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Womens perceptions and self-reports of excessive bleeding during and after delivery: findings from a mixed-methods study in Northern Nigeria

Por: Yargawa · J. · Fottrell · E. · Hill · Z.
Objectives

To explore lay perceptions of bleeding during and after delivery, and measure the frequency of self-reported indicators of bleeding.

Setting

Yola, North-East Nigeria.

Participants

Women aged 15–49 years who delivered in the preceding 2 years of data collection period (2015–2016), and their family members who played key roles.

Methods

Data on perceptions of bleeding were collected through 7 focus group discussions, 21 in-depth interviews and 10 family interviews. Sampling was purposive and data were analysed thematically. A household survey was then conducted with 640 women using cluster sampling on postpartum bleeding indicators developed from the qualitative data; data were analysed descriptively.

Results

Perceptions of excessive bleeding fell under four themes: quantity of blood lost; rate/duration of blood flow; symptoms related to blood loss and receiving birth interventions/hearing comments from birth attendants. Young and less educated rural women had difficulty quantifying blood loss objectively, including when shown quantities using bottles. Respondents felt that acceptable blood loss levels depended on the individual woman and whether the blood is ‘good’ or ‘diseased/bad.’ Respondents believed that ‘diseased’ blood was a normal result of delivery and universally took steps to help it ‘come out.’ In the quantitative survey, indicators representing less blood loss were reported more frequently than those representing greater loss, for example, more women reported staining their clothes (33.6%) than the bed (18.1%) and the floor (6.2%). Overall, indicators related to quantity and rate of blood flow had higher frequencies compared with symptom and intervention-related/comment-related indicators.

Conclusion

Women quantify bleeding during and after delivery in varied ways and some women do not see bleeding as problematic. This suggests the need for standard messaging to address subjectivity. The range of indicators and varied frequencies highlight the challenges of measuring excessive bleeding from self-reports. More work is needed in improving and testing validity of questions.

Community risk perception and barriers for the practice of COVID-19 prevention measures in Northwest Ethiopia: A qualitative study

by Aragaw Tesfaw, Getachew Arage, Fentaw Teshome, Wubet Taklual, Tigist Seid, Emaway Belay, Gashaw Mehiret

Background

According to the World Health Organization, viral diseases continue to emerge and represent a serious issue for public health. The elderly and those with underlying chronic diseases are more likely to become severe cases. Our study sets out to present in-depth exploration and analyses of the community’s risk perception and barriers to the practice of COVID-19 prevention measures in South Gondar Zone, Northwest Ethiopia.

Methods

A qualitative study was done in three districts of South Gondar Zone. Community key informants and health extension workers were selected purposely for in-depth interviews and focus group discussion. The interviews were conducted by maintaining WHO recommendations for social distancing and use of appropriate personal protective equipment. The sample size for the study depended on the theoretical saturation of the data at the time of data collection. The qualitative data generated from in-depth interviews and focus group discussions was transcribed verbatim and translated into English language and thematically analyzed using open code software version 4.02.

Results

Three main themes and five categories emerged from the narrations of the participants regarding the perceived barriers for the practice of COVID-19 prevention measures. A total of 9 community key informants (5 women development armies (HDA), 2 health extension workers (HEW), and 2 religious leaders participated in the in-depth interview, while two focus group discussions (7 participants in each round) were conducted among purposely selected community members. The age of the participants ranged from 24 to 70 years with the median age of 48 years. The major identified barriers for practicing COVID-19 prevention measures were the presence of strong cultural and religious practices, perceiving that the disease does not affect the young, misinformation about the disease, and lack of trust in the prevention measures.

Conclusions

Socio-cultural, religious, and economic related barriers were identified from the participant’s narratives for the practice of COVID-19 prevention measures in south Gondar Zone. Our findings suggest the need to strengthen community awareness and education programs about the prevention measures of COVID-19 and increase diagnostic facilities with strong community-based surveillance to control the transmission of the pandemic.

