A regional multidisciplinary network enhances child abuse case management.

BACKGROUND: We previously reported an inadequate response to intracranial hemorrhage (ICH) cases under 24 months of age in Yokohama from 2011 to 2013. Hence, it is very important to evaluate how the establishment of a regional multidisciplinary network for child abuse affects the response to ICH cases in medical institutions. METHODS: We conducted a questionnaire survey of ICH cases under 24 months of age from 2014 to 2016 using a regional multidisciplinary network for child abuse established in Yokohama in September 2013. We investigated the patients' characteristics, examinations to identify inflicted injury, and reports made to the hospital-based child protection team (CPT) or regional child protective service (CPS), and compared the results of a previous study and the current study, which corresponds to before and after the establishment of the regional network, respectively. RESULTS: The total number of ICH cases was 50 in 3 years. The number of cases surveyed for covert fracture and fundus hemorrhage increased significantly after the establishment of the regional network (P = 0.0001 and P = 0.0182, respectively). The number of cases reported as suspected child abuse was 41 (82%) to the hospital-based CPTs and 27 (54%) to the regional CPSs. There were significant differences between before and after the establishment of the regional network regarding CPT (P = 0.0062) and CPS (P = 0.0215) reports. CONCLUSIONS: A regional multidisciplinary network can enhance response and cooperation to address child abuse. It deepens our understanding of such care and improves awareness by hospital personnel of child abuse.

Effectiveness of high-flow nasal cannula on pulmonary rehabilitation in subjects with chronic respiratory failure.

BACKGROUND: The effects of exercise training using both high fraction of inspired oxygen (FIO2) and high flow oxygen delivered through a high-flow nasal cannula (HFNC) on exercise capacity in patients with chronic respiratory failure (CRF) receiving long-term oxygen therapy (LTOT) are unknown. METHODS: In this randomized study, 32 patients with CRF receiving LTOT were assigned to undergo 4 weeks of exercise training on a cycle ergometer using an HFNC (flow: 50 L/min) with a FIO2 of 1.0 (HFNC group; n = 16) or ordinary supplemental oxygen via a nasal cannula (flow: 6 L/min) (oxygen group; n = 16). A 6-min walking test and a constant-load test were performed before and after 4 weeks of exercise training. RESULTS: Following 4 weeks of exercise training, change in the 6-min walking distance was significantly greater in the HFNC than in the oxygen group (55.2 ± 69.6 m vs. -0.5 ± 87.3 m; p = 0.04). However, there was no significant difference between the two groups in the degree of improvement in the duration of the constant-load exercise test after exercise training. CONCLUSIONS: Considering the effect on daily activities (e.g., walking), exercise training using both high FIO2 and high flow through an HFNC is a potentially superior exercise training modality for patients with CRF receiving LTOT. Clinical Trial Registration - http://www. CLINICALTRIALS: gov. Unique identifier: NCT02804243.

Epidemiology of child mortality and challenges in child death review in Japan: The Committee on Child Death Review: A Committee Report: The Committee on Child Death Review: A Committee Report.

