bluuebunny/crossref_metadata_2025 huggingface dataset:
Midwives’ perceptions towards the ministry of health guidelines for the provision of immediate postpartum care in rural health facilities in Uganda
Authors: Namutebi Mariam , Nalwadda Gorrette K. , Kasasa Simon , Muwanguzi Patience A. , Kaye Dan K.
Published: April 2023

Background

Guidelines for clinical practice have been part of the Ministry of health’s efforts to improve the quality of care for over two decades. Their benefits have been documented in Uganda. However, having practice guidelines may not always result in their use in care provision. We explored the midwives’ perceptions towards the ministry of health guidelines for providing immediate postpartum care.

Methods

An exploratory descriptive qualitative study was conducted in three districts in Uganda from September 2020 to January 2021. In-depth interviews with 50 midwives from 35 health centers and 2 hospitals in Mpigi, Butambala, and Gomba districts were done. Thematic analysis of data was done.

Results

Three themes emerged; awareness and use of the guidelines, perceived drivers, and perceived barriers to the provision of immediate postpartum care. The subthemes for theme I included; awareness of the guidelines, variations in the postpartum care practices, variations in preparedness to manage women with complications, and varied access to continuing midwifery education. Fear of complications and litigation were the perceived drivers of guideline use. On the other hand, lack of knowledge, busy maternity units, organization of the care, and the midwives’ perceptions about their clients were the barriers to guideline use. Midwives felt that new guidelines and policies regarding immediate postpartum care should be disseminated widely.

Conclusion

The midwives felt that the guidelines were good for the prevention of postpartum complications but their knowledge of the guidelines for the provision of immediate postpartum care was suboptimal. They desired on-job training and mentorship to help them bridge the knowledge gaps. Variations in patient assessment, monitoring, and pre-discharge care were acknowledged and said to be due to a poor reading culture and health facility factors like patient-midwife ratios, unit setup, and prioritization of labor.
Individual and contextual-level factors associated with iron-folic acid supplement intake during pregnancy in Ethiopia: a multi-level analysis
Authors: Yalew Melaku , Getachew Shiferaw , Mohammed Keriya , Hankarso Hailu , Bayile Adane , Asmamaw Shambel Dessale , Assefa Mesfin Getahun , Bazie Getaw Walle , Mebratu Wondwosen , Kefale Bereket , Damtie Yitayish , Arefaynie Mastewal , Birhane Tesfaye , Dewau Reta , Cherie Nigus , Addisu Elsabeth , Mitiku Kefale , Tadese Fentaw , Wendie Teklehaimanot Fentie , Habtie Adane , Mekonnen Tefera Chane , Tadesse Sisay Eshete , Bedane Getachew Tadesse , Wasihun Yitbarek , Tsega Tilahun Degu , Taddele Mekuanint , Tefera Zenebe , Adane Bezawit , Wagaye Birhanu , Ayele Fanos Yeshanew , Zerga Aregash Abebayehu , Molla Abebaw , Desalegn Biruk , Birkie Mengesha , Bewket Bekalu , Alemu Belete Kassa , Zewdie Segenet , Tsegaye Meseret Kefale , Bitew Abebayehu , Mehari Kassu , Derseh Lemma
Published: April 2023

Background

Anemia is still one of the major public health problems in many developing countries including Ethiopia. Thus, this study aimed to assess individual and contextual-level factors associated with iron-folic acid supplement intake during pregnancy in Ethiopia.

Methods

A secondary analysis was done on the 2019 mini-Ethiopian Demographic and Health Survey (EDHS) dataset. A total of 3,927 pregnant women who gave birth five years before the survey were included in the analysis. Multi-level mixed-effect logistic regression analysis was done by STATA/SE version 14.0 to identify individual and contextual-level factors. Adjusted Odds Ratio (AOR) with 95% Confidence Interval (CI) was used to show the strength and direction of the association. The level of statistical significance was declared at a P value less than 0.05.

Results

Those primary educated [AOR = 1.83, 95% CI: (1.24, 2.74)], secondary educated [AOR = 2.75, 95% CI: (1.57, 4.824)], women who had greater than 5 living children [AOR = 2.02, 95% CI: (1.25, 3.27)], women who had ANC visit [AOR = 21.26, 95% CI: (13.56, 33.32)] and women who lived in a cluster with high proportion of women had ANC visit [AOR = 1.72, 95% CI: (1.17, 2.54)] and women who lived in Somali [AOR = 0.44 0.73, 95% CI: (0.22, 0.87)] were significantly associated with iron-folic acid intake during pregnancy.

Conclusions

Both individual and contextual-level factors were significantly associated with iron-folic acid intake during pregnancy. From individual-level factors: education status of women, the total numbers of living children, and ANC follow-up are significant and from contextual-level factors: region and living in a high proportion of women who had ANC follow-up were found to have a statistically significant association. Promoting women’s education and maternal health services like ANC and intervention targeting the Somali region would be the recalled area of the government.
Protocol of the OPTIMAL study: Optimization of polypharmacy in geriatric oncology - A randomized controlled trial
Authors: Schöttker Ben , Chen Li-Ju , Caspari Reiner , Brenner Hermann
Published: April 2023

Background

Polypharmacy is very common in older cancer patients and these patients are particularly vulnerable to drug-drug interactions and adverse drug reactions because they often receive chemotherapy and symptom-relieving agents.

