Fever is a common symptom of influenza and coronavirus disease 2019 (COVID-19), yet its physiological role in host resistance to viral infection remains less clear. Here, we demonstrate that exposure of mice to the high ambient temperature of 36 °C increases host resistance to viral pathogens including influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). High heat-exposed mice increase basal body temperature over 38 °C to enable more bile acids production in a gut microbiota-dependent manner. The gut microbiota-derived deoxycholic acid (DCA) and its plasma membrane-bound receptor Takeda G-protein-coupled receptor 5 (TGR5) signaling increase host resistance to influenza virus infection by suppressing virus replication and neutrophil-dependent tissue damage. Furthermore, the DCA and its nuclear farnesoid X receptor (FXR) agonist protect Syrian hamsters from lethal SARS-CoV-2 infection. Moreover, we demonstrate that certain bile acids are reduced in the plasma of COVID-19 patients who develop moderate I/II disease compared with the minor severity of illness group. These findings implicate a mechanism by which virus-induced high fever increases host resistance to influenza virus and SARS-CoV-2 in a gut microbiota-dependent manner.

Few studies have assessed the association between health literacy (HL) and healthy lifestyle characteristics among Japanese people, and reports on the association between HL and prevalence of metabolic syndrome are also scarce. The present cross-sectional study included 1817 (781 men and 1036 women) Japanese individuals who participated in a medical health checkup at Bange Kosei General Hospital and Takada Kosei Hospital in Fukushima, Japan, from April 2013–2014. Information regarding HL and healthy lifestyle characteristics listed in Breslow’s seven health practices was collected by self-administered questionnaire. In multivariate logistic analysis, higher HL (≥14) was positively associated with healthy lifestyle characteristics [odds ratio (OR) = 2.08, 95 % confidence interval (CI) = 1.33–3.23] and inversely associated with prevalence of metabolic syndrome (OR = 0.67, 95 % CI = 0.48–0.95) among men. Among HL items, the ability to make decisions based on health-related information was significantly associated with healthy lifestyle characteristics (OR = 2.04, 95 % CI = 1.34–3.10 for men, OR = 1.38, 95 % CI = 1.30–1.85 for women) and inversely associated with prevalence of metabolic syndrome (OR = 0.62, 95 % CI = 0.44–0.88 for men, OR = 0.68, 95 % CI = 0.49–0.95 for women) in both sexes. We found positive associations between HL and healthy lifestyle characteristics and an inverse association with prevalence of metabolic syndrome among men. Our findings also suggest that men and women are likely to engage in health-promoting behaviors and make decisions based on health-related information. These findings highlight the importance of comprehensive assessments, including HL, for health promotion in the community.

Objective Fever of unknown origin (FUO) can be caused by many diseases, and varies depending on region and time period. Research on FUO in Japan has been limited to single medical institution or region, and no nationwide study has been conducted. We identified diseases that should be considered and useful diagnostic testing in patients with FUO. Design A nationwide retrospective study. Setting 17 hospitals affiliated with the Japanese Society of Hospital General Medicine. Participants This study included patients ≥18 years diagnosed with ‘classical fever of unknown origin’ (axillary temperature ≥38°C at least twice over a ≥3-week period without elucidation of a cause at three outpatient visits or during 3 days of hospitalisation) between January and December 2011. Results A total of 121 patients with FUO were enrolled. The median age was 59 years (range 19–94 years). Causative diseases were infectious disease in 28 patients (23.1%), non-infectious inflammatory disease in 37 (30.6%), malignancy in 13 (10.7%), other in 15 (12.4%) and unknown in 28 (23.1%). The median interval from fever onset to evaluation at each hospital was 28 days. The longest time required for diagnosis involved a case of familial Mediterranean fever. Tests performed included blood cultures in 86.8%, serum procalcitonin in 43.8% and positron emission tomography in 29.8% of patients. Conclusions With the widespread use of CT, FUO due to deep-seated abscess or solid tumour is decreasing markedly. Owing to the influence of the ageing population, polymyalgia rheumatica was the most frequent cause (9 patients). Four patients had FUO associated with HIV/AIDS, an important cause of FUO in Japan. In a relatively small number of cases, cause remained unclear. This may have been due to bias inherent in a retrospective study. This study identified diseases that should be considered in the differential diagnosis of FUO.

