Identification of Factors Associated with Hematology-Oncology Fellow Academic Success and Career Choice.

Factors affecting hematology-oncology trainees' academic success and career choices have not been well characterized. We performed a retrospective study of 57 hematology-oncology fellows trained at Mayo Clinic between 2008 and 2017 in an attempt to identify factors associated with success during fellowship and with career choice (academic versus private). Sex, age, residency quality, and letters of recommendation indicating a "top" applicant were not associated with hematology or oncology in-training examination (ITE) scores, research productivity (abstracts/publications during fellowship), or career choice (academic versus private). Fellows with higher United States Medical Licensing Examination (USMLE) scores were more likely to perform well on ITE, but examination scores did not predict academic productivity or academic versus private career choice. More academically productive fellows were more likely to choose academic careers. Both ITE scores and productivity were associated with receipt of national and/or institutional awards. Finally, fellows who were non-US citizens and/or international medical graduates (IMG) had higher academic productivity both pre-fellowship and during fellowship and as per the observations above were more likely to choose academic careers. In conclusion, predictors of superior knowledge differ from predictors of academic productivity/career choice, and it is important to take multiple factors into account when selecting candidates most likely to succeed during fellowship.

Chromosomal instability in women with primary ovarian insufficiency.

STUDY QUESTION: What is the prevalence of somatic chromosomal instability among women with idiopathic primary ovarian insufficiency (POI)? SUMMARY ANSWER: A subset of women with idiopathic POI may have functional impairment in DNA repair leading to chromosomal instability in their soma. WHAT IS KNOWN ALREADY: The formation and repair of DNA double-strand breaks during meiotic recombination are fundamental processes of gametogenesis. Oocytes with compromised DNA integrity are susceptible to apoptosis which could trigger premature ovarian aging and accelerated wastage of the human follicle reserve. Genomewide association studies, as well as whole exome sequencing, have implicated multiple genes involved in DNA damage repair. However, the prevalence of defective DNA damage repair in the soma of women with POI is unknown. STUDY DESIGN, SIZE, DURATION: In total, 46 women with POI and 15 family members were evaluated for excessive mitomycin-C (MMC)-induced chromosome breakage. Healthy fertile females (n = 20) and two lymphoblastoid cell lines served as negative and as positive controls, respectively. PARTICIPANTS/MATERIALS, SETTING, METHODS: We performed a pilot functional study utilizing MMC to assess chromosomal instability in the peripheral blood of participants. A high-resolution array comparative genomic hybridization (aCGH) was performed on 16 POI patients to identify copy number variations (CNVs) for a set of 341 targeted genes implicated in DNA repair. MAIN RESULTS AND THE ROLE OF CHANCE: Array CGH revealed three POI patients (3/16, 18.8%) with pathogenic CNVs. Excessive chromosomal breakage suggestive of a constitutional deficiency in DNA repair was detected in one POI patient with the 16p12.3 duplication. In two patients with negative chromosome breakage analysis, aCGH detected a Xq28 deletion comprising the Centrin EF-hand Protein 2 (CETN2) and HAUS Augmin Like Complex Subunit 7 (HAUS7) genes essential for meiotic DNA repair, and a duplication in the 3p22.2 region comprising a part of the ATPase domain of the MutL Homolog 1 (MLH1) gene. LIMITATIONS REASONS FOR CAUTION: Peripheral lymphocytes, used as a surrogate tissue to quantify induced chromosome damage, may not be representative of all the affected tissues. Another limitation pertains to the MMC assay which detects homologous repair pathway defects and does not test deficiencies in other DNA repair pathways. WIDER IMPLICATIONS OF THE FINDINGS: Our results provide evidence for functional impairment of DNA repair in idiopathic POI, which may predispose the patients to other DNA repair-related conditions such as accelerated aging and/or cancer susceptibility. STUDY FUNDING/COMPETING INTEREST(S): Funding was provided by the National Institute of Child Health and Human Development. There were no competing interests to declare.

A Cross-Sectional Study on Attitudes to and Understanding of Risk of Acquisition of HIV: Design, Methods and Participant Characteristics.

BACKGROUND: The annual number of new human immunodeficiency virus (HIV) infections in the United Kingdom among men who have sex with men (MSM) has risen, and remains high among heterosexuals. Increasing HIV transmission among MSM is consistent with evidence of ongoing sexual risk behavior in this group, and targeted prevention strategies are needed for those at risk of acquiring HIV. OBJECTIVE: The Attitudes to and Understanding of Risk of Acquisition of HIV (AURAH) study was designed to collect information on HIV negative adults at risk of HIV infection in the United Kingdom, based on the following parameters: physical and mental health, lifestyle, patterns of sexual behaviour, and attitudes to sexual risk. METHODS: Cross-sectional questionnaire study of HIV negative or undiagnosed sexual health clinic attendees in the United Kingdom from 2013-2014. RESULTS: Of 2630 participants in the AURAH study, 2064 (78%) were in the key subgroups of interest; 580 were black Africans (325 females and 255 males) and 1484 were MSM, with 27 participants belonging to both categories. CONCLUSIONS: The results from AURAH will be a significant resource to understand the attitudes and sexual behaviour of those at risk of acquiring HIV within the United Kingdom. AURAH will inform future prevention efforts and targeted health promotion initiatives in the HIV negative population.

