Utilizing Video versus Direct Laryngoscopy to Intubate Simulated Newborns while Contained within the Incubator: A Randomized Crossover Study.

OBJECTIVE: The use of video laryngoscopy for intubating neonates in ergonomically challenging settings has not been studied well. We aimed to assess the usefulness of video laryngoscopy for experienced neonatologists to intubate neonatal manikins in incubators via side hand ports or head window. STUDY DESIGN: In this randomized crossover trial at three neonatal intensive care units in Japan, 27 neonatologists were randomized into two groups, namely, those intubating neonatal simulators using video laryngoscopy and then using direct laryngoscopy, or vice versa. The intubations were performed via hand ports or head window without opening top and side walls in incubators in two manikin positions (rotated 90° or unrotated). Glottis visualization (0-100%), success rate, intubation time, and ease of laryngoscopy (from 1 [very difficult] to 10 [very easy]) were compared between video laryngoscopy and direct laryngoscopy. Generalized linear models were used for the analyses. RESULTS: This study assessed 108 intubations performed by 27 neonatologists. The use of video laryngoscopy improved the glottis visualization by 14% (95% confidence interval, 7.4-20%; p < 0.01) and easiness scores of laryngoscopy by 0.8 (0.2-1.4; p < 0.01), but did not reduce the intubation time. CONCLUSION: Video laryngoscopy is useful for experienced neonatologists for intubating neonatal manikins in incubators without opening the top or side walls.

Umbilical catheterization training: Tissue hybrid versus synthetic trainer.

BACKGROUND: This study of umbilical catheterization deliberate practice training compared skill and knowledge outcomes of umbilical catheterization using a tissue-hybrid simulator (REAL) versus a synthetic simulated umbilical cord task trainer (ART). METHODS: This was a prospective randomized control study. Pediatric residents were randomized to REAL or ART umbilical catheterization deliberate practice training. Pre-post-training changes in skill performance and knowledge scores for REAL and ART groups were compared. Fidelity of REAL and ART were compared by neonatologists. RESULTS: Twenty-seven pediatric residents completed training. Post-training mean skill scores were improved compared to pre-test scores (REAL, P < 0.001; ART, P < 0.0001). Post-training skill, knowledge, and self-efficacy scores were not different between the REAL and ART groups. Fidelity of REAL was higher than ART for neonatologists (P < 0.01). CONCLUSIONS: The face validity of REAL was superior to ART, but resident umbilical cord deliberate practice training demonstrated no difference in skill, knowledge, and self-efficacy improvements between REAL and ART. Further studies on real patients are needed to evaluate the impact of using real or simulated umbilical cords for umbilical venous catheter/umbilical arterial catheter training.

Asian Neonatal Network Collaboration (AsianNeo): a study protocol for international collaborative comparisons of health services and outcomes to improve quality of care for sick newborn infants in Asia - survey, cohort and quality improvement studies.

INTRODUCTION: Reducing neonatal deaths in premature infants in low- and middle-income countries is key to reducing global neonatal mortality. International neonatal networks, along with patient registries of premature infants, have contributed to improving the quality of neonatal care; however, the involvement of low-to-middle-income countries was limited. This project aims to form an international collaboration among neonatal networks in Asia (AsianNeo), including low-, middle- and high-income countries (or regions). Specifically, it aims to determine outcomes in sick newborn infants, especially very low birth weight (VLBW) infants or very preterm infants, with a view to improving the quality of care for such infants. METHODS AND ANALYSIS: Currently, AsianNeo comprises nine neonatal networks from Indonesia, Japan, Malaysia, Philippines, Singapore, South Korea, Sri Lanka, Taiwan and Thailand. AsianNeo will undertake the following four studies: (1) institutional questionnaire surveys investigating neonatal intensive care unit resources and the clinical management of sick newborn infants, with a focus on VLBW infants (nine countries/regions); (2) a retrospective cohort study to describe and compare the outcomes of VLBW infants among Asian countries and regions (four countries/regions); (3) a prospective cohort study to develop the AsianNeo registry of VLBW infants (six countries/regions); and (4) implementation and evaluation of educational and quality improvement projects in AsianNeo countries and regions (nine countries/regions). ETHICS AND DISSEMINATION: The study protocol was approved by the Research Ethics Board of the National Center for Child Health and Development, Tokyo, Japan (reference number 2020-244, 2022-156). The study findings will be disseminated through educational programmes, quality improvement activities, conference presentations and medical journal publications.

