Prognostic impact of pre-treatment neutrophil-to-lymphocyte ratio (NLR) in nasopharyngeal carcinoma: A retrospective study of 180 Taiwanese patients.

OBJECTIVES: Nasopharyngeal cancer (NPC) is an endemic disease in Taiwan. Prognostic factors the anatomical TNM stage are important for its prognostic stratification. An elevated neutrophil-to-lymphocyte ratio (NLR) has been reported to be associated with poor prognosis in various solid tumours. In this study, we analysed the prognostic impact of the NLR in NPC in Taiwan. DESIGN: Single-institution retrospective study. SETTING: Medical centre. PARTICIPANTS: One hundred and eighty patients with NPC treated at the Far Eastern Memorial Hospital, Taiwan, from January 2007 to December 2013. MAIN OUTCOME MEASURES: The association between the clinical or haematological presentations and the prognosis. RESULTS: The majority of the 180 patients included in this study were men (80%) and were <65 years old (91.7%). A neck mass (55.6%) was the most common clinical presentation, followed by nasal (39.4%) and aural (30.6%) symptoms. In addition, the majority (75.4%) of patients had advanced stage (III and IV) disease. Patients with a high NLR (≧3.6) had significantly lower progression-free survival, overall survival and disease-specific survival rates. The association between high NLR and poor prognosis was more pronounced in patients with advanced disease than in those with early-stage NPC. The results of a multivariate analysis revealed that advanced age, clinical symptoms including headache, diplopia and facial numbness, advanced disease stage, and high NLR were independent prognostic factors. CONCLUSION: A high NLR is an independent poor prognostic factor of NPC in Taiwan.

Pharmacokinetics and tolerability of paritaprevir, a direct acting antiviral agent for hepatitis C virus treatment, with and without ritonavir in healthy volunteers.

AIMS: Paritaprevir is a direct acting antiviral agent for use as part of a multidrug hepatitis C virus infection treatment regimen. To characterize the pharmacokinetics, safety, and tolerability of paritaprevir and determine an optimal dosing regimen for subsequent evaluations, clinical studies were conducted with paritaprevir alone or with ritonavir, a cytochrome P450 3A4 inhibitor anticipated to increase paritaprevir exposure. METHODS: Two phase 1, double-blind, placebo-controlled, parallel group studies were conducted in healthy volunteers (NCT00850044 and NCT00931281). Single dose study participants (n = 87) were randomized to one time administration of either paritaprevir or placebo, or paritaprevir with ritonavir or placebo. Participants (n = 38) enrolled in the multiple dose study received paritaprevir with ritonavir or placebo once or twice daily for 14 days. Pharmacokinetics, safety and tolerability were assessed throughout the study treatment periods. RESULTS: After single or multiple dose administration, paritaprevir displayed non-linear pharmacokinetics, with maximum plasma concentration and area under the plasma concentration-time curve increasing in a greater than dose proportional manner. Concomitant administration of 100 mg ritonavir increased paritaprevir exposure from a 300 mg dose approximately 30- to 50-fold and extended paritaprevir half-life. The tolerability of paritaprevir was similar with or without ritonavir. Asymptomatic, transient increases in bilirubin were observed but were not associated with abnormalities in other liver function tests. CONCLUSIONS: Paritaprevir exhibits non-linear pharmacokinetics with greater than dose proportional increases in exposure after single or multiple dosing. Co-administration with ritonavir increases paritaprevir exposure and half-life without adversely influencing tolerability.

Benign prostatic enlargement is not associated with diabetes: a population-based study.