Methods

The primary aim of the randomized, controlled Optimization of Polypharmacy in Geriatric Oncology (OPTIMAL) trial is to test whether an advisory letter with the results of a comprehensive medication review conducted with the Fit fOR The Aged (FORTA) list to the caring physician in rehabilitation clinics improves the quality of life (QoL) of older cancer patients exposed to polypharmacy more than usual care. The FORTA list detects medication overuse, underuse, and potentially inappropriate drug use among older adults. In the oncology departments of approximately 10 German rehabilitation clinics, we aim to recruit 514 cancer patients (22 common cancers; diagnosis or recurrence requiring treatment in the last 5 years; all stages) who are ≥ 65 years old, regularly take ≥ 5 drugs, and have ≥ 1 medication-related problem. All necessary information about the patients will be provided to a pharmacist at the coordinating center (German Cancer Research Center, Heidelberg), who will perform randomization (1:1) and conduct the medication review with the FORTA list. For the intervention group only, the results are sent by letter to the treating physician in the rehabilitation clinics, who shall discuss medication changes with the patient at the discharge visit, as well as implement them afterwards and disclose them in the discharge letter to the general practitioner. The control group gets the usual care provided in German rehabilitation clinics, which usually does not include a comprehensive medication review but can include medication changes. Patients will be blinded, as they cannot know whether proposed medication changes were part of the study or part of usual care. Study physicians cannot be blinded. The primary endpoint will be the EORTC-QLQ-C30 global health status/QoL score, assessed via self-administered questionnaires 8 months after baseline.

Discussion

If the planned study shows that a medication review with the FORTA list improves the QoL of older cancer patients in oncological rehabilitation more than usual care, it would provide the necessary evidence to translate the trial’s findings into routine care.

Trial registration

German Clinical Trials Register (DRKS): DRKS00031024.
Identification of immunotherapy-related lncRNA signature for predicting prognosis, immunotherapy responses and drug candidates in bladder cancer
Authors: Hui Pengyu , Ni Feng , Zheng Liang , Jia Lei , Wang Zhe
Published: April 2023

Background

Bladder cancer (BC) is one of the most common malignant diseases and the most common causes of cancer death worldwide. Immunotherapy has opened new avenues for precision treatment of bladder tumours, and immune checkpoint inhibitors (ICIs) have revolutionized the clinical treatment strategy of bladder tumours. In addition, long non-coding RNA (lncRNA) plays an important role in regulating tumour development and immunotherapy efficacy.

Methods

We obtained genes with significant differences between anti-PD-L1 response and non-response from the Imvogor210 data set and combined with the bladder cancer expression data in the TCGA cohort to obtain immunotherapy-related lncRNA. Based on these lncRNAs, the prognostic risk model of bladder cancer was constructed and verified by GEO external data set. The characterization of immune cell infiltration and immunotherapy effects between high-risk and low-risk groups were then analysed. We predicted the ceRNA network and performed molecular docking of key target proteins. The functional experiments verified the function of SBF2-AS1.

Results

Three immunotherapy-related lncRNAs were identified as independent prognostic biomarkers for bladder cancer and a prognostic model of immunotherapy-related prognosis was constructed. Prognosis, immune cell infiltration, and immunotherapy efficacy were significantly different between high- and low-risk groups based on risk scores. Additionally, we established a ceRNA network of lncRNA(SBF2-AS1)-miRNA(has-miR-582-5p)-mRNA (HNRNPA2B1). Targeting the protein HNRNPA2B1 identified the top eight small molecule drugs with the highest affinity.

Conclusion

We developed a prognostic risk score model based on immune-therapy-related lncRNA, which was subsequently determined to be significantly associated with immune cell infiltration and immunotherapy response. This study not only helps to promote our understanding of immunotherapy-related lncRNA in the prognosis of BC, but also provides new ideas for clinical immunotherapy and the development of novel therapeutic drugs for patients.
Analysis of patients with colorectal cancer shows a specific increase in serum anti-ING1 autoantibody levels
Authors: Arasawa Takahiro , Hiwasa Takaki , Kagaya Akiko , Maruyama Tetsuro , Uesato Masaya , Kano Masayuki , Kobayashi Sohei , Takizawa Hirotaka , Iwase Katsuro , Nomura Fumio , Matsushita Kazuyuki , Matsubara Hisahiro
Published: April 2023

Colorectal cancer (CRC) is the third most prevalent cancer in the world, yet the sensitivity and specificity of biomarkers for CRC diagnosis are insufficient. In the present study, we performed a protein microarray screening method to identify antibody markers for CRC. Inhibitor of growth family 1 (ING1) was identified as a candidate tumor antigen for CRC using protein microarrays (ProtoArray). Subsequent amplified luminescence proximity homogeneous assay-linked immunosorbent assay using recombinant ING1 protein showed that the serum levels of anti-ING1 antibodies were increased not only in patients with CRC but also in those with esophageal cancer (EC), gastric cancer (GC), breast cancer (BrC), and pancreatic cancer (PC) compared with those of healthy donors (HDs). Antibodies against the ING1 amino acids between 239 and 253 were present at significantly higher levels in patients with CRC than in those with EC, GC, BrC, or PC. Anti-ING1 antibody levels were significantly higher in the patients with CRC at any stages than in the HDs. Immunohistochemical staining revealed higher expression of ING1 protein in CRC cells than in the adjacent normal tissues. In luciferase reporter assays using a CRC cell line, ING1 augmented p53-mediated NOXA promoter activity but attenuated p53-stimulated Bax, p21, and PUMA promoter activities. Consequently, serum anti-ING1 antibodies can be used for sensitive and specific diagnoses of CRC.
Maternal and umbilical cord blood lactate for predicting perinatal death: a secondary analysis of data from a randomized controlled trial
Authors: Musaba Milton W. , Nambozo Brendah , Mukunya David , Wandabwa Julius , Barageine Justus K. , Kiondo Paul , Napyo Agnes , Sserwanja Quraish , Weeks Andrew D , Tumwine James K , Ndeezi Grace
Published: April 2023