Variations in medical practice of retinopathy of prematurity among 8 Asian countries from an international survey.

Advances in perinatal care have led to the increased survival of preterm infants with subsequent neonatal morbidities, such as retinopathy of prematurity (ROP). This study aims to compare the differences of neonatal healthcare systems, resources, and clinical practice concerning ROP in Asia with review of current literature. An on-line survey at the institutional level was sent to the directors of 336 neonatal intensive care units (NICU) in 8 collaborating national neonatal networks through the Asian Neonatal Network Collaboration (AsianNeo). ROP screening was performed in infants born at < 34 weeks in Indonesia and Japan. In South Korea, Malaysia, and Taiwan, most screened for ROP in infants born at < 32 weeks. In all networks, majority of NICUs conducted ROP screening to infants with birth weight < 1500 g. In most NICU's in-hospital ophthalmologists performed indirect ophthalmoscopy and some were supplemented with digital imaging. Both laser photocoagulation and anti-vascular endothelial growth factor injection are performed for treatment and, vitreous surgeries are conducted less frequently in all countries. Despite limited information collected by the survey, this first study to compare ROP practices implemented in eight Asian countries through AsianNeo will enable an understanding of the differences and facilitate quality improvement by sharing better practices.

Efficacy and safety of permissive hypercapnia in preterm infants: A systematic review.

CONTEXT: In adults, permissive hypercapnia reduces mortality and ventilation duration. However, in preterm infants, the findings from past research regarding the efficacy and safety of permissive hypercapnia are controversial. OBJECTIVE: To evaluate the efficacy and safety of permissive hypercapnia versus normocapnia in preterm infants on mechanical ventilation. DATA SOURCES: MEDLINE, EMBASE, CENTRAL, and CINAHL STUDY SELECTION: Published randomized controlled trials (RCTs), non-RCTs, interrupted time series, cohort studies, case-control studies, and controlled before-and-after studies were included. DATA EXTRACTION: Two reviewers independently screened the title, abstract, and full text, extracted data, assessed the risk of bias, and evaluated certainty of evidence (CoE) according to the Grading of Recommendations Assessment and Development and Evaluation approach. A meta-analysis of RCTs was performed using the random-effects model. RESULTS: Four RCTs (693 infants) and one cohort study (371 infants) were included. No significant differences existed between the permissive hypercapnia and normocapnia groups for bronchopulmonary dysplasia (BPD) (risk ratio [RR], 0.94; 95% confidence interval [CI], 0.74-1.18; very low CoE) and a composite outcome of death or BPD (RR, 1.05; 95% CI, 0.90-1.23; very low CoE). Permissive hypercapnia may increase necrotizing enterocolitis (RR, 1.69; 95% CI, 0.98-2.91; very low CoE), but the null or trivial effect cannot be excluded. No significant differences existed between the two groups for any other outcome assessed (very low-to-low CoE). LIMITATIONS: The sample sizes were less than the optimal sizes for all outcomes assessed, indicating the need for further trials. CONCLUSIONS: Permissive hypercapnia did not have any significant benefit or harm in preterm infants.

Quality of life of children with neurodevelopmental disorders and their parents during the COVID-19 pandemic: a 1-year follow-up study.