The association between diabetes and benign prostatic hyperplasia remains inconclusive. In this case-control study, we examined the association of diabetes with benign prostatic enlargement (BPE) using the Longitudinal Health Insurance Database 2000 in Taiwan. In total, 20 152 patients with BPE as cases and 20 152 age-matched patients without BPE were included as controls. Conditional logistic regression analyses were performed to calculate the odds ratio (OR) and corresponding 95% CI for having been previously diagnosed with diabetes between cases and controls. We found that of the 40 304 sampled patients, 9492 (23.6%) had a history of diabetes before the index date. This mean age for the sampled patients was 65.9 with a standard deviation of 12.0 years. A Chi-squared test revealed that there was a significant difference in the prevalence of prior diabetes between cases and controls (25.3% vs. 21.8%, p < 0.001). The conditional logistic regression found that the OR of prior diabetes for cases was 1.21 (95% CI = 1.15-1.27) compared with controls. However, after adjusting for geographic region, monthly income, urbanization level, hypertension, coronary heart disease (CHD), hyperlipidemia, tobacco use disorder, and obesity, the association between prior diabetes and BPE did not reach a statistically significant level (OR = 1.03, 95% CI = 0.98-1.08). In addition, it was noteworthy that hypertension (OR = 1.25, 95% CI = 1.20-1.31), CHD (OR = 1.40, 95% CI = 1.32-1.48), and hyperlipidemia (OR = 1.30, 95% CI = 1.24-1.36) were all significantly associated with BPE. We found that men with a diagnosis of diabetes were not significantly associated with BPE after adjusting for patient's sociodemographic characteristics and comorbidities.

Effects of secondary phase and grain size on the corrosion of biodegradable Mg-Zn-Ca alloys.

The bio-corrosion behaviour of Mg-3Zn-0.3Ca (wt.%) alloy in simulated body fluid (SBF) at 37°C has been investigated using immersion testing and electrochemical measurements. Heat treatment has been used to alter the grain size and secondary phase volume fraction; the effects of these on the bio-corrosion behaviour of the alloy were then determined. The as-cast sample has the highest bio-corrosion rate due to micro-galvanic corrosion between the eutectic product (Mg+Ca2Mg6Zn3) and the surrounding magnesium matrix. The bio-corrosion resistance of the alloy can be improved by heat treatment. The volume fraction of secondary phases and grain size are both key factors controlling the bio-corrosion rate of the alloy. The bio-corrosion rate increases with volume fraction of secondary phase. When this is lower than 0.8%, the dependence of bio-corrosion rate becomes noticeable: large grains corrode more quickly.

Use of complementary and alternative medicine among midlife Arab women living in Qatar.

The prevalence of use of complementary and alternative medicine (CAM) is widespread and is growing worldwide. This cross-sectional study in Qatar examined the use of CAM and its correlates among Arab women in their midlife years. Women aged 40-60 years (n = 814) were recruited at primary care centres in Qatar and completed a specially designed, pre-tested questionnaire. Overall, 38.2% of midlife women in Qatar had used CAM in the previous 12 months. Nutritional remedies and herbal remedies were the most commonly used CAM therapies, followed by physical methods. Qatari nationality and higher level of education were independently associated with CAM use. Menopause transition status was not independently associated with use of CAM. The prevalence of CAM use by women in Qatar was high, consistent with other reports worldwide. It is essential to educate and inform patients and health-care providers about the benefits and limitations associated with CAM.

Sleep apnoea adversely affects the outcome in patients who undergo posterior lumbar fusion: a population-based study.

Despite the increasing prevalence of sleep apnoea, little information is available regarding its impact on the peri-operative outcome of patients undergoing posterior lumbar fusion. Using a national database, patients who underwent lumbar fusion between 2006 and 2010 were identified, sub-grouped by diagnosis of sleep apnoea and compared. The impact of sleep apnoea on various outcome measures was assessed by regression analysis. The records of 84,655 patients undergoing posterior lumbar fusion were identified and 7.28% (n = 6163) also had a diagnostic code for sleep apnoea. Compared with patients without sleep apnoea, these patients were older, more frequently female, had a higher comorbidity burden and higher rates of peri-operative complications, post-operative mechanical ventilation, blood product transfusion and intensive care. Patients with sleep apnoea also had longer and more costly periods of hospitalisation. In the regression analysis, sleep apnoea emerged as an independent risk factor for the development of peri-operative complications (odds ratio (OR) 1.50, confidence interval (CI) 1.38;1.62), blood product transfusions (OR 1.12, CI 1.03;1.23), mechanical ventilation (OR 6.97, CI 5.90;8.23), critical care services (OR 1.86, CI 1.71;2.03), prolonged hospitalisation and increased cost (OR 1.28, CI 1.19;1.37; OR 1.10, CI 1.03;1.18). Patients with sleep apnoea who undergo posterior lumbar fusion pose significant challenges to clinicians.

Grail as a molecular determinant for the functions of the tumor suppressor p53 in tumorigenesis.

