The risk of fatal bleeding complications in jugular catheterization in patients with coagulopathy: A retrospective analysis of death cases in closed claims and the Medical Accident Investigating System in Japan.

BACKGROUND: To prevent recurrence of medical accidents, the Medical Accident Investigating System was implemented in October 2015 by the Japan Medical Safety Research Organization (Medsafe Japan) to target deaths from medical care that were unforeseen by the administrator. Medsafe Japan analyzed the 10 cases of central venous catheterization-related deaths reported in the system and published recommendations in March 2017. However, the particular emphasis for the prevention of central venous catheterization-related deaths is unclear. METHODS: This study aimed to identify the recommendation points that should be emphasized to prevent recurrence of central venous catheterization-related deaths. We assessed central venous catheterization in 8530 closed-claim cases between January 2002 and December 2016 covered by the medical insurer Sompo-Japan. Moreover, we compared central venous catheterization-related death in closed-claim cases with death in reported cases. RESULTS: The background, error type, anatomic insertion site, and fatal complication data were evaluated for 37 closed-claim cases, of which 12 (32.4%) were death cases. Of the 12 closed-claim cases and 10 reported cases, 9 (75.0%) closed-claim cases and 9 (90.0%) reported cases were related to vascular access. Among these, 5 closed-claim cases (41.7%) and 7 reported cases (77.8%) were related to internal jugular vein catheterization (p = 0.28). Coagulopathy was observed in 3 (60.0%) of 5 closed-claim cases and 6 (85.7%) of 7 reported cases. CONCLUSIONS: The risk of internal jugular catheterization in patients with coagulopathy must be carefully considered.

New adalimumab formulation associated with less injection site pain and improved motivation for treatment.

Objectives: We aimed to evaluate the effect of change to the existing formulation of adalimumab (ADA) on pain and treatment motivation.Methods: We classified injection pain into the following categories: overall pain, pain at needle insertion, pain during drug injection, and pain 10 min after injection; we evaluated the effect of change to the existing formulation on pain using a visual analogue scale. In addition, a faces pain scale was used to evaluate the effect of change in injection pain intensity on treatment motivation.Results: Compared with the existing ADA formulation, the new formulation was associated with lower scores of overall pain (1.6 vs. 6.7), pain at needle insertion (1.8 vs. 4.7), pain during injection (1.6 vs. 7.0), and pain 10 min after the injection (0.4 vs. 3.1). All results showed a significant difference. p < .001. Paired t-tests were used. In the survey, 68% and 80% of the patients reported injection pain with influenza vaccine and the existing formulation, respectively; however, the proportion of the patients who experienced pain with the new formulation decreased to 20%.Conclusions: The new ADA formulation may alleviate the burden on RA patients and improve the quality of adherence to treatment, thereby influencing the RA treatment outcomes.

Characteristics of claims in the management of septic arthritis in Japan: Retrospective analyses of judicial precedents and closed claims.

BACKGROUND: Septic arthritis (SA) cases can result in claims or litigation because of poor prognosis even if it is unavoidable. Although these claims or litigation are useful for understanding causes and background factors of medical errors, the characteristics of malpractice claims associated with SA remain undetermined in Japan. This study aimed to increase our understanding of malpractice claims in the clinical management of SA. METHODS: We analyzed 6 civil precedents and 16 closed claims of SA from 8530 malpractice claims processed between July 2004 and June 2014 by the Tokyo office of Sompo Japan Nipponkoa Insurance, Incorporated. We also studied 5 accident and 21 incident reports of SA based on project data compiled by the Japan Council for Quality Health Care. RESULTS: The rate of negligence was 83.3% in the precedents and 75.0% in closed claims. Two main malpractice claim patterns were revealed: SA in a lower extremity joint following sepsis caused by methicillin-resistant Staphylococcus aureus in newborns and SA in an injection site following joint injection. These two patterns accounted for 83.3% and 56.3% of judicial cases and closed claim cases, respectively. Breakdowns in care process of accident and incident reports were clearly differentiated from judicial cases or closed claim cases (Fisher's exact test, p < 0.001). CONCLUSION: It is important to pay particular attention to SA following sepsis in newborns and to monitor for any signs of SA after joint injection to ensure early diagnosis. Analysis of both malpractice claims and accident and incident reports is essential to ensure a full understanding of the situation in Japan.

Analysis of Closed Claims in the Clinical Management of Rheumatoid Arthritis in Japan.