We performed a retrospective survey and verification of the medical records of death cases of children (and adolescents; aged <18 years) between 2014 and 2016 in pediatric specialty training facilities in Japan. Of the 2,827 registered cases at 163 facilities, 2,348 cases were included. The rate of identified deaths compared with the demographic survey, was 18.2%-21.0% by age group. The breakdown of deaths was determined as follows: 638 cases (27.2%) were due to external factors or unknown causes, 118 (5.0%) were suspected to involve child maltreatment, 932 (39.7%) were of moderate or high preventability or were indeterminable. Further detailed verification was required for 1,333 cases (56.8%). Comparison of the three prefectures with high rates of identified deaths in Japan revealed no significant differences, such as in the distribution of diseases, suggesting that there was little selection bias. The autopsy rate of deaths of unknown cause was 43.4%, indicating a high ratio of forensic autopsies. However, sufficient clinical information was not collected; therefore, thorough evaluations were difficult to perform. Cases with a moderate or high possibility of involvement of child maltreatment accounted for 5%, similar to previous studies. However, more objective evaluation is necessary. Preventable death cases including potentially preventable deaths accounted for 25%, indicating that proposals need to be made for specific preventive measures. Individual primary verification followed by secondary verification by multiple organizations is effective. It is anticipated that a child death review (CDR) system with such a multi-layered structure will be established; however, the following challenges were revealed: The subjects of CDR are all child deaths. Even if natural death cases are entrusted to medical organizations, and complicated cases to other special panels, the numbers are very high. Procedures need to be established to sufficiently verify these cases. Although demographic statistics are useful for identifying all deaths, care must be taken when interpreting such data. Detailed verification of the cause of death will affect the determination of subsequent preventability. Verification based only on clinical information is difficult, so a procedure that collates non-medical information sources should be established. It is necessary to organize the procedures to evaluate the involvement of child maltreatment objectively and raise awareness among practitioners. To propose specific preventive measures, a mechanism to ensure multiprofessional diverse perspectives is crucial, in addition to fostering the foundation of individual practitioners. To implement the proposed measures, it is also necessary to discuss the responsibilities and authority of each organization. Once the CDR system is implemented, verification of the system should be repeated. Efforts to learn from child deaths and prevent deaths that are preventable as much as possible are essential duties of pediatricians. Pediatricians are expected to undertake the identified challenges and promote and lead the implementation of the CDR system. This is a word-for-word translation of the report in J. Jpn. Pediatr. Soc. 2019; 123 (11): 1736-1750, which is available only in the Japanese language.

Overlapping Features in Kawasaki Disease-Related Arthritis and Systemic-Onset Juvenile Idiopathic Arthritis: A Nationwide Study in Japan.

Background: Arthritis may occur after the diagnosis of Kawasaki disease (KD). Most cases are self-limiting; however, some patients require prolonged treatment. Method: To characterize KD-related arthritis, 14 patients who required arthritis treatment within 30 days after the diagnosis of KD were recruited from the 23rd KD survey in Japan. Twenty-six additional patients were included from our tertiary center and literature review cohorts. Results: The estimated prevalence of KD-related arthritis in Japan was 48 per 100,000 KD patients. Patients with KD-related arthritis had an older age at onset (52 vs. 28 months, P = 0.002) and higher rate of intravenous immunoglobulin (IVIG) resistance in comparison to those without arthritis (86 vs. 17%, P < 0.001). Among 40 patients, 18 had arthritis in the acute phase KD (continued fever-onset type) and 22 did in the convalescent phase (interval fever-onset type). Both showed a similar rate of complete KD or IVIG response. Interval-type patients required biologics for arthritis control less frequently (5 vs. 39%, P = 0.02) and had a higher 2-year off-treatment rate (100 vs. 43%, P = 0.009) than continued-type ones. Interval-types showed lower serum ferritin and interleukin-18 levels than continued-types. When continued-types were grouped according to whether or not they required biologics (n = 7 and n = 11, respectively), the former subgroup had higher ferritin and interleukin-18 levels (P = 0.01 and 0.02, respectively). A canonical discriminant analysis differentiated interval-type from continued-type with the combination of age, time to arthritis, and the ferritin and matrix metalloproteinase-3 levels. Conclusion: Arthritis requiring treatment is a rare complication of KD. KD-associated arthritis includes interval-type (KD-reactive) and continued-type (true systemic-onset juvenile idiopathic arthritis [JIA] requiring biologics), and overlapping arthritis, suggesting the pathophysiological continuity of autoinflammation between KD and JIA.

Effective plasma concentrations of itraconazole and its active metabolite for the treatment of pulmonary aspergillosis.

