Diagnostic outcomes after colposcopy at a tertiary clinic for women aged 50-74 referred after detection of oncogenic human papillomavirus at primary screening.

AIMS: To examine outcomes in women aged 50-74 years after detection of oncogenic human papillomavirus (HPV) at cervical screening. MATERIALS AND METHODS: A retrospective observational study of 464 women seen in the Royal Women's Hospital Colposcopy Clinic from 1 January 2018 to 31 July 2020, 292 (62.9%) were positive for HPV16/18 and 172 (37.1%) for HPV (not 16/18). RESULTS: Fifty-four women (11.6%) had histologically proven CIN2+ including seven cancers, up to two years after first colposcopy visit (FCV): 48 (88.9%) detected at FCV or at excisional treatment (Excision) arranged after no CIN2+ detected at FCV. There was no significant difference (P = 0.14) in proportion of CIN2+ detected between the two groups, 'HPV16/18' (9.9%) or 'HPV (not 16/18)' (14.5%), nor with reflex cytology types. The positive predictive value (PPV) of high-grade impression at colposcopy was 63.6%. There were 243 (52.4%) who had Type 3 transformation zone (TZ3) with 20 CIN2+ detected, 13 at FCV including all three cancers and five at Excision. There were 214 (73.3%) with positive HPV16/18 who had reflex negative cytology, of which seven had CIN2+ including one cancer but only two (1.4%) CIN2+ when their repeat cytology at colposcopy was negative. CONCLUSIONS: Most CIN2+ were detected at first colposcopy or at subsequent excision. We would encourage high biopsy rates at colposcopy and vigilance in selection for excisional treatment in TZ3 cases if there is no significant suspicion of high-grade abnormality. There is a need to refine the algorithm for management of persistent HPV16/18 infections with reflex negative cytology to reduce colposcopy referrals in women aged 50 and above.

Patients Surviving Critical COVID-19 have Impairments in Dual-task Performance Related to Post-intensive Care Syndrome.

OBJECTIVE: The purpose was to examine Dual Task (DT) performance in patients surviving severe and critical COVID-19 compared to patients with chronic lung disease (CLD). Secondarily, we aimed to determine the psychometric properties of the Timed Up and Go (TUG) test in patients surviving COVID-19. DESIGN: Prospective, cross-sectional, observational study. SETTING: Academic medical center within United States. PATIENTS: Ninety-two patients including 36 survivors of critical COVID-19 that required mechanical ventilation (critical-COVID), 20 patients recovering from COVID-19 that required supplemental oxygen with hospitalization (severe-COVID), and 36 patients with CLD serving as a control group. MEASUREMENTS AND MAIN RESULTS: Patients completed the TUG, DT-TUG, Short Physical Performance Battery (SPPB), and Six Minute Walk Test (6MWT) 1-month after hospital discharge. A subset of patients returned at 3-months and repeated testing to determine the minimal detectable change (MDC). Critical-COVID group (16.8 ± 7.3) performed the DT-TUG in significantly slower than CLD group (13.9 ± 4.8 s; P = .024) and Severe-COVID group (13.1 ± 5.1 s; P = .025). Within-subject difference between TUG and DT-TUG was also significantly worse in critical-COVID group (-21%) compared to CLD (-10%; P = .012), even despite CLD patients having a higher comorbid burden (P < .003) and older age (P < .001). TUG and DT-TUG demonstrated strong to excellent construct validity to the chair rise test, gait speed, and 6MWT for both COVID-19 groups (r = -0.84to 0.73, P < .05). One- and 3-months after hospital discharge there was a floor effect of 14% (n = 5/36) and 5.2% (n = 1/19), respectively for patients in the critical-COVID group. Ceiling effects were noted in four (11%) critical-COVID, six (30%) severe-COVID patients for the TUG and DT-TUG at 1-month. CONCLUSION: The ability to maintain mobility performance in the presence of a cognitive DT is grossly impaired in patients surviving critical COVID-19. DT performance may subserve the understanding of impairments related to Post-intensive care syndrome (PICS) for survivors of critical illness.

Safety and Feasibility of an Interdisciplinary Treatment Approach to Optimize Recovery From Critical Coronavirus Disease 2019.

