Fatigue on Waking, Insomnia, and Workplace Relationship Problems May Help to Detect Suicidal Ideation among New Middle-Aged Primary Care Patients: A 6-Month Prospective Study in Japan.

Signs of suicidal depression often go undetected in primary care settings. This study explored predictive factors for depression with suicidal ideation (DSI) among middle-aged primary care patients at 6 months after an initial clinic visit. New patients aged 35-64 years were recruited from internal medicine clinics in Japan. Baseline characteristics were elicited using self-administered and physician questionnaires. DSI was evaluated using the Zung Self-Rating Depression Scale and the Profile of Mood States at enrollment and 6 months later. Multiple logistic regression analysis was conducted to calculate adjusted odds ratios for DSI. Sensitivity, specificity, and likelihood ratios for associated factors were calculated. Among 387 patients, 13 (3.4%) were assessed as having DSI at 6 months. Adjusted for sex, age, and related factors, significant odds ratios for DSI were observed for "fatigue on waking ≥1/month" (7.90, 95% confidence intervals: 1.06-58.7), "fatigue on waking ≥1/week" (6.79, 1.02-45.1), "poor sleep status" (8.19, 1.05-63.8), and "relationship problems in the workplace" (4.24, 1.00-17.9). Fatigue on waking, sleep status, and workplace relationship problems may help predict DSI in primary care. Because the sample size in this investigation was small, further studies with larger samples are needed to confirm our findings.

Inquiring about insomnia may facilitate diagnosis of depression in the primary care setting.

AIM: Depression is often undiagnosed in primary care. Asking about sleep status is much easier than asking about mood. This study was conducted to examine the relation between insomnia and depression. METHODS: New patients aged 35-64 years were recruited from internal medicine clinics in Japan. Self-administered questionnaires were employed. Depression was evaluated by the Zung Self-Rating Depression Scale and the Profile of Mood States. Sleep status was investigated using the Pittsburgh Sleep Quality Index. Likelihood ratios of insomnia for depression were calculated. To assess the relation between insomnia and depression independent of confounding factors, adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using multiple logistic regression analyses. RESULTS: Among 598 subjects, 153 (25.6%) were assessed as having depression. 'Very bad sleep quality, with difficulty falling asleep within 30 min ≥3 times/week' showed a positive likelihood ratio of 20.36 (95%CI, 2.53-164) while 'not very good sleep quality' had a negative likelihood ratio of 0.32 (95%CI, 0.14-0.72). Adjusted for sex, age, underlying diseases, major life events, lifestyle habits, and relationship problems, significant OR for depression were observed for 'difficulty falling asleep within 30 min ≥3 times/week' (OR, 2.53; 95%CI, 1.07-5.98), 'waking up in the middle of the night or early morning ≥3 times/week' (OR, 3.09; 95%CI, 1.58-6.05), and 'fairly bad sleep quality' (OR, 3.65; 95%CI, 1.34-9.96). CONCLUSION: Inquiring about the weekly frequency of difficulty 'falling asleep within 30 min,' 'waking up in the middle of the night or early morning,' and 'sleep quality' may help to diagnose depression.

Reactogenicity of trivalent inactivated influenza vaccine in young children: Pronounced reactions by previous successive vaccinations.

In order to assess factors associated with reactogenicity of trivalent inactivated influenza vaccine (IIV3) among young children, data on 1538 vaccinees aged 0-5 years in a previous vaccine effectiveness study were analyzed. The most frequent reaction was redness (19%), followed by induration, swelling, itching, and pain (6-12%); there were no serious adverse events. For some local reactions, multivariate analyses indicated associations of younger age, preschool attendance, presence of siblings, and allergy with lower risk, and use of thinner needles with higher risk. Most notably, administration of one or more IIV3 vaccines during the previous 3 seasons was positively associated with each local reaction (adjusted odds ratios: 3.6-5.4). For subjects aged ≥3 years, prior successive annual vaccinations were associated with substantially increased local reactions, with clear dose-response relationships (P for trend: <0.001 for each); for example, an 9.8-fold greater risk of swelling following three successive annual vaccinations before the study season.

Detection of influenza vaccine effectiveness among nursery school children: Lesson from a season with cocirculating respiratory syncytial virus.

In the winter influenza epidemic season, patients with respiratory illnesses including respiratory syncytial virus (RSV) infections increase among young children. Therefore, we evaluated the effectiveness of influenza vaccine against influenza-like illness (ILI) using a technique to identify outbreaks of RSV infection and to distinguish those patients from ILI patients. The study subjects were 101 children aged 12 to 84 months attending nursery school. We classified the cases into 6 levels based on the definitions of ILI for outcomes. We established observation periods according to information obtained from regional surveillance and rapid diagnostic tests among children. Multivariate odds ratios (ORs) for each case classification were obtained using a logistic regression model for each observation period. For the entire observation period, ORs for cases with fever plus respiratory symptoms were reduced marginally significantly. For the local influenza epidemic period, only the OR for the most serious cases was significantly decreased (0.20 [95%CI: 0.04-0.94]). During the influenza outbreak among the nursery school children, multivariate ORs for fever plus respiratory symptoms decreased significantly (≥ 38.0°C plus ≥ one symptoms: 0.23 [0.06-0.91), ≥ 38.0°C plus ≥ 2 symptoms: 0.21 [0.05-0.85], ≥ 39.0°C plus ≥ one symptoms: 0.18 [0.04-0.93] and ≥ 39.0°C plus ≥ 2 symptoms: 0.16 [0.03-0.87]). These results suggest that confining observation to the peak influenza epidemic period and adoption of a strict case classification system can minimize outcome misclassification when evaluating the effectiveness of influenza vaccine against ILI, even if influenza and RSV cocirculate in the same season.

