the Hep-Net-International-Delta-Hepatitis-Intervention-Study 1 (HIDIT-1) trial. Long-term follow-up data were available for 58 out of 77 patients (75%) with a median time of follow-up of 4.5 (0.5-5.5) years and a median 3 visits per patient. Patients treated with ADV alone received retreatment with PEG-IFNa (48% versus 19%; P = 0.02) more often. Hepatitis B virus surface antigen (HBsAg) became negative in six PEG-IFNa-treated patients until the end of long-term follow-up (10%). Sixteen patients tested HDV RNA-negative 6 months after PEG-IFNa treatment who were entered in the long-term follow-up study. Out of these, nine individuals tested HDV RNA-positive at least once during further long-term follow-up, with seven patients being HDV RNA-positive at the most recent visit. Clinical endpoints (liver-related death, liver transplantation, hepatic decompensation, hepatocellular carcinoma) were observed in three PEG-IFNa-treated (8%) and three ADV-treated (14%) patients during posttreatment long-term follow-up with an overall annual event rate of 2.5% (4.9% in cirrhosis). Sequencing confirmed the reappearance of pretreatment virus strains in all cases. Late HDV RNA relapses may occur after PEG-IFNa therapy of hepatitis delta and thus the term sustained virological response should be avoided in HDV infection. The annual posttreatment rate of clinical events in hepatitis delta patients eligible for PEG-IFNa therapy is about 2.5% and 4.9% in patients with cirrhosis.

Long‐term outcomes after cyclosporine or mycophenolate withdrawal in kidney transplantation – results from an aborted trial

Long-term triple immunosuppressive therapy with cyclosporine (CsA), mycophenolate mofetil (MMF) and prednisolone may be excessively powerful for many transplant recipients. We compared withdrawal of either MMF or CsA in stable kidney transplants on triple immunosuppression. The study was a prospective, randomized, controlled 12-months trial in stable kidney transplants. The patients who withdrew CsA were given MMF 2 g/d, and CsA troughs were between 75 and 125 ng/mL in MMF withdrawal. Planned inclusion was 298 patients. The study was prematurely aborted after inclusion of 39 patients. Acute rejection rates were 6/20 (30%) in the MMF group compared with 0/19 (0%) in the CsA group (p = 0.02). Time to acute rejections was 4.0-28.7 months after withdrawal. Trough concentrations of mycophenolic acid (MPA) and CsA showed therapeutic levels. The subjects have been observed for eight yr, and of the 28 patients remaining on randomized therapy, the MMF patients preserved graft function better than CsA patients. Death-censored graft survival was 75% and 95% (p = 0.18) and patient survival was 70% and 68% (p = 0.99) in the MMF and CsA groups, respectively, at the end of long-term follow-up. CsA withdrawal was associated with a high rate of acute rejections. Initially, the treatment of acute rejections was successful. However, five of six lost their grafts in the long term.

Calcium antagonists for acute ischemic stroke

The sudden loss of blood supply in ischemic stroke is associated with the increase of calcium ions within neurons. Inhibiting this increase could protect neurons and hence might reduce neurological impairment, disability and handicap after stroke. To determine whether calcium antagonists reduce the risk of death or dependency after acute ischemic stroke. To investigate the influence of different drugs, dosages, routes of administration, time intervals after stroke and trial design on the risk of a primary outcome. We searched the Cochrane Stroke Group Trials Register (January 2012), MEDLINE (1950 to December 2011), EMBASE (1980 to December 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2011 issue 4) and four Chinese databases (December 2011): Chinese Biological Medicine Database (CBM-disc), China National Knowledge Infrastructure (CNKI), Chinese scientific periodical database of VIP information and Wanfang Data. We also contacted trialists and researchers. All truly randomized trials comparing a calcium antagonist with control in patients with acute ischemic stroke. Two authors assessed all trials and extracted the data. We used death or dependency at the end of long-term follow-up (at least three months) in activities of daily living as the primary outcome. Analyses were, if possible, intention-to-treat. We included 34 trials including 7731 patients. There was no effect of calcium antagonists on the primary outcome (risk ratio (RR) 1.05; 95% confidence interval (CI) 0.98 to 1.13), or on death at the end of follow-up (RR 1.07, 95% CI 0.98 to 1.17). Comparisons of different doses of nimodipine suggested that the highest doses were associated with poorer outcome. No evidence is available using calcium antagonists in patients with acute ischemic stroke is effective.