Prognostic significance of dipstick proteinuria in heart failure with preserved ejection fraction: insight from the PURSUIT-HFpEF registry

Por: Oeun · B. · Hikoso · S. · Nakatani · D. · Mizuno · H. · Suna · S. · Kitamura · T. · Okada · K. · Dohi · T. · Sotomi · Y. · Kida · H. · Sunaga · A. · Sato · T. · Nakagawa · A. · Nakagawa · Y. · Hayashi · T. · Yano · M. · Tamaki · S. · Yasumura · Y. · Yamada · T. · Sakata · Y. · The OCVC-Heart F
Objective

The semiquantitative urine dipstick test is a simple and convenient method that is available in the smallest community-based healthcare clinics. We sought to clarify the prognostic significance of dipstick proteinuria in patients with heart failure (HF) with preserved ejection fraction (HFpEF).

Design

A Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with preserved Ejection Fraction (PURSUIT-HFpEF) registry.

Participants and setting

We assessed 851 discharged-alive patients in the PURSUIT-HFpEF registry who were initially hospitalised due to an acute decompensated HFpEF (EF≥50%) and elevated N-terminal-pro-brain natriuretic peptide (≥400 ng/L) at Osaka University Hospital and other 30 affiliated hospitals in the Kansai region of Japan. Patients received a urine dipstick test, and were divided into two groups according to the absence or presence of proteinuria. A trace or more of dipstick proteinuria was defined as the presence of proteinuria.

Main outcome measures

A composite of cardiac death or HF rehospitalisation.

Results

Median age was 83 years and 473 patients (55.6%) were female. Five hundred and two patients (59%) were proteinuria (–) and 349 patients (41%) were proteinuria (+). The composite endpoint and HF rehospitalisation occurred more often in proteinuria (+) individuals than proteinuria (–) individuals (log-rank p=0.006 and p=0.007, respectively); but cardiac death did not (log-rank p=0.139). Multivariable Cox regression analysis showed that the presence of proteinuria was associated with the composite endpoint (HR: 1.47, 95% CI 1.07 to 2.01, p=0.016), and HF rehospitalisation (HR: 1.48, 95% CI 1.07 to 2.05, p=0.020), but not with cardiac death (HR: 1.52, 95% CI 0.83 to 2.76, p=0.172).

Conclusions

Dipstick proteinuria may be a prognostic marker in patients with HFpEF. Evaluation of proteinuria by a urine dipstick test may be a simple but useful method for risk stratification in HFpEF.

UMIN-CTR ID

UMIN000021831.

Analysing effects of financial support for regional suicide prevention programmes on methods of suicide completion in Japan between 2009 and 2018 using governmental statistical data

Por: Hasegawa · T. · Matsumoto · R. · Yamamoto · Y. · Okada · M.
Objectives

To explore the mechanisms of reduction of suicide mortality in Japan (from 25.7 to 16.5 per 100 000 population) between 2009 and 2018, the present study determined the effects of execution amounts of regional suicide prevention programmes (Emergency Fund to Enhance Community-Based Suicide Countermeasure: EFECBSC) on gender-specific trends of suicide mortality by disaggregated methods.

Design and setting

Stepwise multiple regression analysis was used to determine the effects of execution amounts of 10 subdivisions of execution amounts of financial support for regional suicide prevention programmes (EFECBSC) on suicide methods and gender disaggregated suicide mortalities in Japan between 2009 and 2018 using the statistical data obtained from national governmental database.

Results

The suicide mortalities by the most common/frequent suicide methods, hanging, charcoal burning and jumping were significantly decreased between 2009 and 2018. Male hanging suicide was decreased by prefectural enlightenment, municipal development programmes, but female hanging suicide was decreased by municipal personal consultation programmes. Municipal development and enlightenment programmes decreased male and female charcoal-burning suicide mortalities, respectively. Jumping suicide was decreased by prefectural telephone consultation programmes but was unexpectedly increased by municipal personal consultation and enlightenment programmes.

