Implementation and impact of the World Health Organization integrated care for older people (ICOPE) program in China: a randomised controlled trial.

BACKGROUND: Fragmentation of services increases health and social care burden as people live longer with higher prevalence of diseases, frailty and dependency. Local evidence for implementing person-centred integrated care is urgently needed to advance practice and policies to achieve healthy ageing. OBJECTIVE: To test the feasibility and impact of World Health Organization's (WHO) Integrated Care for Older People (ICOPE) approach in China. DESIGN: A randomised controlled trial examining the feasibility of implementing ICOPE approach, evaluating its impact on health outcomes and health resource utilisation. SETTING: Primary care setting in urban and suburban communities of Chaoyang District, Beijing, China. SUBJECTS: Community-dwelling older adults screened as at-risk of functional declines and randomised into intervention (537) and control (1611) groups between September 2020 and February 2021. METHODS: A 6-month intervention program following WHO's ICOPE care pathways implemented by integrated care managers compared to standard available care. RESULTS: After 1 to 1 propensity score matching, participants in intervention and control groups (totally 938) had comparable baseline characteristics, demonstrated feasibility of implementing ICOPE with satisfaction by participants (97-99%) and providers (92-93%). All outcomes showed improvements after a 6-month intervention, while statistically significant least-squares mean differences (control-intervention) in vitality (Mini-Nutritional Assessment Short Form to measure vitality, -0.21, 95% CI, -0.40-0.02), mobility (Short Physical Performance Battery to measure mobility, -0.29, 95% CI, -0.44-0.14) and psychological health (Geriatric Depression Scale five items to measure psychological health, 0.09, 95% CI, 0.03-0.14) were observed (P < 0.05). CONCLUSIONS: It is feasible to localise and implement WHO's ICOPE approach in regions with fragmented resources such as China. Preliminary evidence supports its acceptance among key stakeholders and impact on health outcomes.

Novel biomarkers of oxidative stress as predictive indicators of neurological outcome after out-of-hospital cardiopulmonary arrest.

AIM: Among patients of out-of-hospital cardiopulmonary arrest (OHCPA), only 6% resume their pre-OHCPA social life. The prediction of neurological outcome immediately after the return of spontaneous circulation (ROSC) is urgently needed in OHCPA patients. Novel biomarkers, biological antioxidant potential (BAP), and diacron-reactive oxygen metabolites (d-ROM) are potential predictors of neurological outcome after OHCPA. This study was conducted to evaluate the utility of BAP and d-ROM in the prediction of patient outcomes after OHCPA. METHODS: Blood samples were collected immediately after OHCPA patients were admitted to our hospital between May 2011 and June 2013. BAP and d-ROM concentrations were measured with the simple equipment FRAS4 ™ (Wismerll, Italy). Their association with favorable (cerebral performance category [CPC], 1 and 2) and unfavorable (CPC 3-5) clinical outcomes was compared. BAP and d-ROM values from 23 normal healthy volunteers (HV) were used as controls. RESULTS: Overall, 152 OHCPA patients were included, and 26 patients achieved ROSC. Eleven died during hospitalization were allocated a CPC of 5 and remaining patients were discharged or transported (CPC 1: n = 4; CPC 2: n = 6; CPC 3: n = 3; CPC 4: n = 2; CPC 5: n = 11). The receiver operating characteristics curve of d-ROM and BAP for predicting survival 28 days after OHCPA was 0.596 and 0.834, respectively. Patients without ROSC had significantly higher BAP than HV and patients with ROSC (p < 0.001). A significant correlation was evident between BAP and the time to ROSC (r = 0.641, p < 0.01). CONCLUSION: Oxidative stress, indicated by BAP on admission, strongly correlated with the neurological outcome after OHCPA.

Circulating mitochondrial DAMPs cause inflammatory responses to injury.