This study aimed to reveal changes in the quality of life (QOL) of children with neurodevelopmental disorders and their parents, and the interaction between their QOL and parental mental state during the coronavirus 2019 (COVID-19) pandemic. Eighty-nine school-aged children and parents participated in surveys in May 2020 (T1) and May 2021 (T2). The parents completed questionnaires that assessed their QOL, depression, parenting stress, and living conditions. Children's temporary mood status was evaluated using the self-reported visual analog scale (VAS). Children's QOL and VAS at T2 were higher than their QOL at T1. Parents' QOL at T2 was lower than their QOL at T1. Severe parental depression at T1 had a synergistic effect on severe parenting stress and severe depressive state at T2. Additionally, children's high QOL at T1 had a synergistic effect on low parenting stress and children's high QOL at T2. Furthermore, children's low VAS scores and parents' low QOL at T2 were associated with deterioration of family economic status. Children and parents' QOL changed during the prolonged COVID-19 pandemic. Improvement in children's QOL was influenced by reduced maternal depressive symptoms. Public support for parental mental health is important to avoid decreasing QOL.

Psychological Status Associated With Low Quality of Life in School-Age Children With Neurodevelopmental Disorders During COVID-19 Stay-At-Home Period.

Background: This study seeks to ascertain how the COVID-19 stay-at-home period has affected the quality of life (QOL) of children with neurodevelopmental disorders (NDDs) who had experienced sleep schedules alteration and clarify what psychological status predicted low QOL in children with and without altered sleep patterns. Materials and Methods: Study participants were 86 children between 8 and 17 years of age (mean age, 11.7 years; 70 boys, 16 girls; mean intellectual quotient, 83.6). QOL was evaluated using the self-assessment KINDLR. Participants answered questions regarding depression and anxiety on a visual analog scale (VAS) for temporary mood. Their parents answered questionnaires regarding their maladaptive behaviors and differences in sleep patterns before and during the COVID-19 pandemic. The student's t-test was performed to examine the presence or absence of sleep changes in the children, which affected QOL, temporary mood, and maladaptive behaviors. Multiple or simple linear regression analyses were also performed to identify the psychogenic factors that significantly affected decreased QOL for each group with and without changes in sleep schedule. Results: During the COVID-19 stay-at-home period, 46.5% of participants experienced changes in sleep patterns. These changes were associated with decreased QOL as well as internalized symptoms. The decreased QOL of children with sleep patterns changed was predicted by a high level of depression. In addition, low QOL in children with unchanged sleep patterns was predicted by a high level of depression and low current mood status. Conclusions: Almost half of the participants experienced a poor sleep schedule during the stay-at-home period. These alterations in sleep patterns were associated with a low QOL. The QOL of children with a stable life schedule was affected not only by depressive tendencies but also temporary moods. Therefore, they need to live a fulfilling life to maintain their QOL. However, the QOL of children with poor sleep patterns was affected only by depressive tendencies. Hence, clinicians need to ensure that children with NDDs are well-diagnosed with depression and treated for sleep problems.

The quality of life of children with neurodevelopmental disorders and their parents during the Coronavirus disease 19 emergency in Japan.

This study aimed to reveal how the COVID-19 stay-at-home period has affected the quality of life (QOL) of children with neurodevelopmental disorders and their parents and to identify possible factors that enabled them to maintain their QOL. We enrolled 136 school-aged children (intellectual quotient ≥ 50) and their parents and administered QOL questionnaires to assess the maladaptive behavior of the children; depression, anxiety, and stress of the parents; and activities of their daily lives. The relationship between their QOL and clinical features was examined. The decrease in QOL of children and parents was associated with the mother's limited job flexibility. Decreased QOL was also associated with changes in the sleep rhythms of the children. Maladaptive behaviors in children were associated with parental stress. However, maintained QOL of some families who faced these same conditions of job stress and sleep disorders was associated with less parental stress, less parental depression and anxiety, and milder maladaptive behavior in children. Both mothers with limited job flexibility and changes in the sleep rhythm of children were associated with reduced QOL of children and their parents. Low parental stress was associated with decreased maladaptive behavior in children and with maintained QOL of the family.