Conclusions

This study revealed the contribution of ECEFBSC on reduction of suicide mortalities, especially hanging, charcoal-burning and jumping suicides, via enhancement of regional suicide prevention programmes in Japan; however, notably, the ‘means substitution’ from parts of hanging and charcoal burning to jumping is probably generated by EFECBSC. Therefore, these findings provide important aspects for planning evidence-based and cost-effective regional suicide prevention programmes.

Nafamostat mesilate, a nuclear factor kappa B inhibitor, enhances the antitumor action of radiotherapy on gallbladder cancer cells

by Naoki Takada, Hiroshi Sugano, Yoshihiro Shirai, Nobuhiro Saito, Ryoga Hamura, Tomohiko Taniai, Tadashi Uwagawa, Katsuhiko Yanaga, Toru Ikegami, Toya Ohashi, Ken Eto

Nuclear factor kappa B (NF-κB) is a transcriptional factor that can be activated by radiotherapy and chemotherapy. The synthetic protease inhibitor nafamostat mesilate (NM) inhibits NF-κB activity and exerts antitumor actions in various types of cancer. In the present study, we hypothesized that NM might enhance the antitumor action of radiotherapy on gallbladder cancer (GBC) cells by inhibiting radiation-induced NF-κB activity. Thus, we investigated the correlation between radiotherapy and NF-κB activity in GBC cells. We assessed the in vitro effects of radiotherapy with or without NM on NF-κB activity, apoptosis of GBC cells (NOZ and OCUG-1), induction of apoptotic cascade, cell cycle progression, and viability of GBC cells using four treatment groups: 1) radiation (5 Gy) alone; 2) NM (80 μg/mL and 40 μg/mL, respectively) alone; 3) combination (radiation and NM); and 4) vehicle (control). The same experiments were performed in vivo using a xenograft GBC mouse model. In vitro, NM inhibited radiation-induced NF-κB activity. Combination treatment significantly attenuated cell viability and increased cell apoptosis and G2/M phase cell cycle arrest compared with those in the other groups for NOZ and OCUG-1 cells. Moreover, combination treatment upregulated the expression of apoptotic proteins compared with that after the other treatments. In vivo, NM improved the antitumor action of radiation and increased the population of Ki-67-positive cells. Overall, NM enhanced the antitumor action of radiotherapy on GBC cells by suppressing radiation-induced NF-κB activity. Thus, the combination of radiotherapy and NM may be useful for the treatment of locally advanced unresectable GBC.

Clinical and phenotypical characteristics of submucosal invasive carcinoma in non-ampullary duodenal cancer

by Katsunori Matsueda, Hiromitsu Kanzaki, Ryuta Takenaka, Masahiro Nakagawa, Kazuhiro Matsueda, Masaya Iwamuro, Seiji Kawano, Yoshiro Kawahara, Tomohiro Toji, Takehiro Tanaka, Takahito Yagi, Toshiyoshi Fujiwara, Hiroyuki Okada

Objective

The rare incidence of submucosal invasive non-ampullary duodenal carcinoma has led to scant information in literature; therefore, we compared the clinicopathological features between submucosal invasive carcinoma (SM-Ca), mucosal carcinoma (M-Ca), and advanced carcinoma (Ad-Ca).

Materials

We retrospectively analyzed 165 patients with sporadic non-ampullary duodenal carcinomas (SNADCs) from four institutions between January 2003 and December 2018. The SNADCs were divided to three groups according to histological diagnosis: SM-Ca, M-Ca, and Ad-Ca. The clinicopathological characteristics and mucin phenotypes were compared between groups.

Results

Among the 165 SNADCs, 11 (7%) were classified as SM-Ca, 70 (42%) as M-Ca, and 84 (51%) as Ad-Ca. We found that all SM-Ca (P = 0.013) and most Ad-Ca (P = 0.020) lesions were located on the oral-Vater; however, an almost equal distribution of M-Ca lesions was found between the oral- and anal-Vater. No significant difference was observed between the tumor diameter of M-Ca and SM-Ca; however, 45% (5/11) of SM-Ca were ≤10 mm. A total of 73% (8/11) of SM-Ca were classified as gastric phenotype and no lesions were classified as intestinal phenotype; whereas most M-Ca were classified as intestinal phenotype (67%, 8/12).