BACKGROUND: Itraconazole (ITCZ) is used to treat pulmonary aspergillosis, but findings regarding the range of effective plasma concentrations are often contradictory. This study attempted to determine effective plasma concentrations of ITCZ and its active metabolite hydroxyitraconazole (OH-ITCZ) by retrospectively analyzing their relationships to clinical efficacy. METHODS: The study included 34 patients with pulmonary aspergillosis treated using ITCZ (mean age, 70 years). Each patient was treated with 200 mg ITCZ once daily (mean duration of treatment: 384 days). Plasma concentrations of ITCZ and OH-ITCZ at trough levels from 7 to 889 days after the start of treatment were determined using high-performance liquid chromatography. Clinical efficacy was assessed through the improvement clinical symptoms. RESULTS: Fifteen patients were classified as effective group and the other 19 patients as non-effective group. Mean (±standard deviation) ITCZ trough plasma concentration was significantly higher in effective group (1254 ± 924 ng/mL) than in non-effective group (260 ± 296 ng/mL). Mean OH-ITCZ plasma concentration was significantly higher in effective group (1830 ± 1031 ng/mL) than in non-effective group (530 ± 592 ng/mL). Receiver operating characteristic curve analysis revealed the optimal cutoff for ITCZ trough plasma concentration was 517 ng/mL, and 86.7% of effective group showed concentrations exceeding this value. The optimal cutoff for total ITCZ + OH-ITCZ plasma concentration was 1025 ng/mL, and 93.3% of effective group showed a concentration exceeding this value. CONCLUSIONS: Our findings indicate that effective plasma concentration ranges for the treatment of pulmonary aspergillosis begin at an ITCZ trough plasma concentration of 500 ng/mL and a total ITCZ + OH-ITCZ plasma concentration of 1000 ng/mL.

Low Levels of PaO2 after Long-term Noninvasive Ventilation are a Poor Prognostic Factor in Patients with Restrictive Thoracic Disease.

Objective The effects of partial pressure of arterial oxygen (PaO2) after introducing long-term noninvasive ventilation (NIV) on the prognosis of patients with restrictive thoracic disease and chronic respiratory failure are not exactly known. Methods Data from 141 patients with restrictive thoracic disease under long-term nocturnal NIV were retrospectively examined. We divided the patients into 2 groups according to the daytime PaO2 value while breathing spontaneously with prescribed oxygen at 12 months after introducing NIV: PaO2≥80 Torr group (n=76) and PaO2<80 Torr group (n=65). Results During the 4-year follow-up, the mortality was significantly higher in the PaO2<80 Torr group than in the PaO2≥80 Torr group (50.8% vs. 32.9%, p=0.03). Independent factors associated with the 4-year mortality after introducing NIV determined by a multivariate logistic regression analysis were a low body mass index [odds ratio (OR) 0.87; 95% confidence interval (CI) 0.77 to 0.97; p=0.01], assisted mode with NIV (OR 4.11; 95% CI, 1.79 to 9.45; p=0.0009), hospitalization during the first year of introducing NIV (OR 1.72; 95% CI, 1.06 to 2.79; p=0.03), and daytime PaO2<80 Torr at 12 months after introducing NIV (OR 2.30; 95% CI, 1.03 to 5.10; p=0.04). Conclusion A low daytime PaO2 at 12 months after introducing NIV was an independent risk factor for mortality. Keeping the daytime PaO2≥80 Torr through the adjustment of the nocturnal NIV settings or increased diurnal supplemental oxygen may help improve the prognosis in patients with restrictive thoracic disease who are under NIV.

Fever Responses Are Enhanced with Advancing Age during Respiratory Syncytial Virus Infection among Children under 24 Months Old.

The most important risk factor for severe respiratory syncytial virus (RSV) infection is considered young age due to the immature immune system. The risk at young age is reported greater for RSV than for other respiratory infectious agents. Based on the strong association between young age and severity of RSV infection due to immature immunity, we aimed to assess whether there were any age-related differences in fever responses, as one clinical aspect of the immune response. In our observational study over two seasons (2014-2015 and 2015-2016), daily body temperatures of children under 3 years old with RSV infection were recorded from the first medical visit during the acute phase to defervescence. The body temperature records were analyzed among 171 children of four age groups (< 6, < 12, < 24 and ≥ 24 months), in terms of fever development, degrees of fever onset, the highest fever during the period, and fever duration. There were 54 patients in the group of < 6 months, 41 in the group of < 12 months, 58 in the group of < 24 months, and 18 in the group of ≥ 24 months. We thus found the correlation between age and fever responses under 24 months old; namely, the more the age advanced, the more frequently high and prolonged fever was experienced. Importantly, infants under 6 months old tend to show the suppressed fever responses. In conclusion, young infants with reduced fever response during RSV infection do not implicate less severity and needs attentive management.