Background

In high resource settings, lactate and pH levels measured from fetal scalp and umbilical cord blood are widely used as predictors of perinatal mortality. However, the same is not true in low resource settings, where much of perinatal mortality occurs. The scalability of this practice has been hindered by difficulty in collecting fetal scalp and umbilical blood sample. Little is known about the use of alternatives such as maternal blood, which is easier and safer to obtain. Therefore, we aimed to compare maternal and umbilical cord blood lactate levels for predicting perinatal deaths.

Methods

This was secondary analysis of data from a randomized controlled trial assessing the effect of sodium bicarbonate on maternal and perinatal outcomes among women with obstructed labour at Mbale regional referral hospital in Eastern Uganda. Lactate concentration in maternal capillary, myometrial, umbilical venous and arterial blood was measured at the bedside using a lactate Pro 2 device (Akray, Japan Shiga) upon diagnosis of obstructed labour. We constructed Receiver Operating Characteristic curves to compare the predictive ability of maternal and umbilical cord lactate and the optimal cutoffs calculated basing on the maximal Youden and Liu indices.

Results

Perinatal mortality risk was: 102.2 deaths per 1,000 live births: 95% CI (78.1–130.6). The areas under the ROC curves were 0.86 for umbilical arterial lactate, 0.71 for umbilical venous lactate, and 0.65 for myometrial lactate, 0.59 for maternal lactate baseline, and 0.65 at1hr after administration of bicarbonate. The optimal cutoffs for predicting perinatal death were 15 0.85 mmol/L for umbilical arterial lactate, 10.15mmol/L for umbilical venous lactate, 8.75mmol/L for myometrial lactate, and 3.95mmol/L for maternal lactate at recruitment and 7.35mmol/L after 1 h.

Conclusion

Maternal lactate was a poor predictor of perinatal death, but umbilical artery lactate has a high predictive value. There is need for future studies on the utility of amniotic fluid in predicting intrapartum perinatal deaths.
Seroprevalence and risk factors associated with hepatitis C: a cross-sectional study of persons who inject drugs in Puerto Rico, 2018
Authors: Colón-López Vivian , Alvelo-Fernández Paola M. , Centeno-Alvarado Nadia , Agudelo Salas Ivony Y. , Rolón Colón Yadira , Pabón Martínez María , Rodríguez-Lebrón Jorge L. , Reyes-Pulliza Juan C.
Published: April 2023

Background

People Who Inject Drugs (PWID) are at a higher risk of acquiring bloodborne infections. We aimed to estimate the seroprevalence of the Hepatitis C Virus (HCV) in PWID and identify correlates and risk factors using data from the Puerto Rico National HIV Behavioral Surveillance System, PWID cycle 5, conducted in 2018.

Methods

A total of 502 San Juan Metropolitan Statistical Area participants were recruited through the Respondent Driven Sampling method. Sociodemographic, health-related, and behavioral characteristics were assessed. Testing for HCV antibodies was completed after the face-to-face survey. Descriptive and logistic regression analyses were performed.

Results

Overall seroprevalence of HCV was 76.5% (95% CI: 70.8-81.4%). A significantly (p < 0.05) higher HCV seroprevalence was observed among PWID with the following characteristics: heterosexuals (78.5%), high school graduates (81.3%), tested for sexually transmitted infections (STI) in the past 12 months (86.1%), frequent speedball injection (79.4%), and knowing the HCV serostatus of the last sharing partner (95.4%). Adjusted logistic regression models showed that having completed high school and reported STI testing in the past 12 months were significantly associated with HCV infection (ORa = 2.23; 95% CI: 1.06–4.69; ORa = 2.14; 95% CI: 1.06–4.30, respectively).

Conclusions

We report a high seroprevalence of HCV infection in PWID. Social health disparities and potential missed opportunities validate the continuing call for local action for public health and prevention strategies.
Weight self-perception and weight loss attempts in Chinese cardiovascular patients and non-cardiovascular patients: evidence from a population-based study
Authors: Gao Qingyuan , Li Ruotong , Chen Zhiteng , Yin Wenyao , Liao Guanghong , Zhang Haifeng , Wang Jingfeng , Chen Yangxin
Published: April 2023

Background

Weight loss is a significant improvement for individuals with overweight or obesity, especially for cardiovascular patients. The driving effects of weight self-perception and attempts to lose weight are vital in weight management, yet weight misperception is a direct culprit for the undesirability of weight control and obesity prevention. This study aimed to investigate weight self-perception and misperception and weight loss attempts in Chinese adults, especially among cardiovascular and non-cardiovascular patients.