OBJECTIVES: Examine the safety and feasibility of a multimodal in-person or telehealth treatment program, administered in acute recovery phase for patients surviving critical coronavirus disease 2019. DESIGN: Pragmatic, pre-post, nonrandomized controlled trial with patients electing enrollment into one of the two recovery pathways. SETTING: ICU Recovery Clinic in an academic medical center. PATIENTS: Adult patients surviving acute respiratory failure due to critical coronavirus disease 2019. INTERVENTIONS: Patients participated in combined ICU Recovery clinic and 8 weeks of physical rehabilitation delivered: 1) in-person or 2) telehealth. Patients received medical care by an ICU Recovery Clinic interdisciplinary team and physical rehabilitation focused on aerobic, resistance, and respiratory muscle training. MEASUREMENTS AND MAIN RESULTS: Thirty-two patients enrolled with mean age 57 ± 12, 62% were male, and the median Sequential Organ Failure Assessment score was 9.5. There were no differences between the two groups except patients in telehealth pathway (n = 10) lived further from clinic than face-to-face patients (162 ± 60 vs 31 ± 47 kilometers, t = 6.06, p < 0.001). Four safety events occurred: one minor adverse event in the telehealth group, two minor adverse events, and one major adverse event in the in-person group. Three patients did not complete the study (two in-person and one telehealth). Six-minute walk distance increased to 101 ± 91 meters from pre to post (n = 29, t = 6.93, p < 0.0001), which was similar between the two groups (110 vs 80 meters, t = 1.34, p = 0.19). Self-reported levels of anxiety, depression, and distress were high in both groups with similar self-report quality of life. CONCLUSIONS: A multimodal treatment program combining care from an interdisciplinary team in an ICU Recovery Clinic with physical rehabilitation is safe and feasible in patients surviving the ICU for coronavirus disease 2019 acute respiratory failure.

Primary HPV cervical screening: Clinical audit of outcomes of women seen at a tertiary referral centre for colposcopy in Australia.

BACKGROUND: Primary human papillomavirus (HPV) screening was introduced in Australia in December 2017. AIMS: Outcomes for women after positive HPV in their cervical screening test (CST). MATERIALS AND METHODS: A retrospective observational study of 4458 women seen at the Royal Women's Hospital Colposcopy Clinic from 1 January 2018 to 31 July 2020. RESULTS: HPV16/18 was positive (considered higher-risk CST) in 42.2% of women in the study, 16.6% with reflex possible with high-grade squamous intraepithelial lesions (pHSIL) or worse and 54.9% with normal cytology. There were 24.8% of women with positive HPV16/18 who had histological confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+), 10.3% CIN2+ (including six cancers) among women with reflex negative cytology and 87.7% CIN2+ among women with reflex HSIL cytology. In women with positive HPV (not 16/18), CIN2+ was found in 60.2% with reflex pHSIL or worse cytology (higher risk) and 10.2% with reflex low-grade SIL (LSIL) or normal cytology (intermediate risk). Median waiting time to colposcopy with the intermediate-risk group went up to 181 days. Our colposcopists were able to achieve a positive predictive value (PPV) for CIN2+ of 69.9%, higher than 57.8% PPV in the National Cervical Screening Program (NCSP) 2020 monitoring report. Women with type 3 transformation zone on colposcopy could be followed up with CST if no HSIL was suspected on screening or at colposcopy as their risk of CIN2+ was only 2.5%. CONCLUSIONS: Our findings support direct referral to colposcopy for women with higher-risk CST, with all cancers confined to this group. The NCSP recommendation to refer for colposcopy only after three intermediate-risk CST will need monitoring with the LSIL triage group.

Physical Therapy Management of an Individual With Post-COVID Syndrome: A Case Report.