Successful desensitization therapy for a patient with isoniazid-induced hypersensitivity pneumonia.

A 57-year-old male was diagnosed with mycobacterium tuberculoma and was treated with isoniazid, rifampicin, ethambutol, and pyrazinamide. Three weeks after initiation of treatment, he presented with fever and appetite loss. Chest radiograph showed diffuse micronodular shadows on both lung fields. High-resolution chest computed tomography findings were diffuse parenchymal micronodules in both lungs, which was consistent with hypersensitivity pneumonia. Because drug-induced pneumonia was suspected, the antituberculous regimen was discontinued. The symptoms and diffuse micronodular shadows improved. A drug lymphocyte stimulation test was only positive for isoniazid, so we suspected that the pneumonia was induced by isoniazid. Rifampicin and ethambutol were reintroduced without any recurrence of the abnormal shadows. Next, we tried desensitization to isoniazid over a period of two weeks, which was successful without any adverse events. Although isoniazid-induced pneumonia is extremely rare, it is important to recognize that isoniazid can cause such an adverse reaction. In addition, drug desensitization may be useful in drug-induced pneumonia.

Inadequate sociomedical evaluation of possible abusive head trauma in Yokohama.

BACKGROUND: There have been no previous studies on the adequacy of combined evaluation of possible abusive head trauma cases by frontline medical personnel, hospital-based child protection teams, and child protective services in local districts of Japan. METHODS: We conducted a questionnaire survey of hospitalized patients under 24 months old with a diagnosis of intracranial hemorrhage (ICH) from January 2011 to December 2013. Eleven large-scale general hospitals in Yokohama, Japan were surveyed, which provide centralized inpatient care to moderately-severely ill children. RESULTS: A total of 51 ICH patients were listed from eight hospitals. Median patient age was 7 months, and 84% were younger than 12 months. The most common diagnosis on computed tomography was subdural hematoma (n = 26; 51%). Of a total of 51 cases, 31 (61%) occurred inside the home; the injury scene was unknown in six cases (12%). We reviewed these 37 cases from the viewpoint of evaluation with concern for suspected child abuse. Three out of 37 patients (8%) were not examined for inflicted skin lesions, and skeletal surveys and funduscopy were not conducted in 14 (38%) and 15 (41%), respectively. Thirteen out of 37 cases (35%) were not reported to hospital-based child protection teams and 22 (59%) were not reported to regional child protective services. CONCLUSION: The sociomedical evaluation of possible child abuse appears to be systematically inadequate in Yokohama.

Chylothorax associated with child abuse.

We report a case of right chylothorax associated with physical abuse in a 10-month-old boy who presented with respiratory decompensation. Chylothorax was improved by thoracic drainage and nutrition management, such as fasting followed by medium-chain triglyceride milk. Chest computed tomography on admission showed bilateral old rib fractures. Accordingly, physical abuse was suspected. Chylothorax of unknown cause in infancy, especially in those with coexisting rib fractures, must be scrutinized for child abuse.

Bacterial meningitis after radiofrequency diathermy for adenoid hypertrophy.

A 6-year-old otherwise healthy girl who underwent radiofrequency diathermy for adenoid hypertrophy presented with fever on the same day and was diagnosed as having bacterial meningitis 2 days later. Culture of cerebrospinal fluid indicated that the pathogens were penicillin-sensitive Streptococcus pneumoniae and methicillin-sensitive Staphylococcus aureus. The serotype of the causative pneumococcus, 11A, was not covered by the 7-valent pneumococcal conjugate vaccine the patient had been inoculated with. Although not previously reported, radiofrequency diathermy for adenoid hypertrophy can be considered a risk factor for bacteremia and meningitis.

Clinical and microbiological differences between Mycobacterium abscessus and Mycobacterium massiliense lung diseases.