Injury causes a systemic inflammatory response syndrome (SIRS) that is clinically much like sepsis. Microbial pathogen-associated molecular patterns (PAMPs) activate innate immunocytes through pattern recognition receptors. Similarly, cellular injury can release endogenous 'damage'-associated molecular patterns (DAMPs) that activate innate immunity. Mitochondria are evolutionary endosymbionts that were derived from bacteria and so might bear bacterial molecular motifs. Here we show that injury releases mitochondrial DAMPs (MTDs) into the circulation with functionally important immune consequences. MTDs include formyl peptides and mitochondrial DNA. These activate human polymorphonuclear neutrophils (PMNs) through formyl peptide receptor-1 and Toll-like receptor (TLR) 9, respectively. MTDs promote PMN Ca(2+) flux and phosphorylation of mitogen-activated protein (MAP) kinases, thus leading to PMN migration and degranulation in vitro and in vivo. Circulating MTDs can elicit neutrophil-mediated organ injury. Cellular disruption by trauma releases mitochondrial DAMPs with evolutionarily conserved similarities to bacterial PAMPs into the circulation. These signal through innate immune pathways identical to those activated in sepsis to create a sepsis-like state. The release of such mitochondrial 'enemies within' by cellular injury is a key link between trauma, inflammation and SIRS.

Hospital disaster response using business impact analysis.

INTRODUCTION: The catastrophic Great East Japan Earthquake in 2011 created a crisis in a university-affiliated hospital by disrupting the water supply for 10 days. In response, this study was conducted to analyze water use and prioritize water consumption in each department of the hospital by applying a business impact analysis (BIA). Identifying the minimum amount of water necessary for continuing operations during a disaster was an additional goal. PROBLEM: Water is essential for many hospital operations and disaster-ready policies must be in place for the safety and continued care of patients. METHODS: A team of doctors, nurses, and office workers in the hospital devised a BIA questionnaire to examine all operations using water. The questionnaire included department name, operation name, suggested substitutes for water, and the estimated daily amount of water consumption. Operations were placed in one of three ranks (S, A, or B) depending on the impact on patients and the need for operational continuity. Recovery time objective (RTO), which is equivalent to the maximum tolerable period of disruption, was determined. Furthermore, the actual use of water and the efficiency of substitute methods, practiced during the water-disrupted periods, were verified in each operation. RESULTS: There were 24 activities using water in eight departments, and the estimated water consumption in the hospital was 326 (SD = 17) m³ per day: 64 (SD = 3) m³ for S (20%), 167 (SD = 8) m³ for A (51%), and 95 (SD = 5) m³ for B operations (29%). During the disruption, the hospital had about 520 m³ of available water. When the RTO was set to four days, the amount of water available would have been 130 m³ per day. During the crisis, 81% of the substitute methods were used for the S and A operations. CONCLUSION: This is the first study to identify and prioritize hospital operations necessary for the efficient continuation of medical treatment during suspension of the water supply by applying a BIA. Understanding the priority of operations and the minimum daily water requirement for each operation is important for a hospital in the event of an unexpected adverse situation, such as a major disaster.

Pannexin-1 hemichannel-mediated ATP release together with P2X1 and P2X4 receptors regulate T-cell activation at the immune synapse.

Engagement of T cells with antigen-presenting cells requires T-cell receptor (TCR) stimulation at the immune synapse. We previously reported that TCR stimulation induces the release of cellular adenosine-5'-triphosphate (ATP) that regulates T-cell activation. Here we tested the roles of pannexin-1 hemichannels, which have been implicated in ATP release, and of various P2X receptors, which serve as ATP-gated Ca(2+) channels, in events that control T-cell activation. TCR stimulation results in the translocation of P2X1 and P2X4 receptors and pannexin-1 hemichannels to the immune synapse, while P2X7 receptors remain uniformly distributed on the cell surface. Removal of extracellular ATP or inhibition, mutation, or silencing of P2X1 and P2X4 receptors inhibits Ca(2+) entry, nuclear factors of activated T cells (NFAT) activation, and induction of interleukin-2 synthesis. Inhibition of pannexin-1 hemichannels suppresses TCR-induced ATP release, Ca(2+) entry, and T-cell activation. We conclude that pannexin-1 hemichannels and P2X1 and P2X4 receptors facilitate ATP release and autocrine feedback mechanisms that control Ca(2+) entry and T-cell activation at the immune synapse.