Ca2+ channel subtypes and pharmacology in the kidney.

A large body of evidence has accrued indicating that voltage-gated Ca(2+) channel subtypes, including L-, T-, N-, and P/Q-type, are present within renal vascular and tubular tissues, and the blockade of these Ca(2+) channels produces diverse actions on renal microcirculation. Because nifedipine acts exclusively on L-type Ca(2+) channels, the observation that nifedipine predominantly dilates afferent arterioles implicates intrarenal heterogeneity in the distribution of L-type Ca(2+) channels and suggests that it potentially causes glomerular hypertension. In contrast, recently developed Ca(2+) channel blockers (CCBs), including mibefradil and efonidipine, exert blocking action on L-type and T-type Ca(2+) channels and elicit vasodilation of afferent and efferent arterioles, which suggests the presence of T-type Ca(2+) channels in both arterioles and the distinct impact on intraglomerular pressure. Recently, aldosterone has been established as an aggravating factor in kidney disease, and T-type Ca(2+) channels mediate aldosterone release as well as its effect on renal efferent arteriolar tone. Furthermore, T-type CCBs are reported to exert inhibitory action on inflammatory process and renin secretion. Similarly, N-type Ca(2+) channels are present in nerve terminals, and the inhibition of neurotransmitter release by N-type CCBs (eg, cilnidipine) elicits dilation of afferent and efferent arterioles and reduces glomerular pressure. Collectively, the kidney is endowed with a variety of Ca(2+) channel subtypes, and the inhibition of these channels by their specific CCBs leads to variable impact on renal microcirculation. Furthermore, multifaceted activity of CCBs on T- and N-type Ca(2+) channels may offer additive benefits through nonhemodynamic mechanisms in the progression of chronic kidney disease.

Clinical patterns in extremely preterm (22 to 24 weeks of gestation) infants in relation to survival time and prognosis.

We investigated time-related predictors of death or neurological sequelae in extremely preterm infants (EPI) born at 22 to 24 weeks' gestation by categorizing clinical patterns according to their survival time and morbidity. Data on 113 infants born at 22 to 24 weeks' gestation from January 1991 through April 2006 were analyzed by a case-control approach. Cesarean section, Apgar score or= 24 hours, pulmonary hemorrhage and intraventricular hemorrhage (IVH) were significantly associated with death by day 6. Among those surviving >or= 7 days, sepsis and severe IVH were significantly associated with death. Assessment of survivors at a minimum follow-up period of 2 years revealed that protracted mechanical ventilation was significantly associated with a poor neurological outcome. There are various characteristic key events in relation to the outcome at different ages of life in EPI born at 22 to 24 weeks' gestation. Clinicians and parents should discuss management options for the infant on the basis of these findings.

Premedication with neuromuscular blockade and sedation during neonatal intubation is associated with fewer adverse events.

OBJECTIVE: To determine the impact of premedication for tracheal intubation (TI) on adverse TI associated events, severe oxygen desaturations, and first attempt success STUDY DESIGN: Retrospective cohort study in neonatal intensive care units (NICU) participating in the National Emergency Airway Registry for Neonates from 10/2014 to 6/2017. Premedication for TI was categorized as sedation with neuromuscular blockade, sedation only, or no medication. RESULTS: 2260 TIs were reported from 11 NICUs. Adverse TI associated events occurred less often in sedation with neuromuscular blockade group (10%) as compared to sedation only (29%), or no medication group (23%), p < 0.001. The adjusted odds ratio (aOR) for adverse TI associated events were: sedation with neuromuscular blockade aOR 0.48 (95%CI 0.34-0.65, p < 0.001) compared to no medication. CONCLUSION: Use of sedation with neuromuscular blockade was associated with favorable TI outcomes. This study supports the recommendation for the standard use of sedation with neuromuscular blockade in non-emergency TIs.