In recent years, many novel nontuberculous mycobacterial species have been discovered through genetic analysis. Mycobacterium massiliense and M. bolletii have recently been identified as species separate from M. abscessus. However, little is known regarding their clinical and microbiological differences in Japan. We performed a molecular identification of stored M. abscessus clinical isolates for further identification. We compared clinical characteristics, radiological findings, microbiological findings, and treatment outcomes among patients with M. abscessus and M. massiliense lung diseases. An analysis of 102 previous isolates of M. abscessus identified 72 (71%) M. abscessus, 27 (26%) M. massiliense, and 3 (3%) M. bolletii isolates. Clinical and radiological findings were indistinguishable between the M. abscessus and M. massiliense groups. Forty-two (58%) patients with M. abscessus and 20 (74%) patients with M. massiliense infections received antimicrobial treatment. Both the M. abscessus and M. massiliense groups showed a high level of resistance to all antimicrobials, except for clarithromycin, kanamycin, and amikacin. However, resistance to clarithromycin was more frequently observed in the M. abscessus than in the M. massiliense group (16% and 4%, respectively; P = 0.145). Moreover, the level of resistance to imipenem was significantly lower in M. abscessus isolates than in M. massiliense isolates (19% and 48%, respectively; P = 0.007). The proportions of radiological improvement, sputum smear conversion to negativity, and negative culture conversion during the follow-up period were higher in patients with M. massiliense infections than in those with M. abscessus infections. Patients with M. massiliense infections responded more favorably to antimicrobial therapy than those with M. abscessus infections.

[Pneumonitis induced by rifampicin].

An 86-year-old male with pulmonary tuberculosis developed fever, rash, and interstitial pneumonia 3 weeks after the beginning of treatment with isoniazid (INH), rifampicin (RFP), and ethambutol (EB). Chest CT showed new infiltration shadows that were diffuse bilateral ground-glass opacities mixed with dense consolidation and septal thickening, accompanied by a small amount of pleural effusion. Drug-induced pneumonitis was suspected, and therefore the antituberculous regimen was discontinued. The radiologic findings and symptoms improved promptly. A provocation trial with RFP lead to fever, diarrhea, and rash. Therefore, RFP was considered to be the causative drug. INH and EB were reintroduced without any recurrence of the symptoms. Clinicians should be aware not only of paradoxical reactions but also of drug-induced pneumonitis, when a new pulmonary infiltrate develops in the course of tuberculosis treatment.

PaCO2 six months after the initiation of long-term noninvasive ventilation in patients with COPD.

BACKGROUND AND OBJECTIVE: The appropriate target level for PaCO(2) after the introduction of long-term noninvasive positive pressure ventilation (NPPV) in patients with COPD remains uncertain, and therefore must be tested. METHODS: Data on 54 patients with COPD receiving long-term domiciliary NPPV were examined retrospectively. PaCO(2) a few months after NPPV and potential confounders were analyzed with discontinuation of long-term NPPV as the primary outcome. The differences in annual hospitalization rates due to respiratory deterioration between those from 1 year before to 2 years after initiation of NPPV were compared according to the PaCO(2) measured at 6 months after NPPV (6-mo PaCO(2)). RESULTS: 6-mo PaCO(2) seemed to be most related to continuation of NPPV (p=0.019). Patients with 6-mo PaCO(2) of less than 60 mmHg had maintained a significantly lower PaCO(2) value 6 to 24 months after NPPV (p=0.04) and had a significantly higher continuation rate of NPPV (p=0.03) than those with a 6-mo PaCO(2) of 60 mmHg or more. Annual hospitalization rates due to respiratory deterioration were not associated with the 6-mo PaCO(2) level, but fatal hospitalization rates during the first year of NPPV were significantly correlated with relatively high 6-mo PaCO(2) (p=0.008). CONCLUSION: A relatively low 6-mo PaCO(2) value was predictive of long-term use of NPPV. The target values of 6-mo PaCO(2) may, therefore, be less than 60 mmHg in COPD patients with extremely severe hypercapnia, although more prospective studies are needed.

[A case of squamous cell lung carcinoma with gastric metastasis diagnosed by gastroendoscopic biopsy].

A 59-year-old man was referred to our hospital due to of a right pulmonary hilar mass shadow found on a chest X-ray film in October 2008. Bronchoscopy and transbronchial biopsy at that time revealed squamous cell carcinoma. The clinical stage was IIIB (T4N2M0). He was readmitted 2 months later because of appetite loss and severe anemia. An abdominal CT scan showed thickening of the stomach wall. Gastroendoscopy showed a submucosal tumor with central depression in the middle body of the stomach. We histologically confirmed that the gastric lesion was metastasis from the squamous cell lung carcinoma. Here we report a rare case of squamous cell lung carcinoma with gastric metastasis diagnosed by gastroendoscopic biopsy while the patient was alive.

A contact investigation of the transmission of Mycobacterium tuberculosis from a nurse working in a newborn nursery and maternity ward.

A nurse working in a newborn nursery and maternity ward developed 3+ smear-positive lung tuberculosis. The hospital infection control committee, in collaboration with the local public health and welfare center, conducted a contact investigation. The infection period was defined as April to August 2006. The investigation included 109 infant and mother pairs, 28 children aged under 10 years and their guardians, 62 coworkers, and 63 household visitors to the ward. Tuberculosis infection in infants and children aged under 5 years was primarily determined by tuberculin skin test (TST), while subjects aged 5 years or more were tested using QuantiFERON-TB Gold (QFT). The first investigation, in August 2006, was conducted in all subjects, and the second investigation, in October 2006, targeted selected subjects. No infants were TST-positive. Two children aged 1 year or under, vaccinated with bacillus Calmette-Guérin, were positive for TST, as determined by the criteria of the Japan Anti-Tuberculosis Association; however, other tests for tuberculosis were negative. Of the 13 QFT-positive adult subjects, 1 mother and 2 coworkers could have become infected with Mycobacterium tuberculosis through exposure to the index nurse. Fifty-four infants and 6 children underwent "window-period" prophylaxis, and 4 adults completed 6-month prophylactic treatment with isoniazid. To date, no secondary cases of tuberculosis disease have occurred.

Axonal spherical bodies in the peripheral nerves of leprosy patients.

Spherical bodies, roughly 10 micro m in diameter, which have not been reported before, were found in the peripheral nerve axons of specimens collected during post-mortem examination of leprosy patients. These bodies were found in the fascicles of all peripheral nerves of the extremities examined (median, radial, ulnar, peroneal and sciatic nerves). Their incidence was not related to the type of leprosy. The area immediately below the thickened perineurium, a feature associated with leprosy, often showed a large number of spherical bodies. When observed under a transmission electron microscope, the spherical lesions often showed a lamellar structure, although some of them were amorphous. No structure resembling organelles was seen within the bodies. Observation with the merge technique showed a clearly lamellar structure in most of the spherical bodies. These bodies and the surrounding myelin sheaths were partially polarized. The axonal spherical bodies observed in our study seem to represent lesions gradually formed due to glycoprotein denaturation over long periods of time and to be associated with leprosy-caused thickening of the perineurium of peripheral nerves.

[Evaluation of the Mycobacteria Growth Indicator Tube system for detection and quantification of mycobacteria from clinical specimens].

The Mycobacteria Growth Indicator Tube (MGIT) system, a broth system for detection of mycobacterial growth, has been shown to be more sensitive and rapid compared with the egg-based Ogawa solid media, while the lack of ability to quantitate bacterial growth is the problem. We compared mycobacterial growth in the MGIT and the Ogawa systems, and evaluated the relationship between detection time in the MGIT system and bacterial CFU on Ogawa egg medium. A total of 413 respiratory specimens from 245 patients were included in the study, of which Mycobacterium tuberculosis (MTB), M. avium complex (MAC) and M. kansasii were recovered from 127, 42 and 6 specimens, respectively. Recovery rates were significantly higher and detection time was significantly shorter in the MGIT than in the Ogawa for MTB and MAC. Detection time in the MGIT was significantly shorter in smear positive specimens than in smear negative ones for MTB and MAC. There was a significant negative correlation between CFUs on Ogawa egg medium and detection time in the MGIT system for the MTB, therefore, this system may have an ability to quantitate live mycobacteria according to the detection time.