Meta-Analysis of Scalp Acupuncture for Acute Hypertensive Intracerebral Hemorrhage

Scalp acupuncture (SA) is a commonly used therapeutic approach for primary intracerebral hemorrhage (ICH) in Traditional Chinese Medicine (TCM), but the efficacy and safety of SA therapy are still undetermined. The aim of this study is to systematically evaluate the efficacy and safety of SA therapy for the treatment of acute hypertensive ICH. Literature reports with randomized controlled clinical trials and controlled clinical trials on SA therapy for acute hypertensive ICH were searched, and the efficacy and safety of SA therapy were evaluated by using the Cochrane systematic review methods. The primary outcome measures were death or dependency at the end of long-term follow-up (at least 3 months) and adverse events. The secondary outcome measure was neurological deficit improvement at the end of the treatment course. Seven (7) independent trials (230 patients) were included in this study. All trials described the methods of randomization in which four trials had adequate concealment of randomization at the level of grade A, but no trial included sham acupuncture as a control group. None of the trials included "death or dependency" as a primary outcome measure. Four (4) trials contained safety assessments and stated that no adverse event was found, whereas the other three trials did not provide the information about adverse events. By using random effects statistical model, it was found that patients with acute hypertensive ICH who received SA therapy had significantly improved neurological deficit scores (Z = 4.97, p < 0.01). Although SA therapy is widely used to treat acute hypertensive ICH in TCM, the efficacy and safety of SA therapy remain to be further determined. No evidence is available on whether SA therapy can be used to treat acute ICH according to the primary outcome measure. However, SA therapy appears to be able to improve neurological deficit in patients with acute hypertensive ICH.

A Simulation Study of Control Sampling Methods for Nested Case-Control Studies of Genetic and Molecular Biomarkers and Prostate Cancer Progression

Incidence density sampling is typically the least biased efficient method for control sampling in nested case-control studies. However, in studies of genetic variants and prostate cancer progression, some argue that controls should be sampled from men who did not progress by end of follow-up. Thus, we examined the validity of relative risk (RR) estimates of prostate cancer progression using three methods for control sampling from cohorts of men with prostate cancer generated by Monte Carlo simulation. Data were simulated for nine scenarios for combinations of genotype frequency (10%, 30%, and 50%) and association (RR, 1.0, 1.5, and 2.0) using prostate progression rates from Johns Hopkins Hospital. RRs estimated from conditional logistic regression for the genetic association from case-control studies nested in the nine cohort scenarios using three control sampling methods, (a) incidence density sampling, (b) incidence density sampling without replacement of selected controls, and (c) "pure" control sampling (i.e., men who did not progress by end of long-term follow-up), were compared with the true RRs. Use of controls selected by incidence density sampling produced unbiased RR estimates of progression. In our setting, only a slight bias was produced by use of incidence density sampling without replacement. In contrast, use of controls selected by pure control sampling produced biased RR estimates, except when there was no association; extent of bias increased with increasing size of the association and duration of follow-up. Nested case-control studies designed to estimate the association of genetic variants with risk of prostate cancer progression should use incidence density sampling to provide a valid RR estimate.

Molecular Evolution of Human Immunodeficiency Virus Type 1 upon Transmission between Human Leukocyte Antigen Disparate Donor-Recipient Pairs