Methods

We collected data from China HeartRescue Global Evaluation Baseline Household Survey 2015. Questionnaires were used to assess self-reported weight and cardiovascular patients. We used kappa statistics to check the consistency between weight self-perception and BMI. Logistic regression models were fitted to identify risk factors associated with weight misperception.

Results

A total of 2690 participants were enrolled in the household survey, while 157 respondents were cardiovascular patients. According to questionnaire results, 43.3% of cardiovascular patients thought they were overweight and obese, while the percentage is 35.3% among non-cardiovascular patients. Kappa statistics indicated higher consistency of self-reported weight and actual weight among cardiovascular patients. Multivariate analysis showed weight misperception was significantly associated with gender, education level, and actual BMI. Lastly, 34.5% of non-cardiovascular patients and 35.0% of cardiovascular patients were trying to lose weight or keep weight. The majority of these people adopted combined strategies of controlling diet and exercise to lose or maintain weight.

Conclusions

Weight misperception was highly prevalent among cardiovascular or non-cardiovascular patients. Obese respondents, women, and individuals with lower education levels were more vulnerable to make weight misperception. However, no difference in the purpose of weight loss attempts was indicated among cardiovascular and non-cardiovascular patients.
Intravascular large B-cell lymphoma appearance on dual-energy computed tomography: a case report
Authors: Yamada Daisuke , Imai Ryosuke , Matsusako Masaki , Kurihara Yasuyuki
Published: April 2023

Background

Intravascular large B-cell lymphoma (IVLBCL) is the proliferation of neoplastic B lymphocytes in the vascular space. Since conventional computed tomography (CT) shows nonspecific findings, differentiation between IVLBCL and other lung diseases, such as diffuse interstitial lung disease, is difficult.

Case presentation

A 73-year-old man presented with dyspnea and hypoxemia. Laboratory findings showed an increased lactate dehydrogenase level of 1690 U/L (normal: 130–235 U/L) and soluble interleukin-2 receptor level of 1140 U/mL (normal: 157–474U/mL). Dual-energy CT iodine mapping showed a significant symmetrical decrease in iodine distribution in the upper lungs, suggesting an unusual distribution of pulmonary hypoperfusion. Therefore, IVLBCL was suspected. A random skin biopsy confirmed the diagnosis of IVLBCL. Due to the severity of the disease, lung biopsy was averted. After admission to the hospital, high-dose methotrexate was administered for central nervous system involvement, due to findings of suspected intracranial infiltration on a brain magnetic resonance imaging and elevated cell counts on lumbar puncture. Subsequently, oxygen demand improved, and rituximab along with cyclophosphamide, doxorubicin, vincristine, and prednisone was added to the patient’s regime. Eventually, oxygen administration was terminated, the patient’s general condition improved, and the patient was discharged after 47 days of hospitalization.

Conclusions

Since the diagnosis of IVLBCL depends on whether it is possible to suspect IVLBCL, the finding of decreased iodine perfusion demonstrated on dual-energy CT is considered important information for diagnosis. An immediate diagnosis of IVLBCL is needed to avoid rapid disease progression and introduce early treatment for a favorable prognosis. In this case, unique pulmonary hypoperfusion demonstrated by dual-energy CT promoted early diagnosis of IVLBCL.
Clinical outcomes of various types of revision surgeries after unicompartmental knee arthroplasty failure
Authors: Peng Shih-Hui , Chen Chun-Chieh , Lee Sheng-Hsun , Lin Yu-Chih , Chiang Jui-Fan , Chen Szu-Yuan , Hu Chih-Chien , Chang Yuhan , Hsieh Pang-Hsin , Shih Hsin-Nung , Chang Chih-Hsiang
Published: April 2023

Purpose

The advantages of unicompartmental knee arthroplasty (UKA) have led to the procedure being increasingly performed worldwide. However, revision surgery is required after UKA failure. According to the literature review, the choice of implant in revision surgery remains a debatable concern. This study analyzed the clinical results of different types of prostheses used in treating failed UKA.

Materials and methods

This is a retrospective review of 33 failed medial UKAs between 2006 and 2017. Demographic data, failure reason, types of revision prostheses, and the severity of bone defects were analyzed. The patients were classified into three groups: primary prosthesis, primary prosthesis with a tibial stem, and revision prosthesis. The implant survival rate and medical cost of the procedures were compared.

Results

A total of 17 primary prostheses, 7 primary prostheses with tibial stems, and 9 revision prostheses were used. After a mean follow-up of 30.8 months, the survival outcomes of the three groups were 88.2%, 100%, and 88.9%, respectively (P = 0.640). The common bone defect in tibia site is Anderson Orthopedic Research Institute [AORI] grade 1 and 2a (16 versus 17). In patients with tibial bone defects AORI grade 2a, the failure rates of primary prostheses and primary prostheses with tibial stems were 25% and 0%, respectively.