OBJECTIVE: The purpose of this case report is to provide the clinical presentation and physical therapist management for a patient with post-COVID syndrome. Secondarily, the report highlights the importance of assessing cognitive and emotional health in patients with post-COVID syndrome. METHODS (CASE DESCRIPTION): A 37-year-old woman tested positive for SARS-CoV-2 and developed mild COVID-19 disease but did not require supplemental oxygen or hospitalization. The patient experienced persistent symptoms, including dyspnea, headaches, and cognitive fog. On day 62, they participated in an outpatient physical therapist evaluation that revealed deficits in exercise capacity, obtaining 50% of their age-predicted 6-minute walk distance. They had minor reductions in muscle strength and cognitive function. Self-reported quality of life was 50, and they scored above established cut-off scores for provisional diagnosis of posttraumatic stress disorder (PTSD). RESULTS: The patient participated in biweekly physical therapist sessions for 8 weeks, which included aerobic training, strengthening exercises, diaphragmatic breathing techniques, and mindfulness training. Metabolic equivalent for task levels increased with variability over the course of the program. The patient's muscle strength, physical function, and exercise capacity improved. 6-Minute walk distance increased by 199 m, equating to 80% of their age-predicted distance. Quality of life and PTSD scores did not improve. At evaluation after physical therapy, the patient was still experiencing migraines, dyspnea, fatigue, and cognitive dysfunction. CONCLUSION: This case report described the clinical presentation and physical therapist management of a person with post-COVID syndrome, a novel health condition for which little evidence exists to guide rehabilitation examination and interventions. Physical therapists should consider cognitive function and emotional health in their plan of care for patients with post-COVID syndromes. IMPACT: This case alerts physical therapists to post-COVID syndrome-which can include debilitating symptoms of decreased aerobic tolerance, anxiety, PTSD, and cognitive dysfunction-and to the role that therapists can play in assessing these symptoms and managing these patients.

Examining the disconnect between prolactin and parental care in avian brood parasites.

Prolactin is often referred to as the "parental hormone" but there are examples in which prolactin and parental behavior are disconnected. One intriguing example is in avian obligate brood parasites; species exhibiting high circulating prolactin but no parental care. To understand this disconnect, we examined transcriptional and behavioral responses to prolactin in brown-headed (Molothrus ater) and bronzed (M aeneus) brood parasitic cowbirds. We first examine prolactin-dependent regulation of transcriptome wide gene expression in the preoptic area (POA), a brain region associated with parental care across vertebrates. We next examined prolactin-dependent abundance of seven parental care-related candidate genes in hypothalamic regions that are prolactin-responsive in other avian species. We found no evidence of prolactin sensitivity in cowbirds in either case. To understand this prolactin insensitivity, we compared prolactin receptor transcript abundance between parasitic and nonparasitic species and between prolactin treated and untreated cowbirds. We observed significantly lower prolactin receptor transcript abundance in brown-headed but not bronzed cowbird POA compared with a nonparasite and no prolactin-dependent changes in either parasitic species. Finally, estrogen-primed female brown-headed cowbirds with or without prolactin treatment exhibited significantly greater avoidance of nestling begging stimuli compared with untreated birds. Taken together, our results suggest that modified prolactin receptor distributions in the POA and surrounding hypothalamic regions disconnect prolactin from parental care in brood parasitic cowbirds.

Hostility and cognitive control: Evidence of increased cardiovascular reactivity as a function of exposure to affective stress using a dichotic listening paradigm.

Indices of cognitive control were examined in men with high and low levels of trait hostility as a function of exposure to affective and cognitive stress. A dual concurrent task paradigm was used whereby participants intentionally directed focus to the left or right ear under dichotic listening conditions before and after exposure to angry infant vocalizations. Analysis of the behavioral data supports the prediction of reduced right frontal regulatory control in men with high levels of hostility as indicated by diminished capacity to suppress report of phonemes presented to the language dominant left hemisphere (right ear) in the Focus Left condition. This diminishment in the capacity to suppress report of phonemes presented to the right ear in the Focus Left condition is suggestive of reduced cognitive control. With respect to the neurophysiological data, heart rate increased for only men with high levels of hostility in the Focus Left condition, and this was especially evident in the post-affective stress condition. This increase in right hemisphere arousal provides additional evidence of reduced cognitive control and support for the capacity model of hostility by implicating poor right frontal regulatory control over right posterior cerebral regions under dual task conditions. The results are discussed in terms of integrating the construct of cognitive control into the capacity model as well as providing implications regarding reductions in the capacity to suppress predominant aggressive responses in domestic settings.