Implementing care for healthy ageing.

The WHO concept of Healthy Ageing (ie, the process of developing and maintaining the functional ability that enables well-being in older age) has initiated a global discussion about the need for shifting paradigms to reorient health and social services towards person-centred and coordinated models of care. In particular, the integration of health and social care services is critical to provide the basis for comprehensive information sharing and service delivery to support the evolution of the older person over time. The capability to monitor and respond to an older person's changing health and social care needs will enable prompt and personalised health and social care plans to be implemented.The implementation of an integrated care approach involves all the settings where persons age, but also requires a concerted action among micro (clinical), meso (service delivery) and macro (system) level. The community is of particular relevance given the primary objective of "ageing in place". However, from the perspective of the continuum of care and services acting synergistically, all health and social care settings (including long-term care facilities and hospitals) need to evolve and embrace an integrated way of operating to support functional ability in older people, while maximising resource and information sharing efficiencies.In this paper, we explain that government actions to promote well-being in older age should be built on a seamless continuum of care starting from the assessment of the older person's intrinsic capacity and functional ability with the final aim of providing care aligned with the individual's needs and priorities.

What long-term care interventions have been published between 2010 and 2020? Results of a WHO scoping review identifying long-term care interventions for older people around the world.

OBJECTIVE: The global population is rapidly ageing. To tackle the increasing prevalence of older adults' chronic conditions, loss of intrinsic capacity and functional ability, long-term care interventions are required. The study aim was to identify long-term care interventions reported in scientific literature from 2010 to 2020 and categorise them in relation to WHO's public health framework of healthy ageing. DESIGN: Scoping review conducted on PubMed, CINHAL, Cochrane and Google Advanced targeting studies reporting on long-term care interventions for older and frail adults. An internal validated Excel matrix was used for charting.Setting nursing homes, assisted care homes, long-term care facilities, home, residential houses for the elderly and at the community. INCLUSION CRITERIA: Studies published in peer-reviewed journals between 1 January 2010 to 1 February 2020 on implemented interventions with outcome measures provided in the settings mentioned above for subjects older than 60 years old in English, Spanish, German, Portuguese or French. RESULTS: 305 studies were included. Fifty clustered interventions were identified and organised into four WHO Healthy Ageing domains and 20 subdomains. All interventions delved from high-income settings; no interventions from low-resource settings were identified. The most frequently reported interventions were multimodal exercise (n=68 reports, person-centred assessment and care plan development (n=22), case management for continuum care (n=16), multicomponent interventions (n=15), psychoeducational interventions for caregivers (n=13) and interventions mitigating cognitive decline (n=13). CONCLUSION: The identified interventions are diverse overarching multiple settings and areas seeking to prevent, treat and improve loss of functional ability and intrinsic capacity. Interventions from low-resource settings were not identified.

WHO working definition of vitality capacity for healthy longevity monitoring.

Intrinsic capacity, a crucial concept in healthy ageing, is defined by WHO as "the composite of all the physical and mental capacities that an individual can draw on at any point in time". Vitality capacity is considered the underlying physiological determinant of intrinsic capacity. To advance the measurement and monitoring of vitality capacity, a working group of WHO staff members and twenty experts representing six WHO regions was convened to discuss and clarify the attributes of vitality capacity and to develop a clear working definition of the concept. Potential biomarkers to measure vitality capacity were identified, and the following consensual working definition was developed: vitality capacity is a physiological state (due to normal or accelerated biological ageing processes) resulting from the interaction between multiple physiological systems, reflected in (the level of) energy and metabolism, neuromuscular function, and immune and stress response functions of the body.