Conclusions

The most common cause for UKA failure was aseptic loosening. The adoption of a standardized surgical technique makes it easier to perform revision surgeries. Primary prostheses with tibial stems provided higher stability, leading to a lower failure rate due to less risk of aseptic loosening in patients with tibial AORI grade 2a. In our experience, we advise surgeons may try using primary prostheses in patients with tibial AORI grade 1 and primary prostheses with tibial stems in patients with tibial AORI grade 2a.
The interaction between MC4R gene variant (rs17782313) and dominant dietary patterns on depression in obese and overweight women: a cross sectional study
Authors: Hajmir Mahya Mehri , Mirzababaei Atieh , Clark Cain C. T. , Ghaffarian-Ensaf Rasool , Mirzaei Khadijeh
Published: April 2023

Background

Previous studies have shown that the minor allele (C allele) for melanocortin 4 receptor (MC4R) rs17782313 may be associated with depressed mood. Moreover, dietary patterns have potentially adverse effects on depression. This study investigates the interactions between the MC4R gene variant (rs17782313) and dietary patterns on depression among Iranian obese and overweight women.

Methods

A total of 289 Iranian overweight and obese women, aged 18–50 years, were enrolled in this cross-sectional study. Biochemical, anthropometric, and body composition indices were assessed in all participants. Moreover, MC4R rs17782313, by the restriction fragment length polymorphism (PCR-RFLP) method, and depression, using the 21-item Depression Anxiety Stress Scales (DASS) questionnaire, were assessed. Food intakes were assessed by completing a 147-item semi-quantitative food frequency questionnaire (FFQ).

Results

By the use of factor analysis, 2 major dietary patterns were extracted: healthy dietary pattern (HDP) and unhealthy dietary pattern (UDP). Binary logistic analysis showed that individuals with minor allele risk (CC) with high adherence to the unhealthy pattern increased odds for depression (OR: 8.77, 95%CI: -0.86-18.40, P: 0.07), after controlling for confounders. Also, a logical inverse relationship was observed between CT genotype and HDP on depression in the crude and adjusted models (OR: -0.56, 95% CI: -3.69-2.57, P: 0.72) (OR: -4.17, 95% CI: -9.28-0.94, P: 0.11), although this interaction was not statistically significant.

Conclusion

According to the above findings, adherence to unhealthy food intake pattern increases odds of depression in MC4R risk allele (C allele) carriers. To confirm these findings, more studies are needed in the form of clinical trials and prospective studies with higher sample sizes.
Revealing a gap in the clinical competence of nursing staff in nursing homes: a cross-sectional study with the Ms. Olsen test
Authors: Vikström-Dahl Irén , Bing-Jonsson Pia Cecile , Rauhala Auvo , Fagerström Lisbeth
Published: April 2023

Background

Nursing staff, caring for frail older people in long-term care, needs to have a certain level of clinical competence to identify diseases at an early stage and to assess and provide good nursing care. In Finland, nursing care is based on evidence-based and high-quality nursing care. However, earlier inspections by the National Supervisory Authority for Welfare and Health showed many discrepancies between the nursing staff’s clinical competence and adequate and continuous education.

Aim

This study aimed to explore nursing staff, i.e. the clinical competence and decision-making skills of registered and practical nurses in nursing homes for older people in Finland and to analyse the association between nurses’ clinical competence and fundamental background factors.

Methods

We conducted a cross-sectional study of 337 participants in 50 nursing homes in the western part of Finland, between December 2020 and January 2021. The instrument used was the validated Ms. Olsen test, an extraction of NOP-CET. Statistical analyses were conducted with descriptive statistics and correlations and a cut-off for clinical competence.

Results

This study with the Ms. Olsen test revealed that only one-fourth of the RNs and a third of the PNs passed the clinical competence test. In the self-evaluation, almost all participants evaluated themselves with good clinical competence. The Finnish Current Care Guidelines were used on a daily basis by 7.4% and weekly by 30%. Significant correlation was found between Swedish as a working language and mother tongue and the score for clinical competence.

Conclusion

The clinical competence test, the Ms. Olsen test, was used in Finland for the first time to evaluate the nursing staffs´ clinical competence in nursing homes. We found gaps in the clinical competence in Finnish nursing homes, both for PNs and RNs. The result differed remarkably from their self-assessments and the staff did not use the national nursing guidelines as required to develop their nursing skills and knowledge. Gaps in the clinical competence have been identified and can be used to develop targeted continuous education.
The effect of medical innovation on the cost-effectiveness of Covid 19-related policies in the United States using a SIR model
Authors: Atherly Adam J. , van den Broek-Altenburg Eline M.
Published: April 2023

Background

During 2020–21, the United States used a multifaceted approach to control SARS-CoV-2 (Covid-19) and reduce mortality and morbidity. This included non-medical interventions (NMIs), aggressive vaccine development and deployment, and research into more effective approaches to medically treat Covid-19. Each approach had both costs and benefits. The objective of this study was to calculate the Incremental Cost Effectiveness Ratio (ICER) for three major Covid-19 policies: NMIs, vaccine development and deployment (Vaccines), and therapeutics and care improvements within the hospital setting (HTCI).

Methods

To simulate the number of QALYs lost per scenario, we developed a multi-risk Susceptible-Infected-Recovered (SIR) model where infection and fatality rates vary between regions. We use a two equation SIR model. The first equation represents changes in the number of infections and is a function of the susceptible population, the infection rate and the recovery rate. The second equation shows the changes in the susceptible population as people recover. Key costs included loss of economic productivity, reduced future earnings due to educational closures, inpatient spending and the cost of vaccine development. Benefits included reductions in Covid-19 related deaths, which were offset in some models by additional cancer deaths due to care delays.

Results

The largest cost is the reduction in economic output associated with NMI ($1.7 trillion); the second most significant cost is the educational shutdowns, with estimated reduced lifetime earnings of $523B. The total estimated cost of vaccine development is $55B. HTCI had the lowest cost per QALY gained vs “do nothing” with a cost of $2,089 per QALY gained. Vaccines cost $34,777 per QALY gained in isolation, while NMIs alone were dominated by other options. HTCI alone dominated most alternatives, except the combination of HTCI and Vaccines ($58,528 per QALY gained) and HTCI, Vaccines and NMIs ($3.4 m per QALY gained).

Conclusions

HTCI was the most cost effective and was well justified under any standard cost effectiveness threshold. The cost per QALY gained for vaccine development, either alone or in concert with other approaches, is well within the standard for cost effectiveness. NMIs reduced deaths and saved QALYs, but the cost per QALY gained is well outside the usual accepted limits.
L-Arginine in diabetes: clinical and preclinical evidence
Authors: Forzano Imma , Avvisato Roberta , Varzideh Fahimeh , Jankauskas Stanislovas S. , Cioppa Angelo , Mone Pasquale , Salemme Luigi , Kansakar Urna , Tesorio Tullio , Trimarco Valentina , Santulli Gaetano
Published: April 2023

L-Arginine (L-Arg), is a semi-essential amino acid involved in the formation of nitric oxide. The functional relevance of L-Arg in diabetes mellitus has been evaluated both in animal models and in human subjects. In the literature there are several lines of evidence indicating that L-Arg has beneficial effects in diabetes and numerous studies advocate its administration to attenuate glucose intolerance in diabetic patients. Here we present a comprehensive overview of the main studies exploring the effects of L-Arg in diabetes, including preclinical and clinical reports on this topic.
Application of a scoring system in Japanese patients diagnosed with atypical hemolytic uremic syndrome to assess the relationship between the score and clinical responses to eculizumab
Authors: Wada Hideo , Teranishi Hirofumi , Shimono Akihiko , Kato Noritoshi , Maruyama Shoichi , Matsumoto Masanori
Published: April 2023

Background

Atypical hemolytic uremic syndrome (aHUS) is caused by complement dysregulation and is generally diagnosed by exclusion from other disorders of thrombotic microangiopathy (TMA). Eculizumab, a terminal complement inhibitor, has been approved for aHUS treatment since 2013 in Japan. Recently, a scoring system was published to support diagnosis of aHUS. Herein we modified this scoring system to apply it to patients diagnosed with aHUS and treated with eculizumab, and assessed the association between the score and clinical responses to eculizumab.

Methods

One hundred eighty-eight Japanese patients who were clinically diagnosed with aHUS, treated with eculizumab, and enrolled in post-marketing surveillance (PMS) were included in this analysis. Some of parameters in the original scoring system were replaced with clinically similar parameters collected in the PMS to modify the system, hereafter referred to as the TMA/aHUS score, which ranges from -15 to 20 points. Treatment responses within 90 days after eculizumab initiation were also assessed, and the relationship between treatment response and TMA/aHUS scores calculated at TMA onset was explored.

Results

The median (range) TMA/aHUS score was 10 (3–16). Receiver operating characteristic curve analysis showed that the cutoff value of TMA/aHUS score to predict treatment response to eculizumab was estimated as 10, and negative predictive value indicated that ≥ 5 points was appropriate to consider assessing the treatment response to eculizumab; 185 (98%) patients had ≥ 5 points and 3 (2%) had < 5 points. Among the patients with ≥ 5 points, 96.1% showed partial response and 31.1% showed complete response. One of the three patients with < 5 points met partial response criteria. No significant difference in the TMA/aHUS scores was observed between survivors and non-survivors, suggesting that the score was not appropriate to predict the outcome (i.e., survival/death) in patients treated with eculizumab.

Conclusion

Almost all patients clinically diagnosed with aHUS scored ≥ 5 points and responded to eculizumab. The TMA/aHUS score system could become a supporting tool for the clinical diagnosis of aHUS and probability of response to treatment with a C5 inhibitor.

Trial registration

This study was conducted as per good PMS practice guidelines for drugs (MHLW Ministerial Ordinance No. 171 of 2004).
Addition of mental health to the lady health worker curriculum in Pakistan: now or never
Authors: Rabbani Fauziah , Akhtar Samina , Nafis Javeria , Khan Shahid , Siddiqi Sameen , Merali Zul
Published: April 2023

The technical advisory group of the World Health Organization (Geneva, Switzerland) has suggested person-centered and community-based mental health services in response to the long-term and far-reaching mental health impacts of the COVID-19 pandemic. Task shifting is a pragmatic approach to tackle the mental health treatment gap in low- and middle-income countries. Pakistan is dismally resourced to address the mental health challenges. Pakistan’s government has established a lady health worker’s program (LHW-P) which can be effectively utilized to provide some basic mental health services at community doorsteps. However, lady health workers’ current curriculum does not include mental health as a subject. WHO’s Mental Health Gap Intervention Guide (mhGAP-IG) Version 2.0 for mental, neurological, and substance use disorders in non-specialist health settings can be adapted and utilized to be included as part of the LHW-P curriculum in Pakistan. Thus, the historical lack of access to mental health support workers, counsellors, and specialists can be addressed. Additionally, this will also help to reduce the stigma associated with seeking mental health care outside the boundaries of home, mostly at a huge cost.
Why so low? An unusual case of myositis in a child
Authors: Chriswell Meagan E. , Fuhlbrigge Robert C. , Lovell Mark A. , Monson Matthew , Bloom Jessica L.
Published: April 2023

Background

Sarcoidosis is characterized by non-caseating epithelioid granulomas in various tissues throughout the body, most commonly the lung. Non-caseating granulomas may be seen in skeletal muscle, though typically asymptomatic and under-recognized. While rare in children, there is a need to better characterize the disease and its management. Here we present a 12-year-old female with bilateral calf pain who was ultimately found to have sarcoid myositis.

Case Presentation

A 12-year-old female presented to rheumatology with significantly elevated inflammatory markers and isolated lower leg pain. MRI of the distal lower extremities demonstrated extensive bilateral myositis with active inflammation, atrophy, and to a lesser extent fasciitis. This distribution of myositis in a child garnered a broad differential requiring a systematic evaluation. Ultimately, muscle biopsy revealed non-caseating granulomatous myositis with perivascular inflammation, extensive muscle fibrosis, and fatty replacement of the muscle with a CD4+ T cell predominant, lymphohistiocytic infiltrate consistent with sarcoidosis. Review of histopathology from age 6 of an extraconal mass resected from her right superior rectus muscle further confirmed the diagnosis. She had no other clinical symptoms or findings of sarcoidosis. The patient improved significantly with methotrexate and prednisone, though flared again after self-discontinuation of medications and was subsequently lost to follow-up.

Conclusion

This is the second reported case of granulomatous myositis associated with sarcoidosis in a pediatric patient, and the first to present with a chief complaint of leg pain. Increased knowledge of pediatric sarcoid myositis within the medical community will enhance recognition of the disease, improve the evaluation of lower leg myositis, and advance outcomes for this vulnerable population.
Appearance of a transparent protrusion containing two pairs of legs on the apodous ring preceding the anamorphic molt in a millipede, Niponia nodulosa
Authors: Chiyoda Soma , Oguchi Kohei , Miura Toru
Published: April 2023

Background

Arthropods gradually change their forms through repeated molting events during postembryonic development. Anamorphosis, i.e., segment addition during postembryonic development, is seen in some arthropod lineages. In all millipede species (Myriapoda, Diplopoda), for example, postembryonic processes go through anamorphosis. Jean-Henri Fabre proposed 168 years ago the “law of anamorphosis”, that is, “new rings appear between the penultimate ring and the telson” and “all apodous rings in a given stadium become podous rings in the next stadium”, but the developmental process at the anamorphic molt remains largely unknown. In this study, therefore, by observing the morphological and histological changes at the time of molting, the detailed processes of leg- and ring-addition during anamorphosis were characterized in a millipede, Niponia nodulosa (Polydesmida, Cryptodesmidae).

Results

In the preparatory period, a few days before molting, scanning electron microscopy, confocal laser scanning microscopy, and histological observations revealed that two pairs of wrinkled leg primordia were present under the cuticle of each apodous ring. In the rigidation period, just prior to molt, observations of external morphology showed that a transparent protrusion was observed on the median line of the ventral surface on each apodous ring. Confocal laser scanning microscopy and histological observations revealed that the transparent protrusion covered by an arthrodial membrane contained a leg bundle consisting of two pairs of legs. On the other hand, ring primordia were observed anterior to the telson just before molts.

Conclusions

Preceding the anamorphic molt in which two pairs of legs are added on an apodous ring, a transparent protrusion containing the leg pairs (a leg bundle) appears on each apodous ring. The morphogenetic process of the rapid protrusion of leg bundles, that is enabled by thin and elastic cuticle, suggested that millipedes have acquired a resting period and unique morphogenesis to efficiently add new legs and rings.
Results of treatment of congenital vertical talus by the Dobbs method
Authors: Grzegorzewski Andrzej , Lipiński Łukasz , Pruszczyński Błażej , Grzegorzewski Paweł , Buchcic Piotr
Published: April 2023

Congenital vertical talus is a rare foot deformity. The hindfoot is valgus and equinus, the midfoot is dorsiflexed and forefoot is abducted due to a fixed dorsal dislocation of the navicular on the head of the talus and the cuboid on the anterior part of the calcaneus. The epidemiology and etiology of vertical talus is unknown. Dobbs et al. (J Bone Joint Surg Am 88(6):1192–200, 2006) described a minimally invasive alternative which allowed to avoid the need for extensive soft tissue release procedures in treatment of congenital vertical talus. Eleven congenital vertical talus feet (group 5 according to Hamanishi) in eight children (four boys and four girls) constituted the study material. Upon the diagnosis, the patients’ age ranged from 5 to 26 months old (the mean – 14.6). The treatment involved serial manipulation and casting according to the reverse Ponseti method (from 4 to 7 casts) followed by a minimally invasive approach consisting in temporary stabilization of the talonavicular joint with the use of K-wire and Achilles tenotomy according to the Dobbs technique. Then patients continued the shoe and bar program for 2 years. The X-ray measurements on lateral radiographic included the talocalcaneal angle, tibiotalar angle and talar axis—first metatarsal base angle whereas AP radiographic images—the talocalcaneal angle and talar axis—first metatarsal angle. The Wilcoxon test was used to compare dependent variables. The final clinical assessment made during the last follow-up (the mean: 35.8 months, the range: 25–52) revealed that neutral position of the foot and normal range of motion were observed in ten cases and recurrence of foot deformity in one case. The last X-ray examination showed normalization all of radiological parameters, except for one case, and examined parameters were statistically significant. The minimally invasive technique described by Dobbs should be the first option in treatment of congenital vertical talus. It allows to reduce the talonavicular joint, brings good results and preserves foot mobility. The attention should be put on early diagnosis.
COMMD3 loss drives invasive breast cancer growth by modulating copper homeostasis
Authors: Hancock Janelle L. , Kalimutho Murugan , Straube Jasmin , Lim Malcolm , Gresshoff Irma , Saunus Jodi M. , Lee Jason S. , Lakhani Sunil R. , Simpson Kaylene J. , Bush Ashley I. , Anderson Robin L. , Khanna Kum Kum
Published: April 2023

Background

Despite overall improvement in breast cancer patient outcomes from earlier diagnosis and personalised treatment approaches, some patients continue to experience recurrence and incurable metastases. It is therefore imperative to understand the molecular changes that allow transition from a non-aggressive state to a more aggressive phenotype. This transition is governed by a number of factors.

Methods

As crosstalk with extracellular matrix (ECM) is critical for tumour cell growth and survival, we applied high throughput shRNA screening on a validated ‘3D on-top cellular assay’ to identify novel growth suppressive mechanisms.

Results

A number of novel candidate genes were identified. We focused on COMMD3, a previously poorly characterised gene that suppressed invasive growth of ER + breast cancer cells in the cellular assay. Analysis of published expression data suggested that COMMD3 is normally expressed in the mammary ducts and lobules, that expression is lost in some tumours and that loss is associated with lower survival probability. We performed immunohistochemical analysis of an independent tumour cohort to investigate relationships between COMMD3 protein expression, phenotypic markers and disease-specific survival. This revealed an association between COMMD3 loss and shorter survival in hormone-dependent breast cancers and in particularly luminal-A-like tumours (ER+/Ki67-low; 10-year survival probability 0.83 vs. 0.73 for COMMD3-positive and -negative cases, respectively). Expression of COMMD3 in luminal-A-like tumours was directly associated with markers of luminal differentiation: c-KIT, ELF5, androgen receptor and tubule formation (the extent of normal glandular architecture; p < 0.05). Consistent with this, depletion of COMMD3 induced invasive spheroid growth in ER + breast cancer cell lines in vitro, while Commd3 depletion in the relatively indolent 4T07 TNBC mouse cell line promoted tumour expansion in syngeneic Balb/c hosts. Notably, RNA sequencing revealed a role for COMMD3 in copper signalling, via regulation of the Na+/K+-ATPase subunit, ATP1B1. Treatment of COMMD3-depleted cells with the copper chelator, tetrathiomolybdate, significantly reduced invasive spheroid growth via induction of apoptosis.

Conclusion

Overall, we found that COMMD3 loss promoted aggressive behaviour in breast cancer cells.
Peritoneal cell-free DNA as a sensitive biomarker for detection of peritoneal metastasis in colorectal cancer: a prospective diagnostic study
Authors: Yuan Zixu , Chen Wenle , Liu Duo , Qin Qiyuan , Grady William M. , Fichera Alessandro , Wang Huaiming , Hou Ting , Lv Xinze , Li Chanhe , Wang Hui , Cai Jian
Published: April 2023

Background

The detection of peritoneal metastasis (PM) is limited by current imaging tools. In this prospective study, we aimed to evaluate the sensitivity and specificity of peritoneal cell-free DNA (cfDNA) for diagnosis of PM.

Methods

Colorectal cancer (CRC) patients with/without PM were enrolled. The cfDNA experimental personnel and statists were blinded to the diagnosis of PM. Ultradeep sequencing covering large genomic regions (35000X, Next-generation sequencing) of cfDNA in peritoneal lavage fluid (FLD) and matched tumor tissues was performed.

Results

A total of 64 cases were recruited prospectively and 51 were enrolled into final analysis. In training cohort, 100% (17/17) PM patients obtained positive FLD cfDNA, comparing to 5/23 (21.7%) in patients without PM. Peritoneal cfDNA had a high sensitivity of 100% and specificity of 77.3% for diagnosis of PM (AUC: 0.95). In validation group of 11, 5/6 (83%) patients with PM obtained positive FLD cfDNA, comparing to 0/5 in non-PM (P = 0.031) with a sensitivity of 83.3% and specificity of 100%. Positive FLD cfDNA was associated with poor recurrence-free survival (P = 0.013) and was preceding radiographic evidence of recurrence.

Conclusions

Peritoneal cfDNA is a promising sensitive biomarker for earlier detection of PM in CRC than current radiological tools. It can potentially guide selection for targeted therapies and serve as a surrogate instead of laparoscopic explore in the future.

Trial Registration Chinese Clinical Trial Registry at chictr.org.cn (ChiCTR2000035400). URL: http://www.chictr.org.cn/showproj.aspx?proj=57626