Conclusions

SM-Ca lesions were all located on the oral-Vater and were highly associated with the gastric mucin phenotype, which were different from the features of most M-Ca.

Can emergency nurses safely and effectively insert fascia iliaca blocks in patients with a fractured neck of femur? A prospective cohort study in an Australian emergency department

Aims and objectives

To compare the effectiveness and safety of ultrasound-guided fascia iliaca block (FIB) insertion in patients with fractured neck of femur by trained emergency nurses with insertion by doctors.

Background

The FIB is an effective and safe form of analgesia for patients with hip fracture presenting to the emergency department (ED). While it has traditionally been inserted by medical doctors, no evidence exists comparing the effectiveness and safety of FIB insertion by nurses compared with doctors.

Design

A prospective cohort study.

Methods

The study was conducted in an Australian metropolitan ED. Patients admitted to the ED with suspected or confirmed fractured neck of femur had a FIB inserted under ultrasound guidance by either a trained emergency nurse or doctor. A retrospective medical record audit was undertaken of consecutive ED patients presenting between January 2013–December 2017. Reporting of this study followed the Strengthening the Reporting of Observational Studies in Epidemiology guidelines for cohort studies.

Results

Of the 472 patients eligible for a FIB, 322 (68%) had one inserted. A majority were inserted by doctors (n = 207, 64.3%) with 22.4% (n = 72) by nurses and in 13.3% (n = 43) of patients the clinician was not documented. There were no differences between the nurse-inserted and doctor-inserted groups for mean pain scores 1 hr post-FIB insertion; clinically significant reduction (≥30%) in pain score 1 hr post-FIB insertion; pain score 4 hr post-FIB insertion; delirium incidence; opioid use post-FIB insertion; or time to FIB insertion. No adverse events were identified in either group.

Conclusion

Insertion of FIBs by trained emergency nurses is as effective and safe as insertion by doctors in patients with fractured neck of femur in the ED. Senior emergency nurses should routinely be inserting FIB as a form of analgesia for patients with hip fracture.

Relevance to clinical practice

Our study showed trained emergency nurses can safely and effectively insert fascia iliaca blocks in patients with hip fractures. Pain was significantly reduced in a majority of patients with no reported complications. Emergency nurses should be trained to insert fascia iliaca blocks in patients with hip fractures.

Prediction of early recurrence of pancreatic ductal adenocarcinoma after resection

by Toshitaka Sugawara, Daisuke Ban, Jo Nishino, Shuichi Watanabe, Aya Maekawa, Yoshiya Ishikawa, Keiichi Akahoshi, Kosuke Ogawa, Hiroaki Ono, Atsushi Kudo, Shinji Tanaka, Minoru Tanabe

Background

Even after curative resection, pancreatic ductal adenocarcinoma (PDAC) patients suffer a high rate of recurrence. There is an unmet need to predict which patients will experience early recurrence after resection in order to adjust treatment strategies.

Methods

Data of patients with resectable PDAC undergoing surgical resection between January 2005 and September 2018 were reviewed to stratify for early recurrence defined as occurring within 6 months of resection. Preoperative data including demographics, tumor markers, blood immune-inflammatory factors and clinicopathological data were examined. We employed Elastic Net, a sparse modeling method, to construct models predicting early recurrence using these multiple preoperative factors. As a result, seven preoperative factors were selected: age, duke pancreatic monoclonal antigen type 2 value, neutrophil:lymphocyte ratio, systemic immune-inflammation index, tumor size, lymph node metastasis and is peripancreatic invasion. Repeated 10-fold cross-validations were performed, and area under the receiver operating characteristic curve (AUC) and decision curve analysis were used to evaluate the usefulness of the models.