BACKGROUND: Despite an increasing awareness of the risk of medical errors, few data sources are available to highlight the characteristics and patterns of medical errors in the clinical management of rheumatoid arthritis (RA). The present study aimed to evaluate medical malpractice claims associated with the management of RA and other autoimmune connective tissue diseases (ACTDs). METHODS: We analyzed 38 ACTD-associated closed claims extracted from a total of 8530 claims processed between July 2004 and June 2014 by the Tokyo headquarters office of Sompo Japan Nipponkoa Incorporated, a leading malpractice insurer in Japan. RESULTS: RA was the most common ACTD assessed in this study, accounting for 20 cases. Although the male-to-female ratio among these cases was 5:15, in accordance with the general demographic distribution of RA, the proportion of patients older than 60 years (77.8%) was relatively high as the general range of RA susceptibility is 30-50 years. The analysis of allegation types among RA cases revealed statistically significant differences from non-RA cases (Fisher's exact test) as well as the following key findings: diagnosis-related allegations were absent (P < 0.01), whereas medication-related allegations were distinctively common (P = 0.02). Clinical processes related to the assessment process were most vulnerable to breakdown and leading to negligence identified with subsequent medication-related allegations, particularly among RA cases. CONCLUSIONS: The characteristics of malpractice claims associated with RA management, including the high frequency of medication-related allegations, breakdowns in the assessment process, and high claim numbers among patients older than 60 years, suggest the importance of caution exercised by physicians when administering immunosuppressants for the clinical treatment of RA.

Procalcitonin is a specific marker for detecting bacterial infection in patients with rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease accompanied by many complications, and serious infections are associated with many of the advanced therapeutics used to treat it. We assessed serum procalcitonin (PCT) levels to distinguish bacterial infection from other complications in patients with RA. METHODS: One hundred eighteen patients experiencing an RA flare, noninfectious complication of RA or its treatment, nonbacterial infection, or bacterial infection were studied. Serum PCT concentrations were determined with a chemiluminescent enzyme immunoassay. RESULTS: All patients experiencing an RA flare showed negative PCT levels (≤ 0.1 ng/ml; n = 18). The PCT level was higher in the bacterial infection group (25.8% had levels ≥ 0.5 ng/ml) than in the other 3 groups (0.0-4.3% had levels ≥ 0.5 ng/ml) and the difference was significant among groups (p = 0.003). Conversely, no statistically significant difference was observed among the groups with C-reactive protein (CRP) concentration ≥ 0.3 mg/dl (p = 0.513), white blood cell (WBC) count > 8500/mm(3) (p = 0.053), or erythrocyte sedimentation rate (ESR) > 15 mm/h (p = 0.328). The OR of high PCT level (≥ 0.5 ng/ml) for detection of bacterial infection was 19.13 (95% CI 2.44-149.78, p = 0.005). Specificity and positive likelihood ratio of PCT ≥ 0.5 ng/ml were highest (98.2% and 14.33, respectively) for detection of bacterial infection, although the sensitivity was low (25.8%). CONCLUSION: Serum PCT level is a more specific marker for detection of bacterial infection than either CRP, ESR, or WBC count in patients with RA. High PCT levels (≥ 0.5 ng/ml) strongly suggest bacterial infection. However, PCT < 0.5 ng/ml, even if < 0.2 ng/ml, does not rule out bacterial infection and physicians should treat appropriately.

Acute renal failure as a complication of acquired hemophilia due to autoantibody to factor VIII.

A 53-year-old Japanese woman, without any specific medical or family history, was admitted to our hospital for acute renal failure with macrohematuria. Routine blood analysis, including blood coagulation test, revealed azotemia accompanied by prolonged activated partial thromboplastin time (aPTT). Computed tomography revealed bilateral kidney swelling with dilatation of the renal pelvis. An extensive coagulation analysis revealed that the concentration of factor VIII had decreased to 1.8% and the level of factor VIII inhibitor was markedly elevated to 19 BU/ml. The final diagnosis was acquired hemophilia induced by autoantibodies against factor VIII, which was complicated by postrenal acute renal failure due to the obstruction of urinary tracts by renal bleeding and clots. The patient was treated with a combination of prednisolone at a dose of 50 mg/day (1 mg/kg body weight) and cyclophosphamide. The levels of factor VIII inhibitor decreased gradually, and the activity of factor VIII was improved after treatment. The levels of aPTT and concentrations of factor VIII and factor VIII inhibitor were monitored during the subsequent follow-ups.