Adrenergic receptor activation involves ATP release and feedback through purinergic receptors.

Formyl peptide receptor-induced chemotaxis of neutrophils depends on the release of ATP and autocrine feedback through purinergic receptors. Here, we show that adrenergic receptor signaling requires similar purinergic feedback mechanisms. Real-time RT-PCR analysis revealed that human embryonic kidney (HEK)-293 cells express several subtypes of adrenergic (α(1)-, α(2)-, and ß-receptors), adenosine (P1), and nucleotide receptors (P2). Stimulation of G(q)-coupled α(1)-receptors caused release of cellular ATP and MAPK activation, which was blocked by inhibiting P2 receptors with suramin. Stimulation of G(i)-coupled α(2)-receptors induced weak ATP release, while G(s)-coupled ß-receptors caused accumulation of extracellular ADP and adenosine. ß-Receptors triggered intracellular cAMP signaling, which was blocked by scavenging extracellular adenosine with adenosine deaminase or by inhibiting A2a adenosine receptors with SCH58261. These findings suggest that adrenergic receptors require purinergic receptors to elicit downstream signaling responses in HEK-293 cells. We evaluated the physiological relevance of these findings using mouse aorta tissue rings. Stimulation of α(1)-receptors induced ATP release and tissue contraction, which was reduced by removing extracellular ATP with apyrase or in the absence of P2Y(2) receptors in aorta rings from P2Y(2) receptor knockout mice. We conclude that, like formyl peptide receptors, adrenergic receptors require purinergic feedback mechanisms to control complex physiological processes such as smooth muscle contraction and regulation of vascular tone.

Spontaneous occlusion of splenic and renal pseudoaneurysm after blunt abdominal trauma: a case report and literature review.

Pseudoaneurysms caused by blunt abdominal trauma are rarely observed in solid organs. The preferred therapy for pseudoaneurysm after blunt abdominal trauma is often angiography and embolization. Here, we report a case of a spontaneous occlusion of splenic pseudoaneurysm and renal pseudoaneurysm after blunt abdominal trauma. Angiography and embolization were not required, and contrast-enhanced multi-detector computed tomography was used to monitor the patient. This case shows that spontaneous occlusion can be one of the possible outcomes of intraparenchymal splenic pseudoaneurysm and renal pseudoaneurysm after blunt abdominal trauma.

Evaluation of posttraumatic venous sinus occlusion with CT venography.

BACKGROUND: Although cerebral venous sinus occlusion (CVSO) is reported to be associated with intracranial hypertension, its incidence or significance in head trauma is not clear. This study investigated with CT venography the incidence of posttraumatic CVSO, its clinical course, and relation to intracranial hypertension. PATIENTS: This study comprised 97 consecutive patients admitted to our Trauma Center from 2002 through 2008 with skull fracture of the petrous portion of the temporal bone or that crossed the dural sinus. Patients with CVSO were examined with CT venography and followed up with CT venography or magnetic resonance imaging. The relation of CVSO to patient outcome and incidence of "talk and deteriorate" was also investigated. RESULTS: CVSO was observed in 22 of 97 patients (22.4%). Mortality was significantly higher in the CVSO group versus no-CVSO group (50.0% vs. 9.3%, p < 0.001). Incidence of lethal intracranial hypertension was higher in the CVSO versus no-CVSO group (40.9% vs. 5.3%, p < 0.001), although there was no difference in Glasgow Coma Scale score at admission between the two groups (CVSO group, 8 +/- 5 vs. no-CVSO group, 10 +/- 4). Recanalization without treatment for CVSO occurred by 6 months in 9 of the 11 survivors (81.8%) who could be followed up. CONCLUSION: CVSO incidence after head injury was much higher than ever thought. It was associated with mortality and lethal intracranial hypertension, indicating that CVSO may induce acute increase in intracranial pressure in some cases. Early recognition of CVSO may be important to predict deterioration after admission and for starting immediate treatment.