Young Scholars Award Lecture: Intratubular angiotensinogen in hypertension and kidney diseases.

Recent findings related to the renin-angiotensin system have provided a more elaborated understanding of the pathophysiology of hypertension and kidney diseases. These findings have led to unique concepts and issues regarding the intrarenal renin-angiotensin system. Angiotensinogen is the only known substrate for renin that is the rate-limiting enzyme of the renin-angiotensin system. Because the level of angiotensinogen in human beings is close to the Michaelis-Menten constant value for renin, changes in angiotensinogen levels can control the activity of the renin-angiotensin system, and its upregulation may lead to elevated angiotensin peptide levels and increases in blood pressure. Enhanced intrarenal angiotensinogen mRNA or protein levels or both have been observed in multiple models of hypertension including angiotensin II-dependent hypertensive rats, Dahl salt-sensitive hypertensive rats, and spontaneously hypertensive rats, as well as in kidney diseases including diabetic nephropathy, immunoglobulin A (IgA) nephropathy, and radiation nephropathy. Renal angiotensinogen is formed primarily in proximal tubular cells and is secreted into the tubular fluid. Urinary angiotensinogen excretion rates show a clear relationship to kidney angiotensin II contents and kidney angiotensinogen levels, suggesting that urinary angiotensinogen may serve as an index of the intrarenal renin-angiotensin system status. Establishment of concise and accurate methods to measure human angiotensinogen may allow clinical studies that would provide important information regarding the roles of intrarenal angiotensinogen in the development and progression of hypertension and kidney diseases.

Quantification of human angiotensinogen by a novel sandwich ELISA.

The urinary angiotensinogen excretion rates show a clear relationship to kidney angiotensin II content, suggesting that urinary angiotensinogen may serve as an index of angiotensin II-dependent hypertensive rats. However, simple and accurate methods to measure human angiotensinogen are unavailable at this time. We have developed two antibodies and a sensitive and specific quantification ELISA system for human angiotensinogen to be applicable to human subjects. The ELISA is able to detect human angiotensinogen at range of 0.01-1 microg/well (R(2)=0.9945) using standard ELISA plates. This ELISA will be a useful tool to investigate the relationship between urinary angiotensinogen excretion rates and reactivity to antihypertensive drugs in hypertensive human subjects.

Role of protein kinase C in Ca channel blocker-induced renal arteriolar dilation in spontaneously hypertensive rats--studies in the isolated perfused hydronephrotic kidney.

The present study examined the role of L-/T-type Ca channels and the interaction between these channels and protein kinase C (PKC) in hypertension. The isolated perfused hydronephrotic rat kidney model was used to visualize directly the renal microvascular effects of L-/T-type Ca channel blockers (nifedipine and mibefradil, respectively). Nifedipine reversed the angiotensin II-induced constriction of afferent, but not efferent, arterioles in kidneys from Wistar-Kyoto rats (WKY), and similar magnitude in dilation was observed in spontaneously hypertensive rats (SHR). Although mibefradil elicited dilation of both arterioles, the afferent arteriolar dilation was less in SHR than in WKY (57+/-5% vs. 80+/-4% reversal at 1 micrommol/L). The pretreatment with staurosporine did not alter the angiotensin II-induced afferent arteriolar constriction in WKY, but attenuated this response in SHR. Furthermore, staurosporine enhanced the nifedipine-induced afferent arteriolar dilation (62+/-3% vs. 50+/-3% reversal at 10 nmol/L), and restored the attenuated afferent arteriolar response to mibefradil in SHR. The pretreatment with thapsigargin (a blocker of IP3-mediated intracellular calcium release) prevented the angiotensin II-induced afferent arteriolar constriction in WKY, but caused a significant constriction of afferent arterioles in SHR and efferent arterioles in WKY and SHR; in this setting, mibefradil did not alter efferent arteriolar tone. In conclusion, although both L-type (nifedipine) and T-type Ca channel blockers (mibefradil) exerted potent vasodilation of rat renal microvessels, these actions were modified by PKC, which determined the afferent arteriolar sensitivity to these blockers in SHR. Furthermore, the enhancement in nifedipine-induced afferent arteriolar dilation by staurosporine in SHR suggests that L-type Ca channel activity is augmented in hypertensive animals.