The transcription factor p53 is a multifunctional tumor suppressor that arrests the cell cycle in response to stress and modulates the DNA repair process or induces apoptosis. The cellular level and activity of p53 are tightly controlled to maintain proper functioning. This study identified a novel p53-binding glycoprotein, gene related to anergy in lymphocytes (Grail), which formed a negative feedback loop (similar to that of Mdm2). Grail physically and functionally interacted with the N-terminus of p53 to target its degradation and modulate its transactivation activity. Grail also senses and regulates cellular p53 levels, modulates a panel of p53-targeted promoters, and has a role in p53-induced apoptosis in cultured cells. Overexpression of Grail inhibited p53-induced apoptosis by increasing p53 degradation. However, cells not expressing Grail failed to undergo p53-dependent apoptosis, resulting in p21-dependent G1 arrest. Thus, Grail may provide a novel regulatory route for controlling p53 activity under stress conditions.

National in-hospital morbidity and mortality trends after lumbar fusion surgery between 1998 and 2008.

Increasing numbers of posterior lumbar fusions are being performed. The purpose of this study was to identify trends in demographics, mortality and major complications in patients undergoing primary posterior lumbar fusion. We accessed data collected for the Nationwide Inpatient Sample for each year between 1998 and 2008 and analysed trends in the number of lumbar fusions, mean patient age, comorbidity burden, length of hospital stay, discharge status, major peri-operative complications and mortality. An estimated 1 288 496 primary posterior lumbar fusion operations were performed between 1998 and 2008 in the United States. The total number of procedures, mean patient age and comorbidity burden increased over time. Hospital length of stay decreased, although the in-hospital mortality (adjusted and unadjusted for changes in length of hospital stay) remained stable. However, a significant increase was observed in peri-operative septic, pulmonary and cardiac complications. Although in-hospital mortality rates did not change over time in the setting of increases in mean patient age and comorbidity burden, some major peri-operative complications increased. These trends highlight the need for appropriate peri-operative services to optimise outcomes in an increasingly morbid and older population of patients undergoing lumbar fusion.

Elevated C-reactive protein level in hemodialysis patients with moderate/severe uremic pruritus: a potential mediator of high overall mortality.

BACKGROUND: Dialysis patients with uremic pruritus have worse outcomes. However, the pathophysiology of the high mortality in these patients remains inconclusive except for links with calcium/phosphate imbalance and sleep disturbance. Whether inflammation, an outcome predictor in dialysis patients, plays a role is unknown. METHODS: This prospective study included 321 chronic hemodialysis (HD) patients (>3 months) for survival analysis. A visual analog scale (VAS) was used to measure the severity of itching, and the patients were divided into four groups: no pruritus (VAS = 0, N = 118), mild (VAS 1-3, N = 76), moderate (VAS 4-7, N = 89) and severe pruritus (VAS 8-10, N = 38). The Pittsburgh Sleep Quality Index (PSQI) was used to define sleep disturbance, while high-sensitive C-reactive protein (hs-CRP) and tumor necrosis factor α (TNF-α) were used to evaluate inflammation. The patients were followed-up for 30 months. RESULTS: Patients with moderate/severe pruritus had higher hs-CRP, but similar TNF-α levels; they also had a worse survival rate (P = 0.0197, log rank test). By stratifying hs-CRP levels, those with higher hs-CRP had worse survival regardless of the severity of uremic pruritus. In a Cox proportional hazard model, hs-CRP levels and moderate/severe uremic pruritus were independent predictors of mortality after adjusting for age, poor sleeper (PSQI > 5), diabetes, albumin, phosphate, hemoglobin and parathyroid hormone levels and (hs-CRP) × (moderate/severe uremic pruritus) (all P < 0.05). CONCLUSION: In moderate/severe pruritic HD patients, those with higher hs-CRP suffer from worse overall mortality. Inflammation may bridge uremic pruritus to high mortality, and elevated hs-CRP predicts a worse outcome in this population.

The roles of smoking and cooking emissions in lung cancer risk among Chinese women in Hong Kong.