Tocilizumab dramatically ameliorated life-threatening diarrhea due to secondary amyloidosis associated with rheumatoid arthritis.

Severe diarrhea improved dramatically with administration of the humanized anti-interleukin-6 receptor antibody tocilizumab (TCZ) in a patient with secondary reactive amyloidosis, which was associated with rheumatoid arthritis (RA). A 53-year-old woman with RA went into hypovolemic shock because of severe watery diarrhea associated with gastrointestinal amyloidosis. The high-dose prednisolone therapy and glucocorticoid pulse therapy did not improve her intractable diarrhea. After TCZ administration, the life-threatening diarrhea lessened in about 6 h, and her vital signs became stable the next day. Perforation of the small intestine, however, occurred 2 days after TCZ administration. Whether TCZ could have been involved in the perforation in such a short time is unknown. Surgery was successful, and the patient recovered. TCZ may work immediately in diarrhea associated with secondary amyloidosis.

Slit diaphragm dysfunction in proteinuric states: identification of novel therapeutic targets for nephrotic syndrome.

Several recent studies have demonstrated that the slit diaphragm of the glomerular epithelial cell (podocyte) is the structure likely to be the principal barrier in the glomerular capillary wall. Nephrin identified as a gene product mutated in congenital nephrotic syndrome located at the outer leaflet of plasma membranes of the slit diaphragm. The anti-nephrin antibody is capable of inducing massive proteinuria, which indicates that nephrin is a key functional molecule in the slit diaphragm. Expression of nephrin was reduced in glomeruli of minimal change nephrotic syndrome. Some recent studies demonstrated that podocin, CD2-associated protein and NEPH1 are also functional molecules in the slit diaphragm, and their expressions are altered in membranous nephropathy and also in focal glomerulosclerosis. These observations suggested that the alteration of the molecular arrangement in the slit diaphragm is involved in the development of proteinuria in several kinds of glomerular diseases. Recent studies of our group have demonstrated that type 1 receptor-mediated angiotensin II action reduced the expression of the slit diaphragm-associated molecules and that type 1 receptor blockade ameliorated proteinuria by preventing the function of angiotensin II on the slit diaphragm. By the subtraction hybridization techniques using glomerular cDNA of normal and proteinuric rats, we detected that synaptic vesicle protein 2B and ephrin B1 are involved in the maintenance of the barrier function of the slit diaphragm.

Dissociation of NEPH1 from nephrin is involved in development of a rat model of focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is a disease showing severe proteinuria, and the disease progresses to end-stage kidney failure in many cases. However, the pathogenic mechanism of FSGS is not well understood. The slit diaphragm (SD), which bridges the neighboring foot processes of glomerular epithelial cells, is understood to function as a barrier of the glomerular capillary wall. To investigate the role of SD dysfunction in the development of FSGS, we analyzed the expression of SD-associated molecules in rat adriamycin-induced nephropathy, a mimic of FSGS. The staining of the SD molecules nephrin, podocin, and NEPH1 had already shifted to a discontinuous dotlike pattern at the initiation phase of the disease, when neither proteinuria nor any morphological alterations were detected yet. The alteration of NEPH1 expression was the most evident among the molecules examined, and NEPH1 was dissociated from nephrin at the initiation phase. On day 28, when severe proteinuria was detected and sclerotic changes were already observed, alteration of the expressions of nephrin, podocin, and NEPH1 worsened, but no alteration in the expression of other SD-associated molecules or other podocyte molecules was detected. It is postulated that the dissociation of NEPH1 from nephrin initiates proteinuria and that the SD alteration restricted in these molecules plays a critical role in the development of sclerotic changes in FSGS.

A case of AA amyloidosis associated with rheumatoid arthritis effectively treated with Infliximab.

We report the case of a 55-year-old Japanese woman with reactive AA amyloidosis associated with rheumatoid arthritis, in which inflammatory disease was completely suppressed with infliximab. Nephrotic syndrome was observed and renal biopsy specimens revealed amyloidosis deposits. Treatment with infliximab normalized the serum amyloid A (SAA) protein level, and subsequently nephritic syndrome disappeared and her creatinine clearance improved. Serial gastrointestinal biopsy specimens showed marked lasting regression of amyloid deposits. Thus treatment with infliximab represents an important therapeutic strategy for AA amyloidosis associated with RA.