Inactivated influenza vaccine effectiveness against influenza-like illness among young children in Japan--with special reference to minimizing outcome misclassification.

The aim of the present study was to investigate the influenza vaccine effectiveness among young children in Japan. Study subjects were recruited from 43 pediatric clinics. Influenza-like illness (ILI) was defined as an acute febrile illness with respiratory symptoms; ILI with a fever of > or =39 degrees C was considered to be severe ILI (SILI). The adjusted OR of vaccination significantly decreased to 0.75 for SILI. Influenza vaccination for young children had a protective effect on the occurrences of SILI. This study also indicated that three key tools (case surveillance with equal scrutiny, confining observation to the peak epidemic period, and adoption of strict criteria for ILI) could minimize outcome misclassification and thus provide adequate methodology for monitoring vaccine effectiveness without laboratory confirmation.

Selection bias in evaluating of influenza vaccine effectiveness: a lesson from an observational study of elderly nursing home residents.

Selection bias is of critical concern in the study of influenza vaccine effectiveness when using an observational study design. This bias is attributable to the inherently different characteristics between vaccinees and non-vaccinees. The differences, which are related both to vaccination and signs of clinical disease as an outcome, may lead to erroneous estimation of the effectiveness. In this report, we describe how selection bias among elderly nursing home residents may lead to a spurious interpretation of the protective effect of influenza vaccine. Our results should be a lesson in the importance of regarding selection bias when assessing influenza vaccine effectiveness.

Essential tools for assessing influenza vaccine efficacy in improperly conducted studies: a Japanese perspective.

The fundamental issue in assessing influenza vaccine efficacy is to observe all study subjects with equal intensity throughout the surveillance period. The case definition can be adopted within the scope of the budget and the logistics of the study; however, there is no doubt that culture-proven influenza is currently the best outcome index. More pronounced vaccine efficacy can be detected if stricter case definition criteria are applied and/or if observations are confined to the peak epidemic period. Patients identified through passive case-finding in clinics do not properly represent all influenza cases that occur in the study subjects. Almost all non-randomized studies which have so far been conducted by Japanese clinicians do not take confounders into consideration. Even though laboratory-confirmed influenza is identified, vaccine efficacy should primarily be estimated based on the presence of any influenzal illness, since efficacy calculated by virus type or subtype often results in loss of statistical power. The results from post hoc subgroup analysis may not offer a solid base for assessing vaccine efficacy and should be cautiously interpreted.

Influenza vaccine effectiveness and confounding factors among young children.

This study, done during the 2002--2003 season among children <6 years of age to investigate influenza vaccine effectiveness and confounding factors, involved 2913 children (1512 vaccinees, 1401 non-vaccinees) recruited from 54 paediatric clinics. Between December 2002 and April 2003, parents reported their children's maximum body temperatures weekly. Influenza-like illness (ILI) was defined as an acute febrile illness (> or =38.0 degrees C) during the peak epidemic period. Adjusted odds ratios (ORs) for ILI were obtained using a logistic regression model. In analysis for total subjects, the ORs were significantly decreased for vaccinees (OR: 0.76, 95% CI: 0.66-0.88) and significantly increased for younger age groups, including children aged 2.0-3.9 years (1.42, 1.18-1.72) and those < 2.0 years (2.02,1.61-2.54), compared to those between 4.0 and 5.9 years. ORs were significantly increased for children who visited a physician within the last 6 months for a cold (1.27, 1.08-1.50), attended preschool (1.72, 1.45-2.04), and had > or =3 siblings (1.42, 1.15-1.74). These confounding factors are suggested to be considered in estimating vaccine effectiveness among young children. In subgroup analysis by age groups, significantly decreased ORs were seen in 2.0-3.9-year-old (0.59, 0.47-0.74) and 4.0-5.9-year-old (0.75, 0.58-0.98) vaccinees; no significant vaccine effectiveness was detected for those < 2.0 years (1.07, 0.80-1.44). Thus, among very young children vaccine effectiveness could not be demonstrated.

[Target groups for influenza vaccination].