BACKGROUND: We conducted this case-control study to evaluate smoking effect on lung cancer conditional on the level of exposure to cooking emissions and to explore whether there is a joint effect of these two risk factors. SUBJECTS AND METHODS: We selected 279 newly diagnosed primary lung cancer cases and 322 community controls from Hong Kong females, frequency matched by age group, and collected relevant data. We applied logistic regression to estimate lung cancer risk related to smoking and cooking fume exposure, expressed as total cooking dish-years, while adjusting for various potential confounding factors. RESULTS: Current smoking was associated with four-fold increased risk, and ex-smoking with two-fold risk, which was not much influenced by cooking dish-years. No increased risk was observed in environmental tobacco smoking. Increasing intakes of yellow/orange vegetables and multivitamins were significant protective factors in all models. In the analysis of joint effect, the combination of smoking and cooking dish-years tended to have a greater risk than exposure to cooking fumes alone. There was a dose-response gradient with total dish-years in nonsmokers, but not in smokers. Smoking was more strongly associated with nonadenocarcinoma, whereas exposure to cooking fumes appeared to be related to both adenocarcinoma and nonadenocarcinoma. CONCLUSION: We confirmed the important roles of smoking and cooking emissions in lung cancer risk among the women. These two major risk factors appeared to act independently.

Effects of a needs-based education programme for family carers with a relative in an intensive care unit: a quasi-experimental study.

Critical illness and subsequent hospitalisation of a relative to an intensive care unit (ICU) can result in many physiological and psychosocial problems for patients and their family members. Caring for the anxiety and frustration of these families is an integral part of critical care nursing. The purpose of this study was to examine the effect of a needs-based education programme provided within the first 3 days of patients' hospitalisation, on the anxiety levels and satisfaction of psychosocial needs of their families. This was a quasi-experimental study with pre- and post-test design. A convenience sample was recruited over a period of three months, consisting of one primary family carer of each critically ill patient who had been admitted to an ICU in Hong Kong. Conducted by an ICU nurse specially assigned for the purpose, family carers in the experimental group (n=34) received an individual education programme based on the results of a literature review and an individual family needs assessment carried out at the time of patient admission, using the Critical Care Family Needs Inventory. The subjects in the control group (n=32) received the usual orientation and explanation given by the ICU nurses. Anxiety and need satisfaction were measured in the two groups at pre- and post-test and their mean scores were compared. Of the ten most important statements identified by the family carers in the two groups, the statements regarding the needs for information and assurance were found to predominate. After the needs-based intervention, the experimental group reported significantly lower levels of anxiety and higher levels of satisfaction of family needs than the control group at the post-test. The findings support the effectiveness of providing families of newly admitted critically ill patients, with a needs-based educational intervention to allay anxiety and satisfy immediate psychosocial needs. The formulation of a family education programme should be based on the results of a needs assessment, in order to meet family carers' individual needs.

Intravenous and oral lansoprazole are equivalent in suppressing stimulated acid output in patient volunteers with erosive oesophagitis.

BACKGROUND: Some patients requiring acid suppression may be unable to take oral medications. AIM: To compare the gastric acid inhibition effects of lansoprazole 30 mg administered either intravenous or orally in erosive oesophagitis patients. METHODS: The study included 87 Helicobacter pylori-negative patients with erosive oesophagitis. Each patient received 7 days of lansoprazole 30 mg orally prior to being randomized in a 3:1 fashion to intravenously lansoprazole 30 mg or intravenously placebo for 7 days. Basal acid output and pentagastrin-stimulated acid output were measured on days 8, 9 and 15. RESULTS: Median pentagastrin-stimulated acid output was 7.2 mmol/h after 7 days of oral lansoprazole. The median pentagastrin-stimulated acid output increased to 7.6 mmol/h after 7 days of intravenous lansoprazole compared with 26.9 mmol/h after intravenous placebo (P < 0.001). CONCLUSIONS: Lansoprazole 30 mg administered intravenous was equivalent to the 30 mg oral capsule in gastric acid suppression. Intravenous proton pump inhibitor therapy represents an important treatment option for those with acid-related diseases who are unable to take oral medications.

Evaluation of the pharmacokinetics and pharmacodynamics of intravenous lansoprazole.