This study examined the prevalence of chronic comorbidities and the use of co-medications among people living with HIV (PLWH) on antiretrovirals in Japan, compared with age-matched controls without HIV. This was an observational, retrospective, cross-sectional study using a hospital claims database of Japanese hospitals with advanced medical capabilities (i.e., advanced treatment hospitals, general hospitals, acute care hospitals). We extracted data for PLWH aged ≥18 years with a prescription record of antiretrovirals between January 2010 and December 2015, and for age-, sex-, and hospital-matched people without HIV. For each group, chronic comorbidities (diabetes, hypertension, lipid disorders, vascular diseases, chronic kidney failure, cancers, psychiatric disorders, osteoporosis, and hepatitis B/C co-infection), and co-medications were examined by age group. We analyzed data for 1445 PLWH and 14,450 people without HIV. The proportion of patients with multiple comorbidities was much greater among PLWH than controls of the same age group. Lipid disorders and diabetes were more prevalent in PLWH than controls (31.6% vs. 10.3% and 26.8% vs. 13.2%, respectively), both of which were more common in PLWH at earlier ages. Cancer was present in 8.1% of PLWH and 8.9% of controls. A greater proportion of PLWH used multiple co-medications other than antiretrovirals at earlier ages than controls. PLWH taking antiretrovirals in Japan had a greater burden of comorbidities and co-medications with increasing age than people without HIV. In addition to appropriate management of comorbidities, medication reconciliation according to patients' co-medication profiles is important for successful management of this patient population.

Objective To identify the key diagnostic features and causes of fever of unknown origin (FUO) in Japanese patients. Design Multicentre prospective study. Setting Sixteen hospitals affiliated with the Japanese Society of Hospital General Medicine, covering the East and West regions of Japan. Participants Patient aged ≥20 years diagnosed with classic FUO (axillary temperature≥38.0°C at least twice within a 3-week period, cause unknown after three outpatient visits or 3 days of hospitalisation). A total of 141 cases met the criteria and were recruited from January 2016 to December 2017. Intervention Japanese standard diagnostic examinations. Outcome measures Data collected include usual biochemical blood tests, inflammatory markers (erythrocyte sedimentation rate (ESR), C reactive (CRP) protein level, procalcitonin level), imaging results, autopsy findings (if performed) and final diagnosis. Results The most frequent age group was 65–79 years old (mean: 58.6±9.1 years). The most frequent cause of FUO was non-infectious inflammatory disease. After a 6-month follow-up period, 21.3% of cases remained undiagnosed. The types of diseases causing FUO were significantly correlated with age and prognosis. Between patients with and without a final diagnosis, there was no difference in CRP level between patients with and without a final diagnosis (p=0.121). A significant difference in diagnosis of a causative disease was found between patients who did or did not receive an ESR test (p=0.041). Of the 35 patients with an abnormal ESR value, 28 (80%) had causative disease identified. Conclusions Age may be a key factor in the differential diagnosis of FUO; the ESR test may be of value in the FUO evaluation process. These results may provide clinicians with insight into the management of FUO to allow adequate treatment according to the cause of the disease.

Objectives Comorbidities are associated with a high burden of disease in people living with HIV (PLWH). The objective was to investigate the prevalence of chronic comorbidities and use of co-medications in PLWH in Japan. Methods This study retrospectively analysed clinical information from PLWH receiving antiretroviral therapy (ART) between April 2009 and March 2019. Demographic characteristics, numbers and types of chronic comorbidities, and numbers and types of non-ART co-medications, were described by age groups. The source of data was the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB). Results Overall, 28 089 PLWH (male 91.9%) who used ART were identified. Out of 28 089 PLWH, 81.5% had at least one chronic comorbidity. The numbers of AIDS-defining cancers and non-AIDS-defining cancers in this Japanese cohort were 2432 (8.7%) and 2485 (8.8%), respectively. The cumulative burden of comorbidities including non-AIDS-defining cancer increased with age. Changes in trend between 2009 and 2019 were observed, including a higher proportion of PLWH diagnosed at ≥ 70 years old [2019 (4.7%) vs. 2009 (2.4%)] and a decreasing percentage of patients with AIDS-defining cancers (down from 6.3% to 4.8% between 2009 and 2019). The most common co-medications during the most recent 3-month period were lipid-regulating/anti-atheroma preparations (11.3%), antacids, antiflatulents and anti-ulcerants (9.6%), and agents acting on the renin–angiotensin system (8.1%). The three most common therapeutic categories of co-medications during the study period were antacids, antiflatulents and anti-ulcerants (35.0%), systemic antihistamines (33.7%) and psycholeptics (27.1%). More than 30% of PLWH aged > 40 years used at least one co-medication in a 3-month period, while more than half of PLWH aged > 30 years had at least one co-medication prescribed concomitantly for a total of ≥ 90 days during the study period, and the numbers of co-medications used were greater in the older age groups. Conclusions The burden of chronic comorbidities and co-medication were found to be greater in older, as compared to younger patients, among 28 089 PLWH in a nationwide study in Japan. This finding suggests the need to identify elderly PLWH and to appropriately manage their HIV and comorbidities.