Alpha2-adrenergic receptor subtype alterations in the brainstem in the sudden infant death syndrome.

BACKGROUND: The sudden infant death syndrome (SIDS) is still the main cause of postneonatal infant death. However, the causes and mechanisms of SIDS have never been completely elucidated. Catecholamines, via alpha2-adrenergic receptor (alpha2-AR) interactions, are known to influence brainstem autonomic and respiratory activity. AIMS: To examine the catecholaminergic system abnormalities in SIDS victims, we investigated the alterations of alpha2-AR subtypes. SUBJECTS AND METHODS: We examined the developmental changes of alpha2-AR subtypes in the brainstem, especially in cardiorespiratory nuclei, in 21 SIDS victims and 17 age-matched controls by means of immunohistochemical methods. For statistical analysis, the chi2-test or Fisher's exact probability test was performed. RESULTS: There was a significant decrease in alpha2A-AR immunoreactivity in the solitary nucleus and ventrolateral medulla (VLM) in the medulla oblongata in SIDS victims compared with in control cases, but there were no significant differences of the alpha2B and alpha2C-AR immunoreactivity in the brainstem between SIDS victims and controls. CONCLUSION: Alpha2A-AR immunoreactivity was selectively decreased in the solitary nucleus and VLM in the medulla oblongata in SIDS victims, so there was no possibility that it was secondary to chronic hypoxia or repeated ischemia. It may be related to some impairment of the cardiorespiratory neuronal system. Therefore, SIDS victims may be vulnerable to asphyxia, hypoxia, and/or hypercapnia, and fail to exhibit brainstem responses.

Catecholaminergic neurons in the brain-stem and sleep apnea in SIDS victims.

BACKGROUND: Tyrosine hydroxylase (TH) is a specific marker for catecholaminergic neurones. Some reports have demonstrated a decrease of TH in the Sudden Infant Death Syndrome (SIDS) compared with controls. To further investigate this, the correlation between TH and sleep apnea was investigated here. MATERIALS AND METHODS: Among 27,000 infants studied prospectively to characterize their sleep-wake behavior, 38 infants died under 6 months of age. They included 26 cases of SIDS. All the infants had been recorded during one night in a pediatric sleep laboratory some 3 to 12 weeks before death. The frequency and the duration of sleep apnea were analyzed. The brain stem material was collected and subjected to immunohistochemical studies for TH. The density of TH-immunoreactive neurons was measured in the nucleus hypoglossus, nervus vagus dorsalis, solitary and ambiguous and the ventrolateral medulla (VLM) in the medulla oblongata. Correlation analyses were carried out between the density of TH-immunoreactive neurons and the data from the sleep apnea studies. RESULTS: There was no SIDS specific correlation between TH-immunoreactive neurons in the nucleus hypoglossus, nervus vagus dorsalis, solitary and ambiguous and the ventrolateral medulla (VLM) in the medulla oblongata and the frequency and duration of sleep apnea. CONCLUSIONS: No significant association between the pathological data and the physiological data refers to TH positive neurons in the medulla oblongata in SIDS victims.

Substance P in the midbrains of SIDS victims and its correlation with sleep apnea.