AIM: To compare the pharmacokinetics and pharmacodynamics of lansoprazole 30 mg administered intravenously in 0.9% NaCl or in polyethylene glycol, or orally. METHODS: Twenty-nine subjects received lansoprazole orally on days 1-7 and intravenous lansoprazole in NaCl on days 8-14. Blood samples were collected on days 1, 7, 8 and 14. Fasting basal acid output and pentagastrin-stimulated maximal acid output were determined on days -1, 8, 9 and 15. Thirty-six different subjects received one of four regimen sequences: intravenous lansoprazole in NaCl, intravenous in polyethylene glycol, per orally, or intravenous placebo, each for 5 days. Twenty-four hour intragastric pH was recorded on days 1 and 5. RESULTS: Intravenous and per oral lansoprazole for 7 days produced equivalent basal acid output and maximal acid output suppression. Pharmacokinetics and mean pH values with intravenous lansoprazole in NaCl or polyethylene glycol were equivalent. Both produced mean pH and percentages of time pH above 3, 4, 5 and 6 that were significantly greater than did per orally. CONCLUSIONS: Intravenous lansoprazole inhibits acid secretion as effectively in NaCl as in polyethylene glycol, and its onset of action is faster than per oral lansoprazole.

Agreement between hearing thresholds measured in non-soundproof work environments and a soundproof booth.

AIMS: To study the agreement between audiometric test results measured in non-soundproof environments at the worksite, and in a soundproof booth. METHODS: In a cross sectional prevalence study on noise induced hearing loss, 885 transport workers whose hearing thresholds were measured by a standard audiometric test method in non-soundproof environments at the worksite were identified to have some hearing loss (>25 dB), and were retested in a soundproof booth. RESULTS: At 4-8 KHz, the mean of the absolute differences in hearing threshold obtained by these two methods was 2 dB or less. When the proportions of hearing loss (> or =30 dB for any frequencies at 3-8 KHz, or > or =90 dB for three low frequencies at 0.5-2 KHz, or > or =90 dB for three high frequencies at 3-6 KHz) were compared, considerable differences existed. A much better agreement was obtained when the criteria for hearing loss as measured in the field test under non-soundproof conditions were relaxed by 5 dB. At 4 KHz, the difference between the proportion of subjects with hearing loss as measured in the field and that as measured in the booth was the smallest. The kappa statistic was highest at 3 and 4 KHz. CONCLUSIONS: Audiometric test results conducted in non-soundproof environments in the field are comparable to those obtained in a soundproof environment among transport workers with a hearing loss of >25 dB. The hearing threshold at 4 KHz appears suitable for the estimation of the prevalence of hearing loss when appropriate adjustments are made in the diagnostic criteria.

Long-term safety analysis of preventive HIV-1 vaccines evaluated in AIDS vaccine evaluation group NIAID-sponsored Phase I and II clinical trials.

This report evaluates long-term safety data from 3189 human immunodeficiency virus type 1 (HIV-1) uninfected, healthy volunteers who were enrolled into 51 National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Phase I and II multicentred, randomized, double-blind trials of recombinant HIV-1 subunit vaccines (23 studies), synthetic peptide vaccines (7 studies), live vaccinia-vector recombinant envelope vaccines (7 studies), canarypox vector recombinant vaccines (13 studies), a DNA vaccine (1 study), and a Salmonella-vector vaccine (1 study). During the 12,340 person-years of follow-up, participants were monitored for adverse events including immune dysfunction/autoimmunity, anaphylaxis, cancer, death, and vaccine allergy. The analysis provides evidence that a preparation of a C4-V3 polypeptide vaccine emulsified in incomplete Freund's caused serious toxicity, but otherwise no safety problems considered serious were identified for any of the vaccines and adjuvants studied. These data serve to solidify the growing safety base of current vaccine technologies utilized in candidate vaccines for HIV-1 infection.

Comparative pharmacokinetics and safety of lansoprazole oral capsules and orally disintegrating tablets in healthy subjects.