The growth of maternal-fetal emotional attachment in pregnant adolescents: a prospective cohort study.

STUDY OBJECTIVE: To describe self-reported maternal-fetal emotional attachment in adolescent women over the course of pregnancy, compare it with adult pregnant women, and identify risk factors for poor attachment. DESIGN: A prospective cohort study. SETTING: Young mothers' clinics in 2 public hospitals in metropolitan Melbourne, Australia. PARTICIPANTS: English-speaking young women aged 20 years and under attending their first antenatal visit. METHODS: Self-report questionnaires were completed in each trimester. Validated measures were used to assess anxiety and depression symptoms and maternal-fetal emotional attachment. Data were analyzed with existing data from pregnant adults. Regression analyses were conducted to establish factors independently associated with higher mean first-trimester attachment score and lowest-quartile third trimester score adjusting for confounding variables. MAIN OUTCOME MEASURE: Maternal-fetal emotional attachment, assessed by the Quality and Intensity subscales and Global score on Maternal Antenatal Attachment Scale (MAAS). RESULTS: 165/194 (85%) completed the first questionnaire; 130/165 (79%) provided complete data. Mean anxiety but not depression scores were significantly higher in adolescents than adults across pregnancy. Mean (95%CI) first-trimester adolescent Global MAAS was significantly lower than adults (70.3 (68.4, 72.2) vs 76.8 (75.4, 78.2) P < .01), but there were no significant second- or third-trimester between-group differences. Adjusted odds of a lowest-quartile third-trimester MAAS score was significantly associated with lower first-trimester score (P < .001), previous abortion (P = .02) and being born overseas (P = .002). CONCLUSION: Adolescents report slower development of antenatal emotional attachment than adults. Women with risk factors for poor attachment in late pregnancy are identifiable in early pregnancy and may benefit from additional multidisciplinary care.

What are we screening for? Development of a psychiatric referral tool for use with adolescent pregnant women.

OBJECTIVE: Psychiatric disorders commonly occur during pregnancy and in the postpartum period, posing substantial risks to both mother and unborn child. Consequently, screening for maternal psychiatric disorder during pregnancy and in the postnatal period has been advocated. In this paper, we describe the development and evaluation of a screening tool for use with a 'high risk' demographic group--adolescent women seeking maternity care. CONCLUSIONS: The tool was developed to identify women with, or at risk of, psychiatric disorders requiring specialist assessment and/or treatment, rather than only those with psychosocial concerns and/or distress, or with depressive symptoms alone. The tool was administered by midwives and used during discussion at the maternity team multidisciplinary meeting to facilitate referral or seek advice through secondary consultation. The tool was well accepted by the women attending the clinic. All women in the group who received psychiatric care later--either during confinement or during the 6-week postnatal period of follow-up--had already been identified by the tool in the antenatal period. Arguably, the tool enabled early intervention, treatment planning and effective care. We suggest that rather than adopting a 'one size fits all' approach, any screening should be tailored to the population of interest.

Novel and functional norepinephrine transporter protein variants identified in attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is a highly heritable disorder of impaired behavioral inhibition, increased motor activity, and inattention. The norepinephrine transporter (NET, SLC6A2) represents an important candidate gene for contribution to ADHD because it regulates catecholamine extracellular and tissue concentrations and contributes to executive functions disrupted in ADHD, and NET is a target for most effective ADHD therapeutics. We identified four NET coding single nucleotide polymorphisms (SNPs) in two ADHD sample sets; two SNPs produce protein variants (T283M, V245I), one of which, T283M, is a novel variant. Examination of the maternal family members through whom the T283M mutation was transmitted, provided no additional ADHD diagnoses. Given the previous identification of a NET mutation that contributes to a familial tachycardia syndrome, we examined autonomic function to reveal in the proband the highest standing-induced increase in heart rate among the ADHD subjects examined. We measured [3H]NE and [3H]dopamine transport for T283M, V245I, and a previously identified NET variant, T283R. T283M and V245I demonstrated decreased substrate transport, as did T283R, suggesting that the T283 residue is sensitive to mutation. Identification of polymorphic sites within NET, specifically those that produce functional consequences, is one critical step in elucidating the genetic variation contributing to the heritable component of diseases such as ADHD.