BACKGROUND: Substance P (SP) is a neuropeptide transmitter found in sensory neurons of the central nervous system and related to pain sensation and respiratory regulation. Some reports claim an increase in SP in the brains of SIDS victims, so the correlation between SP and sleep apnea was investigated here. MATERIALS AND METHODS: Among 27,000 infants studied prospectively to characterize their sleep-wake behavior, 38 infants died under 6 months of age, which included 26 cases of Sudden Infant Death Syndrome (SIDS). All the infants had been recorded during one night in a pediatric sleep laboratory some 3 to 12 weeks before death. The frequency and duration of sleep apnea were analyzed. Brainstem material was collected and immunohistochemistry for SP was carried out. The density of SP positive fibers was measured in the nucleus spinal and mesencephalic nervi trigemini and nucleus parabranchialis in the brainstem of abovementioned cases. Correlation analyses were carried out between the density of SP and the data of sleep apnea. RESULTS: There was no SIDS specific correlation of SP through the above-listed parts of the midbrain with frequency and duration of sleep apnea. CONCLUSIONS: There was no significant association between the SP findings and apnea data in SIDS; this is not in agreement with the association of apnea in pathophysiology of SIDS.

Serotonergic receptors in the midbrain correlated with physiological data on sleep apnea in SIDS victims.

BACKGROUND: Recently it has been reported that serotonin and related matters are associated with the sudden infant death syndrome (SIDS), which is still the main cause of postneonatal infant death. To further explore this claim, the correlation between serotonin receptors in the brainstem and sleep apnea in SIDS victims was investigated. MATERIALS AND METHODS: Among 27,000 infants studied prospectively to characterize their sleep-wake behavior, 38 infants died under 6 months of age including 26 cases of SIDS. All the infants had been recorded during one night in a pediatric sleep laboratory some 3-12 weeks before death. The frequency and duration of sleep apnea were analyzed. Brainstem material was collected and immunohistochemistry on 5-hydroxy tryptamine 1A (5HT1A) receptor was carried out. The density of 5HT1A receptor-positive neurons was measured quantitatively. Nonparametric analysis of the density of 5HT1A receptor-positive neurons was carried out between SIDS and non-SIDS cases. Correlation analyses were performed between the density of 5HT1A receptor-positive neurons and the data on sleep apnea. RESULTS: There was no correlation between the pathological data on 5HT1A receptors and the physiological data on sleep apnea in SIDS victims. CONCLUSIONS: No correlation between pathological findings of serotonin and physiological findings of sleep apnea were not in agreement with the association of sleep apnea in pathophysiology of SIDS.

Time-course changes in nerve conduction velocity (NCV) in type 2 diabetes.

AIM: Changes in NCV were surveyed over 10 years in type 2 diabetes patients to clarify the time-course relationships between NCV and retinopathy stage and between NCV and HbA1c. In addition, the natural course of diabetic sensorimotor polyneuropathy (DSPN) was discussed based on the findings. METHODS: Using a simple NCV measurement device, NCV (MCV and SCV) was measured once a year over 10 years in 474 patients with type 2 diabetes. These patients were grouped based on the retinopathy stage and HbA1c level in the course to investigate the time-course relationships between the retinopathy stage and NCV and between HbA1c and NCV. RESULTS: The retinopathy stage and NCV reduction were strongly correlated, and NCV decreased as retinopathy progressed. On comparison of time-course NCV among the retinopathy stages, continuity of NCV reduction along with the retinopathy progression was noted. Regarding the relationship between HbA1c and NCV, NCV reduction was moderate in the group maintaining HbA1c at a relatively favorable level, but morbid reduction of NCV could not be prevented even though favorable control was maintained. CONCLUSION: NCV reduction is strongly correlated with retinopathy progression from more than 10 years before its manifestation through reaching proliferative retinopathy. It was also suggested that NCV reduction can be attenuated by controlling blood glucose, but the reduction cannot be prevented completely. Based on these findings, DSPN is a progressive complication that starts from an early phase after onset of diabetes and steadily aggravates, keeping step with retinopathy aggravation, and it may be difficult to completely prevent the progression.