BACKGROUND: Many individuals with acid-related gastrointestinal disorders have difficulty in swallowing oral agents. AIM: To compare the bio-availability of a single dose of lansoprazole orally disintegrating tablet with that of an intact capsule. METHODS: One hundred and twenty healthy subjects participated in two prospective, Phase I, open-label, two-period cross-over studies to receive lansoprazole, 15 mg or 30 mg. Within each study, subjects were randomized into two parallel cohorts consisting of 30 subjects per regimen, dispensed in opposing sequence over two periods separated by a 7-day washout period. Blood samples were collected on day 1 of both periods to determine the pharmacokinetic parameters. RESULTS: Tmax occurred at 1.8 and 2.0 h with the 15-mg and 30-mg tablets, respectively. Dose proportional increases in Cmax, AUCt and AUC infinity were observed in the 15-mg and 30-mg groups. The terminal elimination half-lives (t1/2) were identical in both dose groups (1.18 h). Lansoprazole administered as the orally disintegrating tablet was bio-equivalent to the intact capsule formulation with respect to Cmax, AUCt and AUC infinity. CONCLUSIONS: Lansoprazole orally disintegrating tablets, 15 mg and 30 mg, are bio-equivalent to the respective dose administered as the intact capsule. This novel dosage formulation represents an option for patients who have difficulty in swallowing oral agents.

Acid suppression in healthy subjects following lansoprazole or pantoprazole.

AIM: To compare the effect of lansoprazole, 30 mg once daily, with that of pantoprazole, 40 mg once daily, for the inhibition of gastric acid secretion. METHODS: Two randomized, single-blind, two-way, crossover studies were conducted in 74 healthy male volunteers. Lansoprazole, 30 mg, or pantoprazole, 40 mg, was administered once daily for five consecutive days with at least a 2-week washout period between regimens. Ambulatory 24-h intragastric pH was recorded at baseline and on days 1 and 5 of each crossover treatment period. RESULTS: On day 1 in both studies, lansoprazole, 30 mg, produced significantly higher mean 24-h intragastric pH values when compared to pantoprazole, 40 mg (3.78 vs. 3.08, P < 0.001, and 3.97 vs. 3.20, P < 0.001, in the first and second studies, respectively). In both studies, lansoprazole, 30 mg, produced significantly greater proportions of time that the intragastric pH was above 3, 4 and 5 when compared with pantoprazole, 40 mg (P < 0.005 in all comparisons). By treatment day 5 in the first study, lansoprazole, 30 mg, continued to produce a higher mean 24-h intragastric pH (4.15 vs. 3.91, P=0.014) and a significantly greater percentage of time that the intragastric pH was above 4 (63% vs. 56%, P=0.017) and 5 (41% vs. 30%, P < 0.001) when compared with pantoprazole, 40 mg. In the second study, the effects on intragastric pH were comparable between the two treatment groups. Headache was the most commonly reported adverse experience (nine lansoprazole-treated subjects, seven in the first study and two in the second study; six pantoprazole-treated subjects, five in the first study and one in the second study). CONCLUSIONS: Lansoprazole, 30 mg once daily, produces a faster onset and greater degree of acid inhibition than pantoprazole, 40 mg once daily. The implications for these differences on symptom relief and healing of erosive oesophagitis should be explored.

A comparison of simplified lansoprazole suspension administered nasogastrically and pantoprazole administered intravenously: effects on 24-h intragastric pH.

AIM: To compare the 24-h intragastric pH effects of simplified lansoprazole suspension, 30 mg, administered nasogastrically, with pantoprazole, 40 mg, administered intravenously. METHODS: Thirty-six healthy adults were enrolled and given simplified lansoprazole suspension, 30 mg (nasogastrically), or pantoprazole, 40 mg (intravenously), once daily for five consecutive days in a cross-over fashion. Intragastric pH was monitored at baseline and on Days 1 and 5 of each treatment period. The pharmacokinetic parameters of lansoprazole and pantoprazole were also determined on Days 1 and 5. RESULTS: No statistically significant changes in pharmacokinetic parameters occurred between Days 1 and 5 with either regimen, except for pantoprazole Cmax. On Days 1 and 5, significantly higher mean 24-h intragastric pH values were observed with 30 mg simplified lansoprazole suspension compared with 40 mg intravenous pantoprazole (Day 1, 3.13 vs. 2.67; Day 5, 3.95 vs. 3.61, respectively; P < 0.05). Additionally, 30 mg simplified lansoprazole suspension produced significantly (P < 0.05) higher percentages of time intragastric pH was above 3, 4, 5 or 6 as compared with 40 mg intravenous pantoprazole throughout Days 1 and 5. CONCLUSIONS: A 30 mg dose of simplified lansoprazole suspension administered nasogastrically was consistently more effective at controlling intragastric pH than pantoprazole, 40 mg, administered intravenously.