BackgroundTo address evolution of HIV-1 after transmission, we studied sequence dynamics in and outside predicted epitopes of cytotoxic T lymphocytes (CTL) in subtype B HIV-1 variants that were isolated from 5 therapy-naive horizontal HLA-disparate donor-recipient pairs from the Amsterdam Cohort Studies on HIV-1 infection and AIDS.Methodology/Principal FindingsIn the first weeks after transmission, the majority of donor-derived mutations in and outside donor-HLA-restricted epitopes in Gag, Env, and Nef, were preserved in the recipient. Reversion to the HIV-1 subtype B consensus sequence of mutations in- and outside donor-HLA-restricted CTL epitopes, and new mutations away from the consensus B sequence mostly within recipient-HLA-restricted epitopes, contributed equally to the early sequence changes. In the subsequent period (1–2 years) after transmission, still only a low number of both reverting and forward mutations had occurred. During subsequent long-term follow-up, sequence dynamics were dominated by forward mutations, mostly (50–85%) in recipient-HLA-restricted CTL epitopes. At the end of long-term follow-up, on average 43% of the transmitted CTL escape mutations in donor-HLA-restricted epitopes had reverted to the subtype B consensus sequence.Conclusions/SignificanceThe relatively high proportion of long-term preserved mutations after transmission points to a lack of back selection even in the absence of CTL pressure, which may lead to an accumulating loss of critical CTL epitopes. Our data are supportive for a continuous adaptation of HIV-1 to host immune pressures which may have implications for vaccine design.

Meta-Analysis of Traditional Chinese Patent Medicine for Ischemic Stroke

A large number of traditional Chinese patent medicine (TCPM) are widely used for ischemic stroke in China. The aim of this study was to systematically review the existing clinical evidence on TCPM for ischemic stroke. We identified all TCPM that were listed in the Chinese National Essential Drug list of 2004 and those commonly used TCPM in current clinical practice for ischemic stroke. Fifty-nine TCPM were identified for further evaluation. We applied Cochrane systematic review methods. We searched for reports of randomized controlled trials and controlled clinical trials on any of the 59 TCPM for ischemic stroke comparing one TCPM with control. PRIMARY OUTCOMES included death or dependency at the end of follow-up (at least 3 months) and adverse events. Effects on neurological impairments were a secondary outcome. One-hundred ninety-one trials (19,338 patients) on 22 TCPM were available and included, of which 120 were definite or possible randomized controlled trials and 71 were controlled clinical trials. The methodological quality of included trials was generally "poor." Few trials reported methods of randomization. Three trials were randomized, double blind, and placebo-controlled. one trial on Puerarin and one trial on Shenmai injection assessed death or dependency at the end of long-term follow-up (at least 3 months) and found no statistically significant difference between 2 groups. The reported adverse events including allergic reaction, headache, nausea, diarrhea, bellyache, blood pressure change, and subcutaneous ecchymosis. Most of the adverse events were not severe. analysis of the secondary outcome, "marked improvement in neurological deficit," showed apparent benefits of about the same magnitude for all the TCPM studied. Of the 22 TCPM, 8 drugs (Milk vetch, Mailuoning, Ginkgo biloba, Ligustrazine, Danshen agents, Xuesetong, Puerarin, and Acanthopanax) had relatively more studies and patient numbers. There was insufficient good quality evidence on the effects of TCPM in ischemic stroke on the primary outcome (death or dependency). We considered the apparent benefit on neurological impairment was as likely to be attributable to bias from poor methodology as to a real treatment effect. However, because the agents assessed appeared potentially beneficial and nontoxic, further randomized controlled trials are justified. Eight drugs could be further research priorities.

メニエール病の初期症状と予後

Meniere's disease was diagnosed in 182 cases or 5.8% of 3, 150 patients who had consulted the Neuro-otological clinic in Kitasato University Hospital between 1990 and 1995. Females were dominant comprising 70% of 151 patients. Patient age at the onset of the disease ranged from the third to fifth decade. Patients were treated by medication and Portmann's sac procedure was done in 12 cases.Initial symptoms and prognosis of vertigo and hearing impairments were investigated in 28 selected patients who were successfully followed over a long term. Tinnitus and/or deafness started before the first vertigo attack in 61% of the 28 patients. The left ear was more frequently affected than the right and both ears were affected in 12.7%. The interval between the first and second attacks of vertigo was more than one year in 21.4%. More than one year passed since the last vertigo attack in 60.7%. However, an interval of more than one year during the long term course was also observed in the same percentage. Average of hearing levels did not change or had worsened at the end of long term follow-up in all 28 cases.