Results

A total of 136 patients was included in the final analysis, of which 35 (34%) experienced early recurrence. Using Elastic Net, we found that 7 of 14 preoperative factors were useful for the predictive model. The mean AUC of all models constructed in the repeated validation was superior to the standard marker CA 19–9 (0.718 vs 0.657), whereas the AUC of the model constructed from the entire patient cohort was 0.767. Decision curve analysis showed that the models had a higher mean net benefit across the majority of the range of reasonable threshold probabilities.

Conclusion

A model using multiple preoperative factors can improve prediction of early resectable PDAC recurrence.

Prevalence of stunting and associated factors among public primary school pupils of Bahir Dar city, Ethiopia: School-based cross-sectional study

by Getasew Mulat Bantie, Amare Alamirew Aynie, Kidist Hailu Akenew, Mahlet Tilahun Belete, Eyerusalem Teshome Tena, Genet Gebreselasie Gebretsadik, Aynalem Nebebe Tsegaw, Tigist Birru Woldemariam, Ashenafi Abate Woya, Amare Alemu Melese, Agumas Fentahun Ayalew, Getenet Dessie

Background

Stunting is a well-established child-health indicator of chronic malnutrition, which reliably gives a picture of the past nutritional history and the prevailing environmental and socioeconomic circumstances.

Objective

To investigate the prevalence of stunting and associated factors among public primary school children of the Bahir Dar city.

Method

A cross-sectional study was carried out from March to June 2019. Data were coded and entered into the Epi-Data and exported to SPSS version 23 software. The pupil was stunted if the height- for-age was ≤ -2 SDs from the median growth standards according to the WHO. A descriptive summary was computed using frequency, percent, mean, median and standard deviation. A simple logistic regression model was fitted to identify associated factors between the independent variables and the dependent variable at a 95% confidence interval (CI) and p-value Results

370 primary school pupils were included in the study with the mean age of 10.15 (± 2.23 SD) years. 51.6% of the pupils were females. The total prevalence of stunting was 15.13% (95%CI; 11%, 19%). The burden of stunting was higher in the age group of 11 years and older. Pupil’s age older than 11 years (AOR = 15. 6; 95%CI; 3.31, 73.45; p-value Conclusion

The prevalence of stunting was relatively lower than the regional estimated stunting level. Older age and male sex were significantly associated with stunting.

Economic impact of the first wave of the COVID-19 pandemic on acute care hospitals in Japan

by Jung-ho Shin, Daisuke Takada, Tetsuji Morishita, Hueiru Lin, Seiko Bun, Emi Teraoka, Takuya Okuno, Hisashi Itoshima, Hiroyuki Nagano, Kenji Kishimoto, Hiromi Segawa, Yuka Asami, Takuya Higuchi, Kenta Minato, Susumu Kunisawa, Yuichi Imanaka

Background

In response to the coronavirus diseases 2019 (COVID-19) pandemic, the Japanese government declared a state of emergency on April 7, 2020. Six days earlier, the Japan Surgical Society had recommended postponing elective surgical procedures. Along with the growing public fear of COVID-19, hospital visits in Japan decreased.

Methods

Using claims data from the Quality Indicator/Improvement Project (QIP) database, this study aimed to clarify the impact of the first wave of the pandemic, considered to be from March to May 2020, on case volume and claimed hospital charges in acute care hospitals during this period. To make year-over-year comparisons, we considered cases from July 2018 to June 2020.

Results

A total of 2,739,878 inpatient and 53,479,658 outpatient cases from 195 hospitals were included. In the year-over-year comparisons, total claimed hospital charges decreased in April, May, June 2020 by 7%, 14%, and 5%, respectively, compared to the same months in 2019. Our results also showed that per-case hospital charges increased during this period, possibly to compensate for the reduced case volumes. Regression results indicated that the hospital charges in April and May 2020 decreased by 6.3% for hospitals without COVID-19 patients. For hospitals with COVID-19 patients, there was an additional decrease in proportion with the length of hospital stay of COVID-19 patients including suspected cases. The mean additional decrease per COVID-19 patient was estimated to 5.5 million JPY.