Plasma Adenylate Levels are Elevated in Cardiopulmonary Arrest Patients and May Predict Mortality.

Cerebral and cardiac dysfunction cause morbidity and mortality in postcardiac arrest syndrome (PCAS) patients. Predicting clinical outcome is necessary to provide the optimal level of life support for these patients. In this pilot study, we examined whether plasma ATP and adenylate levels have value in predicting clinical outcome in PCAS patients. In total, 15 patients who experienced cardiac arrest outside the hospital setting and who could be reanimated were enrolled in this study. Healthy volunteers (n = 8) served as controls. Of the 15 PCAS patients, 8 died within 4 days after resuscitation. Of the 7 survivors, 2 lapsed into vegetative states, 1 survived with moderate disabilities, and 4 showed good recoveries. Arterial blood samples were drawn immediately after successful resuscitation and return of spontaneous circulation (ROSC). The concentrations of ATP and other adenylates in plasma were assessed with high-performance liquid chromatography. PCAS patients had significantly higher ATP levels than healthy controls. Plasma ATP levels correlated with lactate levels, Acute Physiology and Chronic Health Evaluation II scores, and the time it took to ROSC (time-to-ROSC). Plasma adenylate levels in patients who died after resuscitation were significantly higher than in survivors. Based on our results and receiver-operating characteristic curve analysis, we conclude that plasma adenylate levels may help predict outcome in PCAS patients.

Integrated prevention and management of non-communicable diseases, including musculoskeletal health: a systematic policy analysis among OECD countries.

INTRODUCTION: Development and implementation of appropriate health policy is essential to address the rising global burden of non-communicable diseases (NCDs). The aim of this study was to evaluate existing health policies for integrated prevention/management of NCDs among Member States of the Organisation for Economic Co-operation and Development (OECD). We sought to describe policies' aims and strategies to achieve those aims, and evaluate extent of integration of musculoskeletal conditions as a leading cause of global morbidity. METHODS: Policies submitted by OECD Member States in response to a World Health Organization (WHO) NCD Capacity Survey were extracted from the WHO document clearing-house and analysed following a standard protocol. Policies were eligible for inclusion when they described an integrated approach to prevention/management of NCDs. Internal validity was evaluated using a standard instrument (sum score: 0-14; higher scores indicate better quality). Quantitative data were expressed as frequencies, while text data were content-analysed and meta-synthesised using standardised methods. RESULTS: After removal of duplicates and screening, 44 policies from 30 OECD Member States were included. Three key themes emerged to describe the general aims of included policies: system strengthening approaches; improved service delivery; and better population health. Whereas the policies of most countries covered cancer (83.3%), cardiovascular disease (76.6%), diabetes/endocrine disorders (76.6%), respiratory conditions (63.3%) and mental health conditions (63.3%), only half the countries included musculoskeletal health and pain (50.0%) as explicit foci. General strategies were outlined in 42 (95.5%) policies-all were relevant to musculoskeletal health in 12 policies, some relevant in 27 policies and none relevant in three policies. Three key themes described the strategies: general principles for people-centred NCD prevention/management; enhanced service delivery; and system strengthening approaches. Internal validity sum scores ranged from 0 to 13; mean: 7.6 (95% CI 6.5 to 8.7). CONCLUSION: Relative to other NCDs, musculoskeletal health did not feature as prominently, although many general prevention/management strategies were relevant to musculoskeletal health improvement.

Frontline Science: Escherichia coli use LPS as decoy to impair neutrophil chemotaxis and defeat antimicrobial host defense.