Choline transporter gene variation is associated with attention-deficit hyperactivity disorder.

The neurotransmitter acetylcholine (ACh) plays a critical role in brain circuits mediating motor control, attention, learning and memory. Cholinergic dysfunction is associated with multiple brain disorders including Alzheimer's Disease, addiction, schizophrenia and Attention-Deficit Hyperactivity Disorder (ADHD). The presynaptic choline transporter (CHT, SLC5A7) is the major, rate-limiting determinant of ACh production in the brain and periphery and is consequently upregulated during tasks that require sustained attention. Given the contribution of central cholinergic circuits to the control of movement and attention, we hypothesized that functional CHT gene variants might impact risk for ADHD. We performed a case-control study, followed by family-based association tests on a separate cohort, of two purportedly functional CHT polymorphisms (coding variant Ile89Val (rs1013940) and a genomic SNP 3' of the CHT gene (rs333229), affording both a replication sample and opportunities to reduce potential population stratification biases. Initial genotyping of pediatric ADHD subjects for two purportedly functional CHT alleles revealed a 2-3 fold elevation of the Val89 allele (n = 100; P = 0.02) relative to healthy controls, as well as a significant decrease of the 3'SNP minor allele in Caucasian male subjects (n = 60; P = 0.004). In family based association tests, we found significant overtransmission of the Val89 variant to children with a Combined subtype diagnosis (OR = 3.16; P = 0.01), with an increased Odds Ratio for a haplotype comprising both minor alleles. These studies show evidence of cholinergic deficits in ADHD, particularly for subjects with the Combined subtype, and, if replicated, may encourage further consideration of cholinergic agonist therapy in the disorder.

A polymorphism in the norepinephrine transporter gene alters promoter activity and is associated with attention-deficit hyperactivity disorder.

The norepinephrine transporter critically regulates both neurotransmission and homeostasis of norepinephrine in the nervous system. In this study, we report a previously uncharacterized and common A/T polymorphism at -3081 upstream of the transcription initiation site of the human norepinephrine transporter gene [solute carrier family 6, member 2 (SLC6A2)]. Using both homologous and heterologous promoter-reporter constructs, we found that the -3081(T) allele significantly decreases promoter function compared with the A allele. Interestingly, this T allele creates a new palindromic E2-box motif that interacts with Slug and Scratch, neural-expressed transcriptional repressors binding to the E2-box motif. We also found that both Slug and Scratch repress the SLC6A2 promoter activity only when it contains the T allele. Finally, we observed a significant association between the -3081(A/T) polymorphism and attention-deficit hyperactivity disorder (ADHD), suggesting that anomalous transcription factor-based repression of SLC6A2 may increase risk for the development of attention-deficit hyperactivity disorder and other neuropsychiatric diseases.

Impact of demographic factors, early family relationships and depressive symptomatology in teenage pregnancy.

AIM: Teenage pregnancy has been well studied from a demographic risk perspective, but less data examining the early interpersonal family experiences of teenage mothers are available. We aimed to explore the relative impact of demographic, early interpersonal family relationships and depressive symptomatology as associations for teenage, as compared to non-teenage, childbearing. METHOD: A prospective cross-sectional cohort study was undertaken. Institutional ethics committee approval and informed consent were obtained. Data from consecutive teenage (teenage) and non-teenage (control) subgroups of antenatal women were compared. Subjects were interviewed and completed the following questionnaires: demographic, drug use and lifestyle; early life experiences; Hospital Anxiety and Depression Scale (HADS); and General Health Questionnaire-28. RESULTS: In multivariate analysis, the following factors had a significant independent association with younger age of motherhood in order of magnitude: a history of parental separation/divorce in early childhood; exposure to family violence in early childhood; illicit drug use (ever or in pregnancy); idealization of the pregnancy; low family income; a positive HADS-A or HADS-D subscale score; and a low level of education. CONCLUSIONS: Interventions to reduce the rate of teenage births need to be multifocal and should include strategies to address early childhood exposure to parental separation and violence, reduce idealization of pregnancy, diagnose psychological symptomatology and offer alternative career choices to children defaulting in the education system.