PURPOSE: To assess target groups for influenza vaccination. METHODS: The target groups for influenza vaccination specified in the recommendations of the US Advisory Committee on Immunization Practices (ACIP) were summarized and compared between 1997 and 2006. RESULTS: Principal changes after the 1997's recommendation are as follows: 1) all children aged 6-59 months became included into the high risk group for active vaccination; 2) recommendation for vaccination timing of pregnant women was extended from those at the second trimester or after to all women who are pregnant during the influenza season; 3) persons with neuro- or muscular-disorders and therefore prone to development of respiratory systems or aspiration pneumonia became included into the high risk group; 4) a category with increased risk to visit a clinic, hospital or emergency department due to influenza-related symptoms was newly established, covering children aged 24-59 months and persons aged 50-64 years; 5) healthy household contacts and caregivers of children aged 0-59 months were included into the group who can transmit influenza to persons in the high risk group; 6) people likely to transmit influenza to persons in the high risk group were classified into 3 categories (health-care providers, household contacts and caregivers, and those in close contact with children aged 0-59 months). CONCLUSION: The ACIP has gradually expanded the target populations for routine influenza vaccination. The most notable change during past 10 years seems to be the recommendation for inclusion of all children aged 6-59 months and people in close contact with babies for active vaccination.

[Immunogenicity of trivalent-inactivated influenza vaccine among children less than 4 years old].

We studied the immunogenicity of trivalent-inactivated influenza vaccine. Subjects were 259 children under 4 years old who visited six pediatric clinics to undergo influenza vaccination. Age distribution was 64 aged <1.0, 65 aged 1.0-1.9, 64 aged 2.0-2.9, and 66 aged 3.0-3.9 years, including subjects who had been previously vaccinated within the last three years, 0% (0/64) aged <1.0, 26% (17/65) aged 1.0-1.9, 72% (46/64) aged 2.0-2.9, and 77% (51/66) aged 3.0-3.9 years old. Two doses of vaccine were given subcutaneously four weeks apart. Dosage was 0.l mL for children under 1 year old, while for children aged one year or older, dosage was 0.2mL, based on standard Japanese recommendations. To measure hemagglutination inhibition (HI) antibody titer, triplet sera were obtained before vaccination (S0), 4 weeks after the first vaccination (S1), and 4 weeks after the second vaccination (S2). The geometric mean of HI antibody titer, the response proportion (titer rise > or =4-fold), and the achievement proportion (postvaccination titer > or =1 : 40) were calculated by age group. Analysis of variance was used to estimate the independent effect of age and prevaccination titer on antibody increase. The geometric means of HI antibody titer were lower among the two younger age groups than among the two older age groups, regardless of vaccine strain or when blood samples were collected. The achievement proportion after 2 doses of vaccine in the <1.0, 1.0-1.9, 2.0-2.9, 3.0-3.9 year age groups were 38%, 58%, 89%, and 85% against A (HI) ; 52%, 54%, 81%, and 73% against A (H3) ; and 23%, 49%, 67%, and 71% against B. Regarding the analysis of variance, prevaccination titer consistently indicated strong effects on antibody increase, regardless of vaccine strain or combination of paired sera. After two doses of vaccine (S2/S0), significant effects of age on antibody induction were shown against A (H1) and B (p = 0.000 and 0.002). Thus, the immunogenicity of trivalent-inactivated influenza vaccine was strongly influenced by prevaccination titer and age. Even two doses of vaccine did not induce a protective antibody level in about 50 to 80% of subjects among infants aged <1.0 year, and 40 to 50% among children 1.0-1.9 year old.

Inactivated influenza vaccine effectiveness in children under 6 years of age during the 2002-2003 season.

This study was carried out to investigate the effectiveness of influenza vaccine among 2913 children (1512 vaccinees and 1401 nonvaccinees) under 6 years of age during the 2002-2003 season. Study subjects were recruited from 54 paediatric clinics, located in eight areas in Japan. Maximum body temperatures were obtained weekly from parents between 2002 December 16 and 2003 April 13. Influenza-like illness (ILI) was defined as an acute febrile illness (> or =38.0 degrees C) during the peak epidemic period in each study area. The vaccine antigens included were A/New Caledonia/20/99(H1N1), A/Panama/2007/99(H3N2) and B/Shandong/7/97. Vaccine effectiveness was analyzed by comparing the frequencies of ILI between vaccinees and nonvaccinees. The adjusted odds ratio (OR) and its 95% confidence interval (95% CI) were calculated by the proportional odds model using logistic regression with three-level outcome variables (<38.0/38.0-38.9/> or =39.0 degrees C). A significantly decreased OR of vaccination was observed (OR: 0.76; 95% CI: 0.66-0.88), corresponding to a vaccine effectiveness (1-OR) of 24% (95% CI: 12%-34%). When the analysis was confined to those aged > or =2 years, a more pronounced OR (0.67, 0.56-0.79) was obtained with a vaccine effectiveness of 33% (21%-44%). On the other hand, no significant vaccine effectiveness was detected among very young children; the ORs were 1.84 (0.81-4.19) for those <1 year of age and 0.99 (0.72-1.36) for those 1.0-1.9 years of age and 1.07 (0.80-1.44) when these two age groups were combined. Thus, among very young children vaccine effectiveness could not be demonstrated.