Bacterial infections and sepsis are leading causes of morbidity and mortality in critically ill patients. Currently, there are no effective treatments available to improve clinical outcome in sepsis. Here, we elucidated a mechanism by which Escherichia coli (E. coli) bacteria impair neutrophil (PMN) chemotaxis and we studied whether this mechanism can be therapeutically targeted to improve chemotaxis and antimicrobial host defense. PMNs detect bacteria with formyl peptide receptors (FPR). FPR stimulation triggers mitochondrial ATP production and release. Autocrine stimulation of purinergic receptors exerts excitatory and inhibitory downstream signals that induce cell polarization and cell shape changes needed for chemotaxis. Here we show that the bacterial cell wall product LPS dose-dependently impairs PMN chemotaxis. Exposure of human PMNs to LPS triggered excessive mitochondrial ATP production and disorganized intracellular trafficking of mitochondria, resulting in global ATP release that disrupted purinergic signaling, cell polarization, and chemotaxis. In mice infected i.p. with E. coli, LPS treatment increased the spread of bacteria at the infection site and throughout the systemic circulation. Removal of excessive systemic ATP with apyrase improved chemotaxis of LPS-treated human PMNs in vitro and enhanced the clearance of E. coli in infected and LPS-treated mice. We conclude that systemic ATP accumulation in response to LPS is a potential therapeutic target to restore PMN chemotaxis and to boost the antimicrobial host immune defense in sepsis.

The anticoagulant treatment for sepsis induced disseminated intravascular coagulation; network meta-analysis.

INTRODUCTION: The benefits and harm caused by anticoagulant treatments for sepsis induced disseminated intravascular coagulation (DIC) remain unclear. Therefore, we performed a network meta-analysis to assess the effect of available anticoagulant treatments on patient mortality, DIC resolution and the incidence of bleeding complication in patients with septic DIC. MATERIALS AND METHODS: We considered all studies from four recent systematic reviews and searched the PubMed, MEDLINE, and Cochrane databases for other studies that investigated anticoagulant treatment for septic DIC using antithrombin, thrombomodulin, heparin, or protease inhibitors in adult critically ill patients. These four anticoagulants and placebo were compared. The primary outcome in this study was patient mortality, and the secondary outcomes were the DIC resolution rate and incidence of bleeding complications. RESULTS: The network meta-analysis included 1340 patients from nine studies. There were no significant differences in the risks of mortality and bleeding complications among all direct comparisons and the network meta-analysis. Using a placebo was associated with a significantly lower rate of DIC resolution, compared to antithrombin in the direct comparison (odds ratio [OR]: 0.20, 95% credible interval [95% CrI]: 0.046-0.81) and in the network meta-analysis (OR: 0.20, 95% CrI: 0.043-0.84). CONCLUSIONS: Our study revealed no significant differences in the risks for mortality and bleeding complications when a placebo and all four anticoagulants were compared in septic DIC patients. The results also indicated that antithrombin was associated with a five-fold higher likelihood of DIC resolution, compared to placebo.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016).

BACKGROUND AND PURPOSE: The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 and published in the Journal of JSICM, [2017; Volume 24 (supplement 2)] 10.3918/jsicm.24S0001 and Journal of Japanese Association for Acute Medicine [2017; Volume 28, (supplement 1)] http://onlinelibrary.wiley.com/doi/10.1002/jja2.2017.28.issue-S1/issuetoc.This abridged English edition of the J-SSCG 2016 was produced with permission from the Japanese Association of Acute Medicine and the Japanese Society for Intensive Care Medicine. METHODS: Members of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ) and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (> 66.6%) majority vote of each of the 19 committee members. RESULTS: A total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation, and its supporting evidence were also added to each recommendation statement. We conducted meta-analyses for 29 CQs. Thirty-seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for five CQs. CONCLUSIONS: Based on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016).

Background and Purpose: The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 in Japanese. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. Methods: Members of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ), and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (>66.6%) majority vote of each of the 19 committee members. Results: A total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation and its supporting evidence were also added to each recommendation statement. We conducted meta-analyses for 29 CQs. Thirty seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for 5 CQs. Conclusions: Based on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals.