Schizophrenia risk proteins ZNF804A and NT5C2 interact in cortical neurons.

The zinc finger protein 804A (ZNF804A) and the 5'-nucleotidase cytosolic II (NT5C2) genes are amongst the first schizophrenia susceptibility genes to have been identified in large-scale genome-wide association studies. ZNF804A has been implicated in the regulation of neuronal morphology and is required for activity-dependent changes to dendritic spines. Conversely, NT5C2 has been shown to regulate 5' adenosine monophosphate-activated protein kinase activity and has been implicated in protein synthesis in human neural progenitor cells. Schizophrenia risk genotype is associated with reduced levels of both NT5C2 and ZNF804A in the developing brain, and a yeast two-hybrid screening suggests that their encoded proteins physically interact. However, it remains unknown whether this interaction also occurs in cortical neurons and whether they could jointly regulate neuronal function. Here, we show that ZNF804A and NT5C2 colocalise and interact in HEK293T cells and that their rodent homologues, ZFP804A and NT5C2, colocalise and form a protein complex in cortical neurons. Knockdown of the Zfp804a or Nt5c2 genes resulted in a redistribution of both proteins, suggesting that both proteins influence the subcellular targeting of each other. The identified interaction between ZNF804A/ZFP804A and NT5C2 suggests a shared biological pathway pertinent to schizophrenia susceptibility within a neuronal cell type thought to be central to the neurobiology of the disorder, providing a better understanding of its genetic landscape.

Balloon catheters versus vaginal prostaglandins for labour induction (CPI Collaborative): an individual participant data meta-analysis of randomised controlled trials.

BACKGROUND: Induction of labour is one of the most common obstetric interventions globally. Balloon catheters and vaginal prostaglandins are widely used to ripen the cervix in labour induction. We aimed to compare the effectiveness and safety profiles of these two induction methods. METHODS: We did an individual participant data meta-analysis comparing balloon catheters and vaginal prostaglandins for cervical ripening before labour induction. We systematically identified published and unpublished randomised controlled trials that completed data collection between March 19, 2019, and May 1, 2021, by searching the Cochrane Library, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and PubMed. Further trials done before March 19, 2019, were identified through a recent Cochrane review. Data relating to the combined use of the two methods were not included, only data from women with a viable, singleton pregnancy were analysed, and no exclusion was made based on parity or membrane status. We contacted authors of individuals trials and participant-level data were harmonised and recoded according to predefined definitions of variables. Risk of bias was assessed with the ROB2 tool. The primary outcomes were caesarean delivery, indication for caesarean delivery, a composite adverse perinatal outcome, and a composite adverse maternal outcome. We followed the intention-to-treat principle for the main analysis. The primary meta-analysis used two-stage random-effects models and the sensitivity analysis used one-stage mixed models. All models were adjusted for maternal age and parity. This meta-analysis is registered with PROSPERO (CRD42020179924). FINDINGS: Individual participant data were available from 12 studies with a total of 5460 participants. Balloon catheters, compared with vaginal prostaglandins, did not lead to a significantly different rate of caesarean delivery (12 trials, 5414 women; crude incidence 27·0%; adjusted OR [aOR] 1·09, 95% CI 0·95-1·24; I2=0%), caesarean delivery for failure to progress (11 trials, 4601 women; aOR 1·20, 95% CI 0·91-1·58; I2=39%), or caesarean delivery for fetal distress (10 trials, 4441 women; aOR 0·86, 95% CI 0·71-1·04; I2=0%). The composite adverse perinatal outcome was lower in women who were allocated to balloon catheters than in those allocated to vaginal prostaglandins (ten trials, 4452 neonates, crude incidence 13·6%; aOR 0·80, 95% CI 0·70-0·92; I2=0%). There was no significant difference in the composite adverse maternal outcome (ten trials, 4326 women, crude incidence 22·7%; aOR 1·02, 95% CI 0·89-1·18; I2=0%). INTERPRETATION: In induction of labour, balloon catheters and vaginal prostaglandins have comparable caesarean delivery rates and maternal safety profiles, but balloon catheters lead to fewer adverse perinatal events. FUNDING: Australian National Health and Medical Research Council and Monash Health Emerging Researcher Fellowship.

The impact of body mass index on labour management and mode of delivery: A retrospective matched cohort study.

AIM: This study aims to examine the association between body mass index (BMI) and mode of delivery, progression of labour, and intrapartum interventions. METHODS: This was a retrospective matched cohort study including Class III obese (BMI ≥40 kg/m2 ) and normal BMI (BMI <25 kg/m2 ) women planning a vaginal birth who had a live, singleton delivery from January 2015 to December 2018. Patients were matched (1:1) based on age, gestational age, parity, onset of labour and birth weight. The primary outcome was caesarean delivery (CD). Secondary outcomes were delivery outcomes, intrapartum management and interventions. Rates of each outcome were compared with matched analysis, and duration of labour with time-to-event analysis. RESULTS: We studied two groups of 300 pregnant women. The CD rate was significantly higher for obese women than the normal BMI cohort (19.3% vs 13.3%; risk ratio (RR) 1.43, 95% CI 1.02-1.98, P = 0.035). Cervical dilation prior to CD for failure to progress was slower in obese than normal BMI (0.04 vs 0.16 cm/h). The obese cohort had a longer duration of labour in those who underwent induction (13.70 vs 11.48 h, P = 0.024). Intrapartum intervention rates were higher for obese women, with significant differences in rates of fetal scalp electrodes (72.7% vs 22.7%, RR 3.20, 95% CI 2.58-3.99, P < 0.001), intrauterine pressure catheters (18.3% vs 0%, P < 0.001), epidural analgesia (44.0% vs 37.0%, RR 1.20, 95% CI 1.01-1.44, P = 0.040) and fetal scalp lactate sampling (8.0% vs 3.0%, RR = 2.67, 95% CI 1.33-5.33, P = 0.004). CONCLUSION: Class III obesity is associated with an increased risk of CD and intrapartum interventions.

Preferences for Breast and Cervical Cancer Screening Among Women and Men in Kenya: Key Considerations for Designing Implementation Strategies to Increase Screening Uptake.

Breast and cervical cancer incidence rates and mortality rates in Kenya are high. Screening is globally accepted as a strategy for early detection and downstaging of these cancers for better outcomes, but despite the efforts established by the Kenyan government to provide these services to eligible populations, uptake has remained disproportionately low. Using data from a larger study aimed at understanding the implementation and scale-up of cervical cancer screening services, we analyzed data to compare the preferences for breast and cervical cancer screening services between men and women (25-49 years) in rural and urban communities in Kenya. Participants were recruited in concentric circles starting at the center of six subcounties. One woman and one man per household were enrolled for data collection on a continuous basis. More than 90% of both men and women had a monthly income of less than US $500. The top three preferred sources of information on screening for cancers affecting women were health care providers; community health volunteers; and media such as television, radio, newspapers, and magazines. More women (43.6%) than men (28.0%) trusted community health volunteers to provide health information on cancer screening. Printed materials and mobile phone messages were preferred by approximately 30% of both genders. Over 75% of both men and women preferred an integrated model of service delivery. These findings show that there are many similarities that can be leveraged when designing implementation strategies for population-wide breast and cervical cancer screening hence reducing the challenge of addressing diverse preferences of men and women which may not be easy to reconcile.

Acceptability, Utility, and Cost of a Mobile Health Cancer Screening Education Application for Training Primary Care Physicians in India.

PURPOSE: Mobile health (mHealth)-based oncology education can be a powerful tool for providing cancer screening knowledge to physicians, as mobile technology is widely available and inexpensive. We developed a mobile application (M-OncoED) to educate physicians on cancer screening and tested the acceptability, utility, and cost of two different approaches to recruit physicians. METHODS: M-OncoED was designed to perform pre- and postlearning assessments through the in-built quizzes; present case studies and educational materials for cervical, breast, and oral cancer screening; collect responses to interactive queries; document module completion; send reminders and alerts; and track user metrics, including number of sessions to complete each module and time spent per session. We tested two recruitment approaches: a broad-scale recruitment group, for which we relied on e-mails, messaging apps (e.g., WhatsApp), and phone calls, and the targeted recruitment group, for which we conducted a face-to-face meeting for the initial invitation. RESULTS: Overall, about 35% of those invited in the targeted group completed the course compared with about 3% in the broad-based recruitment group. The targeted recruitment approach was more cost-efficient ($55.33 vs. $109.43 per person). Cervical cancer screening knowledge increased by about 30 percentage points, and breast cancer screening knowledge increased by 10 percentage points. There was no change in knowledge for oral cancer scorings. CONCLUSION: This study has demonstrated the feasibility and utility of using an mHealth app to educate physicians. A more intensive hands-on recruitment approach is likely required to engage physicians to download and complete the app. Future studies should assess the impact of mHealth tools on physician behavior and patient outcomes. IMPLICATIONS FOR PRACTICE: Mobile health (mHealth)-based oncology education can be a powerful tool for providing cancer screening knowledge to physicians, as mobile technology is widely available and inexpensive. This study has demonstrated the feasibility and utility of using an mHealth app to educate physicians and illustrates the type of recruitment approach (face-to-face) that is likely required to incentivize physicians to download the app and complete the training.

Treatment cost and access to care: experiences of young women diagnosed with breast cancer.

PURPOSE: Breast cancer is the leading cause of cancer-related deaths in women younger than 40 years. We aim to evaluate cost as a barrier to care among female breast cancer patients diagnosed between 18 to 39 years. METHODS: In early 2017, we distributed a survey to women diagnosed with breast cancer between the ages of 18 and 39 years, as identified by the central cancer registries of California, Georgia, North Carolina, and Florida. We used multivariable statistics to explore cost-related barriers to receiving breast cancer care for the 830 women that completed the survey. RESULTS: About half of the women (47.4%) reported spending more on breast cancer care than expected, and almost two-thirds (65.3%) had not discussed costs with their care team. A third of the patients (31.8%) indicated forgoing care due to cost. Factors associated with not receiving anticipated care due to cost included age less than35 years at diagnosis, self-insurance, comorbid conditions, and late-stage diagnosis. CONCLUSION: Previous studies using breast cancer registry data have not included detailed insurance information and care received by young women. Young women with breast cancer frequently forgo breast cancer care due to cost. Our results highlight the potential for policies that facilitate optimal care for young breast cancer patients which could include the provision of comprehensive insurance coverage.

Cancer screening behaviors and preferences among women in southern India.

INTRODUCTION: In 2020, India's cancer cases were estimated at 1.32 million (International Agency for Research on Cancer et al., 2020) and were predicted to double by 2040 (Smith and Mallath, 2019). METHODS: Starting in March 2019, we recruited 211 adult women in the Trivandrum area of India who had an outpatient office visit within the past 6 months to participate in a structured survey. We identified the study population from the Gokulam Medical College and four peripheral centers. Two trained interviewers collected survey information from the participants, including information on breast, oral, and cervical cancer screening eligibility, history, recommendations, and screening initiation. For analysis, we stratified the sample into two groups by age: a priority screening group, aged 30-65 (n = 132), and an overall group, containing the entire sample, aged 19-85 (n = 211). RESULTS: 14.22% of respondents in the overall group and 14.39% in the priority screening group reported receiving a prior cancer screening. Among women who had not received cancer screening, the most common reasons were "no provider recommendation" (42.18%) and not knowing they needed to be screened (40.76%). Most women estimated their risk of developing cancer to be "very low" (64.93%), although the vast majority also believed early detection could improve cancer outcomes (84.83%). Among those who had not been screened for cancer, 61.61% overall and 65.15% in the priority screening group responded that they would undergo all eligible cancer screenings if recommended by their provider. The figure jumps to 79.62% in the overall group and 77.27% in the priority screening group if additional respondent-identified barriers to screening were addressed. CONCLUSION: Provider recommendations can be used to mitigate the suboptimal screening uptake and late-stage diagnosis that exacerbate the mortality and economic burden due to cancer in India. POLICY SUMMARY: This study finds that provider recommendations can shape the trajectory of outcomes by increasing cancer screening among women.

Factors Affecting the Adoption of Electronic Data Reporting and Outcomes Among Selected Central Cancer Registries of the National Program of Cancer Registries.

PURPOSE: The CDC's National Program of Cancer Registries has expanded the use of electronic reporting to collect more timely information on newly diagnosed cancers. The adoption, implementation, and use of electronic reporting vary significantly among central cancer registries. We identify factors affecting the adoption of electronic reporting among these registries. METHODS: Directors and data managers of nine National Program of Cancer Registries took part in separate 1-hour telephone interviews in early 2019. Directors were asked about their registry's key data quality goals; staffing, resources, and tools used to aid processes; their definition and self-perception of electronic reporting adoption; key helpers and challenges; and cost and sustainability implications for adoption of electronic reporting. Data managers were asked about specific data collection processes, software applications, electronic reporting adoption and self-perception, information technology infrastructure, and helpers and challenges to data collection and processing, data quality, and sustainability of approach. RESULTS: Larger registries identified organizational capacity and technical expertise as key aides. Other help for implementing electronic reporting processes came from partnerships, funding availability, management support, legislation, and access to an interstate data exchange. Common challenges among lower adopters included lack of capacity at both registry and data source levels, insufficient staffing, and a lack of information technology or technical support. Other challenges consisted of automation and interoperability of software, volume of cases received, state political environment, and quality of data received. CONCLUSION: Feedback from the formative evaluation yielded several useful solutions that can guide implementation of electronic reporting and help refine the technical assistance provided to registries. Our findings may help guide future process and economic evaluations of electronic reporting and identify best practices to strengthen registry operations.

Utility of linking survey and registry data to evaluate interventions and policies to address disparities in breast cancer survivorship among young women.

PURPOSE: There is limited research linking data sources to evaluate the multifactorial impacts on the quality of treatment received and financial burden among young women with breast cancer. To address this gap and support future evaluation efforts, we examined the utility of combining patient survey and cancer registry data. PATIENT AND METHODS: We administered a survey to women, aged 18-39 years, with breast cancer from four U.S. states. We conducted a systematic response-rate analysis and evaluated differences between racial groups. Survey responses were linked with cancer registry data to assess whether surveys could reliably supplement registry data. RESULTS: A total of 830 women completed the survey for a response rate of 28.4 %. Blacks and Asian/Pacific Islanders were half as likely to respond as white women. Concordance between survey and registry data was high for demographic variables (Cohen's kappa [k]: 0.879 to 0.949), moderate to high for treatments received (k: 0.467 to 0.854), and low for hormone receptor status (k: 0.167 to 0.553). Survey items related to insurance status, employment, and symptoms revealed racial differences. CONCLUSION: Cancer registry data, supplemented by patient surveys, can provide a broader understanding of the quality of care and financial impacts of breast cancer among young women.

Insurance Coverage, Employment Status, and Financial Well-Being of Young Women Diagnosed with Breast Cancer.

BACKGROUND: The economic cost of breast cancer is a major personal and public health problem in the United States. This study aims to evaluate the insurance, employment, and financial experiences of young female breast cancer survivors and to assess factors associated with financial decline. METHODS: We recruited 830 women under 40 years of age diagnosed with breast cancer between January 2013 and December 2014. The study population was identified through California, Florida, Georgia, and North Carolina population-based cancer registries. The cross-sectional survey was fielded in 2017 and included questions on demographics, insurance, employment, out-of-pocket costs, and financial well-being. We present descriptive statistics and multivariate analysis to assess factors associated with financial decline. RESULTS: Although 92.5% of the respondents were continuously insured over the past 12 months, 9.5% paid a "higher price than expected" for coverage. Common concerns among the 73.4% of respondents who were employed at diagnosis included increased paid (55.1%) or unpaid (47.3%) time off, suffering job performance (23.2%), and staying at (30.2%) or avoiding changing (23.5%) jobs for health insurance purposes. Overall, 47.0% experienced financial decline due to treatment-related costs. Patients with some college education, multiple comorbidities, late stage diagnoses, and self-funded insurance were most vulnerable. CONCLUSIONS: The breast cancer diagnosis created financial hardship for half the respondents and led to myriad challenges in maintaining employment. Employment decisions were heavily influenced by the need to maintain health insurance coverage. IMPACT: This study finds that a breast cancer diagnosis in young women can result in employment disruption and financial decline.

Establishing Cohorts to Generate the Evidence Base to Reduce the Burden of Breast Cancer in Sub-Saharan Africa: Results From a Feasibility Study in Kenya.

PURPOSE: By 2025, Kenya is estimated to experience a two-thirds increase in the incidence of breast cancer. Local research is necessary to generate evidence to inform policy, public health, and medical practice. There have been no longitudinal cohort studies in sub-Saharan Africa of women with and without breast cancer. Our aim is to assess the feasibility of conducting cohort studies in Kenya that consider clinical characteristics, socioeconomic factors, and self-care behaviors. METHODS: We initiated a short-term follow-up cohort study of women with and without a diagnosis of breast cancer with baseline face-to-face data collection and one follow-up interview (at approximately 3 months by telephone). We developed tailored instruments to capture demographics, socioeconomic factors, breast cancer risk, ability to identify breast cancer symptoms, treatments received for breast cancer, and quality of life of survivors. RESULTS: We recruited 800 women between the ages of 20 and 60 years and successfully collected baseline data. Completeness of the data was high for demographic variables, but there was a larger proportion of missing information for specific variables required for assessing breast cancer risk. Respondents were able to complete standardized instruments to assess breast cancer knowledge among those without breast cancer and identification of symptoms among survivors. We were able to successfully contact approximately 80% of the participants for follow-up. CONCLUSION: This short-term follow-up study provides evidence that women can be successfully tracked and contacted for follow-up in the Kenyan setting and offers lessons to establish future longitudinal cohorts to identify approaches to improve breast cancer outcomes.

Modified supine versus prone percutaneous nephrolithotomy: Surgical outcomes from a tertiary teaching hospital.

PURPOSE: The traditional prone positioning of percutaneous nephrolithotomy (PCNL) is associated with various anesthetic and logistic difficulties. We aimed to compare the surgical outcomes of PCNLs performed using our modified supine position with those performed in the standard prone position. MATERIALS AND METHODS: A prospective group of 236 renal units (224 patients) undergoing PCNL were included in this 2 site study: 160 were performed in the modified supine position were compared with 76 undergoing PCNL in the prone position. The outcomes of radiation dose, radiation time, stone free rate, body mass index (BMI), stone size, operative time, length of stay (LOS), in hospital and complications were compared. Chi-square and t-tests were used. RESULTS: There were no significant differences in mean radiation time, radiation dose or stone size between the modified supine and prone groups. The supine group had a higher mean BMI (31 kg/m(2) vs. 28 kg/m(2), p=0.03), shorter mean surgical time (93 minutes vs. 123 minutes, p<0.001), shorter mean LOS (2 days vs. 3 days, p=0.005) and higher stone free rate (70% vs. 50%, p=0.005). There were no differences in septic or bleeding complications but the prone group had a higher rate of overall complications. CONCLUSIONS: Modified supine PCNL has significantly lower operative time, shorter LOS and higher stone-free rate compared with prone in our series, while remaining a safe procedure.