Conclusion

It is suggested that the hospitals treating COVID-19 patients were negatively incentivized.

Detection of acute toxicity of aflatoxin B1 to human hepatocytes <i>in vitro</i> and <i>in vivo</i> using chimeric mice with humanized livers

by Yuji Ishida, Chihiro Yamasaki, Hiroko Iwanari, Hisahiko Yamashita, Yuko Ogawa, Ami Yanagi, Suzue Furukawa, Yuha Kojima, Kazuaki Chayama, Junichi Kamiie, Chise Tateno

Aflatoxin B1 (AFB1), a mycotoxin, is acutely hepatotoxic to many animals including humans. However, there are marked interspecies differences in sensitivity to AFB1-induced toxicity depending on bioactivation by cytochrome P450s (CYPs). In the present study, we examined the applicability of chimeric mice with humanized livers and derived fresh human hepatocytes for in vivo and vitro studies on AFB1 cytotoxicity to human hepatocytes. Chimeric mice with highly humanized livers and SCID mice received daily injections of vehicle (corn oil), AFB1 (3 mg/kg), and carbon tetrachloride (50 mg/kg) for 2 days. Histological analysis revealed that AFB1 promoted hepatocyte vacuolation and inflammatory cell infiltration in the area containing human hepatocytes. A novel human alanine aminotransferase 1 specific enzyme-linked immunosorbent assay demonstrated the acute toxicity of AFB1 to human hepatocytes in the chimeric mouse livers. The sensitivity of cultured fresh human hepatocytes isolated from the humanized liver mice for AFB1 cytotoxicity was comparable to that of primary human hepatocytes. Long-term exposure to AFB1 (6 or 14 days) produced a more severe cytotoxicity. The half-maximal lethal concentration was 10 times lower in the 2-week treatment than after 2 days of exposure. Lastly, the significant reduction of AFB1 cytotoxicity by a pan-CYP inhibitor or transfection with CYP3A4 specific siRNA clearly suggested that bioactivation of AFB1 catalyzed by CYPs was essential for AFB1 cytotoxicity to the human hepatocytes in our mouse model. Collectively, our results implicate the humanized liver mice and derived fresh human hepatocytes are useful models for studies of AFB1 cytotoxicity to human hepatocytes.

Age-related differences in correction behavior for unintended acceleration

by Kunihiro Hasegawa, Motohiro Kimura, Yuji Takeda

Although unintended acceleration caused by pedal misapplication is a cause of traffic accidents, fatal accidents may be avoided if drivers realize their error immediately and quickly correct how they are stepping on the pedal. This correction behavior may decline with age because the rate of fatal accidents is fairly higher for older adults than for younger adults. To investigate this possibility, the present study recruited older adults (n = 40, age range = 67–81 years) as well as younger adults (n = 40, age range = 18–32 years). In this study, they performed a pedal stepping task during which they were required to stop the simulated vehicle as quickly as possible when a red signal was presented on a monitor. During most trials, the vehicle decelerated/stopped when the brake pedal was applied in a normal manner. In a few trials, however, stepping on the brake pedal resulted in sudden acceleration of the vehicle (i.e., the occurrence of the unintended acceleration); when this occurred, the participants had to release the pedal and re-step on another pedal to decelerate/stop the vehicle as quickly as possible. We focused on the age-related differences of the reaction latencies during three time periods: from the appearance of the red signal on the screen until stepping on the pedal (Period 1), from stepping on the pedal until the release of the pedal (Period 2), and from the release of the pedal until re-stepping of another pedal (Period 3). The results showed that there was no age-related difference in the latency of Period 1, p = .771, whereas those of Periods 2 and 3 were longer for the older adults (ps

Objective evaluation of visual fatigue in patients with intermittent exotropia

by Masakazu Hirota, Kozue Yada, Takeshi Morimoto, Takao Endo, Tomomitsu Miyoshi, Suguru Miyagawa, Yoko Hirohara, Tatsuo Yamaguchi, Makoto Saika, Takashi Fujikado

Purpose

The purpose of this study was to evaluate the degree of visual fatigue in patients with intermittent exotropia (IXT) using the binocular fusion maintenance (BFM) test.