Opportunities to improve postpartum care for mothers and infants: design of context-specific packages of postpartum interventions in rural districts in four sub-Saharan African countries.

BACKGROUND: Postpartum maternal and infant mortality is high in sub-Saharan Africa and improving postpartum care as a strategy to enhance maternal and infant health has been neglected. We describe the design and selection of suitable, context-specific interventions that have the potential to improve postpartum care. METHODS: The study is implemented in rural districts in Burkina Faso, Kenya, Malawi and Mozambique. We used the four steps 'systems thinking' approach to design and select interventions: 1) we conducted a stakeholder analysis to identify and convene stakeholders; 2) we organised stakeholders causal analysis workshops in which the local postpartum situation and challenges and possible interventions were discussed; 3) based on comprehensive needs assessment findings, inputs from the stakeholders and existing knowledge regarding good postpartum care, a list of potential interventions was designed, and; 4) the stakeholders selected and agreed upon final context-specific intervention packages to be implemented to improve postpartum care. RESULTS: Needs assessment findings showed that in all study countries maternal, newborn and child health is a national priority but specific policies for postpartum care are weak and there is very little evidence of effective postpartum care implementation. In the study districts few women received postpartum care during the first week after childbirth (25 % in Burkina Faso, 33 % in Kenya, 41 % in Malawi, 40 % in Mozambique). Based on these findings the interventions selected by stakeholders mainly focused on increasing the availability and provision of postpartum services and improving the quality of postpartum care through strengthening postpartum services and care at facility and community level. This includes the introduction of postpartum home visits, strengthening postpartum outreach services, integration of postpartum services for the mother in child immunisation clinics, distribution of postpartum care guidelines among health workers and upgrading postpartum care knowledge and skills through training. CONCLUSION: There are extensive gaps in availability and provision of postpartum care for mothers and infants. Acknowledging these gaps and involving relevant stakeholders are important to design and select sustainable, context-specific packages of interventions to improve postpartum care.

A novel maternally inherited 8q24.3 and a rare paternally inherited 14q23.3 CNVs in a family with neurodevelopmental disorders.

A 7-year-old female with developmental delay (DD), autism spectrum disorder (ASD), intellectual disability (ID), attention deficit hyperactivity disorder (ADHD), and seizures was referred to our laboratory for oligomicroarray analysis. The analysis revealed a 540 kb microdeletion in the chromosome 8q24.3 region (143,610,058-144,150,241) encompassing multiple genes. Two siblings of the proband were also analyzed. The proband's older sister with DD, seizures, and ASD has a 438 kb intragenic microdeletion of the GPHN gene in the chromosome 14q23.3 region (67,105,512-67,543,291) containing multiple exons, while the proband's older brother with DD, ASD, ID, and ADHD has both the 8q24.3 and the 14q23.3 deletions. All three siblings have a normal karyotype at the 650 G-band level of resolution. Parental FISH analysis indicates that the mother is a carrier for the 8q24.3 deletion and the father is a carrier for the 14q23.3 deletion. The 8q24.3 deletion seen in our patients has not been reported in the literature, while the small deletions of the 14q23.3 region involving multiple exons of the GPHN gene have been reported in a handful of patients in a recent study. The size of the 8q24.3 deletion and its genomic content, as well as the maternal family history, strongly suggest the association between the deletion and the neurodevelopmental disorders. Our study also provides more evidence in support of the association between GPHN deletion and neurodevelopmental disorders.

A comparison of the expected and actual pain experienced by women during insertion of an intrauterine contraceptive device.

OBJECTIVE: To compare the expected and actual pain experienced with the insertion of intrauterine contraception in women, and to determine whether either of these are related to their personal circumstances, or affected their satisfaction with the procedure. DESIGN: A convenience sample of 89 women aged 15-50 years attending a sexual health clinic for same day intrauterine contraception insertion were given a questionnaire that they completed following the procedure. The women were asked to rate their expectation of pain prior to insertion and to rate the actual pain they experienced immediately after insertion, on a scale of 1-10, with 10 being severe pain. Information on the women's circumstances and their level of satisfaction with the procedure was also obtained. RESULTS: Overall, the median actual pain experienced by women during insertion (4) was significantly lower than the expected pain median (6) (P<0.001). For those women who had not had a previous vaginal delivery, actual pain was significantly higher compared with women who had had a previous vaginal delivery (median [interquartile range]: 6 [3.5-7.5] and 3 [1-5], P<0.001, respectively), but there was no significant difference between expected and actual pain experiences. In women who had a previous vaginal delivery, actual pain was much lower than expected (P<0.001). Neither actual nor expected pain experiences were linked to any other sociodemographic reproductive health or service use factors. CONCLUSION: All women had a high expectation of pain prior to IUD insertion, but for those who had had a previous vaginal delivery, this was significantly greater than that actually experienced. Satisfaction levels overall were high. Counseling of women should take into account their expected pain prior to IUD insertion and consideration should be given to alternative and additional methods of pain relief in women who have not had a previous vaginal delivery.

High performance teamwork training and systems redesign in outpatient oncology.

BACKGROUND: Oncology care is delivered largely in ambulatory settings by interdisciplinary teams. Treatments are often complex, extended in time, dispersed geographically and vulnerable to teamwork failures. To address this risk, we developed and piloted a team training initiative in the breast cancer programme at a comprehensive cancer centre. METHODS: Based on clinic observations, interviews with key staff and analyses of incident reports, we developed interventions to address four high-risk areas: (1) miscommunication of chemotherapy order changes on the day of treatment; (2) missing orders on treatment days without concurrent physician appointments; (3) poor follow-up with team members about active patient issues; and (4) conflict between providers and staff. The project team developed protocols and agreements to address team members' roles, responsibilities and behaviours. RESULTS: Using a train-the-trainer model, 92% of breast cancer staff completed training. The incidence of missing orders for unlinked visits decreased from 30% to 2% (p<0.001). Patient satisfaction scores regarding coordination of care improved from 93 to 97 (p=0.026). Providers, infusion nurses and support staff reported improvement in efficiency (75%, 86%, 90%), quality (82%, 93%, 93%) and safety (92%, 92%, 90%) of care, and more respectful behaviour (92%, 79%, 83%) and improved relationships among team members (91%, 85%, 92%). Although most clinicians reported a decrease in non-communicated changes, there was insufficient statistical power to detect a difference. CONCLUSIONS: Team training improved communication, task coordination and perceptions of efficiency, quality, safety and interactions among team members as well as patient perception of care coordination.

What influences young women to choose between the emergency contraceptive pill and an intrauterine device? A qualitative study.

OBJECTIVE: To explore key factors influencing young women when choosing between two methods of emergency contraception (EC). METHODS: We interviewed 26 young women who accessed community sexual and reproductive health services for emergency contraception after they had chosen an EC. RESULTS: Most women had an unrealistically high expectation about efficacy of the emergency contraceptive pill (ECP) and lacked knowledge of the intrauterine device (IUD) as an alternative method of EC. Previous use, easy accessibility, ease of use, and advice from peers, influenced women to choose the ECP, whereas past experience of abortion, firm motivation to avoid pregnancy, presentation after 72 hours, and considering that an IUD may provide long-term contraception as well, inclined women to choose the IUD. When participants were shown the IUD, many found it to be smaller and less frightening than they had imagined. CONCLUSIONS: Women need better information and education about the IUD as a highly effective method of EC. Health professionals must provide such information at every opportunity. Showing the IUD during counselling might help correct misconceptions and would improve acceptability. Wider availability of expertise concerning EC-IUDs is essential to assist more women in making informed decisions when choosing a method for EC.

Mortality rate comparison after switching from continuous to prolonged intermittent renal replacement for acute kidney injury in three intensive care units from different countries.

BACKGROUND: Prolonged intermittent renal replacement therapy (PIRRT) is a dialysis modality for critically ill patients that in theory combines the superior detoxification and haemodynamic stability of the continuous renal replacement therapy (CRRT) with the operational convenience, reduced haemorrhagic risk and low cost of conventional intermittent haemodialysis. However, the extent to which PIRRT should replace these other modalities is uncertain because comparative studies of mortality are lacking. We retrospectively examined the mortality data from three general intensive care units (ICUs) in different countries that have switched their predominant therapeutic approach from CRRT to PIRRT. We assessed whether this practice change was associated with a change in mortality rate. METHODS: Data were analysed from ICUs in New Zealand, Australia and Italy. The study population comprised all patients requiring renal replacement therapy from 1 January 1995 to 31 December 2005 (n = 1347), the period of time spanning the change from CRRT to PIRRT in each unit. Poisson regression models were used to estimate the incident rate ratio (IRR) for death, comparing the periods before and after change to PIRRT in each unit. Estimates were adjusted for patient illness severity (APACHE II score) and for the underlying time trend in mortality rate over time. RESULTS: The change from CRRT to PIRRT was not associated with any increase in mortality rate, with an adjusted IRR of 1.02 (0.61-1.71). The IRR was virtually identical in the three ICUs (P-value = 0.63 for the difference in the IRR between ICUs). CONCLUSIONS: Switching from CRRT to PIRRT was not associated with a change in mortality rate. Pending the results of a randomized trial, our study provides evidence that PIRRT might be equivalent to CRRT in the general ICU patient.

Role of clinician involvement in patient safety in obstetrics and gynecology.

Patient safety is a significant concern for healthcare providers. Involving physicians in clinical quality activities in obstetrics and gynecology can be difficult for many reasons including time demands, lack of knowledge of process improvement activities, or change fatigue due to failure of adequate implementation of previous activities. This overview for improving the culture of safety identifies roles physicians can play from participating in quality assessment and improvement activities, improving teamwork between disciplines, communicating effectively, creating departmental guidelines, and deciding on outcome measures for benchmarking. An improved culture of safety is better for our patients and may reduce malpractice exposure.

Illness severity scoring for Intensive Care at Middlemore Hospital, New Zealand: past and future.

AIM: The Acute Physiological and Chronic Health Evaluation (APACHE) II score is a popular illness severity scoring system for intensive care units. Scoring systems such as the APACHE II allow researchers and clinicians to quantify patient illness severity with a greater degree of accuracy and precision, which is critical when evaluating practice patterns and outcomes, both within or between intensive care units. The study aims to: assess changes in APACHE II scores and hospital-standardised mortality ratio at our ICU over a nine year period from 1 January 1997 to 31 December 2005; assess for changes in the performance of the APACHE II scoring system in predicting patient hospital mortality over the same period; and assess for any clinical subgroups in which APACHE II scoring was particularly inaccurate or imprecise. METHODS: Retrospective audit of a single centre relational database, with evaluation of the APACHE II scoring system by year through discrimination (ability to discriminate between the patients who will die or survive at hospital discharge) using receiver operating characteristic (ROC) curves, and calibration (ability to predict mortality rate over classes of risk) using goodness-of-fit as assessed by the Hosmer-Lemeshow statistic. RESULTS: Data from 7703 patients were available for analysis. There was a decrease in overall hospital mortality, from approximately 19% at the beginning of the period of observation to approximately 12% at the end. There was also a decrease in the hospital standardised mortality ratio from 0.94 (95%CI 0.82-1.06) to 0.66 (95%CI 0.55-0.76). In general, both the APACHE II score and risk of death model performed adequately in each year with ROC curve AUCs of >0.8, albeit with progressively poorer performance over time and 'model fade' that approached statistical significance. There was progressively poorer calibration with the APACHE II risk of death model as indicated by the Hosmer-Lemeshow statistic, with a statistically significant difference between the predicted and observed mortality from 2003 onwards. Overall, there was moderately poor model performance in the diagnostic groups with the largest number of patients (sepsis and post-surgical complications). CONCLUSION: This study shows the progressively worse performance of the APACHE II illness severity scoring system over time due to 'model fade'. This is especially so in common diagnostic categories, making this a clinically relevant finding. Future approaches to illness severity scoring should be tested and compared, such as re-estimating coefficients of the APACHE II diagnostic categories or using locally developed ones, moving to later evolutions of the system such as the APACHE III or APACHE IV, or developing novel artificial intelligence approaches.

Team approach to care in labor and delivery.

Changing to a teamwork culture in labor and delivery requires a real commitment. The skills involved can be taught to all healthcare providers. The benefits of a teamwork culture may include improved patient outcomes, less medical errors, and improved patient and staff satisfaction. Malpractice claim reduction may possibly occur through these improved outcomes and better communication with our patients.

Generation of baculovirus vectors for the high-throughput production of proteins in insect cells.

The baculovirus expression system is one of the most popular methods used for the production of recombinant proteins but has several complex steps which have proved inherently difficult to adapt to a multi-parallel process. We have developed a bacmid vector that does not require any form of selection pressure to separate recombinant virus from non-recombinant parental virus. The method relies on homologous recombination in insect cells between a transfer vector containing a gene to be expressed and a replication-deficient bacmid. The target gene replaces a bacterial replicon at the polyhedrin loci, simultaneously restoring a virus gene essential for replication. Therefore, only recombinant virus can replicate facilitating the rapid production of multiple recombinant viruses on automated platforms in a one-step procedure. Using this vector allowed us to automate the generation of multiple recombinant viruses with a robotic liquid handler and then rapidly screen infected insect cell supernatant for the presence of secreted proteins.