Methods

Fourteen patients with IXT (32.1 ± 16.4 years) and 15 age-matched healthy volunteers (31.2 ± 9.3 years) participated in the study. BFM was assessed by measuring the transmittance of liquid crystals placed in front of the subject's nondominant eye at the instance when binocular fusion was broken and vergence eye movement was induced. A questionnaire on subjective symptoms was administered to the subjects before and after the visual task. The visual task consisted of a reciprocal movement between 67 and 40 cm.

Results

The change [post–pre] of BFM was significantly lower in the IXT group (−0.185 ± 0.187) than in the control group (−0.030 ± 0.070) (P = 0.010). The change of total subjective eye symptom score was significantly greater in the IXT group (2.28 ± 1.43) than in the control group (0.93 ± 1.27) (P = 0.018). The reduction in BFM rate with increasing total subjective eye symptom score was significantly greater in the IXT group (−0.106 ± 0.017) than in the control group (−0.030 ± 0.013) (P = 0.006).

Conclusion

The present findings objectively showed that patients with IXT are at a greater risk of visual fatigue in comparison with healthy individuals.

Carnitine insufficiency is associated with fatigue during lenvatinib treatment in patients with hepatocellular carcinoma

by Hironao Okubo, Hitoshi Ando, Kei Ishizuka, Ryuta Kitagawa, Shoki Okubo, Hiroaki Saito, Shigehiro Kokubu, Akihisa Miyazaki, Kenichi Ikejima, Shuichiro Shiina, Akihito Nagahara

Background

Fatigue is a common adverse event during lenvatinib treatment in patients with hepatocellular carcinoma. One mechanism contributing to development of fatigue might involve abnormal adenosine triphosphate synthesis that is caused by carnitine deficiency. To address this possibility, we examined the relationship between carnitine levels and fatigue during lenvatinib treatment.

Methods

This prospective study evaluated 20 patients with hepatocellular carcinoma who underwent lenvatinib treatment. Both blood and urine samples were collected from the patients before starting lenvatinib therapy (day 0), and on days 3, 7, 14, and 28 thereafter. Plasma and urine concentrations of free and acyl carnitine (AC) were assessed at each time point. The changes in daily fatigue were evaluated using the Brief Fatigue Inventory (BFI).

Results

Plasma levels of free carnitine (FC) at days 3 and 7 were significantly higher compared with baseline (p = 0.005, p = 0.005, respectively). The urine FC level at day 3 was significantly higher compared with baseline (p = 0.030) and that of day 7 tended to be higher compared with baseline (p = 0.057). The plasma AC concentration at days 14 and 28 was significantly higher compared with that of baseline (p = 0.002, p = 0.005, respectively). The plasma AC-to-FC (AC/FC) ratio on days 14 and 28 was significantly higher compared with baseline (p = 0.001, p = 0.003, respectively). There were significant correlations between the plasma AC/FC ratio and the change in the BFI score at days 14 and 28 (r = 0.461, p = 0.041; r = 0.770, p = 0.002, respectively).

Conclusions

Longitudinal assessments of carnitine and fatigue in patients with hepatocellular carcinoma suggest that lenvatinib affects the carnitine system in patients undergoing lenvatinib therapy and that carnitine insufficiency increases fatigue. The occurrence of carnitine insufficiency may be a common cause of fatigue during the treatment.

Development of Oral Care Chip, a novel device for quantitative detection of the oral microbiota associated with periodontal disease

by Ai Nozawa, Hiroyuki Oshima, Naoyuki Togawa, Takenori Nozaki, Shinya Murakami

Periodontal disease, the most prevalent infectious disease in the world, is caused by biofilms formed in periodontal pockets. No specific bacterial species that can cause periodontitis alone has been found in any study to date. Several periodontopathic bacteria are associated with the progress of periodontal disease. Consequently, it is hypothesized that dysbiosis of subgingival microbiota may be a cause of periodontal disease. This study aimed to investigate the relationship between the subgingival microbiota and the clinical status of periodontal pockets in a quantitative and clinically applicable way with the newly developed Oral Care Chip. The Oral Care Chip is a DNA microarray tool with improved quantitative performance, that can be used in combination with competitive PCR to quantitatively detect 17 species of subgingival bacteria. Cluster analysis based on the similarity of each bacterial quantity was performed on 204 subgingival plaque samples collected from periodontitis patients and healthy volunteers. A significant difference in the number of total bacteria, Treponema denticola, Campylobacter rectus, Fusobacterium nucleatum, and Streptococcus intermedia bacteria in any combination of the three clusters indicated that these bacteria gradually increased in number from the stage before the pocket depth deepened. Conversely, Porphyromonas gingivalis, Tannerella forsythia, Prevotella intermedia, and Streptococcus constellatus, which had significant differences only in limited clusters, were thought to increase in number as the pocket depth deepened, after periodontal pocket formation. Furthermore, in clusters where healthy or mild periodontal disease sites were classified, there was no statistically significant difference in pocket depth, but the number of bacteria gradually increased from the stage before the pocket depth increased. This means that quantitative changes in these bacteria can be a predictor of the progress of periodontal tissue destruction, and this novel microbiological test using the Oral Care Chip could be effective at detecting dysbiosis.

Antimicrobial photodynamic therapy in skin wound healing: A systematic review of animal studies

Abstract

Bacterial infection is a common wound complication that can significantly delay healing. Classical local therapies for infected wounds are expensive and are frequently ineffective. One alternative therapy is photodynamic therapy (PDT). We conducted a systematic review to clarify whether PDT is useful for bacteria‐infected wounds in animal models. PubMed and Medline were searched for articles on PDT in infected skin wounds in animals. The language was limited to English. Nineteen articles met the inclusion criteria. The overall study methodological quality was moderate, with a low‐moderate risk of bias. The animal models were mice and rats. The wounds were excisional, burn, and abrasion wounds. Wound size ranged from 6 mm in diameter to 1.5 × 1.5 cm2. Most studies inoculated the wounds with Pseudomonas aeruginosa or methicillin‐resistant Staphylococcus aureus. Eleven and 17 studies showed that the PDT of infected wounds significantly decreased wound size and bacterial counts, respectively. Six, four, and two studies examined the effect of PDT on infected wound‐cytokine levels, wound‐healing time, and body weight, respectively. Most indicated that PDT had beneficial effects on these variables. PDT accelerated bacteria‐infected wound healing in animals by promoting wound closure and killing bacteria.

Managing keloid scars: From radiation therapy to actual and potential drug deliveries

The aetiology of keloids is becoming clearer, but many questions remain, including about the most optimal treatment. Current therapies include surgical excision, radiotherapy, and various pharmaceutical drugs. However, none of these drugs are keloid‐specific. Moreover, all current interventions are associated with high recurrence rates. Here, we review the pharmaceutical interventions that are currently available. All are based on the fact that keloids are an expanding solid mass with intense chronic inflammation at its advancing edges. Consequently, current pharmaceuticals aim to reduce the mass and/or symptoms of keloids, similar to surgery and radiotherapy. They include chemotherapies, immunotherapies, volume‐reducing therapies, and anti‐inflammatory therapies. We also describe new advances in keloid pharmaceuticals. They include drugs that were designed to treat systemic diseases such as hypertension or breast cancer but were found to also treat keloids. Furthermore, recent progress in genetic, epigenetic, and stem cell therapies suggests that they could become useful in the keloid field. This review of pharmaceutical advances will hopefully promote additional research and the development of effective and specific pharmaceuticals for keloids.

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